RxPG News : Orthopedics

Programme reduces hip fractures by 37 percent

Wed, 05 Nov 2008 15:43:47 PST

( from http://www.rxpgnews.com ) Washington, Nov 5 - Proactive measures can reduce hip fracture rates by an average of 37.2 percent and as much as 50 percent among those at risk, according to a study.

The five-year study, the most exhaustive of its kind, conducted by Kaiser Permanente, tracked more than 625,000 male and female patients over the age of 50 in Southern California, who had specific risk factors for osteoporosis and/or hip fractures.

Of the 10 million Americans who have osteoporosis, 80 percent are women. More than 300,000 hip fractures are reported annually in the US. Twenty-four percent end up in a nursing home, 50 percent never reach their functional capacity, and 25 percent of patients with a hip fracture die in the first year after the incident.

The implementation of a number of initiatives in the Kaiser Permanente Southern California Healthy Bones Program reduced the hip fracture rates beyond the goal rate of 25 percent.

'One-half of all women and one-third of all men will sustain a fragility fracture in their lifetime. The mortality rate due to osteoporosis-related fractures is greater than the rates for breast cancer and cervical cancer combined,' said co-author Richard M. Dell, orthopaedic surgeon at Kaiser Permanente Bellflower Medical Centre.

'Yet it's a misconception that nothing can be done to prevent or treat osteoporosis. It is possible to achieve at least a 25 percent reduction in the hip fracture rate in the United States if a more active role is taken by all orthopedic surgeons in osteoporosis disease management.'

National Osteoporosis Foundation reports that although osteoporosis can affect people of all ages, the problem has reached epidemic proportions with the rapidly ageing population, said a Kaiser Permanente release.

The study was published online by The Journal of Bone & Joint Surgery.

Drink tea for stronger bones, suggests study

Tue, 09 Oct 2007 11:00:41 PST

( from http://www.rxpgnews.com ) Sydney, Oct 9 - Drinking tea regularly, known to have several health benefits, may be good for the bones too, say researchers in Australia.

Health experts in Perth studied 275 elderly women aged 70-85 and found that those who drank tea had higher bone density at their hips and less bone loss than women who didn't drink tea.

It was a larger five-year study of calcium supplements and osteoporosis - a disease that weakens the bones and increases the risk of fractures. The researchers led by Amanda Devine of University of Western Australia, Perth, measured the bone density of the hip at the beginning and end of the study and also kept a tab on the amount of black and green tea the women drank.

Although the study did not find a link between the cups of tea consumed per day and bone mineral density, it found the bone density at two places at the hip was higher in tea drinkers than in non-tea drinkers, the online edition of health Magazine WebMD reported.

Tea drinkers also had less loss of bone density over a four-year period compared to the women who did not drink tea.

These results took into account factors such as smoking history and use of calcium supplements, according to the study published in The American Journal of Clinical Nutrition showed.

'Other variables, such as dietary calcium and coffee intake, physical activity, and smoking did not appear to be important confounders of the relation between tea and bone density,' the researchers said.

People in the past have been using tea in managing and preventing allergies, diabetes, bacterial and viral infections, cavities and to reduce inflammatory diseases.

A previous study by the Yale School of Medicine had indicated that those who consume green tea on an average of 1.2 litres a day get several health benefits.

Separate studies have also revealed that tea can help improve gastrointestinal functions, alcohol metabolism, kidney, liver and pancreatic functions and protect the skin and eyes.

Second SPORT Study Shows Surgery Advantage for Spinal Stenosis and Slipped Vertebra

Thu, 31 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) In one of the three most common back conditions for which patients seek treatment, surgery proved to have substantially better results than non-surgical remedies, according to Dartmouth-led research published in the May 31 New England Journal of Medicine. The paper is the second in a series detailing the findings of the Spine Patient Outcomes Research Trial (SPORT), a seven-year, $21 million national study funded by the National Institutes of Health.

In cases of degenerative spondylolisthesis with spinal stenosis, a condition that affects six times as many women as men and is especially prevalent among African-American women, surgery was twice as effective as non-surgical approaches in reducing pain and restoring functionality for patients.

This publication follows the release of earlier SPORT findings in November, which looked at patients seeking treatment for disk herniation with sciatica. For that condition, the difference in outcomes between the surgical and non-operative groups was less.

The SPORT study was undertaken with one purpose in mind: to give physicians and patients solid information that would allow them to make informed choices when faced with a decision of how to treat their back condition, said lead author Dr. James N. Weinstein, professor and chair of orthopaedics at Dartmouth Medical School and Dartmouth-Hitchcock Medical Center.

Although back surgeries are among the most common surgical procedures performed in the United States, until SPORT, there had been only a few very small controlled trials to gauge their effectiveness.

Degenerative spondylolisthesis (DS) is the forward slippage of one lumbar vertebra on the one below it. It generally occurs after age 50. It is not clear why it occurs more often in African-American women. Although DS alone generally causes no symptoms, in some cases it can result in spinal stenosis?-narrowing of the spinal canal which causes pressure on the nerves?-resulting in significant pain in the legs that is worsened by simply taking a walk.

SPORT followed 601 patients diagnosed with DS and symptomatic spinal stenosis. Of those, 372 received surgery within two years and 235 remained non-operative. Two years after enrollment in the trial, while non-operative patients reported only modest improvement in their condition, patients who had surgery reported significantly reduced pain and improved functionality. Surgical patients saw relief from symptoms fairly quickly, reporting major improvements as early as six weeks after their operation.

Non-operative treatments included physical therapy, steroid injections, and medicines to relieve pain. Surgery involved relieving pressure on the nerves through removal of bone and soft tissue in a procedure called a decompressive laminectomy.

As a surgeon, it's very important to me that I have evidence that I can share with my patients as they are trying to decide how to proceed with treatment, Weinstein said. Up until now, we suspected surgery produced better results, but we had little objective data to support that. With the results of this study, we can now discuss much more fully the surgical and non-surgical options available to our patients so that they can make an informed choice.

Although the study was designed to look at a randomized and an observational cohort, fully 40 percent of participants who had been randomized changed their minds after enrollment in the trial and switched to the other group, i.e. choosing to have surgery after being randomized to the non-operative group, or deciding to proceed non-surgically after being randomized to the surgical group. As a result of the substantial crossover between surgical and non-surgical groups in the randomized cohort, the authors chose to publish the results based on what treatment was actually received in each group. While this is not a randomized comparison, the analysis carefully controlled for differences that existed between the two groups at the outset.

The third major SPORT study, on the effectiveness of surgery vs. non-surgical options for spinal stenosis without any spondylolisthesis, is expected to be released later this year. Additional papers based on the wealth of data gathered from the entire SPORT process will be published over the next several months.

Co-authors on the DS article were Jon D. Lurie MD MS; Tor Tosteson ScD; Brett Hanscom MS; Anna N.A. Tosteson ScD; Emily A. Blood MS; Nancy J.O. Birkmeyer PhD; Alan S. Hilibrand MD; Harry N. Herkowitz MD; Frank P. Cammisa MD; Todd Albert MD; Sanford E. Emery MD MBA; Lawrence G. Lenke MD; William A. Abdu MD MS; Michael Longley MD; Thomas J. Errico MD; and Serena Hu MD.

Centers enrolling patients in the study in addition to Dartmouth-Hitchcock Medical Center were: Wm. Beaumont Hospital, Royal Ok, MI; Emory University, Atlanta; NYU/Hospital for Joint Diseases, New York; Hospital for Special Surgery, New York; Kaiser Permanente, Oakland, CA; Nebraska Foundation for Spinal Research, Omaha; Rothman Institute at Thomas Jefferson University Hospital, Philadelphia; Rush Presbyterian-St. Luke's Medical Center, Chicago; University of California, San Francisco; University Hospitals of Cleveland/Case Western Reserve University, OH; Washington University, St. Louis; Maine Spine and Rehabilitation, Scarborough.

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Molecule that destroys bone also protects it, new research shows

Sun, 20 May 2007 03:59:37 PST

( from http://www.rxpgnews.com ) An immune system component that is a primary cause of bone destruction and inflammation in autoimmune diseases such as rheumatoid arthritis actually protects bone in the oral cavity from infectious pathogens that play a major role in periodontal disease in humans, research at the University at Buffalo has shown.

The component, IL-17, was recognized only in the past 18 months to be a primary cause of bone destruction and inflammation in autoimmune diseases. Therapies that target IL-17 or its cellular receptor currently are being developed.

However, a UB molecular biologist has discovered that, in contrast to its action in rheumatoid arthritis(RA), IL-17 actually protects bone in the oral cavity from infectious pathogens such as Porphyromonas gingivalis, a bacterium that plays a major role in most periodontal disease in humans.

The research findings appear in the current (May) issue of the journal Blood.

Sarah L. Gaffen, Ph.D., associate professor of oral biology in the UB School of Dental Medicine and associate professor of microbiology and immunology in the UB School of Medicine and Biomedical Sciences, is senior author. Jeffrey J. Yu, a medical student and doctoral candidate who is a researcher working in Gaffen's lab, is first author.

Gaffen and colleagues conducted the research in mice bred to have no receptors for IL-17. Other researchers had shown previously, using rats and mice as animal models, that blocking the receptor for IL-17 could be an effective therapy for RA and possibly for other autoimmune diseases such as multiple sclerosis, colitis, psoriasis and lupus.

The effects of an IL-17 deficiency in periodontal disease, however, were unknown, so Gaffen's lab set out to investigate.

I predicted these mice without the IL-17 receptor were going to be protected from periodontal bone loss, just like they're protected from arthritic bone loss, Gaffen said. In fact, we got the opposite result. The mice without IL-17 were much more susceptible to bone loss caused by periodontal disease, compared to normal mice.

What's the difference between an autoimmune disease like RA and periodontal disease Periodontal disease is an infectious disease, and as with most infectious diseases, white blood cells of the innate immune system called neutrophils play a critical role in fighting infections. In fact, humans with neutrophil defects usually lose all their teeth by the time they are 20 due to severe periodontal disease.

It turns out that IL-17 is really important in regulating neutrophils by causing other cells in the vicinity to recruit these infection fighters to the infection site, Gaffen said.

IL-17 is a cytokine, a protein hormone made by T helper cells of the immune system that stimulate immunity. Gaffen noted that until recently, immunologists believed there were only two major types of T helper cells -- TH1 and TH2 -- which were believed to be responsible for nearly all immune system activities.

This paradigm underwent a sea change in 2005 with the discovery of a new type of T cell that produces IL-17, now called TH-17, she said. We know now that almost all autoimmune diseases, at least in the mouse model, are caused by TH-17 cells. This new information has forced scientists to revise completely how they view their favorite disease. Everyone now has to rethink the causative mechanism.

Gaffen said IL-17 likely would be toxic if given systemically, so it may not be a therapeutic candidate to increase immunity. But inhibitors of IL-17 are considered important targets for drugs to treat autoimmune diseases such as RA and psoriasis.

On the down side, however, this new finding indicates that inhibiting IL-17 too much could put people taking such a drug at risk for opportunistic infections such as periodontal disease and tuberculosis, she noted.

Developing knowledge about the molecules that contribute to host defense versus pathology is very important for gaining a fundamental understanding of the immune system, Gaffen said, but also because the consequences of therapies that target these cytokines need to be understood.

Annual treatment with Zoledronic acid significantly reduces bone fractures

Thu, 03 May 2007 04:09:22 PST

( from http://www.rxpgnews.com ) Data published in this weekâs issue of The New England Journal of Medicine show that a once-yearly treatment significantly reduced the incidence of all types of osteoporotic bone fractures over three years in women with postmenopausal osteoporosis. The publication marks the first time that an osteoporosis treatment significantly reduced all types of fractures in a single study.

The Phase III clinical study involved more than 7,700 women between the ages of 65 and 89 in 27 countries. All women involved in the study had postmenopausal osteoporosis and received zoledronic acid Injection or placebo. Results from the study show that Zoledronic acid reduced the frequency of fractures among the areas of the body that are typically affected by osteoporosis, including the hip, spine, and wrist. Specifically, a 70 percent reduction was achieved in spine fractures. The risk of hip fractures, which are associated with significant mortality, was reduced by 41 percent.

The National Osteoporosis Society of UK welcomes this forthcoming and exciting new treatment. This drug is not yet licensed for use in the UK, but when available, it will add to the choice of drug treatments available for people at risk of breaking a bone due to osteoporosis. However, patient safety is paramount and, as with any new drug to market, its safety profile will need to be fully assessed.

Zoledronic acid is one of the bisphosphonate drugs. Oral bisphosphonates can be difficult to take properly and can cause side effects. If not taken correctly these drugs will be less effective. An annual intravenous preparation may prove to be a convenient, cost effective strategy, providing that any potential problems in arranging the administration of the treatment are overcome.

NIST measuring device aims to up hip operation success

Sat, 28 Apr 2007 12:27:46 PST

( from http://www.rxpgnews.com )

NIST prototype hip replacement "phantom" (l.) provides a precisely measured coordinate system and magnetic ball and socket joint to calibrate and to measure the clinically relevant performance of Computer Assisted Orthopaedic Surgery tracking instruments used in delicate operations to install artificial hip joints (r.).

Researchers at the National Institute of Standards and Technology (NIST) are developing state-of-the-art measuring techniques, similar to those used in making aerospace components fit together precisely, that soon could improve success rates for hip replacement surgery. At the request of a group of prominent orthopaedic surgeons and the American Academy of Orthopaedic Surgeons (AAOS), the NIST researchers are working to improve calibrations and operating room testing of the Computer Assisted Orthopaedic Surgery (CAOS) tracking instruments surgeons use to plan the delicate, highly complex operation.

To be completely successful, CAOS hip replacement surgery must take into account tiny human skeletal differences. Imprecise measurements, which could result from conditions seemingly unrelated to the surgery, such as operation room noise or temperature, can lead to poor positioning of implants, leaving some former patients with discomfort during walking and, in rarer cases, a need to redo the operation.

The researchers have built a lightweight device called a âphantomâ that resembles the artificial socket, ball and femur substitutes that surgeons use to replace the joint and bone in hip operations, based on a calibrated XY coordinate frame. They drilled tiny holes at precisely measured intervals into the phantom and made cuts at precisely measured angles, favored by surgeons for CAOS operations. Because the precise coordinates of the mechanical (magnetic) ball and socket joint center of rotation have been measured, manufacturers of CAOS tracking sensors can use the phantom to test the accuracy of their measuring instruments. Surgeons also should be able to test the accuracy of their CAOS devices, just before making their first incision, to measure ball and socket joint center of rotation coordinates, angles for cuts into the bone and places for the insertion of screws

Currently, no standardized approach to the evaluation of CAOS technology exists, but an ASTM International committee is working on the establishment of such standards. In the coming months NIST will submit its hip CAOS phantom to orthopaedic surgeons for review. Clinical trials could follow. If the device wins Federal Drug Administration (FDA) approval, it can be expected to find its way into operating rooms across the country and world. The researchers look forward to extending the application of the technology to surgical procedures on the knee and shoulder.

Mayo Clinic solves painful puzzle of UT ligament split tear in wrist

Wed, 11 Apr 2007 04:59:01 PST

( from http://www.rxpgnews.com ) A Mayo Clinic orthopedic surgeon has discovered a common cause of debilitating wrist pain - a split tear of the UT ligament - that can be reliably detected through a simple physical examination and can be fully repaired through an arthroscopically guided surgical procedure. The findings are published in the April issue of the American Journal of Hand Surgery.

In the study of 272 consecutive patients (53.7 percent males, median age 33.7) with wrist pain who had undergone arthroscopy between 1998 and 2005, the Mayo Clinic team discovered that a positive "ulnar fovea sign" was highly effective in diagnosing either a complete ligament rupture or the newly described condition, a split tear of the ulnotriquetral (UT) ligament. The test involves pressing the ulnar fovea region of the patients' wrists (the side opposite the thumb) to determine tenderness. The researchers found a positive ulnar fovea test was 95 percent sensitive in revealing patients with a rupture or a UT split tear. The test's specificity was 86.5 percent.

Richard Berger, M.D., Ph.D., who led the study, says the UT split tear is a common but heretofore undefined injury, in which the wrist joint is stable but painful. "Typically, ligament injuries involve a rupture in which the ligament is completely severed," he explains. "The joint is unstable because the ligament is no longer holding the bones in their proper positions, and the crosswise rupture is easily visible through magnetic resonance imaging (MRI).

"The UT split tear is different, because the ligament is still attached to the bones on both ends, but is split open lengthwise," Dr. Berger continues. "The joint is stable, and the patient can have an MRI that would be interpreted as normal because there isn't a complete severing of the ligament. Even looking inside the joint with an arthroscope, the split tear isn't immediately obvious unless you know what to look for, and until now no one was looking for it because this type of injury hadn't been discovered. The diagnosis would have been called simple irritation or inflammation."

Dr. Berger says the split tear discovery came as "an epiphany," when he performed the ulnar fovea test on a patient while viewing the joint arthroscopically. "I saw that the source of the pain was exactly where I was pressing," he says. "When I cleared some of the blood vessel debris from the area, it became apparent that what had initially looked like a normal ligament was in fact split open lengthwise, so I was seeing the inside of the ligament."

As Dr. Berger performed the ulnar fovea test on subsequent patients and followed with arthroscopic examination, he noticed that a large majority of those with the positive ulnar fovea sign but stable joints had UT split tears.

"It's good news that this simple test is so effective at pinpointing the problem," he says. "What's even better is that we have a treatment that can restore full, pain-free function and improve quality of life for decades for these mostly younger patients."

