Osteoarthritis

PHILADELPHIA — More physicians are using bone mineral density measurements and biochemical marker testing to identify and treat osteoporosis, according to data from a national survey.

More than 200,000 postmenopausal, nonosteoporotic women were enrolled in the National Osteoporosis Risk Assessment (NORA) in September 1997. In conjunction with the study, 2,836 referring primary care physicians completed a baseline survey in 1998 that tested their knowledge of osteoporosis screening and treatment. In 2006, 808 of these providers responded to a follow-up survey designed to assess changes in their practice patterns and knowledge of the condition, Dr. Paul D. Miller reported in a poster at the annual meeting of the American Society for Bone and Mineral Research.

The number of physicians who reported frequent use of bone mineral density (BMD) measurements to screen for, diagnose, or monitor osteoporosis more than doubled between 1998 and 2006—from 35% to 87%. More impressively, the number of physicians who reported sometimes or often using biochemical marker testing to screen for, diagnose, or monitor osteoporosis almost tripled—from 19% to 54%, wrote Dr. Miller, medical director of the Colorado Center for Bone Research and a professor at the University of Colorado Health Sciences Center in Denver.

In the same period, the percentage of physicians who knew that a bone mineral density T score of −2.5 or less was the threshold indicating the presence of osteoporosis almost doubled, from 34% to 67%.

However, the percentage of physicians who knew the threshold value requiring pharmacologic intervention (T score of −2.5 or less [according to the World Health Organization] or a T score of −2.0 or less with no risk factors [according to the National Osteoporosis Foundation]) remained the same at 60%.

In terms of changes in treatment, the use of hormone therapy dropped sixfold (67% vs. 11%) from 1998 to 2006. In contrast, bisphosphonate use jumped from 15% to 59%.

Dr. Miller reported that he has received funding and consulting fees from F. Hoffmann-La Roche Ltd. and GlaxoSmithKline.

In a separate analysis of data from NORA, Dr. Ethel S. Siris and her colleagues found that most of the women in the study had a repeat BMD measurement within 6 years of baseline.

As part of NORA, the women had their BMD measured at the heel, forearm, or finger at baseline. At 1, 3, and 6 years, the women were asked about repeat measurements.

Within 3 years of baseline, 29% of the women had a repeat BMD, while 58% had one within 6 years, Dr. Siris of the Toni Stabile Osteoporosis Center at Columbia University Medical Center in New York wrote in a poster.

Women were more likely to have repeat BMD measurements within 6 years of baseline if they were taking an osteoporosis medication (odds ratio 3.22), had talked with their physician about their baseline BMD results (OR 1.41), were taking corticosteroids (OR 1.25), were taking thyroid medication (OR 1.16), or weighed less than 127 pounds (OR 1.14) following multivariate adjustment.

Interestingly, women with a baseline T score of −2.5 or lower were less likely to have a repeat BMD (adjusted OR 0.86), while women with a baseline T score between −1.0 and −2.49 were slightly more likely (adjusted OR 1.12).

This study received funding from Merck & Co. Dr. Siris reported receiving consulting fees from Merck & Co., Procter & Gamble, Eli Lilly and Company, and Pfizer Inc.

PHILADELPHIA — More physicians are using bone mineral density measurements and biochemical marker testing to identify and treat osteoporosis, according to data from a national survey.

More than 200,000 postmenopausal, nonosteoporotic women were enrolled in the National Osteoporosis Risk Assessment (NORA) in September 1997. In conjunction with the study, 2,836 referring primary care physicians completed a baseline survey in 1998 that tested their knowledge of osteoporosis screening and treatment. In 2006, 808 of these providers responded to a follow-up survey designed to assess changes in their practice patterns and knowledge of the condition, Dr. Paul D. Miller reported in a poster at the annual meeting of the American Society for Bone and Mineral Research.

The number of physicians who reported frequent use of bone mineral density (BMD) measurements to screen for, diagnose, or monitor osteoporosis more than doubled between 1998 and 2006—from 35% to 87%. More impressively, the number of physicians who reported sometimes or often using biochemical marker testing to screen for, diagnose, or monitor osteoporosis almost tripled—from 19% to 54%, wrote Dr. Miller, medical director of the Colorado Center for Bone Research and a professor at the University of Colorado Health Sciences Center in Denver.

