RxPG News : Osteoporosis

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.

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.

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.

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.

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.

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.

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.

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.

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."

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."

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."

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

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,"