Dr. Berger's treatment for a UT split tear uses arthroscopically guided surgery to suture the ligament and repair the split. After six weeks in a cast that immobilizes the wrist, the patient begins rehabilitation. Dr. Berger says the repair has been highly durable and has helped patients return to full strength at work or play within a few months after surgery.

"We've seen sheet metal workers and dairy farmers return to work," he says. "We've also had athletes restored: bowlers hurling a 16-pound ball, golfers, and even a major league baseball player. They seem good as new, and we haven't seen a risk of reinjury.

"The split tear of the UT ligament will help explain much of the wrist pain for which the cause previously had been unknown," Dr. Berger concludes. "It's especially gratifying to not only diagnose the reasons for the pain, but also to have such an effective treatment."

Benzodiazepine use not associated with hip fractures

Fri, 16 Mar 2007 05:18:01 PST

( from http://www.rxpgnews.com ) Benzodiazepine use was not shown to be associated with hip fractures after all, according to a new study from the Department of Ambulatory Care and Prevention (of Harvard Medical School and Harvard Pilgrim Health Care). Previous epidemiological studies suggesting an association have been used to support legislation and policy decisions that limit access to these drugs among the elderly. These policies may need to be reexamined based on these new findings, which are being published in the Jan. 16 Annals of Internal Medicine.

Benzodiazepines are sedative drugs prescribed for anxiety, sleep, and seizure disorders. Concerns about abuse, misuse, and adverse effects of these drugs--including hip fractures among the elderly--have prompted state and national policies intended to regulate access to them. Since January 2006, benzodiazepines have been excluded from coverage through the Medicare Part D drug benefit.

Hip fractures are the most serious individual and public health risks attributed to benzodiazepines because they often lead to disability and death among the elderly. An expected benefit of limiting access to these drugs is a decrease in the incidence of falls and resulting hip fractures. However, no data exist to demonstrate this policy effect.

Anita Wagner, PharmD, MPH, DrPH, lead author of the study and assistant professor of ambulatory care and prevention in the Department of Ambulatory Care and Prevention (DACP) of Harvard Medical School and Harvard Pilgrim Health Care, and colleagues studied whether a state policy that drastically decreased use of benzodiazepines resulted in fewer hip fractures among the elderly. They looked for changes in hip fracture rates in a stable population of more than 90,000 Medicaid recipients age 65 and older before and after a policy was implemented in New York in 1989 requiring benzodiazepine prescribing on triplicate forms. Since then, all physicians in the state are required to obtain, pay for, and use serially-numbered triplicate forms to prescribe benzodiazepines. Pharmacists forward one copy of the prescription to state health authorities for surveillance, allowing for monitoring of each physician's prescribing, each pharmacy's dispensing, and each patient's receipt of benzodiazepines.

The policy resulted in an immediate 60 percent reduction in benzodiazepine use among women and 58 percent among men. The neighboring demographically-similar state New Jersey did not regulate benzodiazepine prescribing and benzodiazepine use did not change. Incidence of hip fracture before and after the policy change was similar.

"The policy drastically decreased use of benzodiazepines in New York and we did not see any decline in hip fracture rates compared to New Jersey; in fact, we seem to see an increase in New York over New Jersey," says Wagner.

There are several possible explanations for the study results. Most plausible, however, are biases in the previous studies that found a relationship between these drugs and hip fractures.

"It is very challenging to answer the question whether or not benzodiazepines cause hip fractures. People who get benzodiazepines, such as chronically ill elderly patients with dementia, have conditions, like dementia, that can cause hip fractures--and their hip fractures may not be due to their benzodiazepines," says Wagner.

"The challenge of disentangling the effects of benzodiazepines from other causes of hip fractures in the elderly is especially concerning when study results are used to guide policies that restrict access to medicines for huge populations," says senior author Stephen Soumerai, ScD, professor of ambulatory care and prevention at DACP.

Policy makers may expect that reducing access to benzodiazepines under Medicare Part D and other policies will decrease hip fracture risk. "Our study suggests that these expectations are not justified," says Soumerai.

Additionally, if benzodiazepine medications are abruptly terminated, as may be the case when people lose coverage of a drug, negative effects can occur, such as withdrawal reactions, seizures, emergency department visits, and hospital admissions. These may offset any potential savings achieved by limiting coverage of benzodiazepines.

The investigators are currently funded by a grant from the National Institute on Aging to monitor the impact of the Medicare Drug Benefit. They believe future studies based on these new data will shed additional light on how policies that exclude coverage for benzodiazepines affect the rate of hip fracture among the elderly.

Genes may determine success of hip replacement surgery

Thu, 15 Mar 2007 06:00:49 PST

( from http://www.rxpgnews.com ) The success of long term hip replacement surgery may lie in the genes, suggests research published ahead of print in the Annals of the Rheumatic Diseases.

The researchers analysed genetic variations in 312 people, just over half of whom (162) had problems after hip replacement in the 10 years following surgery.

Among those with symptoms, 91 had early signs of aseptic loosening, which describes a condition in which the artificial joint comes loose and the surrounding bone begins to dissolve. The other 71 patients had deep-seated infection, which occurs when the body is unable to control infection caused by bacteria colonising the artificial implants.

DNA samples were taken from all participants to test for genetic variations in genes responsible for generating matrix metalloproteinase 1, or MMP1 for short, interleukin 6, and vitamin D synthesis.

MMP1 is an enzyme that breaks down collagen, the main protein found in bone and cartilage, while interleukin 6 is a chemical involved in bone metabolism and the immune response.

Vitamin D synthesis is important for strong healthy bones.

Variations in the interleukin 6 gene did not seem to have any effect. But those with variations in MMP1 were more than three times as likely to have aseptic loosening as those who did not carry the genetic variation.

And variations in the vitamin D receptor gene almost doubled the chances of bone dissolution and deep infection.

The authors conclude that if confirmed in other research, these findings could be used to predict long term success in patients undergoing hip replacement surgery. And they could also be used to develop targeted genetic treatments.

Obesity associated with a higher risk of complications in women undergoing total hip replacement

Wed, 28 Feb 2007 03:17:55 PST

( from http://www.rxpgnews.com ) Obese patients tend to have a higher prevalence of total hip replacements due to a higher incidence of hip osteoarthritis. This is of particular concern in light of the trend in rising rates of obesity in developed countries. A new study published in the March 2007 issue of Arthritis Care & Research evaluated the effects of obesity on complications and outcomes following total hip replacements and investigated whether the results differed in obese women and men.

Led by Anne Lübbeke, M.D., MSc, of the Geneva University Hospital in Geneva, Switzerland, researchers conducted a study of all patients who underwent total hip replacements between March 1996 and July 2005 at their hospital. Of the 2,495 hip replacements (some were bilateral), 589 were performed in obese patients, with a higher prevalence of obese males than females. Obesity was defined as a body mass index equal to or greater than 30 kg/m2. Researchers evaluated the incidence of infection, dislocation, and revision (redoing the replacement), as well as quality of life, satisfaction, and general health five years after undergoing a hip replacement.

The results showed that obesity was associated with a substantially higher risk for infection in women, led to more dislocations (with a greater increase in women), and resulted in more revisions due to septic loosening (caused by infection). After five years, outcomes for 635 hips in non-obese patients and 183 hips in obese patients were evaluated. Obese women, but not obese men, reported moderately lower functional outcomes and slightly less satisfaction, mostly due to a higher incidence of complications.

The risk factors for infection that are known to be more frequent in obese patients, such as longer operating time and diabetes, were not related to females in the study and do not explain why the women had poorer results. The researchers suggest that other reasons related to sex differences, such as body fat distribution and metabolic response, might be involved. They also note that the higher number of dislocations in obese women may be due to the lower peripheral muscle strength seen in this group of patients, while the lower functional outcomes may be due to additional factors such as a higher incidence of osteoarthritis.

"To the best of our knowledge, this is the first study analyzing sex differences as related to outcomes in obese THA [total hip replacement] patients," the authors state. They note that previous studies on the relationship between obesity, complications, and outcomes following hip replacement are contradictory, but the results are muddied by a lack of information on sex, multiple definitions of obesity, and a limited interpretation of complications. "Because our study revealed increased complications among obese women, we suggest that surgeons counsel this group of patients so that they are made aware of this fact," the authors conclude. "In addition, participating in a weight-loss program prior to surgery might be beneficial for such patients."

Vitamin D supplements may reduce falls in elderly

Thu, 22 Feb 2007 07:53:37 PST

( from http://www.rxpgnews.com ) New research suggests that reducing the number of falls suffered by seniors in nursing homes may be helped by taking a vitamin, along with other measures known to decrease falls. According to a study in Journal of the American Geriatrics Society, seniors taking a high daily dose of vitamin D experienced 72 percent fewer falls compared to those taking a placebo.

Approximately 50 percent of nursing home residents fall every year, and those who are injured become even more prone to future falls. According to study authors Kerry Broe and Douglas Kiel, "lowering the risk of falls with a simple vitamin D supplement could improve the quality of life for nursing home residents by reducing the incidence of falls."

Past studies have shown that vitamin D could help prevent falls in seniors, and may be due to a possible strengthening effect the vitamin has on the musculoskeletal system. Until now, we didnt know what dosage amount would be effective, say Broe and Kiel. The dose that was most effective, 800 International Units per day, is higher than the dose typically prescribed to seniors. Taking this dose of vitamin D should be done only through the approval of a patient's doctor and certain conditions, such as high blood calcium levels, need to be considered by a physician.

The authors note that further research on the subject is required to accurately determine vitamin Ds effect with regard to patients current health conditions and other variables, such as ethnicity. Falls are caused by many factors and vitamin D may be only one of many methods to be discovered that reduce their incidence. Taking vitamin D only may not result in fall reductions and all preventative measures need to be considered.

A novel scaffold could improve cartilage repair

Tue, 06 Feb 2007 12:20:56 PST

( from http://www.rxpgnews.com )

In the near future, surgeons will be able to impregnate custom-designed scaffolds with cartilage-forming stem cells and chemicals that stimulate their growth and then implant them into patients during a single procedure, the researchers said.

Using a unique weaving machine of their design, Duke University Medical Center researchers have created a three-dimensional fabric "scaffold" that could greatly improve the ability of physicians to repair damaged joints with the patient's own stem cells.

"If further experiments are successful, the scaffold could be used in clinical trials within three or four years," said Franklin Moutos, a graduate student in the Orthopedic Bioengineering Laboratory who designed and built the weaving machine. "The first joints to be treated this way would likely be hips and shoulders, though the approach should work for cartilage damage in any joint."

The researchers reported the new technology in the February 2007 issue of the journal Nature Materials. The research was supported by the National Institutes of Health, the National Aeronautics and Space Administration and the Coulter Foundation.

Current therapies to repair cartilage damage are not effective, the researchers said. The only bioengineering approach to such joint repair involves removing cartilage cells from patients and then "growing" them in a laboratory to form new cartilage. However, it can take several months to grow a piece of cartilage large enough to be implanted back into the patient. Additionally, this laboratory-grown cartilage is not as durable as native cartilage.

In laboratory tests, the fabric scaffold that the researchers have created had the same mechanical properties as native cartilage. In the near future, surgeons will be able to impregnate custom-designed scaffolds with cartilage-forming stem cells and chemicals that stimulate their growth and then implant them into patients during a single procedure, the researchers said.

"By taking a synthetic material that already has the properties of cartilage and combining it with living cells, we can build a human tissue that can be integrated rapidly into the body, representing a new approach in the field of tissue engineering," Moutos said.

"Once implanted, the cartilage cells will grow throughout the scaffold, and over time the scaffold will slowly dissolve, leaving the new cartilage tissue" he said. "The use of this scaffold will also permit doctors to treat larger areas of cartilage damage, since the current approaches are only suitable for repairing smaller areas of cartilage damage or injury."

Cartilage is a type of connective tissue that lines the ends of bones, providing cushioning and a smooth surface for their movement within the joint. Damage to cartilage is difficult to treat, the researchers said, because the tissue lacks a supply of blood, nerve and lymph and has limited capacity for repair.

Current strategies for treating cartilage damage, such as surgery or cartilage implants, are fairly limited, said Farshid Guilak, Ph.D., director of orthopedic research at Duke and senior member of the research team.

"We don't currently have a satisfactory remedy for people who suffer a cartilage-damaging injury," Guilak said. "There is a real need for a new approach to treating these injuries. One of the beauties of this system is that since the cells are from the same patients, there are no worries of adverse immune responses or disease transmission.

"The scaffold will give surgeons the opportunity to treat their patients immediately, while patients won't have to wait for months with their painful joint," Guilak said.

Most machines that produce fabrics weave one set of fibers that are oriented perpendicularly to another set of fibers. However, the machine that Moutos developed adds a third set of fibers, which creates a three-dimensional product. Also, since the scaffold is a woven material, there are tiny spaces where cartilage cells can nestle and grow.

How reliable is "probe to bone" test ?

Mon, 05 Feb 2007 12:42:26 PST

( from http://www.rxpgnews.com ) An often-used tool to diagnose very common and sometimes limb-threatening bone infections in persons with diabetes may not be as reliable as many once believed, based on a recent study by a transatlantic team of researchers. The study, published to the Web ahead of print in February's edition of the journal Diabetes Care, longitudinally evaluated a large sample of persons with diabetes with wounds, and tested the commonly performed "probe to bone" test. The test, which uses a sterile instrument to feel for bone inside a wound, has been thought by many to be highly predictive of bone infection.

"It certainly makes sense that if you can feel bone, then it must be infected," noted David G. Armstrong, DPM, PhD, Professor of Surgery at Scholl's Center for Lower Extremity Ambulatory Research (CLEAR) at Rosalind Franklin University of Medicine and Science, and a co-investigator on the study. "Unfortunately, though, this doesn't always seem to be the case. The test, if used by itself in a normal clinical setting, isn't much better than flipping a coin. We therefore recommend it be used with other aids, such as biopsy or appropriate imaging tools."

MR imaging can make a dramatic difference in the management of patients with ankle pain

Mon, 08 Jan 2007 06:23:38 PST

( from http://www.rxpgnews.com ) MR imaging can make a dramatic difference in the management of patients with ankle pain, changing treatment in about one-third of the patients, a new study finds.

The study, of 91 patients, found that MR changed the management plans of 35% of patients, said Philip W.P. Bearcroft, MD, of Cambridge University Hospitals in England. "This is itself is significant, but more significant is the fact that before an MRI was done, 65 of the 91 patients were scheduled to undergo surgery. After an MRI was done, nine of those patients were treated nonsurgically," Dr. Bearcroft said.

Dr. Bearcroft and his colleagues conducted the study in conjunction with an orthopedic foot and ankle surgeon at a regional teaching hospital. The surgeon noted his proposed treatment plan for each patient before and after an MR examination. The surgeon also noted the potential diagnoses for each injury. Before an MR examination was done, the surgeon indicated an average 2.3 possible diagnoses per patient. "After MRI was performed, the number of diagnoses per patient was reduced to 1.2," said Dr. Bearcroft. MRI increased the referring physician's confidence in his diagnoses, Dr. Bearcroft said. "In 66% of the MRI examinations performed, the referring surgeon felt that his understanding of the patient's disease had either depended upon or had been substantially improved by MRI," he added.

"This study is a bit different than the traditional radiological study," Dr. Bearcroft said. "Most studies relate to improving technique or look at the accuracy and predictive value of imaging techniques. This one was designed to determine if we really make a difference to the referring physician and the patient," he said.

Stomach drugs may weaken bones

Wed, 27 Dec 2006 17:34:15 PST

( from http://www.rxpgnews.com ) New York, Dec 27 - Long-term use of certain stomach drugs may weaken the bones and increase the risk of hip fracture, warns a new study that advises doctors to consider the risk when prescribing such drugs.

Researchers at the University of Pennsylvania Medical School studied records from the general practice research database of Britain. All the people involved were aged over 50 and some had been taking proton pump inhibitors -.

PPI's are a group of drugs whose main action is pronounced and long-lasting reduction of gastric acid production.

The research found that people who had been taking the drugs for over a year had a 44 percent greater risk of suffering a hip fracture, reported the online edition of BBC News.

Taking the drugs for even longer seemed to increase the risk further, according to the study that appeared in the Journal of the American Association.

Hip fracture is one of the most significant causes of severe disability in older people - up to one in five people who suffer a fracture following a fall die within 12 months.

Sitting in an upright position places unnecessary strain on your back

Tue, 28 Nov 2006 18:31:57 PST

( from http://www.rxpgnews.com ) Researchers are using a new form of magnetic resonance imaging (MRI) to show that sitting in an upright position places unnecessary strain on your back, leading to potentially chronic pain problems if you spend long hours sitting.

"A 135-degree body-thigh sitting posture was demonstrated to be the best biomechanical sitting position, as opposed to a 90-degree posture, which most people consider normal," said Waseem Amir Bashir, M.B.Ch.B., F.R.C.R., author and clinical fellow in the Department of Radiology and Diagnostic Imaging at the University of Alberta Hospital, Canada. "Sitting in a sound anatomic position is essential, since the strain put on the spine and its associated ligaments over time can lead to pain, deformity and chronic illness."

Back pain is the most common cause of work-related disability in the United States, and a leading contributor to job-related absenteeism, according to the National Institute of Neurological Disorders and Stroke. By identifying bad seating postures and allowing people to take preventative measures to protect the spine, Dr. Bashir and colleagues hope to reduce back strain and subsequent missed work days.

"We were not created to sit down for long hours, but somehow modern life requires the vast majority of the global population to work in a seated position," Dr. Bashir said. "This made our search for the optimal sitting position all the more important."