In the same period, the percentage of physicians who knew that a bone mineral density T score of −2.5 or less was the threshold indicating the presence of osteoporosis almost doubled, from 34% to 67%.

However, the percentage of physicians who knew the threshold value requiring pharmacologic intervention (T score of −2.5 or less [according to the World Health Organization] or a T score of −2.0 or less with no risk factors [according to the National Osteoporosis Foundation]) remained the same at 60%.

In terms of changes in treatment, the use of hormone therapy dropped sixfold (67% vs. 11%) from 1998 to 2006. In contrast, bisphosphonate use jumped from 15% to 59%.

Dr. Miller reported that he has received funding and consulting fees from F. Hoffmann-La Roche Ltd. and GlaxoSmithKline.

In a separate analysis of data from NORA, Dr. Ethel S. Siris and her colleagues found that most of the women in the study had a repeat BMD measurement within 6 years of baseline.

As part of NORA, the women had their BMD measured at the heel, forearm, or finger at baseline. At 1, 3, and 6 years, the women were asked about repeat measurements.

Within 3 years of baseline, 29% of the women had a repeat BMD, while 58% had one within 6 years, Dr. Siris of the Toni Stabile Osteoporosis Center at Columbia University Medical Center in New York wrote in a poster.

Women were more likely to have repeat BMD measurements within 6 years of baseline if they were taking an osteoporosis medication (odds ratio 3.22), had talked with their physician about their baseline BMD results (OR 1.41), were taking corticosteroids (OR 1.25), were taking thyroid medication (OR 1.16), or weighed less than 127 pounds (OR 1.14) following multivariate adjustment.

Interestingly, women with a baseline T score of −2.5 or lower were less likely to have a repeat BMD (adjusted OR 0.86), while women with a baseline T score between −1.0 and −2.49 were slightly more likely (adjusted OR 1.12).

This study received funding from Merck & Co. Dr. Siris reported receiving consulting fees from Merck & Co., Procter & Gamble, Eli Lilly and Company, and Pfizer Inc.

PHILADELPHIA — More physicians are using bone mineral density measurements and biochemical marker testing to identify and treat osteoporosis, according to data from a national survey.

More than 200,000 postmenopausal, nonosteoporotic women were enrolled in the National Osteoporosis Risk Assessment (NORA) in September 1997. In conjunction with the study, 2,836 referring primary care physicians completed a baseline survey in 1998 that tested their knowledge of osteoporosis screening and treatment. In 2006, 808 of these providers responded to a follow-up survey designed to assess changes in their practice patterns and knowledge of the condition, Dr. Paul D. Miller reported in a poster at the annual meeting of the American Society for Bone and Mineral Research.

The number of physicians who reported frequent use of bone mineral density (BMD) measurements to screen for, diagnose, or monitor osteoporosis more than doubled between 1998 and 2006—from 35% to 87%. More impressively, the number of physicians who reported sometimes or often using biochemical marker testing to screen for, diagnose, or monitor osteoporosis almost tripled—from 19% to 54%, wrote Dr. Miller, medical director of the Colorado Center for Bone Research and a professor at the University of Colorado Health Sciences Center in Denver.

In the same period, the percentage of physicians who knew that a bone mineral density T score of −2.5 or less was the threshold indicating the presence of osteoporosis almost doubled, from 34% to 67%.

However, the percentage of physicians who knew the threshold value requiring pharmacologic intervention (T score of −2.5 or less [according to the World Health Organization] or a T score of −2.0 or less with no risk factors [according to the National Osteoporosis Foundation]) remained the same at 60%.

In terms of changes in treatment, the use of hormone therapy dropped sixfold (67% vs. 11%) from 1998 to 2006. In contrast, bisphosphonate use jumped from 15% to 59%.

Dr. Miller reported that he has received funding and consulting fees from F. Hoffmann-La Roche Ltd. and GlaxoSmithKline.

In a separate analysis of data from NORA, Dr. Ethel S. Siris and her colleagues found that most of the women in the study had a repeat BMD measurement within 6 years of baseline.

As part of NORA, the women had their BMD measured at the heel, forearm, or finger at baseline. At 1, 3, and 6 years, the women were asked about repeat measurements.