The researchers studied 22 healthy volunteers with no history of back pain or surgery. A "positional" MRI machine was used, which allows patients freedom of motion—such as sitting or standing—during imaging. Traditional scanners have required patients to lie flat, which may mask causes of pain that stem from different movements or postures.

The patients assumed three different sitting positions: a slouching position, in which the body is hunched forward (e.g., hunched over a desk or slouched over in front of a video game console); an upright 90-degree sitting position; and a "relaxed" position where the patient reclines backward 135 degrees while the feet remain on the floor. Measurements were taken of spinal angles and spinal disk height and movement across the different positions.

Spinal disk movement occurs when weight-bearing strain is placed on the spine, causing the internal disk material to misalign. Disk movement was most pronounced with a 90-degree upright sitting posture. It was least pronounced with the 135-degree posture, indicating that less strain is placed on the spinal disks and associated muscles and tendons in a more relaxed sitting position.

The "slouch" position revealed a reduction in spinal disk height, signifying a high rate of wear and tear on the lowest two spinal levels. Across all measurements, the researchers concluded that the 135-degree position fared the best.

As a result, Dr. Bashir and colleagues advise patients to stave off future back problems by correcting their sitting posture and finding a chair that allows them to sit in an optimal position of 135 degrees.

"This may be all that is necessary to prevent back pain, rather than trying to cure pain that has occurred over the long term due to bad postures," he added. "Employers could also reduce problems by providing their staff with more appropriate seating, thereby saving on the cost of lost work hours."

Modifying NFATc1 Triggers Bone Production

Sun, 08 Oct 2006 16:47:37 PST

( from http://www.rxpgnews.com ) Scientists in the US have found a way to trigger bone production, raising hopes of treatment for osteoporosis in humans.

Gerald Crabtree and colleagues at the Howard Hughes Medical Institute, Maryland, found that they could massively increase bone mass in mice by tweaking the structure of a protein in the body.

Osteoporosis is a disease in which bones become fragile and are prone to fractures.

In vertebrates, bone is constantly being formed and broken down throughout life. Cells called osteoclasts continuously degrade bone while cells called osteoblasts replenish it, reported the online edition of BBC News.

In an ideal situation, the two types of cells are perfectly balanced, allowing the bone to maintain bone mass. However, if the balance is upset and more bone is destroyed than formed it can lead to osteoporosis.

The researchers found that they could tip the balance by modifying the structure of a protein called NFATc1.

They modified NFATc1 in mice so it could move more easily into the command centre of cells, and thus become a little more active than usual. This triggered the production of large amounts of new bone, the researchers said.

'It could potentially be possible to develop new drugs to treat osteoporosis by recreating the same effect,' Crabtree said.

The researchers are hopeful that the risk of side effects would be minimal because only small modifications to NFATc1 were required to produce a profound effect.

'Magic formula' accurately predicts fracture risk in osteoporotic women

Tue, 26 Sep 2006 16:39:37 PST

( from http://www.rxpgnews.com ) Researchers have developed a mathematic formula to predict a woman's risk of osteoporotic fracture. The equation has proved 75 percent accurate and will allow physicians to tailor their treatment strategies to help women prevent fractures of fragile bones. The study appears in the October issue of Radiology.

"Approximately 45 percent of women have different levels of bone mineral density between their hip and their spine, leading to uncertainty as to how physicians should assess their future fracture risk," said the study's lead author, Margaret Joy Henry, B.Sc(Hons)., Ph.D., statistician in the Department of Clinical and Biomedical Sciences at The University of Melbourne, Australia. "We have derived an equation that successfully predicted 75 percent of fractures in women, two years after their initial measurements were taken."

Women with osteoporosis have brittle bones that are more likely to break as a result of a minor bump or fall. Bones affected by osteoporosis are less dense than normal bones, due to larger pores in the bone, reduced calcium levels and fewer blood vessels.

The equation developed by Dr. Henry and colleagues takes into account a variety of risk factors, not just bone mineral density. A patient's likelihood of falling, low bone mass, excess or low body weight and additional factors are combined into a single formula that can indicate to a physician how serious a woman's fracture risk may be. Treatment strategies may then be targeted on the basis of a woman's predicted outcome.

A total of 231 elderly women who had sustained a low-trauma fracture of the hip, spine, humerus or forearm during a two-year period were recruited, as well as 448 elderly women who were selected randomly and had not sustained a fracture during the same two-year period.

The equation was developed based on measurements obtained in this study population. It was then tested in a third group of women from the community, who were randomly selected to be followed for a six-year period to determine the success of the formula for predicting fractures.

By using the formula, 75 percent of fractures were successfully predicted two years after the baseline measurements were obtained. The authors also discovered that heavier body weight seemed to increase the force applied to the skeleton during a fall. Findings of most previous studies indicated that lighter body weight led to increased risk of fracture, due to lower bone mass.

Development of this formula to predict future fracture risk is important because it will allow physicians to better adapt treatment strategies for women with osteoporosis, especially by taking into consideration different bone density measurements throughout the body. A variety of treatment regimens can be used, including hormone replacement therapy, non-hormonal medicines, vitamin D and calcium supplements, and additional therapies such as calcitriol--an active form of vitamin D that improves the absorption of calcium from the digestive process.

"As the average age of the population increases, the number of fractures attributable to osteoporosis is set to increase dramatically," said Dr. Henry. "The ability to predict fracture risk, based on simple clinical measurements, will assist in targeting treatment for people at highest risk, thus helping reduce the burden of this disease."

Dr. Henry and colleagues are currently assessing risk factors in a large cohort of men to develop a similar formula for use in the male population.

Calcium supplements fail to prevent bone fractures in children

Fri, 15 Sep 2006 18:01:37 PST

( from http://www.rxpgnews.com ) Calcium supplements have very little benefit for preventing fractures in childhood and later adulthood, concludes a study in the BMJ.

Children taking such supplements are have only small improvements in bone density, which are unlikely to reduce fracture risk, says the study carried out by researchers at the Menzies Research Institute in Australia and other approaches could be more beneficial such as increasing vitamin D concentrations and eating more fruit and vegetables.

Osteoporosis is a major public health problem, particularly in women, and low bone mineral density is an important risk factor for osteoporotic fractures. Bone density worsens for women after the menopause, so intervention in childhood to maximise peak bone mass by improving factors such as diet and physical activity can minimise the impact of bone loss related to age.

The researchers analysed the findings of 19 different studies involving 2,859 children collectively aged between three and 18. They included randomised trials of calcium supplementation in healthy children that lasted at least three months and which measured bone outcomes after at least six months of follow-up.

They found there was a small effect on total body bone mineral content and upper limb bone mineral density children taking the supplements only had 1.7% better bone density in their upper limbs than children not taking the supplements.

However, there was no effect at important sites in the body for fracture in later life namely the hip and lumbar spine. After children stopped taking calcium supplements, the effect persisted at the upper limb, but disappeared for total body bone mineral content.

The authors conclude: "The small effect of calcium supplementation on bone mineral density in the upper limb is unlikely to reduce the risk of fracture, either in childhood or later life, to a degree of major public health importance. It may be appropriate to explore alternative nutritional interventions, such as increasing vitamin D concentrations and intake of fruit and vegetables."

Estrens might not be the answer for osteoporosis

Sun, 03 Sep 2006 15:40:37 PST

( from http://www.rxpgnews.com ) A new study appearing in the September issue of the Journal of Clinical Investigation indicates that caution might be needed if a new group of drugs known as estrens are to be developed for the treatment of osteoporosis. The researchers found that although estrens improved bone strength in mice with osteoporosis, they also had adverse effects on reproductive organs and human breast cancer cells.

Many individuals, in particular women who have gone through the menopause, suffer from osteoporosis -- a disease in which the bones become fragile and highly susceptible to fracture. Bone strength is naturally maintained by a group of hormones known as sex hormones (for example, estrogen). However, unnaturally high levels of these hormones cause cancer of the reproductive organs and breast tissue, meaning that they cannot be used to treat individuals with osteoporosis. So, researchers have long been searching for estrogen-like molecules that increase bone strength but do not cause cancer. Recently, a new set of molecules (known as estrens) said to have these properties were identified. However, the wisdom behind developing estrens for use in the clinic is questioned by Roland Baron and colleagues from Yale University. They showed that although mice with osteoporosis treated with estrens showed some improvement in bone strength, their reproductive organs increased in size. Furthermore, estrens induced the proliferation of human breast cancer cells. This study indicates that estrens might not be the sought after estrogen-like molecules that improve bone strength but do not cause cancer, and has important implications for their clinical development.

In an accompanying commentary, Ushma S. Neill from The Journal of Clinical Investigation discusses the evidence for and against the use of estrens to treat osteoporosis, and concludes that we will have to wait for the completion of clinical trials before we have a definitive answer.

Increasing NFATc1 activity causes massive bone accumulation

Tue, 06 Jun 2006 14:52:37 PST

( from http://www.rxpgnews.com ) Howard Hughes Medical Institute (HHMI) researchers at Stanford University have found that they can increase bone mass in mice by tweaking the shape of a regulatory protein.

HHMI investigator Gerald Crabtree and HHMI predoctoral fellow Monte Winslow report that slightly increasing the activity of a protein called NFATc1 causes massive bone accumulation, suggesting that NFATc1 or other proteins that regulate its activity will make good targets for drugs to treat osteoporosis.

In vertebrates, bone is constantly being formed and being broken down throughout life. Cells called osteoclasts continuously degrade bone, while cells called osteoblasts replenish it.

Ideally, they are perfectly balanced, said Crabtree, the senior author of the study. Over the course of a lifetime, if everything goes well, we'll maintain almost exactly identical bone mass. However, if the balance is upset, and more bone is destroyed than formed, osteoporosis results, increasing the risk of fractures.

Those patients were also at increased risk of bone fractures, said first author Winslow, who led the study as an HHMI predoctoral fellow in Crabtree's lab. Cyclosporine inhibits a signaling protein complex known as calcineurin, which chemically modifies the NFATc family of proteins. This modification changes its shape. Although initially shown to regulate immune cell function, NFATc also functions in other cells to regulate heart development, blood vessel formation, neural development and function, and muscle development. In bone, it is NFATc1 that seems particularly important.

Since people with suppressed calcineurin/NFATc activity experience bone loss, Winslow, Crabtree, and their colleagues wanted to see whether this pathway would be important in bone development and function as well. Mice with the hyperactive NFATc in their osteoblasts had an immense increase in bone mass compared to normal mice, suggesting that the balance between bone formation and breakdown had tipped.

When the researchers examined the cells in these mice, they found that up-regulating NFATc signaling in osteoblasts increased the numbers of both types of bone cells. It was clear that increased NFATc activity in osteoblasts influenced both osteoblasts and osteoclasts, Winslow said.

The researchers found that mice with enhanced NFATc activity in their osteoblasts had many more of these bone-forming cells, which explained the increase in bone mass. Osteoblasts with hyperactive NFATc expressed higher levels of inflammatory proteins called chemokines, which promote osteoclast development.

Osteoblasts produce factors that recruit the progenitors of osteoclasts, and so when osteoblast numbers go up, osteoclast numbers go up, Crabtree said. Mice with abnormally active NFATc probably develop so much bone mass because this delicate balance between osteoblasts and osteoclasts has been altered, Crabtree suggested. The balance has been tipped.

This imbalance between bone formation and degradation could potentially be recreated by drug treatments for osteoporosis, Crabtree said. Very little NFATc1 must be activated to build extra bone, Winslow noted, which means that it may be possible to up-regulate the calcineurin/NFATc pathway to promote bone formation without disturbing other organ systems that use this same pathway.

NFATc1 in the mice that developed extra bone mass was only 10 percent more active than it is in normal mice.

The researchers are now screening chemical libraries for small molecules that could increase NFATc just enough to promote bone formation in people with osteoporosis, without causing undesirable side effects. If you could find a small molecule that would flip 10 percent of the existing NFATc into the active form, Crabtree said, you could favor the formation of osteoblasts and make stronger bones."

Second-Hand Smoke, First-Hand Problem

Tue, 06 Jun 2006 14:49:37 PST

( from http://www.rxpgnews.com ) Young or old, man or woman, smoker or non-smoker no matter what category you fit into, cigarette smoke can weaken your bones and increase your risk for fractures, according to new research presented this week at the IOF World Congress on Osteoporosis in Toronto.

Smoking has long been known to increase the risk for osteoporosis in women, but the new studies, two conducted in Sweden and one in China, find that smoking also hastens the erosion of men's bones. In addition, the Chinese study demonstrates, for the first time, that even second-hand smoke can significantly increase the risk for osteoporosis and fractures in both men and women.

The deleterious effects of smoking can readily be detected in young bones. That's one conclusion from the Gothenburg Osteoporosis and Obesity Determinants (GOOD) study, which has been following the health of young Swedish men.

"Though smoking has previously been linked to low bone density in the elderly population, its effects on adolescents has remained controversial. Now, we clearly demonstrate that young smokers also have significant losses in bone density," said Mattias Lorentzon, lead author on the study.

Lorentzon, working with Prof. Claes Ohlsson and colleagues at the Center for Bone Research at the Sahlgrenska Academy, Gothenburg University, measured bone mineral density--a measure of bone strength--in over 1,000 Swedish men between 18 and 20 years old. They found that in smokers, bone density in the spine, hip, and body as a whole, was lower than in their non-smoking peers. The most significant effects were in the hip, where the mineral density was over 5% lower than in non-smokers--typically, a 10% loss of bone mineral density doubles the risk of fracture.

Their results explain why previous findings have been equivocal. In this case the researchers used a sophisticated computer assisted X-ray machine (CAT scanner) to get three-dimensional images of bone. These 3D images showed that smoking primarily affects a specific type of bone called cortical bone. This very dense bone forms a layer, similar to the enamel on teeth, around softer, spongy bone. Lorentzon and colleagues found that smoking reduces the thickness of cortical bone. The findings indicate that smoking may significantly affect bone strength. "If you think of bone as a pencil, then the thicker the pencil the harder it will be to break," said Lorentzon.

In a separate study, Center for Bone Research colleagues Dan Mellström and co-workers have been measuring how a variety of lifestyle and biological factors influence the likelihood of bone fracture in elderly men. Mr. OS, as it is called, is being conducted internationally. Mellström and colleagues have recruited over 3,000 elderly men for the Swedish part of the study and correlated smoking history with bone density measurements and fracture incidence. "We find that in elderly men a history of smoking is associated with weak bones and almost a twofold increase in vertebral fracture incidence," said Mellström, who presented the data this week in Toronto. Vertebral fractures are a major sign of osteoporosis and a strong predictor of future fractures.

Mellström and colleagues took X-rays of the neck and back spine in over 1,300 men to screen for vertebral fractures--these fractures are often asymptomatic and go undetected. They found that nearly 17 percent of the men had an identifiable vertebral fracture, but when they compared fracture rate to smoking history they found that 24% of smokers had fractures compared to only 14% or those who never smoked. They also measured bone mineral density in the hip, thigh bone, and spine. Mellström reported that bone density in all regions tested was significantly lower in men who were current smokers, or who used to smoke. Overall the findings suggest that smoking reduces bone strength and dramatically increases the risk for bone fractures.

In the first ever analysis of the effects of second-hand smoke on bone density, researchers in the U.S. have found that Chinese men and pre-menopausal women have significantly lower bone density if they are exposed to second-hand smoke, even if they are themselves smokers.

Yu-Hsiang Hsu and colleagues from the Harvard School of Public Health measured hip bone mineral density in over 14,000 men and women in rural China--hip fractures are a major cause of morbidity and mortality worldwide. They also used recorded non-spine fractures and smoking history.

When they correlated smoking with osteoporosis and fracture history, they found that the largest effects were seen in pre-menopausal, non-smoking women--only 6% of women in the study were smokers, versus 87% of men. "Compared to non-smokers that are not exposed to second-hand smoke, premenopausal women exposed to second-hand smoke have a threefold higher risk of having osteoporosis and a 2.6 times greater risk for a non-spine fracture," said Hsu. Though smoking itself is a risk factor for osteoporosis, Hsu and colleagues also deduced that smokers were at increased risk if they were also exposed to smoke from other family members on a daily basis.

Though this is the first reported study of the effects of second-hand smoke on bone health, previous studies have reported that second-hand smoke may alter levels of estrogen, which is a key hormone for bone health in both women and men, Hsu explained. "Our finding is consistent with this hypothesis," said Hsu, who now plans a follow up study to correlate serum levels of cotinine, a nicotine derivative that only appears in blood of those exposed to tobacco smoke, with serum hormone levels.

Using gene therapy to accelerate damaged muscle regeneration

Mon, 05 Jun 2006 16:43:37 PST

( from http://www.rxpgnews.com ) University of Pittsburgh School of Medicine researchers have successfully used gene therapy to accelerate muscle regeneration in experimental animals with muscle damage, suggesting this technique may be a novel and effective approach for improving skeletal muscle healing, particularly for serious sports-related injuries.

Skeletal muscle injuries are the most common injuries encountered in sports medicine. Although such injuries can heal spontaneously, scar tissue formation, or fibrosis, can significantly impede this process, resulting in incomplete functional recovery. Of particular concern are top athletes, who, when injured, need to recover fully as quickly as possible.

In this study, the Pitt researchers injected mice with a gene therapy vector containing myostatin propeptide--a protein that blocks the activity of the muscle-growth inhibitor myostatin--three weeks prior to experimentally damaging the mice's skeletal muscles. Four weeks after skeletal muscle injury, the investigators observed an enhancement of muscle regeneration in the gene-therapy treated mice compared to the non-gene-therapy treated control mice. There also was significantly less fibrous scar tissue in the skeletal muscle of the gene-therapy treated mice compared to the control mice.