Within 3 years of baseline, 29% of the women had a repeat BMD, while 58% had one within 6 years, Dr. Siris of the Toni Stabile Osteoporosis Center at Columbia University Medical Center in New York wrote in a poster.

Women were more likely to have repeat BMD measurements within 6 years of baseline if they were taking an osteoporosis medication (odds ratio 3.22), had talked with their physician about their baseline BMD results (OR 1.41), were taking corticosteroids (OR 1.25), were taking thyroid medication (OR 1.16), or weighed less than 127 pounds (OR 1.14) following multivariate adjustment.

Interestingly, women with a baseline T score of −2.5 or lower were less likely to have a repeat BMD (adjusted OR 0.86), while women with a baseline T score between −1.0 and −2.49 were slightly more likely (adjusted OR 1.12).

This study received funding from Merck & Co. Dr. Siris reported receiving consulting fees from Merck & Co., Procter & Gamble, Eli Lilly and Company, and Pfizer Inc.

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day based on a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000-IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published (Am. J. Clin. Nutr. 2004;80:1689S-96S). This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

“It's one thing to say high doses of vitamin D are bad, but it's also very important to recognize how high we are talking about. What dose are we talking about?” he asked. “At least in animals, these doses are way off the curve in terms of anything we've been talking about.”

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]2D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment.

Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

In support of a UL of 10,000 IU/day, Dr. Vieth noted that a colleague has used 1,250 mcg/day vitamin D₃ “for some time,” and induced 25(OH)D levels of up to 643 nmol/L without hypercalcemia. Others also have used vitamin D several times higher than the current upper limit of 2,000 IU/day. Sunshine also can safely provide a dose of 10,000 IU/day to an adult, he said.

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day based on a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000-IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published (Am. J. Clin. Nutr. 2004;80:1689S-96S). This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

“It's one thing to say high doses of vitamin D are bad, but it's also very important to recognize how high we are talking about. What dose are we talking about?” he asked. “At least in animals, these doses are way off the curve in terms of anything we've been talking about.”

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]2D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment.

Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

In support of a UL of 10,000 IU/day, Dr. Vieth noted that a colleague has used 1,250 mcg/day vitamin D₃ “for some time,” and induced 25(OH)D levels of up to 643 nmol/L without hypercalcemia. Others also have used vitamin D several times higher than the current upper limit of 2,000 IU/day. Sunshine also can safely provide a dose of 10,000 IU/day to an adult, he said.

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day based on a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000-IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published (Am. J. Clin. Nutr. 2004;80:1689S-96S). This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

“It's one thing to say high doses of vitamin D are bad, but it's also very important to recognize how high we are talking about. What dose are we talking about?” he asked. “At least in animals, these doses are way off the curve in terms of anything we've been talking about.”

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]2D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment.

Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

In support of a UL of 10,000 IU/day, Dr. Vieth noted that a colleague has used 1,250 mcg/day vitamin D₃ “for some time,” and induced 25(OH)D levels of up to 643 nmol/L without hypercalcemia. Others also have used vitamin D several times higher than the current upper limit of 2,000 IU/day. Sunshine also can safely provide a dose of 10,000 IU/day to an adult, he said.

MIAMI BEACH — The cervical injuries and vertebral insufficiency stress fractures that follow traumatic injury in elderly patients present special diagnostic challenges, Dr. Richard H. Daffner said at a symposium on emergency radiology sponsored by Baptist Health South Florida.

Decreased vision and hearing, diminished motor skills, slower reaction times, and multiple comorbidities disproportionately affect patients 65 years and older, he explained.

“What complicates this, particularly because falls are the biggest source of injury and trauma to the elderly, is fractures—which can contribute significantly to their ultimate demise,” said Dr. Daffner, director of musculoskeletal, trauma, and emergency radiology, Allegheny General Hospital, Pittsburgh.

Emergency physicians are most likely to encounter cervical fractures and vertebral insufficiency stress fractures in the elderly trauma patient. The majority of cervical fractures in the elderly tend to cluster at the C1 and C2 level, Dr. Daffner said. Hyperextension injury is the leading cause of a C2 fracture. “As you get older, your neck tends to be stiffer, but the C1-C2 region remains the most mobile,” he explained.