According to corresponding author Johnny Huard, Ph.D., the Henry J. Mankin Endowed Chair and Professor in Orthopaedic Surgery, University of Pittsburgh School of Medicine, and Director of the Stem Cell Research Center of Children's Hospital of Pittsburgh, this approach offers a significant, long-lasting method for treating serious, sports-related muscle injuries.

"Based on our previous studies, we expect that gene-therapy treated cells will continue to overproduce myostatin propeptide for at least two years. Since the remodeling phase of skeletal muscle healing is a long-term process, we believe that prolonged expression of myostatin propeptide will continue to contribute to recovery of injured skeletal muscle by inducing an increase in muscle mass and minimizing fibrosis. This could significantly reduce the amount of time an athlete needs to recover and result in a more complete recovery," he explained.

Low carbohydrate diet did not increase bone loss

Thu, 25 May 2006 13:15:37 PST

( from http://www.rxpgnews.com ) A strict low-carbohydrate diet had no effect on bone loss for adults following an Adkins-type diet for weight loss, a three-month study by rheumatologists at the University of South Florida found.

Low carbohydrate diets have become popular as a weight loss technique; however, critics contend such diets may have harmful side effects. One concern has been that low carbohydrate diets, which replace calories from carbohydrates with more consumption of high-protein foods like meat and eggs, alter the body's acid balance. This imbalance could lead to increased bone turnover (more rapid depletion than formation of bone) -- increasing the risk for osteoporosis.

"That's not what our study found," said lead author John D. Carter, assistant professor in the Division of Rheumatology, USF College of Medicine. "Patients on the low carbohydrate diet did lose weight, but the diet did not appear to compromise bone integrity or lead to bone loss."

Earlier animal studies suggested that low carbohydrate, high protein diets could adversely affect bone quality.

"I was surprised by the results," Dr. Carter said. "People on low carbohydrate diets absorb less calcium through the gut and excrete more calcium in the urine, so you'd expect they would be leaching their bones."

Dr. Carter emphasized he does not advocate strict low-carbohydrates for long-term weight management. Such diets may adversely overload the kidneys with protein and lead dieters to consume more artery-clogging saturated fats and cholesterol, he said.

The USF study followed 30 overweight patients for three months. Half followed a strict low carbohydrate diet consuming less than 20 grams of carbohydrates a day the first month and then less than 40 grams a day for the remaining two months. The control half ate a normal American diet with no restrictions. The researchers used blood tests to measure the patients' breakdown and formation of bone and checked urine for signs that the dieters were complying with their low-carbohydrate diets.

The difference in bone turnover between the low carbohydrate dieters and the non-dieters was insignificant after three months. But, the dieters lost significantly more weight -- an average of 14 pounds -- than the patients on unrestricted diets.

A potential limitation of the USF study was that the researchers looked for at least a 50 percent difference in bone turnover between the dieters and non-dieters. It's possible that more subtle effects on bone quality might have been found, Dr. Carter said, particularly if the low carbohydrate diet was maintained beyond three months.

Teriparatide to be tested for osteogenesis imperfecta

Fri, 19 May 2006 19:35:37 PST

( from http://www.rxpgnews.com ) Jimmy Fox isn't typical of a person with the genetic, "brittle bone" disorder osteogenesis imperfecta (OI). He lifts weights almost daily, participates in grueling wheelchair races, chops wood and enjoys hunting in rough backcountry.

Still, Fox, who owns a busy combination grocery store-gun shop in Cloverdale, Ore., is eager to participate in an Oregon Health & Science University-led study of a drug that may help reduce the debilitating effects of OI, an inherited disorder characterized by weak bones that break easily. People with the most severe forms of OI have short stature, can suffer hundreds if not thousands of fractures in a lifetime, and are confined to a wheelchair.

"I didn't think it could do me any harm," Fox, 40, said of the study. He has a less-severe form of OI, allowing him to be more mobile - he walks on his hands when he's not in his wheelchair - and suffer fewer fractures than many others with the disorder. Fox had both of his legs amputated when he was 18 due to continued fracturing. "The study might do me some good, so I thought I might as well do it and give it a try. It will help other people."

The alternative is unacceptable to Fox, who acknowledges that his significant upper-body strength has kept many of the disorder's most debilitating effects at bay. "They told me 'If you weren't as active as you are, you would be totally screwed up by now.' To be honest, that's what really swayed me to do this."

The study, headed by Eric Orwoll, M.D., professor of medicine (endocrinology, diabetes and clinical nutrition) and director of the Bone and Mineral Unit, OHSU School of Medicine, is examining the effectiveness of the synthesized parathyroid hormone, teriparatide, in increasing bone mass and improving bone structure in adults affected by OI. Teriparatide, derived from the human parathyroid gland, is manufactured and sold by Eli Lilly and Co. under the brand name FORTEO.

FORTEO already is approved for use by men and postmenopausal women with osteoporosis who are at high risk for having fractures, according to Lilly's Web site.

"It gives a lot of hope to a lot of people who wouldn't have much to look forward to," Orwoll said.

In most OI patients, the disorder is caused by a mutation in one of two genes, COL1A1 and COL1A2, that encode for type 1 collagen, the fibrous protein that serves as the scaffolding for bone and which also is present in ligaments, tendons, teeth, the white portion of the eyes, and even skin. The defect impairs the body's ability to mineralize bone and other collagen-containing tissue, leading to bone fragility, loose joints, eye discoloration, dental problems and premature hearing loss.

Although exact incidence isn't known, OI is believed to affect 1 of every 5,000 to 10,000 individuals of all racial and ethnic origins, with between 20,000 and 50,000 Americans living with the disorder. Parents with OI have a 50 percent chance with each pregnancy of having an affected child and most children with the disorder have inherited it from a parent. About a fourth of all children with OI are born into families with no history of the disorder.

Janet Reeder, M.S., PA-C, a former faculty member of the OHSU Bone and Mineral Unit who developed the study, said people with OI are largely ignored by the medical community because few treatment options exist, or doctors fear treatment will cause more fractures.

"Many practitioners say, 'We don't know what to do with you. Sorry, have a nice life,'" Reeder said. "But they pay taxes, they work full time. They have incredible tenacity. This is a group of people that has really triumphed over a lot of disability and deformity. What we're trying to do is help them by hopefully decreasing fractures and thereby increasing quality of life."

There is no cure for the disorder, and while drugs have been studied for use in children with OI, there is no established medical therapy for affected adults. Adult OI treatment varies depending on the degree of impairment and the patient's age. Doctors sometimes surgically implant rods to support long bones or prescribe braces to support lower limbs. Patients also are encouraged to take calcium and vitamin D supplements daily.

"What we're interested in is, after kids make it through childhood and into adulthood, what can we do for them?" Orwoll said.

Each of the three national study sites - OHSU, Kennedy Krieger Institute at Johns Hopkins University, and Baylor School of Medicine - are recruiting a total of 90 men and women ages 18 and older for the 18-month, blinded trial. Participants will receive either FORTEO or a placebo, which is self-administered once a day using an injection pen. They will be examined at the first, third, sixth, 12th and 18th months after initial screening, and their spine, hip, forearm and total body bone mineral density will be measured every six months.

FORTEO offers hope of suffering fewer bone fractures for individuals with OI such as Anton Borissov, a 40-year-old Portland resident who has never walked and lives in his wheelchair. It also will increase awareness about the disorder, which may lead to even more drug therapies.

"For me, it is a big, big thing not to have breaks. When I lift something it's just 'break, break, break,'" said Borissov, a native of Russia who estimates he's suffered a thousand fractures in his lifetime, and who can break ribs just by coughing. He is not a participant in the FORTEO study. "If they're doing this study, it's good. And people will know something about OI, even doctors, and that I'm no different."

A novel vertebroplasty technique strengthens vertebrae after removing spinal tumors

Sat, 06 May 2006 18:59:37 PST

( from http://www.rxpgnews.com ) A radiologist at the University of California, San Diego (UCSD) School of Medicine has developed a new procedure to treat fractured vertebrae caused by spinal tumors, a procedure that may decrease the risk of complications, which are experienced by 5 to 10% of patients with malignant tumors of the spine.

Wade Wong, D.O.F.A.C.R, UCSD professor of radiology, and San Diego clinician Bassem Georgy, M.D., partially removed spinal tumors from 28 patients before repairing the spine with vertebroplasty a procedure to cement and stabilize damaged vertebrae. He used a technology that utilizes plasma-mediated radiofrequency energy combined with saline solution to gently and precisely remove soft tissue at low temperature minimizing damage to healthy tissue.

"This image-guided procedure guarantees ultimate accuracy," said Wong. It enables us to provide pain relief and improved mobility to patients while minimizing risks that have traditionally limited treatment options for cancer patients."

Wong will present his study on May 6 at the American Society of Interventional and Therapeutic Neuroradiology (ASITN.) He added that some patients in the study who were previously bedridden became much more active after their fractures were repaired using this method, increasing their overall quality of life.

Vertebral compression fractures (VCFs) are common complications of spinal tumors. Approximately 10 percent of the estimated one million VCFs that occur each year in the United States are caused by spinal metastases. Unfortunately, spinal tumors present challenges that traditionally have left many cancer patients with very few treatment options. Open surgery is invasive and involves a long recovery. Traditional vertebroplasty and kyphoplasty two procedures that utilize bone cement to stabilize the fractured vertebrae are also risky when a tumor is present, because the procedures can cause cancerous cells to spread into the blood stream. They also carry a higher risk of bone cement leaking out of the vertebral body into the spinal canal, potentially leading to paralysis.

Wong removed the tumor prior to vertebroplasty on 28 patients using the plasma-mediated procedure commonly known as the "Coblation SpineWand." Following the partial removal of the tumor, bone cement was injected into the cavity created by the process in order to stabilize the fractured bone fragments. The researchers report that all 28 patients treated in the study experienced decreased pain and improved function.

"I never dreamed it would be this successful," said Wong, adding that when first approached the ArthroCare Corporation, manufacturers of the Coblation process, they were skeptical. The device was already in use for other medical applications, such as ear, nose and throat surgery, and arthroscopic applications. "Generally, a cancerous lesion of the spine can eat away at the bone, which can cause a mass in the spinal canal resulting in paralysis or great pain," Wong said.

The process first removes tumor bulk, then delivers cement to strength the vertebrae, which reduces pain.

"It's like creating a cast to a fracture," said Wong, "but in the inside of the body instead of on the outside."

Using the process doesn't preclude other treatments, such as chemo or radiation therapy. Though the process doesn't cure the cancer, it can add to the quality of life for the patient.

"Even in patients with a malignancy, it doesn't mean it's the end of their life. This procedure allows them to resume activities, like walking or even rollerblading, that they enjoyed before," said Wong, adding, "Quality of life is what's key."

ACVR1 Gene Responsible for Fibrodysplasia ossificans progressiva (FOP)

Tue, 25 Apr 2006 20:34:37 PST

( from http://www.rxpgnews.com ) Scientists have identified a gene that turns muscle into bone - one of the rarest disorders that affects about one in two million individuals.

The disease named by scientists as Fibrodysplasia ossificans progressiva (FOP) is a connective tissue disorder in which bone grows in tendons, ligaments, and muscles. It begins early in childhood and has no cure.

Researchers led by Frederick Kaplan at the University of Pennsylvania first established that the FOP is likely to be caused by a mutated gene that affects bone morphogenetic proteins (BMPs), which control the formation and repair of the skeleton.

This insight led them to a gene called ACVR1, which controls one of the three main receptors for BMP that determine how cells respond to its signals, the online edition of The Times reported.

In patients with FOP, a tiny mutation in one of the two copies of the ACVR1 gene changes the meaning of its genetic message, so a faulty protein is made, it said.

The discovery of the single gene offers new hope of a first effective therapy for the disorder, they said.

By providing insights into the genetic signals that govern bone growth, the research should also improve understanding and treatment of a wide range of more common skeletal conditions. These include osteoporosis, spinal injuries and sports injuries.

In the longer term, it could also allow scientists to make bone in the laboratory, for treating fractures that fail to heal and skeletal malformations.

Calcium fortified food may not produce stronger bones

Thu, 20 Apr 2006 15:52:37 PST

( from http://www.rxpgnews.com ) Calcium fortified foods may not help build stronger bones in children, says a new study.

Calcium is a mineral important to maintaining bone health. Calcium-rich foods include milk, cheese, yoghurt, greens, broccoli, sardines, beans and peas. The mineral is added to many breakfast cereals, snack bars and drinks as manufacturers try to woo the parental market.

But scientists have found that such products do not produce significantly stronger bones, nor do they reduce the chance of a child suffering fractures, reports the online edition of Daily Mail.

Researchers led by Professor Frank R. Greer of the University of Wisconsin analysed 19 studies where children aged between three and 19 years were given extra calcium in their diet in this way,

They then calculated the impact by measuring their bone mineral density and mineral content.

The team found few significant increases in bone mass and none in the two bones most vulnerable to fracture - the lower spine and upper part of the thigh.

A small impact was noted in bone density of the arm, but it cut the risk of fracture by just 0.2 percent, according to the report published in the Cochrane Library.

Calcium artificially added to food passes through the body too quickly to be properly absorbed and therefore fails to perform the same functions as foods which are naturally rich in calcium, such as milk, cheese and leafy green vegetables, they said.

The findings for children echo those seen in adult studies. "You can get some short-term improvements but as soon as you stop the supplements it goes right back to where it was," Greer said.

Growing body of research links lead to osteoporosis

Tue, 28 Mar 2006 22:19:37 PST

( from http://www.rxpgnews.com ) Bolstered by recent laboratory findings, researchers at the University of Rochester Medical Center are embarking on a National Institutes of Health-funded clinical study to better understand the deceptive role environmental lead exposure plays in bone maturation and loss. The clinical trial is the latest in a growing body of research that is putting yet one more notch in the belt of diseases attributed to lead, and this time, researchers say, its target is older adults at risk for osteoporosis.

For decades, scientists have known that the human skeleton is a repository for lead in people who were exposed to high levels of this environmental toxin in their childhood, but thought this storage to be benign. Recently, a growing body of research is showing that the opposite is true, and that lead in bone actually sets off a bizarre chain reaction, first accelerating bone growth, and then eventually limiting it so that a high peak bone mass is not achieved. Preventing a high peak bone mass will predispose a young person to osteoporosis later in life.

Now, researchers in the Center for Musculoskeletal Research at the University of Rochester Medical Center are set to embark on the next phase of a four-year, $5 million research project funded by the National Institute of Environmental Health Sciences with a clinical study aimed at better understanding the deceptive role lead initially plays in bone development, growth and loss and how this all might lead to earlier onset of osteoporosis in those exposed to high levels of lead as a child.

A metabolic bone disease that predominantly occurs in women, osteoporosis affects one in three American women over the age of 65. It is characterized by low bone mass that eventually leads to fractures, mostly of the hip and vertebrae. These fractures can be life-threatening; experts say that more women die each year from hip fracture complications than from cancer of the ovaries, cervix and uterus combined. Close to $20 billion dollars is spent each year treating osteoporosis and related fractures.

The pattern of growth in the skeleton determines the peak skeletal density of an individual, and this level is established by the time most people reach 20. Recent research completed at the University of Rochester Medical Center shows that lead adversely affects the normal maturation of the growth plate but does so in an odd way.

"As a child, lead appears to accelerate bone development and maturation, so that lead-exposed children actually have a higher bone density than those not exposed to environmental lead," said James Campbell, M.D., M.P.H., associate professor of Pediatrics and a co-investigator of the study. "But, we believe this higher bone density effect is short-lived, and in fact, we believe it actually prevents these children from achieving an optimal peak bone mass later on in life."

J. Edward Puzas, Ph.D., professor of Orthopaedics and director of the overall project, added that limiting peak bone mass has dire consequences as a person begins to age.

"When everyone begins to lose bone mass starting at around age 50, lead-exposed individuals are at a higher risk for bone fractures and osteoporosis and probably at an earlier age than the typical osteoporosis patient."

At what specific age lead-exposed individuals will plateau in bone growth, and at what age they will begin to lose more bone as older adults, is the focus of this clinical research. Puzas and Campbell have used their prior research to guesstimate when these two milestones occur, but are turning to sophisticated lead measurement devices to help them pinpoint exact timeframes.

"We believe that somewhere around age 20, we'll begin to see low-lead exposed individuals surpass high-lead exposed individuals in bone mass density," Campbell said. "Then, in the 50 to 60 age group the age at which any individuals will begin to experience a natural loss of bone we expect to see the high-lead exposed individuals losing more bone sooner."

An X-ray fluorescence spectrometer will be used to measure the bone lead levels in 500 people, separated into three age groups: 8-9 years old, 18-19 years old, and 50-60 years old. One of only a few installed machines worldwide, it provides a precise, noninvasive measurement of the historic accumulated exposure to lead, allowing researchers to place each of the research subjects into an either "low-lead exposure" or "high-lead exposure" category within their age groups. A DEXA-scan will then be used to measure bone density, and with these data in hand, the investigators will have a better sense of when lead-exposed individuals might begin to experience osteoporotic symptoms.

GENOMOS: Weak Links found between COL1A1 Polymorphism, BMD, and Fracture Risk

Fri, 24 Feb 2006 08:46:37 PST

( from http://www.rxpgnews.com ) One out of every two women and one in eight men over 50 will have an osteoporosis-related fracture in their lifetime. Osteoporosis is characterized by low bone mass and structural deterioration of bone tissue, and often progresses without overt symptoms or pain until a bone breaks. Fractures occur typically in the hip, spine, and wrist. Currently, there is no accurate measure of overall bone strength. Bone mineral density (BMD) is frequently used as a proxy measure, but it can explain only a modest proportion of fracture risk.