Dr. Daffner and his colleagues studied 231 elderly patients with a total of 274 cervical injuries. They found that 119 of these injuries (43%) were at C2. In contrast, among the 749 participants in the study who were younger than 65 years with a total of 870 cervical injuries, 221 injuries (25%) occurred at C2.

Dens fractures “can be quite subtle” on a radiograph, Dr. Daffner said. “You see it much better on computed tomography —a slight shift of bone forward around C2.”

A hyperextension injury is often devastating, Dr. Daffner said. “A wide vertebral disk space [on radiograph] is the hallmark sign, and it's never normal in the elderly population.” Patients with a wide disk space should undergo magnetic resonance imaging immediately to determine the extent of injury, he suggested. The injury can be associated with development of edema, osteophytes impinging on the spinal cord, and neurologic compromise.

Insufficiency stress fractures are common in the elderly and are very site-specific for a particular activity, Dr. Daffner said. The sacrum and pelvis are most commonly involved, but the fractures also occur at the femoral neck and tibial plateau. “The diagnosis is not often considered by the clinician—some of these seniors are very active.” Failure to identify these fractures early can lead to progressive disability, a longer healing time, and a fracture that becomes distracted.

An occult fracture can be detected with a bone scan if the injury is more than 24 hours old, Dr. Daffner said. On a bone scan, a butterfly pattern (which can also be described as resembling a Honda car logo) is highly suggestive of a sacral stress fracture.

Radiographs are less useful but sometimes show some osteopenia. Computed tomography is useful if there is an occult fracture in the spine. Computed tomography is also the procedure of choice for pelvic stress fractures.

However, magnetic resonance imaging is recommended for fractures in the peripheral skeleton. “A complete MR study is not needed—we often do coronal and axial images” in less than half an hour in most cases, he said. “MRI is very useful early on when a patient comes in right away complaining of pain.”

Many patients who have an insufficiency stress fracture have bone compromised by osteoporosis and/or a history of malignancy.

“One of the keys to differentiating a malignancy versus a stress fracture is a stress fracture tends to be linear and occurs in the vertical plane, up and down, whereas malignancies tend to be globular,” Dr. Daffner said.

MIAMI BEACH — The cervical injuries and vertebral insufficiency stress fractures that follow traumatic injury in elderly patients present special diagnostic challenges, Dr. Richard H. Daffner said at a symposium on emergency radiology sponsored by Baptist Health South Florida.

Decreased vision and hearing, diminished motor skills, slower reaction times, and multiple comorbidities disproportionately affect patients 65 years and older, he explained.

“What complicates this, particularly because falls are the biggest source of injury and trauma to the elderly, is fractures—which can contribute significantly to their ultimate demise,” said Dr. Daffner, director of musculoskeletal, trauma, and emergency radiology, Allegheny General Hospital, Pittsburgh.

Emergency physicians are most likely to encounter cervical fractures and vertebral insufficiency stress fractures in the elderly trauma patient. The majority of cervical fractures in the elderly tend to cluster at the C1 and C2 level, Dr. Daffner said. Hyperextension injury is the leading cause of a C2 fracture. “As you get older, your neck tends to be stiffer, but the C1-C2 region remains the most mobile,” he explained.

Dr. Daffner and his colleagues studied 231 elderly patients with a total of 274 cervical injuries. They found that 119 of these injuries (43%) were at C2. In contrast, among the 749 participants in the study who were younger than 65 years with a total of 870 cervical injuries, 221 injuries (25%) occurred at C2.

Dens fractures “can be quite subtle” on a radiograph, Dr. Daffner said. “You see it much better on computed tomography —a slight shift of bone forward around C2.”

A hyperextension injury is often devastating, Dr. Daffner said. “A wide vertebral disk space [on radiograph] is the hallmark sign, and it's never normal in the elderly population.” Patients with a wide disk space should undergo magnetic resonance imaging immediately to determine the extent of injury, he suggested. The injury can be associated with development of edema, osteophytes impinging on the spinal cord, and neurologic compromise.

Insufficiency stress fractures are common in the elderly and are very site-specific for a particular activity, Dr. Daffner said. The sacrum and pelvis are most commonly involved, but the fractures also occur at the femoral neck and tibial plateau. “The diagnosis is not often considered by the clinician—some of these seniors are very active.” Failure to identify these fractures early can lead to progressive disability, a longer healing time, and a fracture that becomes distracted.

An occult fracture can be detected with a bone scan if the injury is more than 24 hours old, Dr. Daffner said. On a bone scan, a butterfly pattern (which can also be described as resembling a Honda car logo) is highly suggestive of a sacral stress fracture.

Radiographs are less useful but sometimes show some osteopenia. Computed tomography is useful if there is an occult fracture in the spine. Computed tomography is also the procedure of choice for pelvic stress fractures.

However, magnetic resonance imaging is recommended for fractures in the peripheral skeleton. “A complete MR study is not needed—we often do coronal and axial images” in less than half an hour in most cases, he said. “MRI is very useful early on when a patient comes in right away complaining of pain.”

Many patients who have an insufficiency stress fracture have bone compromised by osteoporosis and/or a history of malignancy.

“One of the keys to differentiating a malignancy versus a stress fracture is a stress fracture tends to be linear and occurs in the vertical plane, up and down, whereas malignancies tend to be globular,” Dr. Daffner said.

MIAMI BEACH — The cervical injuries and vertebral insufficiency stress fractures that follow traumatic injury in elderly patients present special diagnostic challenges, Dr. Richard H. Daffner said at a symposium on emergency radiology sponsored by Baptist Health South Florida.

Decreased vision and hearing, diminished motor skills, slower reaction times, and multiple comorbidities disproportionately affect patients 65 years and older, he explained.

“What complicates this, particularly because falls are the biggest source of injury and trauma to the elderly, is fractures—which can contribute significantly to their ultimate demise,” said Dr. Daffner, director of musculoskeletal, trauma, and emergency radiology, Allegheny General Hospital, Pittsburgh.

Emergency physicians are most likely to encounter cervical fractures and vertebral insufficiency stress fractures in the elderly trauma patient. The majority of cervical fractures in the elderly tend to cluster at the C1 and C2 level, Dr. Daffner said. Hyperextension injury is the leading cause of a C2 fracture. “As you get older, your neck tends to be stiffer, but the C1-C2 region remains the most mobile,” he explained.

Dr. Daffner and his colleagues studied 231 elderly patients with a total of 274 cervical injuries. They found that 119 of these injuries (43%) were at C2. In contrast, among the 749 participants in the study who were younger than 65 years with a total of 870 cervical injuries, 221 injuries (25%) occurred at C2.

Dens fractures “can be quite subtle” on a radiograph, Dr. Daffner said. “You see it much better on computed tomography —a slight shift of bone forward around C2.”

A hyperextension injury is often devastating, Dr. Daffner said. “A wide vertebral disk space [on radiograph] is the hallmark sign, and it's never normal in the elderly population.” Patients with a wide disk space should undergo magnetic resonance imaging immediately to determine the extent of injury, he suggested. The injury can be associated with development of edema, osteophytes impinging on the spinal cord, and neurologic compromise.

Insufficiency stress fractures are common in the elderly and are very site-specific for a particular activity, Dr. Daffner said. The sacrum and pelvis are most commonly involved, but the fractures also occur at the femoral neck and tibial plateau. “The diagnosis is not often considered by the clinician—some of these seniors are very active.” Failure to identify these fractures early can lead to progressive disability, a longer healing time, and a fracture that becomes distracted.

An occult fracture can be detected with a bone scan if the injury is more than 24 hours old, Dr. Daffner said. On a bone scan, a butterfly pattern (which can also be described as resembling a Honda car logo) is highly suggestive of a sacral stress fracture.

Radiographs are less useful but sometimes show some osteopenia. Computed tomography is useful if there is an occult fracture in the spine. Computed tomography is also the procedure of choice for pelvic stress fractures.

However, magnetic resonance imaging is recommended for fractures in the peripheral skeleton. “A complete MR study is not needed—we often do coronal and axial images” in less than half an hour in most cases, he said. “MRI is very useful early on when a patient comes in right away complaining of pain.”

Many patients who have an insufficiency stress fracture have bone compromised by osteoporosis and/or a history of malignancy.

“One of the keys to differentiating a malignancy versus a stress fracture is a stress fracture tends to be linear and occurs in the vertical plane, up and down, whereas malignancies tend to be globular,” Dr. Daffner said.