Bone resorption and bone formation take place throughout life. Formation outpaces resorption until peak bone mass (maximum bone density and strength) is reached around age 30. From then on, bone resorption slowly begins to exceed bone formation, and the balance is further shifted toward resorption in women after menopause. Osteoporosis develops when bone resorption occurs too quickly or replacement too slowlywhich happens in most individuals at a certain age and often earlier in individuals who did not reach optimal bone mass during their bone building years.

Both bone formation and resorption are under the control of genetic and environmental factors. Osteoporosis is a complex disease, with variations in a number of different genes and in several environmental factors (such as calcium intake or alcohol consumption) thought to affect an individual's risk. A number of candidate genes have been identified, some of them through studies of rare genetic diseases affecting bone health, others through animal studies. They include genes for calciotropic hormones and their receptors, as well as bone matrix proteins.

One of them, COL1A1, encodes collagen 1 alpha 1, a major component of bone and cartilage. Mutations in its coding region cause osteogenesis imperfecta, a rare developmental bone disorder characterized by brittle bones, frequent fractures, and short stature. Apart from these rare mutations, COL1A1 has a number of polymorphic sites outside the coding region, and scientists have examined associations between many of these alleles and osteoporosis. The one that has been studied most intensely is a single-nucleotide polymorphism within the promoter region at a binding site for the Sp1 transcription factor. The more common allele has a guanine nucleotide (G) at the variable position; the rarer one, a thymine (T). In vitro studies suggest that the T allele is associated with less transcript and protein produced.

Several previous studies had examined a possible association between the T allele and low bone mineral density and fractures, and a number of them had found such a link, as had three separate meta-analyses. As a consequence, some researchers have suggested that genetic testing at the population level for this polymorphism would be beneficial. Individuals who carry the T allele could be advised to get enough calcium and do weight-bearing exercises, ideally already during the bone acquisition phase in adolescence. Others have warned that the evidence that links the T allele to a higher risk for osteoporosis is not strong enough to support such action. They have pointed out some of the notorious problems with association studies in general and retrospective meta-analyses based on published studies.

The Genetic Markers for Osteoporosis (GENOMOS) project is a European Unionfunded European collaborative research initiative between universities in the Netherlands, United Kingdom, Italy, Spain, Greece, Poland, and Denmark. The project, which began in 2003, currently involves around 24,000 individuals and seeks to identify genetic risk factors for osteoporosis by prospective meta-analysis. Participants have been recruited from a total of 18 European countries (most of them reside in the UK, the Netherlands, Spain, Italy, Denmark, and Poland). Data on previous and new fractures are collected, together with bone densitometry measurements, information on risk factors, and DNA analysis from blood samples.

The GENOMOS investigators, led by John Ioannidis, report now on their examination of an association between the Sp1 polymorphism in COL1A1, BMD, and fracture risk. Based on data from over 20,000 participants, they found a modest association between homozygosity for the T allele and lower bone mineral density at the femoral neck and the lumbar spine. The researchers also found a weak association between the T allele and vertebral fractures in women. However, T allele carriers did not have an overall increased risk of fractures.

Vertebral compression fractures in a patient with osteoporosis; From: (2006) GENOMOS Study Finds Weak Links between COL1A1 Polymorphism, BMD, and Fracture Risk. PLoS Med 3(4): e152

The effects seen in this large studyGENOMOS participants reported more than five times the number of fractures than participants in all previous studies combinedwere more moderate than those reported in most of the earlier studies. The Sp1 polymorphism in COL1A1 explained only a small part of the differences in BMD and fracture risk among the GENOMOS participants. There was no association between the T allele and BMD in heterozygous carriers (and only approximately 4% of the participants were homozygous for the T allele). Regarding the fracture association, the researchers estimate that the presence of the T allele would explain at most 10% of the risk of vertebral fractures for women.

The authors conclude that large-scale studies are needed to quantify the true effect size of genetic polymorphisms that have been implicated in the pathogenesis of complex genetic disorders. Their findings also argue against widespread genetic testing for this particular polymorphism alone. Researchers need to look at other genes (and possibly other variants in the COL1A1 gene) and validate any findings in large studies like this one before they can predict a substantial fraction of a random individual's genetic risk for osteoporosis.

Denosumab may show promise in the treatment of osteoporosis

Thu, 23 Feb 2006 15:10:37 PST

( from http://www.rxpgnews.com ) Amgen (NASDAQ: AMGN), the world's largest biotechnology company, announced today the publication of Phase 2 data demonstrating twice-yearly injections of denosumab (previously referred to as AMG 162), a RANK Ligand inhibitor, significantly increased bone mineral density (BMD) in the total hip, lumbar spine, distal 1/3 radius and total body compared to placebo. The results of this one-year study appeared in the Feb. 23, 2006 issue of the New England Journal of Medicine.

Data results also included an open-label FOSAMAX® (alendronate)* arm of the same clinical trial.
Researchers reported that subcutaneous injections of denosumab significantly increased BMD at the total hip from 1.9 to 3.6 percent in women who were administered the therapy twice yearly as compared with a decrease of 0.6 percent in the placebo group (p less than 0.001) at one year. The open label FOSAMAX® group receiving 70 mg weekly had an increase of 2.1 percent during the same time frame. Results also indicated that denosumab had a rapid onset of action. A significant decrease in serum levels of C-telopeptide, a biomarker of bone resorption, was achieved within 72 hours after dosing.

"These exciting data suggest that denosumab, when administered in twice-yearly injections, may show promise in the treatment of osteoporosis," said Michael McClung, MD, FACP, principal investigator of the denosumab study, Providence Portland Medical Center, and director of the Oregon Osteoporosis Center, Portland, Ore. "Continued research will further our understanding of the potential of denosumab in bone loss management."

Denosumab targets RANK Ligand, a protein that acts as the primary mediator of osteoclast (cells that break down bone) activity. This investigational therapy is the first RANK Ligand inhibitor in late stage development.

Amgen is studying denosumab for its potential in a broad range of conditions associated with bone destruction including osteoporosis, treatment-induced bone loss, bone metastases, multiple myeloma and rheumatoid arthritis. Data recently presented at the American College of Rheumatology 2005 Annual Scientific Meeting show further increase in bone mineral density in postmenopausal women with osteoporosis after two years of treatment.

"These data reinforce the essential role that RANK Ligand inhibition plays in decreasing bone loss," said Willard Dere, MD, senior vice president of global development and chief medical officer, Amgen. "We are committed to expanding our data on denosumab with an extensive Phase 3 clinical program to evaluate the effect of denosumab on preventing fractures in men and women."

In the one-year trial results, researchers also reported twice-yearly subcutaneous injections of denosumab significantly increased lumbar spine BMD from 3.0 to 6.7 percent after 12 months as compared with a decrease of 0.8 percent in the placebo-treated patients (p less than 0.001). Across all doses and dosing intervals, distal 1/3 radius BMD increased from 0.4 to 1.3 percent as compared with a decrease of 2.0 percent in those taking placebo (p less than 0.001), and total body BMD increased from 0.6 to 2.8 percent as compared with a decrease of 0.2 percent in the placebo group (p less than 0.01).

The incidence of adverse events was similar among the denosumab, placebo, and FOSAMAX® groups, with the exception of dyspepsia. Dyspepsia occurred in 7 percent of placebo patients, 6 to 15 percent of denosumab patients and 26 percent of open-label FOSAMAX® patients. The most common adverse events among all groups included upper respiratory infection (common cold), arthralgia (joint pain), nasopharyngitis (sore throat), back pain and headache. No neutralizing antibodies to denosumab were observed.

Acupressure Relieves Low Back Pain

Fri, 17 Feb 2006 19:04:37 PST

( from http://www.rxpgnews.com ) Acupressure (applying pressure with the thumbs or fingertips to the same points on the body stimulated in acupuncture) seems to be more effective in reducing low back pain than physical therapy, finds a study published online by the BMJ today.

Low back pain is a common health problem worldwide. In previous studies, acupressure has been shown to be effective in alleviating various types of pain, but little is known about its effect on low back pain.

Researchers in Taiwan recruited 129 patients with chronic low back pain from a specialist orthopaedic clinic. All patients completed a standard disability questionnaire before being randomly allocated to two treatment groups: 64 patients received six sessions of acupressure and 65 patients received physical therapy. Results were analysed immediately after treatment and again after six months.

The mean disability score after treatment was significantly lower in the acupressure group than in the physical therapy group.

In fact acupressure conferred an 89% reduction in disability compared with physical therapy, after adjusting for pre-treatment disability. This improvement lasted for six months.

Benefit was also greater in the acupressure group for variables such as leg pain, pain interferes with normal work, and days off from work/school.

This study shows that acupressure is more effective in alleviating low back pain than physical therapy in terms of pain scores, functional status, and disability, say the authors. The effect was not only seen in the short term, but lasted for six months.

These results support the conclusion of previous studies. Acupressure may thus be useful for reducing pain and improving body function and level of disability in low back pain, they conclude.

Warfarin increases risk of bone fracture

Tue, 24 Jan 2006 17:57:37 PST

( from http://www.rxpgnews.com ) Elderly patients taking the commonly prescribed blood thinner warfarin experience an increased risk for osteoporosis-linked bone fractures, according to a study at Washington University School of Medicine in St. Louis. The results suggest physicians should carefully monitor the bone health of patients placed on the medication and that their patients should take steps to decrease the risk of osteoporosis.

Warfarin, also known by the brand-name Coumadin®, is often given to patients with atrial fibrillation, irregular contractions of the upper chambers of the heart. By interfering with vitamin K's role in clotting, the drug decreases formation of blood clots, which often accompany atrial fibrillation.

But because vitamin K also interacts with osteocalcin--a protein vital for bone formation--warfarin's antagonism of vitamin K has the potential to affect bone strength as well. Osteoporotic fractures occur when the bones become so weakened that minor trauma causes breakage.

"We did a retrospective study of Medicare records for about 15,000 patients hospitalized with atrial fibrillation, and we identified fractures related to osteoporosis," says lead author Brian Gage, M.D., associate professor of medicine and medical director of Barnes-Jewish Hospital's Blood Thinner Clinic. "Our analysis showed that long-term use of warfarin--longer than one year-- led to a 25 percent increase in the incidence of fracture."

The study included about an equal number of men and women with an average age of 80. In the general population, 80 percent of those affected by osteoporosis are women, and women in this study were more likely to have an osteoporotic fracture than were men. But the women's risk of fracture did not increase by a statistically meaningful amount on long-term warfarin therapy. However, men in the study who took warfarin for more than a year had a 63 percent higher incidence of fracture than men who did not take the blood thinner.

Patients taking warfarin for less than one year did not have increased fracture risk, and patients taking beta-blockers had fewer fractures than patients not taking beta-blockers.

More than half of the fractures seen in the study group were hip fractures. The rest involved the spine and wrist. Osteoporotic fractures often result in lost mobility and death in many cases. In the study group, 39 percent of patients with hip fractures died within 30 days, with substantial mortality evidenced for other types of osteoporotic fractures as well.

"The results of the study have important implications for treatment of atrial fibrillation," Gage says. "To maintain bone strength, elderly patients taking warfarin should exercise regularly and have adequate intakes of calcium and vitamin D. Those who are prone to falling could use walking aids and proper footwear. Smokers should quit, which will decrease their risk of osteoporosis and other diseases."

The study adds to evidence suggesting that vitamin K is important for bone health. Gage says he hopes that anticoagulants that do not inhibit vitamin K will be developed.

An X-ray robot to scan orthopaedic patients

Sat, 21 Jan 2006 15:32:37 PST

( from http://www.rxpgnews.com ) A US scientist has developed a robot which can take X-ray pictures of sufferers of orthopaedic injuries as they move around. Complaints of orthopaedic injuries are among the most common reasons people visit the doctor.

Surgeons use static X-rays, MRI and CT scans to diagnose patients. They also use X-ray video. But current technologies provide only a tight view of a very limited range of motions in a controlled laboratory setting.

But the robot designed by mechanical and aerospace engineer Scott Banks at the University of Florida shoots X-ray video of sufferers of orthopaedic injuries as they walk, climb stairs, stand up from a seated position or pursue other normal activities - and maybe even athletic ones like swinging a bat.

X-rays, MRI and CT scan can be effective but they do not work well with injuries that manifest themselves when a joint is in motion, Banks said, the online edition of Newswise wire reported.

These include, for example, injuries to the patella, or kneecap, and injuries of the shoulder. Surgeons sometimes have to operate to diagnose these and other injuries, which can lead to unnecessary surgeries.

After operations, surgeons have few tools beyond the patient's experience to tell them whether a procedure worked as intended and whether it will forestall additional joint damage.

But the robot, he says, is a system that uses two robots with one robot used to shoot the X-ray video and another to hold the image sensor.

It can shadow a person's knee, shoulder or other joint with its hand as he or she moves.

Although the robots will be attached to a fixed base, there is room for a person to move around normally within their reach.

And in the future, said Banks, "we could put these robots on wheels and they could follow you around".

Mental therapy could help chronic back pain suffers

Sat, 21 Jan 2006 15:21:37 PST

( from http://www.rxpgnews.com ) Mental therapy could be as effective as physical exercise in reducing back pain, signalling relief for thousands of chronic back pain sufferers.

Researcher Rob Smeets, from the University of Maastricht, Netherlands, and colleagues studied 223 people suffering from chronic back pain and found that training the mind was just as effective as using more physical methods, the online edition of Daily Mail reported.

However, combining the treatments does not improve patients' condition further than following the individual treatments, they said.

Over 10 weeks, one group of the study participants received mental therapy, another underwent physical treatment and the third used a combination of the two.

The physical treatment attempted to restore back muscle strength with aerobic training on a bicycle and strengthening exercises, it said.

The mental therapy tried to help patients overcome their reluctance to be more active, teaching them how to face obstacles for recovery by using problem-solving skills.

The researchers assessed how mobile the patients were before and after treatment.

They discovered that both physical treatment and mental therapy significantly reduced pain experienced by the participants compared to those who received no treatment at all.

The study published in the journal BMC Musculoskeletal Disorders, however, said it did not find improvement of the back pain conditions further in the patients who had a combination of two.

The researchers said their study showed the short-term results of the treatments, but further tests would be conducted in a year's time.

New insights into anti-osteoclastogenic action of vitamin D

Fri, 20 Jan 2006 13:41:37 PST

( from http://www.rxpgnews.com ) The risk of bone fracture resulting from falls increases as we age due to bone loss and osteoporosis. Physicians have routinely prescribed vitamin D and vitamin Drelated drugs to retard bone loss, but until now, little was known about the specific targets of vitamin D in bone.

In a study appearing online on January 19 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Kyoji Ikeda and colleagues from the National Center for Geriatrics and Gerontology in Japan examine mice with severe osteoporosis and show that oral vitamin D treatment inhibits the production of the protein c-Fos. As c-Fos plays a key role in the development of osteoclasts, which are the specialized cells responsible for bone breakdown and resorption, the authors also show that the vitamin Dmediated inhibition of c-Fos prevented bone loss through a suppression of osteoclast development.

In addition, the authors used mice whose ovaries had been removed, in a more "human-like" model of osteoporosis, to screen for other vitamin Dlike agents with c-Fossuppressing activity. They identified a new vitamin Drelated compound (DD281) that could prevent bone loss in these mice more potently than the natural vitamin D.

These findings clarify how vitamin D helps limit bone resorption in conditions such as osteoporosis, and suggest that synthetic vitamin D analogs, including DD281, may warrant clinical trial to asses their potential in the treatment of osteoporosis and other related disorders of bone resorption.

Vertebroplasty improves back pain

Fri, 30 Dec 2005 16:01:38 PST

( from http://www.rxpgnews.com ) A Mayo Clinic study has found patients report less back pain at rest and while active following vertebroplasty, a procedure in which medical cement is injected into painful compression fractures in the spinal vertebrae due to osteoporosis. Patients also reported improved function in their daily activities, such as walking, housework and getting dressed. The findings are published in the November/December issue of American Journal of Neuroradiology, http://www.ajnr.org.

"These findings give us as good evidence as there is -- in a study without a group receiving another or no treatment for comparison -- that patients are more functional for up to a year after vertebroplasty than before vertebroplasty," says David Kallmes, M.D., the Mayo Clinic neuroradiologist who led the study.

The investigators conducted the study to assess vertebroplasty with a well-validated questionnaire specifically designed to measure back pain, the Roland-Morris Disability Questionnaire (RDQ). They reviewed records of 113 Mayo Clinic vertebroplasty patients. Of this group, RDQ scores were available for 108 patients before vertebroplasty treatment, and after treatment for 93 patients at one week, 73 patients at one month, 46 patients at six months and 15 patients at one year. Patients' pain during rest and activity improved an average of seven points one week after treatment and remained improved one year following vertebroplasty. Prior to treatment, the average RDQ score was 18 on a scale of 23. The RDQ dropped to an average score of 11 immediately after treatment and remained at that level throughout the study.

Dr. Kallmes explains that in light of the wide practice of vertebroplasty for vertebral compression fractures, a study using a top-caliber back pain measurement tool like the RDQ was critical, especially in light of the often subjective nature of pain reporting by different patients.

"It's hard to remember your pain," he says. "Also, it's hard to say how bad my pain is compared to your pain. I've had patients say their pain is no better after treatment, yet I look at them and they look 10 times better."

Dr. Kallmes explains that ultimately, vertebroplasty needs evaluation through a study of the highest quality, a clinical trial in which patients are randomly assigned to receive treatment or no treatment and in which the patients and investigators are blinded to which patients receive the real treatment or a placebo used for comparison.

"Vertebroplasty has been promulgated by physicians who performed the procedure without quantifying the benefit," he says. "Yet, medical literature is rife with studies that have debunked therapies that are already in use."

Dr. Kallmes is making strides toward high-quality measurement of vertebroplasty. Currently, he is leading an international, multicenter study looking at whether the cement used in vertebroplasty is responsible for the pain relief reported by patients. Patients in this study are randomly assigned to receive treatment with the real cement used in vertebroplasty or a placebo.

Patients for whom vertebroplasty is appropriate, according to Dr. Kallmes, have osteoporosis or a similar condition and have suffered compression of their spines with no or minimal injury. For example, while bending over to tie their shoes or turning over in bed, patients' vertebrae may fracture because their bones are weakened due to osteoporosis. Each year, 700,000 people suffer this injury. For four out of five patients, the fracture heals and the accompanying pain goes away in approximately four weeks with bed rest and analgesics. However, for one in five patients, the fracture does not heal and the pain persists, requiring treatment. Surgery is not an option for these patients, as their bones are too weak. Vertebroplasty is the only available treatment option for patients in this condition.

Vertebroplasty is not appropriate for patients with back pain due to ligament injuries, joint disease or narrowing of the spinal canal, says Dr. Kallmes.

Prevent bone loss and periodontal disease

Sat, 19 Nov 2005 02:11:38 PST

( from http://www.rxpgnews.com ) Drugs that reverse and prevent bone loss due to osteoporosis also significantly ward off periodontal disease, according to a graduate of the Case Western Reserve University School of Dental Medicine who reports in the current Menopause journal article, "Periodontal Assessments of Postmenopausal Women Receiving Risedronate."
Leena Bahl Palomo, D.D.S and M.S.D., is the lead author on the study with Nabil Bissada, chair and professor of Case's department of periodontology; and James Liu, chair of the department of obstetrics and gynecology of University Hospitals of Cleveland.

During her graduate studies at Case, Palomo conducted one of the first studies to look at the impact of a group of bisphosphonates therapies for women with moderate and mild cases of osteoporosis and periodontal disease.

The study involved 60 postmenopausal women, who had been diagnosed with osteoporosis by doctors at University Hospitals of Cleveland and who had visited the Case dental clinics. She compared the women, who had been on daily or weekly bisphosphonate for at least three months to regenerate bone mass to those on no medications for the disease. The women were between the ages of 51 and 79, had T scores on bone scans of the hip or spine of 22.5. Half the group weighed approximately 127 pounds, and the overall study participants had similar alcohol and coffee daily intakes. The study participants did not smoke or use tobacco or estrogen products or have chronic medical conditions like diabetes that would increase the risks of periodontal disease. The risedronate group reported a higher use of vitamins and calcium supplements.

Each woman received an x-ray of the teeth and jaw and an oral examination that assessed the amount of inflammation, depth of the periodontal pocket, recession of the gums, mobility of the teeth and the presence of plaque--the standard parameters for gum disease as established by the American Academy of Periodontology. The examiner was unaware of who took medication.

In five of the six parameters, the risedronate therapy group had healthier periodontal status. Gum recession was not significantly different for either group.

The therapy group had significantly less plaque, which is an early indicator for periodontal disease. According to the researchers, risedronate therapy "is altering the periodontal status."

"We found a significant difference between the women who used the medications from the women who did not," said Palomo. "In the same way that the bisphosphonate is helping to prevent hip and vertebral fractures, the medications also prevent the loss of bone in the jaws--the bones which support the teeth."

"With a close link established between osteoporosis and periodontal disease, similar treatment and management of the disease might minimize tooth loss and the destruction of the alveolar (jaw) bone," reported Palomo.

Because bone loss is a "silent disease," and is many times diagnosed in older women after a hip or bone fracture, the researcher said dentists have the opportunity to observe signs of osteoporosis during a dental exam and can refer patients to the internist or gynecologist for a bone scan.

Palomo conducted the work under the direction of her thesis adviser, Bissada, and Liu from University Hospitals of Cleveland.

"This is more evidence to support the view of the mouth being a mirror of what's happening in the body," said Bissada. Case researchers have also found a link between periodontal disease and cardiovascular disease and complications in pregnancy.

"It also is nice to see that one medicine can help two diseases at the same time," added Bissada. "Drug companies are interested in better bone status for women," said Palomo, whose research was funded by Procter & Gamble, a maker of one of the leading brands of the bisphosphonate therapies for osteoporosis.

The researchers also suggest that this study could be used as a pilot for a longitudinal study to see what the long-term impact of risedronate therapy has on periodontal disease.

Adequate Vitamin D Maintains Calcium Metabolism

Wed, 09 Nov 2005 20:35:38 PST

( from http://www.rxpgnews.com ) Calcium intake levels of more than 800 mg/day may be unnecessary for maintaining calcium metabolism if vitamin D status is adequate, according to a study in the November 9 issue of JAMA.

The importance of adequate vitamin D status for optimum bone health has received increased recognition in recent years, with higher recommended intake levels being proposed by some investigators, according to background information in the article. The ideal intake is not known, and different criteria have been proposed for estimating population requirements. Serum 25-hydroxyvitamin D has been the generally accepted indicator of vitamin D status, but no universal consensus has been reached regarding which serum values constitute sufficiency. An inverse relationship between serum 25-hydroxyvitamin D and serum parathyroid hormone (PTH) is well established. Parathyroid hormone is a major hormone maintaining normal serum concentrations of calcium and phosphate and is itself regulated through levels of calcitriol and serum calcium. An insufficiency of vitamin D or calcium is generally associated with an increase in PTH.

Laufey Steingrimsdottir, Ph.D., of Landspitali-University Hospital, Reykjavik, Iceland, and colleagues conducted a study to determine the importance of high calcium intake and serum 25-hydroxyvitamin D for calcium homeostasis (metabolic equilibrium) in healthy adults, as determined by serum intact PTH.

The study included 2,310 healthy Icelandic adults who were divided equally into 3 age groups (30-45 years, 50-65 years, or 70-85 years) and recruited from February 2001 to January 2003. They were administered a semi-quantitative food frequency questionnaire, which assessed vitamin D and calcium intake. Participants were further divided into groups according to calcium intake (less than 800 mg/d, 800-1200 mg/d, and greater than1200 mg/d) and serum 25-hydroxyvitamin D level (less than 10 ng/mL, 10-18 ng/mL, and greater than 18 ng/mL). A total of 944 participants completed the dietary questionnaire.

The researchers found that after adjusting for relevant factors, serum intact PTH was lowest in the group with a serum 25-hydroxyvitamin D level of more than 18 ng/mL but highest in the group with a serum 25-hydroxyvitamin D level of less than 10 ng/mL. At the low serum 25-hydroxyvitamin D level (less than 10 ng/mL), calcium intake of less than 800 mg/d vs. more than 1200 mg/d was significantly associated with higher serum PTH; and at a calcium intake of more than 1200 mg/d, there was a significant difference between the lowest and highest vitamin D groups.

"The significance of our study was demonstrated by the strong negative association between sufficient serum levels of 25-hydroxyvitamin D and PTH, with calcium intake varying from less than 800 mg/d to more than 1200 mg/d. Our results suggest that vitamin D sufficiency can ensure ideal serum PTH values even when the calcium intake level is less than 800 mg/d, while high calcium intake (greater than 1200 mg/d) is not sufficient to maintain ideal serum PTH, as long as vitamin D status is insufficient," the authors write.

"Although a cross-sectional study such as our study is not sufficient to demonstrate causality, the association between vitamin D status, calcium intake, and the interaction between these 2 with serum PTH levels is a strong indication of the relative importance of these nutrients," the researchers write. "Although ideal intakes of these 2 nutrients need to be further defined in more elaborate studies, there is already sufficient evidence from numerous studies for physicians and general practitioners to emphasize to a much greater extent the importance of vitamin D status and recommend vitamin D supplements for the general public, when sun exposure and dietary sources are insufficient."

"In conclusion, our study suggests that vitamin D sufficiency may be more important than high calcium intake in maintaining desired values of serum PTH. Vitamin D may have a calcium sparing effect and as long as vitamin D status is ensured, calcium intake levels of more than 800 mg/d may be unnecessary for maintaining calcium metabolism. Vitamin D supplements are necessary to ensure adequate vitamin D status for most of the year in northern climates."

Developing stable, bacteria-resistant implants

Sat, 24 Sep 2005 15:30:38 PST

( from http://www.rxpgnews.com ) Infections associated with inserting a medical device can be devastating, painful, and cause prolonged disability, costing tens of thousands of dollars.

Now, researchers at Jefferson Medical College have found a way to create a permanent chemical bond between antibiotics and titanium, a material used in orthopedic implants. The proof-of-principle study showed that an antibiotic can be connected to the titanium surface in an active form, and can kill bacteria and prevent infection. The work is a critical first step toward developing stable, bacteria-resistant implants to combat infection.

The biggest benefit of this work is to keep the infection from ever starting, says Eric Wickstrom, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College of Thomas Jefferson University, who in collaboration with Noreen Hickok, Ph.D., associate professor of orthopedic surgery at Jefferson Medical College and Allen Zeiger, Ph.D., professor of biochemistry and molecular biology at Jefferson Medical College, developed the bonding method.

Infections associated with orthopedic implants are one of the major causes of implant failure. If bacteria grow on an implant, it cant knit properly with bone. Our technique puts a bed of antibiotic nails on the surface of the implant, Dr. Wickstrom says. In the work, the scientists fastened the antibiotic vancomycin to titanium powder. The vancomycin could then immediately kill bacteria sensitive to vancomycin that landed on the titanium.

The researchers checked to see if vancomycin was indeed attached to the titanium surface using microscopy. The tests proved that the vancomycin was bound and active.

Finally, they added bacteria and showed that titanium beads with vancomycin on the surface killed the bacteria. When the beads were exposed to more bacteria, the vancomycin continued to kill the new infection. The vancomycin was not only chemically bound, but aggressively curtailed re-infection as well.

The researchers, led by Irving Shapiro, Ph.D., professor of orthopedic surgery at Jefferson Medical College, and including collaborators at the Rothman Institute at Jefferson and the University of Pennsylvania are supported by a grant from the U.S. Department of Defense to develop techniques to protect titanium surfaces with antibiotics.

The recent results are another step toward our ultimate goal of preventing infections in battlefield fractures and hip and knee implants, Dr. Shapiro says.

This technology bonding antibiotics to the implant surface is analogous to having land mines, says orthopedic surgeon Javad Parvizi, M.D., who treats implant-related infections and works on the project. When a hip or knee implant is infected, physicians give extensive antibiotic treatment and the old implant is replaced. The treatment can include cement-containing antibiotics. Later, infections can start on the implant from a different source in the body, such as a bladder infection or a dental procedure.

Dr. Wickstrom says the same approach can be used for other antibiotics and other implants. There are plastic devices bladder catheters, implants for kidney dialysis, Hickman tubes, pacemakers every implant you can think of is a magnet for bacteria, he says. While the current work is proof-of-principle for binding titanium to an antibiotic, the research team has received a new grant for $3 million from the National Institutes of Health for five years to investigate ways of encouraging bone growth on implants bearing permanent antibiotics.

When an infected implant is taken out, its usually covered with a slimy layer of bacteria, Dr. Hickok explains. Were moving from just having a bacteria-killing surface to having one that prevents infection while promoting better bone-implant interactions. The idea is to have the implant last for many more years and avoid infection.

Genetic Factors Influence Propensity To Bone Fractures In Elderly

Tue, 13 Sep 2005 13:50:38 PST

( from http://www.rxpgnews.com ) The importance of genetic factors in an elderly individual's propensity to bone fractures depends on the individual's age and the type of fracture, according to a study in the September 12 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Bone fractures resulting from osteoporosis have a profound impact on quality of life, with only one third of patients regaining their pre-fracture level of function and a substantial risk of death following fracture, according to background information in the article. The authors suggest that twin studies provide one of the most natural study populations for evaluating genetic risk (the relative contribution of genes versus environment). If heritable factors contribute to fractures, monozygotic twins (who have all the same genes, commonly called identical twins) are more likely to have similar rates of fracture than dizygotic twins (who share about half the same genes, commonly called fraternal twins).

Karl Michaëlsson, M.D., Ph.D., of the Uppsala University Hospital, Uppsala, Sweden, and colleagues used the Swedish Twin Registry, the Swedish Inpatient Registry and telephone interviews to evaluate the genetic liability to fracture of the elderly. From the registry of Swedish twins born between 1,896 and 1,944 (3,724 identical twins, 6,314 fraternal same-sex twins and 5,736 fraternal different-sex twins), the researchers were able to identify 6,021 twins with any fracture, with a higher proportion among women (23 percent) than men (14 percent). More than half the cases (3,599) were classified as osteoporotic fractures. The most important osteoporotic fracture, hip fracture, was recorded for 1,055 twins.

Genetic variation in liability to fracture differed considerably by type of fracture and age, the authors report. Less than 20 percent of the overall age-adjusted fracture variance was explained by genetic variation. Heritability was considerably greater for first hip fracture before the age of 69 years and between 69 and 79 years than for hip fractures after 79 years of age.

"We conclude that the genetic influence on susceptibility to fractures is dependent on type of fracture and age at fracture event," the authors write. "The heritability of osteoporotic fractures is stronger than has been previously estimated, especially for early-occurring osteoporotic fractures. A search for genes and gene-environmental interactions that affect early osteoporotic fracture risk is likely to be fruitful, but fracture-prevention efforts at older ages should be focused on lifestyle habits."

Consumption Of Soy May Reduce Risk Of Fracture In Postmenopausal Women

Tue, 13 Sep 2005 13:50:38 PST

( from http://www.rxpgnews.com ) Postmenopausal women who consumed high daily levels of soy protein had reduced risk of bone fracture, according to a study in the September 12 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Women experience accelerated bone loss at a rate of three to five percent per year for about five to seven years after menopause, putting them at a high risk for bone fracture, according to background information in the article. The U.S. Food and Drug Administration and new clinical guidelines advise against the use of hormone therapy as a first-line treatment for the prevention of osteoporosis in postmenopausal women and emphasize alternatives including exercise and increasing intake of calcium and vitamin D. Growing evidence suggests a potential role for soy in preventing postmenopausal bone loss.

Xianglan Zhang, M.D., M.P.H., from the Vanderbilt University School of Medicine, Nashville, and colleagues examined the relationship between soy food consumption and bone fractures in 24,403 postmenopausal women. The women were part of the Shanghai Women's Health Study, a study of approximately 75,000 Chinese women aged 40 to 70 years, conducted between March 1997 and May 2000. Participants' usual dietary intake was assessed once at the beginning of the study and then during follow-up, approximately two to three years later. Average age was 60 years.

The researchers found that soy consumption may reduce the risk of fracture in postmenopausal women, especially among those in the early years following menopause. During an average follow-up of four and a half years, 1,770 fractures were reported. The median (middle value) daily intakes of soy protein and soy isoflavones (estrogen-like plant chemicals) were 8.5 grams and 38 micrograms, respectively. Participants were divided into five categories, according to their soy intake, with the lowest intake group consuming less than 4.98 grams of soy per day, and the highest group consuming 13.27 grams or more of soy per day. Those in the highest soy protein intake group had a 37 percent reduced relative risk for fracture compared to the lowest intake group. Women in the highest soy isoflavone group had a 35 percent reduced relative risk for fracture compared to the lowest isoflavone group.

"In this prospective cohort study of postmenopausal women, we found that soy food consumption was associated with a significantly lower risk of fracture, particularly among women in the early years following menopause," the researchers write. "The potential impact of timing on the skeletal effects of soy needs to be further addressed in future studies."

Identifying Previously Undectable Spinal Injuries

Fri, 09 Sep 2005 16:11:38 PST

( from http://www.rxpgnews.com ) A new national study indicates that patients with a cervical spinal injury may harbor additional spinal damage not visible on regular x-rays. In fact, more than a third of patients who were thought to have low-risk injuries actually have additional damage that may include significant fractures with the potential to produce serious spinal problems if not detected and treated properly.

This study, to be published as an early online release in the Annals of Emergency Medicine, contests previous medical thinking in which patients with certain forms of spinal injury were considered at very low risk of having additional injuries. Because of that low risk, physicians were urged to use plain x-rays and avoid computed tomography (CT) in evaluating these cases.

"These findings are significant because they suggest that CT imaging, which allows physicians to view the spine in much greater detail, is necessary in evaluating all patients who have radiographic evidence of cervical spine injuries," said lead study author Dr. William Mower, professor of emergency medicine at the David Geffen School of Medicine at UCLA. "We found that even among patients with low-risk injuries, more than one-third sustained secondary damage that was not diagnosed by plain radiography."

Mower added that approximately one-fourth of these secondary injuries occurred in another part of the cervical spine, which suggests that at least some of these patients may have actually sustained two separate spinal injuries.

Researchers reviewed patient cases from the National Emergency X-Radiography Utilization Study, which was conducted at 21 centers across the United States.

Study authors found that x-rays failed to detect secondary injuries in 81 of the 224 patients identified with cervical spine injuries or 36 percent.

"We also think that this is likely an underestimate, and the true prevalence of missed injury is probably even greater," Mower said.

The researchers believe that patients with any evidence of cervical spine injury, including those with cervical spine injuries previously considered to be at low risk for secondary injuries, should undergo CT imaging of the entire cervical spine. CT should be obtained both to determine whether secondary injuries are present and to identify those non-contiguous injuries that, in fact, occur in a substantial number of cases.

Serial bone mineral density (BMD) measurements can improve fracture risk accuracy

Mon, 29 Aug 2005 21:58:38 PST

( from http://www.rxpgnews.com ) Scientists from the Garvan Institute of Medical Research in Sydney, Australia, are suggesting a new approach to determining the risk of fracture in individuals with the brittle bone disease, osteoporosis, which could have treatment implications. Their finding, published in the Journal of Bone and Mineral Research, is based on data from a fifteen-year epidemiology study and shows that calculating bone loss, by having at least two bone mineral density (BMD) measurements taken a minimum of 1-2 years apart, can improve the accuracy of fracture risk assessment.

Currently a bone density (DXA) scan is used to diagnose osteoporosis but, in Australia, treatment is usually only prescribed when an individual has had a fracture - regardless of BMD levels. Individuals with low BMD, despite being at high risk of fractures, are not commonly considered for drug treatment even though experts suggest that they should have preventative medication.

One in two women and one in three men over the age of 60 will have a fracture due to osteoporosis* and, with an ageing population, the total numbers of sufferers is increasing. Fractures are a major cause of pain, disability and premature death.

There are medicines available to treat those with brittle bones. Many clinical trials have shown that a drug that moderately increases BMD (e.g. by 3 to 4%) can reduce fracture risk by as much as half. The cost of measuring BMD by a DXA scan is relatively small, but the cost of treatment - if all individuals with low BMD are treated - is significant at the population level. The cost/benefit of mass screening of osteoporosis has been debated in Australia for some time and the issue boils down to how much money should be spent to prevent one fracture.

Associate Professor Tuan Nguyen, who is a joint head of the Epidemiology group of the Bone and Mineral Research Program at the Garvan Institute, says: "We know that low bone mineral density is the most important risk factor for fracture; paradoxically, almost half of women with fractures do not have low BMD. If we wish to treat those most at risk from osteoporotic fractures, a two-stage screening approach where individuals with low BMD and increased bone loss are treated could improve the cost-effectiveness".

*This adds up to 70,000 preventable fractures per year, with total direct and indirect costs running to over 7 billion dollars per year (Osteoporosis Australia).

Brain plays an important role in the bone density maintenance

Thu, 25 Aug 2005 03:52:38 PST

( from http://www.rxpgnews.com ) The brain plays an important role in the maintenance of proper bone density, researchers at the Hebrew University of Jerusalem have revealed.

The results of this research, involving a study of the activity of the protein interleukin 1 in the brain, comprise not only a breakthrough in understanding the regulation of bone density by the brain but also hold promise for the development of future treatment for osteoporosis, say the researchers. An article about their work appears in the current edition of the prestigious American journal, Proceedings of the National Academy of Sciences.

The Hebrew University research project is headed by Prof. Itai Bab of the Bone Laboratory, working in cooperation with Prof. Raz Yirmiya of the Department of Psychology, Prof. Esther Shahami of the of the Laboratory for the Study of Brain Trauma, Ph.D. students Alon Bagin and Inbal Goshen and master's degree student Sharon Feldman.

Osteoporosis is the most widespread, degenerative disease in the Western world. It is characterized by loss of bone density and consequent structural weakening of the skeleton. Osteoporosis sufferers are highly susceptible to fractures, in some cases leading to severe physical disability and complications that can even end in death.

In humans and other vertebrates, one-tenth of the bone tissue is involved in an "exchange" process of continuous bone loss and generation. In adult humans and other mammals, this process is balanced; that is, the amount of bone tissue that is generated is equal to that which is lost, thus preserving bone density. With age, this balance is disrupted, and the amount of bone tissue that is lost is greater than that which is created, with the result that bone density declines and bone structure is impaired.

The interleukin 1 protein has been known for many years as a stimulator of the immune system. In the skeleton the protein causes an increase in the number and activity of osteoclastic cells the cells which break down bone tissue and which develop from the same cells as those of the immune system.

By experimenting with genetically engineered laboratory mice whose ability to react to interleukin 1 was controlled, the Hebrew University researchers were able to demonstrate that the proper loss/generation balance in bone tissue is regulated by the level of activity of interleukin 1 in the brain. A normal, optimal level of interleukin 1 activity in the brain is required to protect bone density by impeding bone tissue breakdown, say the scientists.

"The connection between the brain and the bone structure is a new area of research about which very little is known," said Prof Bab. "These new findings from our laboratories at the Hebrew University regarding the action of interleukin 1 on the breakdown of bone tissue indicate a complex neural system controlling bone structure and point the way towards new revelations in the near future in this area."

Dietary calcium can counteract low bone density in oral contraceptive users

Thu, 18 Aug 2005 16:30:38 PST

( from http://www.rxpgnews.com ) Women who take oral contraceptives can counteract bone loss by making sure they have enough calcium in their daily diet, especially early in life, according to Purdue University research.

Earlier research has indicated that optimizing bone mass in adolescence and young adulthood prevents low bone density and osteoporosis later in life. On the other hand, oral contraceptives appear to decrease bone density.

"It's estimated that eight out of 10 women in the United States use oral contraceptives at some time during the years in which peak bone mass is developing," said Dorothy Teegarden, assistant professor in Purdue's Department of Foods and Nutrition. "The results of our study suggest that the loss for this group can be prevented by increasing calcium intake."

According to the National Academy of Sciences, the recommended dietary allowance of calcium for women age 19 to 50 is 1,000 milligrams a day. The recommended daily allowance of calcium for adolescents age 9 to 18 is 1,300 milligrams a day.

The 12-month study, funded by the American Dairy Association/National Dairy Council, was published in the July issue of Journal of Clinical Endocrinology and Metabolism.

The study compared 135 oral contraceptive users to non-users between the ages of 18 and 30. Three groups were randomized to receive one of three diets: control (less than 800 mg calcium a day), medium dairy (1,000-1,100 mg calcium a day) and high dairy (1,200-1,300 mg calcium a day).

At the end of the year, women using oral contraceptives and consuming the medium- or high-dairy diet gained significantly more bone mineral density in their hips and spines compared to the low-dairy group.

"These results suggest that many women who are using oral contraceptives in their peak bone-development years could reduce their risk of osteoporosis by approximately 3 percent to 10 percent over one year by making sure they get enough calcium in their diet," Teegarden said. "This demonstrates the importance of calcium intake, either by getting enough dairy or with supplements."

Diabetics have more complications after ankle fracture surgery

Mon, 15 Aug 2005 17:17:38 PST

( from http://www.rxpgnews.com ) In the largest analysis of its kind, Duke University Medical Center researchers have found that patients with diabetes who require surgery for ankle fractures have significantly higher rates of complications and higher hospital costs compared to non-diabetic patients.

Specifically, the researchers found that diabetics experienced one additional day of hospitalization (an average of 4.7 vs. 3.6 days) with costs approximately 20 percent higher ($12,898 vs. $10,794). Additionally, diabetics had higher mortality rates (0.26 percent vs. 0.11 percent) and higher rates of post-operative complications (4.63 percent vs. 3.27 percent).

Demonstrating this link between diabetes and worse outcomes is important, the researchers said, because ankle fractures are one of the most common injuries treated by orthopedic surgeons, and the study's findings provide guidance on how to improve the care for these patients and reduce health care expenditures.

The results of the Duke analysis were published Aug. 15, 2005, in the Journal of Bone and Joint Surgery.

"While a number of smaller studies have indicated that diabetic patients tended to have worse outcomes after ankle surgery, this is the first large-scale analysis of a cross-section of patients across the U.S.," said Shanti Ganesh, M.P.H., lead author of the study and fourth-year year medical student at Duke University School of Medicine.

"This analysis demonstrated that diabetic patients, no matter how severe the ankle fracture, were more likely to experience higher rates of post-operative complications, mortality, and non-routine discharge, with accompanying longer lengths of hospital stay and higher hospital charges," Ganesh said.

For their analysis, the Duke team consulted the Nationwide Inpatient Samples (NIS) database and identified 169,598 patients who underwent surgery for ankle fractures. The NIS, sponsored by the U.S. Agency for Healthcare Research and Quality, is a publicly available database of more than 8 million patients from more than 1,000 U.S. hospitals. The hospitals vary by region, size, location, teaching status and ownership.

"The strength of this analysis is that it provides a nationally representative and real-world picture of what happens to ankle fracture patients in the U.S.," said Ricardo Pietrobon, M.D., senior member of the research team and director of Duke's Center for Excellence in Surgical Outcomes (CESO), which supported the analysis. "We were unable to extrapolate from the data gathered from smaller, single-center studies what the situation was nationwide.

"Now we have specific data that allows us to quantify the added risks and costs of diabetes for these patients," Pietrobon continued. "This information is crucial in improving outcomes and quality of life for our patients undergoing surgery to repair ankle fractures."

Of the 169,598 ankle fracture patients, the Duke team identified 9,174 (5.71 percent) with diabetes. The diabetic patients tended to be more than 10 years older than the non-diabetic patients, and when they did suffer ankle fractures, they tended to be more severe than those suffered by non-diabetic patients.

Ganesh said that the results of the study indicate that physicians taking care of ankle fracture patients should appreciate the effect that diabetes can have on the treatment and recovery of their patients. Strategies could include close monitoring of glucose levels during and after surgery and the prophylactic use of medications to prevent the formation of deep venous thrombosis (DVT), which can occur in surgery patients who are bedridden for extended periods of time.

It is also widely appreciated that diabetic patients tend to have slower healing rates than non-diabetic patients, Ganesh continued. This can be important not only during hospitalization, but also after discharge, when patients typically begin rehabilitation activities, she added.

One interesting finding, which the researchers said was not a focus of the current study and confirms other findings, was that the percentage of patients with diabetes steadily increased over the 12-year period from 1988 to 2000.

The researchers estimate that of the 260,000 Americans who fracture their ankles every year, about 25 percent will require surgery to stabilize the ankle.

Vitamin D supplements not helpful in black women

Fri, 29 Jul 2005 15:36:38 PST

( from http://www.rxpgnews.com ) Vitamin D supplementation did not appear to prevent bone loss in postmenopausal black women, according to a study in the July 25 issue of the Archives of Internal Medicine, one of the JAMA/Archives journals.

Although there is general agreement on the optimal calcium intake recommended for reducing postmenopausal bone loss, and it is recognized that vitamin D is important in calcium maintenance, the optimal intake of vitamin D is controversial, according to background information in the article. Blood levels of 25-hydroxyvitamin D (25-OHD) are the best indicator of vitamin D status, with very low levels leading to rickets and osteomalacia (softening of bones). Black women have lower blood levels of 25-OHD because they synthesize less through skin exposure to the sun.

John F. Aloia, M.D., from Winthrop University Hospital, Mineola, N.Y., and colleagues, conducted a randomized, double-blind trial comparing bone loss in postmenopausal black women taking vitamin D3 supplements and those not taking supplements. Two-hundred-eight healthy black women, aged 50 to 75 years, received either placebo or 20 µg/day (micrograms per day) of vitamin D3. All participants received calcium supplements to ensure a total calcium intake of 1,200 to 1,500 mg/day. After two years, the vitamin D3 dose was raised to 50 µg/day. Bone mineral density (BMD) was measured at six-month intervals for three years.

The researchers found that there was no significant difference in BMD in women receiving vitamin D and women receiving placebo. There was also no relationship found between 25-OHD blood levels and bone density change in either group. Both groups experienced an increase in BMD in total body, hip, and mid-radius (forearm bone) at one year (between 1.1 and 1.3 percent). However, BMD declined at these sites over the full three years from 0.26 percent to 0.55 percent. Initial total hip BMD ranged from normal (65 percent) to osteopenic (having reduced bone mass; 33.6 percent) to osteoporotic (severely reduced bone mass, 1.4 percent).

"Our study demonstrated a lack of benefit of vitamin D supplementation on loss of skeletal mass in calcium-sufficient African American women in midlife," the researchers report. "Although this may not be extrapolated to women of other ethnic groups, to elderly women, or to greater degrees of vitamin D insufficiency, it lends support to re-examination of optimal vitamin D nutrition for skeletal health in postmenopausal women of other ethnic groups."

TOPAZ(TM) Brings New Hope for Tennis Elbow

Wed, 27 Jul 2005 13:53:38 PST

( from http://www.rxpgnews.com ) New study data published this month in Arthroscopy: The Journal of Arthroscopic & Related Surgery showed the use of a Coblation-based technology known as TOPAZ -- developed by ArthroCare(R) Corp. (Nasdaq:ARTC) -- to be effective when used in the treatment of common tendon disorders such as lateral epicondylitis, the condition commonly known as tennis elbow.

"Our findings from the study demonstrate this procedure is technically simple to perform and is associated with a rapid and uncomplicated recovery," said James P. Tasto, M.D. of San Diego Sports Medicine and Orthopedic Center, one of the study's authors and Professor of Orthopedic Surgery at the University of California, San Diego. "All participating patients showed significant improvement. Based upon the results of this study, the use of TOPAZ in the treatment of tendons is safe and effective for at least two years, post-op. Treatment utilizing the TOPAZ MicroDebrider offers a new, minimally invasive alternative for millions of patients for whom conservative therapies have failed."

The study, titled "Microtenotomy Using a Radiofrequency Probe to Treat Lateral Epicondylitis," consisted of thirteen subjects who had been suffering symptoms for six months or longer. Each of the patients had failed to achieve relief after conservative treatment. After treatment in which TOPAZ was used, the patients reported significant improvement only seven to 10 days after the procedures. In fact, 10 of the 13 subjects reported noticeable improvement only one or two days after the procedure.

"It's extremely gratifying when a study concerning one of our technology applications reveals such dramatically positive results," said Jack Giroux, ArthroCare Sports Medicine's President. "This is especially the case when the device in question, the TOPAZ MicroDebrider, has the opportunity to help such a large population -- those suffering from tendon conditions. While this particular study focused on the most common tendon-related complaint by patients seeking medical attention, TOPAZ is designed to be used to treat most tendons throughout the body."

The TOPAZ MicroDebrider is a wand-like device about the diameter of a pencil tip. Through a small incision, generally an inch in length, the physician applies the device to the problem tendon for multiple 500 millisecond intervals of treatment. By combining low temperature radiofrequency energy with saline, a charged plasma gas is formed at the tip of the TOPAZ wand and is precisely directed into and through the damaged tissues. From start to finish, the whole process takes less than 20 minutes.

"It should be noted," Tasto said, "that over the same period of time that the data was collected for this study, patients with other tendon conditions in the elbow, knee or shoulder were also treated using the TOPAZ wand -- and yielded similar results. I see great promise for this technology in an array of applications."

Carbon nanotubes make an ideal scaffold for the growth of bone tissue

Sun, 10 Jul 2005 15:06:38 PST

( from http://www.rxpgnews.com ) Scientists have shown for the first time that carbon nanotubes make an ideal scaffold for the growth of bone tissue. The new technique could change the way doctors treat broken bones, allowing them to simply inject a solution of nanotubes into a fracture to promote healing.

The report appears in the June 14 issue of the American Chemical Society's journal Chemistry of Materials. ACS is the world's largest scientific society.

The success of a bone graft depends on the ability of the scaffold to assist the natural healing process. Artificial bone scaffolds have been made from a wide variety of materials, such as polymers or peptide fibers, but they have a number of drawbacks, including low strength and the potential for rejection in the body.

"Compared with these scaffolds, the high mechanical strength, excellent flexibility and low density of carbon nanotubes make them ideal for the production of lightweight, high-strength materials such as bone," says Robert Haddon, Ph.D., a chemist at the University of California, Riverside, and lead author of the paper. Single-walled carbon nanotubes are a naturally occurring form of carbon, like graphite or diamond, where the atoms are arranged like a rolled-up tube of chicken wire. They are among the strongest known materials in the world.

Bone tissue is a natural composite of collagen fibers and hydroxyapatite crystals. Haddon and his coworkers have demonstrated for the first time that nanotubes can mimic the role of collagen as the scaffold for growth of hydroxyapatite in bone.

"This research is particularly notable in the sense that it points the way to a possible new direction for carbon nanotube applications, in the medical treatment of broken bones," says Leonard Interrante, Ph.D., editor of Chemistry of Materials and a professor in the department of chemistry and chemical biology at Rensselaer Polytechnic Institute in Troy, N.Y. "This type of research is an example of how chemistry is being used everyday, world-wide, to develop materials that will improve peoples' lives."

The researchers expect that nanotubes will improve the strength and flexibility of artificial bone materials, leading to a new type of bone graft for fractures that may also be important in the treatment of bone-thinning diseases such as osteoporosis.

In a typical bone graft, bone or synthetic material is shaped by the surgeon to fit the affected area, according to Haddon. Pins or screws then hold the healthy bone to the implanted material. Grafts provide a framework for bones to regenerate and heal, allowing bone cells to weave into the porous structure of the implant, which supports the new tissue as it grows to connect fractured bone segments.

The new technique may someday give doctors the ability to inject a solution of nanotubes into a bone fracture, and then wait for the new tissue to grow and heal.

Simple single-walled carbon nanotubes are not sufficient, since the growth of hydroxyapatite crystals relies on the ability of the scaffold to attract calcium ions and initiate the crystallization process. So the researchers carefully designed nanotubes with several chemical groups attached. Some of these groups assist the growth and orientation of hydroxyapatite crystals, allowing the researchers a degree of control over their alignment, while other groups improve the biocompatibility of nanotubes by increasing their solubility in water.

"Researchers today are realizing that mechanical mimicry of any material alone cannot succeed in duplicating the intricacies of the human body," Haddon says. "Interactions of these artificial materials with the systems of the human body are very important factors in determining clinical use."

The research is still in the early stages, but Haddon says he is encouraged by the results. Before proceeding to clinical trials, Haddon plans to investigate the toxicology of these materials and to measure their mechanical strength and flexibility in relation to commercially available bone mimics.

Early infection intervention can prevent amputation in diabetics

Thu, 16 Jun 2005 17:50:38 PST

( from http://www.rxpgnews.com ) A small sore on a toe may not seem like a major medical threat. But for the millions of people who have diabetes and other conditions, it can be the first step on a road that leads to the amputation of a foot -- or even a leg.
Now, a new study from the University of Michigan Cardiovascular Center may help more people save their limbs. Published in the June issue of the Annals of Surgery, it's the first-ever large study of how foot-bone infection, called osteomyelitis, is typically treated and how well the different approaches work.

Because diabetes interferes with the body's ability to heal, even the smallest foot wounds can become infected, spread to the bone, and lead to an amputation. Poor circulation and numb feet, also common in people with diabetes, make the situation worse. More than 80,000 such amputations happen each year in the United States. Experts already recommend that people with diabetes take special care of their feet and have regular foot exams to spot problems early.

The study is the first large account of the prevalence, treatment characteristics and high cost of treating osteomyelitis, which interferes with walking and sends thousands of people to the hospital each year.

On average, it shows, patients stayed in the hospital for about a week at an average cost of $19,000. Almost one in every thousand hospitalizations may be due to foot osteomyelitis, the study suggests.

"This study grew out of our own observations that many osteomyelitis patients were being treated for months or even years with antibiotics, but not healing, and this can contribute to the loss of their foot or leg," says lead author Peter Henke, M.D., an assistant professor of vascular surgery at the U-M Medical School. "But there's little evidence to guide treatment, so we wanted to look at epidemiology and outcomes. Our results show this is a common, costly issue that needs much further study."

Henke and his colleagues performed the study using data from the Nationwide Inpatient Sample, a database of hospital patient information maintained by the federal Agency on Health Care Research and Quality. They also used data from 237 osteomyelitis patients treated at the University of Michigan. Both sets of data were from patients treated between 1993 and 2000.

In all, the national data showed that 8.5 percent of patients hospitalized for foot osteomyelitis had a leg or foot amputated, and 23 percent had a toe amputated. About 1.6 percent died before leaving the hospital. Patients who were older, African American or had kidney problems were more likely to have an amputation.

Of the U-M osteomyelitis patients, 80 percent had diabetes, and 30 percent had chronic kidney problems. Nearly 40 percent also had blockage in the blood vessels of their legs, a condition called peripheral vascular occlusive disease. Nearly a quarter of the patients died within 31 months of their hospital stay.

"This is a patient population in which a non-healing foot wound becomes an ulcer, exposes the bone, and leads to osteomyelitis," says Henke.

About half of the U-M patients had been on antibiotics before being hospitalized, many of them on intravenous doses of the drugs. On average, patients had been on antibiotics for five months, and 30 percent had had more than one course of antibiotics prescribed to them before being admitted.

However, U-M patients who had been on antibiotics before they entered the hospital were much less likely to heal -- perhaps because the bacteria in their infected wound had grown resistant to antibiotics.

Those who had been on antibiotics for a long time before hospitalization were also less likely to keep their limbs, possibly because the non-healing infection spread too far to allow the foot or leg to be saved. The national data did not include pre-hospital antibiotic use.

But the patients who had blood vessel reconstruction to improve circulation in their legs and feet were several times more likely to have successful wound healing and to keep their foot or leg. Toe amputees were also more likely to keep their limbs.

Patients who had clogged leg blood vessels -- the condition known as peripheral vascular occlusive disease or PVOD -- before their hospitalization were far less likely to keep their legs or feet over time. The patients in the study, Henke notes, were younger and more likely to have diabetes than the typical PVOD patient, but had a higher than usual risk of losing a foot or leg.

"This study suggests that antibiotics alone are not as effective as surgery plus antibiotics, both for healing wounds and saving limbs," says Henke. "It also suggests that diabetic patients, especially those with PVOD, have a very high chance of developing osteomyelitis -- and that these patients should be considered for aggressive arterial reconstruction or other early intervention. This also really drives home the need for good foot care for all patients with diabetes."

Among the steps recommended for all people with diabetes are to examine their feet daily for any signs of redness, blisters, cuts or sores; to wear well-fitting shoes and protect their feet from injury; and to remove their shoes and socks at each diabetes-related checkup so feet can be examined

The researchers also find that patients whose wounds didn't heal, and those who didn't receive early surgical intervention, were much more likely to use home-health services after leaving the hospital. This kind of care, and outpatient visits, must also be considered when the costs of osteomyelitis are tallied, says Henke. But since surgery can decrease the need for outpatient visits, it may also help reduce costs of caring for a non-hospitalized osteomyelitis patient.

Because the U-M study was performed using retrospective data, the authors say a large prospective study comparing antibiotic use with surgical therapy will be needed to confirm their results before they have an impact on clinical care.

EXOGEN(TM) Bone Healing System Receives Expanded Medicare Coverage

Sat, 30 Apr 2005 09:00:38 PST

( from http://www.rxpgnews.com ) Smith & Nephew Orthopaedics (NYSE: SNN - News; LSE: SN - News) today announced that the United States Centers for Medicare & Medicaid Services (CMS) has expanded existing Medicare coverage of its EXOGEN(TM) Bone Healing System for the treatment of all nonunion bone fractures, regardless of whether the fracture has had prior surgical intervention.

The EXOGEN(TM) Bone Healing system delivers low-intensity pulsed ultrasound to a fracture site, and is the only ultrasound stimulation device approved by the FDA for the treatment of nonunion fractures. In addition, the EXOGEN(TM) system is the only osteogenic bone stimulator of any kind approved by the FDA for accelerating the healing of indicated fresh fractures*.

Medicare has reimbursed the cost of using the EXOGEN(TM) device since 2000 in nonunion fracture cases where surgery has failed to heal a fracture. Medicare will now offer reimbursement for the use of the EXOGEN(TM) system for all nonunions, regardless of whether they have had prior surgical intervention.

"This decision opens up more options for patients and surgeons, providing a non-invasive alternative to surgical treatment, and offering an opportunity for people to regain their mobility," said Joe Woody, vice president and general manager of the Clinical Therapies division of Smith & Nephew. "We have worked closely with CMS, providing data from clinical studies and other scientific data that consistently demonstrated similar healing rates in patients with and without previous surgery, as well as economic analyses that highlighted the cost-effectiveness of EXOGEN(TM)."

Nonunions are defined clinically as the point when bone healing has stopped and will not proceed without some type of intervention. Three studies conducted on nonunions demonstrated that use of the EXOGEN(TM) Bone Healing System for 20 minutes per day, with no other change in treatment, was highly successful for all bones, all fracture locations, and all types of fracture irrespective of the type of orthopaedic fracture management.

CMS' decision was in response to Smith & Nephew's request that the requirement for failed prior surgical intervention to qualify for reimbursement be removed. Data presented and reviewed by CMS included:

- Newly published scientific data on the EXOGEN(TM) unit mode of action, which indicates that EXOGEN(TM) affects a range of cells important to the fracture healing process.
- Published economic analysis(1) which concludes, based on the high success rates in the clinical studies, that the EXOGEN(TM) system is the most cost-effective bone stimulator for the treatment of nonunion fractures.

In coming to a decision to expand nonunion coverage for the EXOGEN(TM) Bone Healing System, CMS reviewed the science, assessed the overwhelmingly positive public comment from physicians and patients, and conducted their own pooled analysis of the clinical data -- which showed an 85% success rate with the EXOGEN(TM) unit regardless of whether there had been prior surgery or not.

Vitamin D, Calcium Ineffective in Preventing Fractures

Fri, 29 Apr 2005 14:28:38 PST

( from http://www.rxpgnews.com ) A study in this week's BMJ finds no evidence that calcium and vitamin D supplements reduce the risk of fractures in older women living in the community.

The researchers identified 3,314 women aged 70 and over and at high risk of hip fracture from primary care clinics. The women were randomly split into two groups.

The treatment group received advice from a practice nurse on how to reduce the risk of fracture and were given calcium and vitamin D tablets to take daily. The control group received only a leaflet on diet and prevention of falls. All women were monitored for an average of two years.

Over the monitoring period, fracture rates were lower than expected but did not significantly differ between the groups. There was no evidence that supplements reduced the risk of fractures or falling, or improved quality of life.

Putting this study in the context of other trials suggests that calcium and vitamin D supplementation may not be an effective intervention for reducing fractures in primary care, conclude the authors.

Calcium Supplements Unable to Prevent Fractures

Thu, 28 Apr 2005 18:16:38 PST

( from http://www.rxpgnews.com ) The findings are reported today in The Lancet and follow a major 5½ year trial involving almost 5,300 people aged 70 and over who had suffered a fracture in the last 10 years. Participants were recruited through fracture clinics and in-patient wards at 21 hospitals across the UK.

Fractures resulting from osteoporosis are an important cause of ill-health with annual public sector costs estimated to run into hundreds of millions of pounds.

From the age of 50, one in three women and one in twelve men will have an osteoporotic fracture, such as those of the hip, wrist or spine. Those who have already suffered a fracture of this kind are at increased risk of suffering a further fracture.

Vitamin D and calcium, alone or in combination, are often recommended for prevention of osteoporotic fractures.

Up until now it has not been clear if supplements of calcium and/or vitamin D are effective in preventing a further fracture among those who have already had one. However, research led by the University of Aberdeen suggests this is not the case.

Professor Adrian Grant is Director of the Universitys Health Services Research Unit (HSRU), which has a national remit to research the best ways to provide health care and to train those working in the health services in research methods.

Professor Grant, principal investigator in the trial, said: Fracture prevention is now widely practised for those at risk from osteoporosis.

However, our findings indicate that routine supplementation with calcium and vitamin D3, either alone or in combination, is not effective in the prevention of further fractures in older people who have previously suffered a fracture.

The trial was funded by the Medical Research Council, with support from Shire Pharmaceuticals and European pharmaceutical company Nycomed.

It investigated the effect of calcium and/or vitamin D3 on the incidence of further fractures in men and women aged 70 and over with a previous low-trauma fracture.

The trial office at HSRU coordinated the recruitment of 5,292 participants who were randomised to take 1000mg calcium, 800 International Units (IU) vitamin D3, both, or a placebo. Most participants were able to walk out of doors unaccompanied and less than 1% came from nursing homes.

The trial mainly examined the prevention of low-trauma fractures, but other outcomes including health status, mortality, falls and adverse events were also sought. Participants were followed up for between 24 and 62 months. Six hundred and ninety-eight participants (13%) suffered a further low-trauma fracture, including 183 people with hip fractures.

Professor Grant added: We found no statistically significant differences between those allocated calcium and those not; those allocated vitamin D and those not; and those allocated both calcium and vitamin D versus placebo. We also noted no significant differences for hip fractures, mortality, falls or quality of life.

We were a little surprised by our findings because, based on evidence available, the most likely finding was that the combination of calcium and vitamin D would prevent fractures. However, we didnt find this to be the case.

Our results suggest that we should consider other strategies for secondary fracture prevention, including pharmacological intervention with drugs such as bisphosphonates that help maintain bone density and reduce fractures.

· Oral Vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial appears in The Lancet

A Natural Molecule will Help Fractures Heal Fast and Generate New Bone Growth

Sun, 24 Apr 2005 16:18:38 PST

( from http://www.rxpgnews.com ) By studying diseases in which the human body generates too much bone, UCLA researchers have discovered and isolated a natural molecule that can be used to heal fractures and generate new bone growth in patients who lack it.

Bioengineering professor Ben Wu at UCLA's Henry Samueli School of Engineering and Applied Science, and Kang Ting, Thomas R. Bales Professor at UCLA's School of Dentistry, are developing a new molecule they've named UCB, or University of California Bone.

The core technology developed by Wu and Ting is potentially the most significant advancement in bone regeneration since the discovery of bone morphogenetic proteins by Dr. Marshall Urist at UCLA in the 1960s.

"For the average person, this new development potentially means faster, more reliable bone healing with fewer side effects at a lower cost," Ting said. "In more severe cases, such as in children born with congenital anomalies, the new protein may offer an advanced solution to repair cleft palates, which involves bone deficiencies, and also aid in repairing other bone defects such as fractures, spinal fusion and implant integration."

UCB differs significantly from bone morphogenetic protein, the protein currently used by orthopedic surgeons to aid in bone repair, in that UCB potentially has fewer side effects. With bone morphogenetic proteins, bone formation has been observed to occur at locations outside of the intended implant site, and tissue other than bone also has been reported.

In contrast, UCB's main effects appear to be more specific towards bone formation process, giving surgeons increased control over where bone forms.

According to Wu, UCB is more specific because it works downstream from the body's "master switch" for bone formation. Because the two molecules act on different targets, UCB also works synergistically with bone morphogenetic proteins to form more bone than typically is possible with bone morphogenetic proteins alone.

The key to success for these proteins is designing the right carrier -- using the protein alone is not effective. Currently, bone morphogenetic proteins are delivered with a collagen-sponge into the area where bone growth is needed. The sponge offers few biological benefits for the surgeon, and proteins can migrate away from the sponge.

In contrast, the team at UCLA is developing a carrier that is engineered for UCB activities in the biological environment.

"It's the right combination of carrier and protein that further increases the stability and activity of UCB," Ting said. "For certain clinical applications, we will need to develop injectable options that are minimally invasive. For other clinical applications, we will need moldable carriers that can hold the UCB in place better. By making life easier for the surgeons, they can focus on the surgery. Ultimately, the patient benefits."

Another current option is to use the patient's own bone grafted from another part of the body.

"Right now, we are doing a lot of spinal fusions and these fusions require us to have bone graft material. The problem with taking a patient's own bone for this procedure is that aside from the pain, which often becomes severe and persistent, there is a high risk of infection. This adds higher risk to the surgery," said Dr. Jeffrey Wang, chief of orthopaedic spine service at the UCLA Comprehensive Spine Center. "The discovery of UCB could potentially be a better way to do spinal fusion. Used in conjunction with cartilage growth, this discovery may completely change the way we look at things in the future."

Bone morphogenetic proteins, found in demineralized bone, were discovered in the 1960s, but until the advent of biotechnology, the arduous process and high cost associated with making them from animal-derived bone was deemed too difficult. To date, only two companies have received FDA approval for bone morphogenetic proteins, making the product costly and the treatment prohibitive for many.

Ting, who works frequently with children who have congenital anomalies, began his bone research eight years ago. Wu joined him three years ago, and their collaboration resulted in the recent discovery.

"I thought it was important to understand how accelerated bone growth in one situation might be applied to situations where more bone growth could accelerate healing in those patients who lacked normal or necessary bone formation," Ting said. "This discovery will provide another option for patients. Competition will make treatment options safer, less expensive and more accessible for those families who really need it."

The team of UCLA researchers, under the business name Bone Biologics, already has begun forming partnerships that may assist in the development of appropriate carriers for UCB. The Musculoskeletal Transplant Foundation, the nation's largest tissue bank, has signed a collaborative development agreement with Wu and Ting to provide customized tissue forms to support the delivery of UCB.

"We are excited by the initial work of Drs. Wu and Ting," said Bruce Stroever, president and CEO of the Musculoskeletal Transplant Foundation. "The development of new protein sources tied to an appropriate carrier that encourages new bone formation and speeds healing is work that is synergistic to the foundation's mission of advancing the science of bone, ligament, cartilage and skin transplantation. We are pleased to be working with UCLA."

Wu and Ting anticipate FDA approval and first sales of the product in the next seven to nine years. Other collaborators on this technology include Dr. Xinli Zhang and Dr. Chia Soo at UCLA, and Dr. Shunichi Kuroda at Osaka University. The new technology recently has been awarded the prestigious 2005 Hatton Award from the International Association of Dental Research.

IRAK-M - Key regulator of bone cells linked to osteoporosis

Wed, 06 Apr 2005 18:59:38 PST

( from http://www.rxpgnews.com ) Scientists at the Yale School of Medicine identified a molecule in osteoclasts, IRAK-M, that is a key regulator of the loss of bone mass.

Osteoclasts are cells that play a major role in the development and remodeling of bone. They originate from the fusion of macrophages and are important mediators of the loss of bone mass that leads to osteoporosis

Osteoporosis is a serious problem worldwide: it is characterized by loss of bone density leading to fractures in response to relatively mild trauma. Other disorders of localized bone loss include rheumatoid arthritis and periodontal disease.

The research on osteoporosis, led by Associate Professor Agnès Vignery in the Department of Orthopedics and Rehabilitation, focused on IRAK-M (interleukin-1 receptor associated kinase M), an intracellular signaling molecule previously found only in macrophages and in circulating white blood cells. Their theory was that if IRAK-M is maintained as macrophages fuse to form osteoclasts, it would block later steps in the signal pathway and keep osteoclasts from growing out of control.

"IRAK-M appears to be a key signaling molecule in the prevention of bone loss," said Vignery. "In normal mice the level of IRAK-M in osteoclasts is high compared to what is found in macrophages -- and bones are well maintained. Mice that lack IRAK-M develop severe osteoporosis."

The study was done with male mice, and possible association between sex hormones and the expression of IRAK-M remain to be investigated, according to Vignery. "For now, IRAK-M looks like an exciting new target for treating or preventing the devastation of osteoporosis and other localized problems of bone loss,"