LISBON — Long-term treatment with low-molecular-weight heparin during pregnancy did not cause a drop in spinal bone mineral density in a study with 62 women, Dr. Marc A. Roger said at the third World Congress of the International Society of Obstetric Medicine.

The findings are from a subgroup analysis of data collected in the Thrombophilia in Pregnancy Prophylaxis Study (TIPPS), an ongoing, multicenter trial designed to compare prophylaxis using LMWH with placebo for pregnancy outcomes in women with a thrombophilia, explained Dr. Roger, Ottawa Hospital.

TIPPS enrolled women with thrombophilia at less than 20 weeks gestation who were at risk for thromboembolism or had a history of pregnancy complications. They were randomized to placebo or to 5,000 U dalteparin daily through week 20, followed by a regimen of 5,000 U b.i.d. through delivery. All women in the study received dalteparin post partum for 6 weeks. In the substudy of 62 women, the primary end point was the absolute lumbar-spine bone mineral density measured at 6 weeks post partum. Because of crossovers, 33 women received dalteparin and 29 women received placebo.

The average bone mineral density was 1.15 g/cm

LISBON — Long-term treatment with low-molecular-weight heparin during pregnancy did not cause a drop in spinal bone mineral density in a study with 62 women, Dr. Marc A. Roger said at the third World Congress of the International Society of Obstetric Medicine.

The findings are from a subgroup analysis of data collected in the Thrombophilia in Pregnancy Prophylaxis Study (TIPPS), an ongoing, multicenter trial designed to compare prophylaxis using LMWH with placebo for pregnancy outcomes in women with a thrombophilia, explained Dr. Roger, Ottawa Hospital.

TIPPS enrolled women with thrombophilia at less than 20 weeks gestation who were at risk for thromboembolism or had a history of pregnancy complications. They were randomized to placebo or to 5,000 U dalteparin daily through week 20, followed by a regimen of 5,000 U b.i.d. through delivery. All women in the study received dalteparin post partum for 6 weeks. In the substudy of 62 women, the primary end point was the absolute lumbar-spine bone mineral density measured at 6 weeks post partum. Because of crossovers, 33 women received dalteparin and 29 women received placebo.

The average bone mineral density was 1.15 g/cm

LISBON — Long-term treatment with low-molecular-weight heparin during pregnancy did not cause a drop in spinal bone mineral density in a study with 62 women, Dr. Marc A. Roger said at the third World Congress of the International Society of Obstetric Medicine.

The findings are from a subgroup analysis of data collected in the Thrombophilia in Pregnancy Prophylaxis Study (TIPPS), an ongoing, multicenter trial designed to compare prophylaxis using LMWH with placebo for pregnancy outcomes in women with a thrombophilia, explained Dr. Roger, Ottawa Hospital.

TIPPS enrolled women with thrombophilia at less than 20 weeks gestation who were at risk for thromboembolism or had a history of pregnancy complications. They were randomized to placebo or to 5,000 U dalteparin daily through week 20, followed by a regimen of 5,000 U b.i.d. through delivery. All women in the study received dalteparin post partum for 6 weeks. In the substudy of 62 women, the primary end point was the absolute lumbar-spine bone mineral density measured at 6 weeks post partum. Because of crossovers, 33 women received dalteparin and 29 women received placebo.

The average bone mineral density was 1.15 g/cm

PHILADELPHIA — Balicatib, an investigational agent that belongs to a new class of osteoporosis drugs, appears comparable to bisphosphonate therapy in increasing bone mineral density in postmenopausal women, according to trial results presented at the annual meeting of the American Society for Bone and Mineral Research.

“Balicatib was able to increase [bone mineral density] at both the spine and hip, with changes very similar to those seen with bisphosphonates,” said Dr. Silvano Adami.

Balicatib inhibits cathepsin K, a cysteine protease that plays an important role in the pathologic process of bone resorption. Cathepsin K is highly and selectively expressed by osteoclasts. Selective cathepsin K inhibitors provide a new method of action for reducing bone resorption and improving BMD.

In this randomized, placebo-controlled trial, 675 postmenopausal women with lumbar spine BMD T scores of less than −2 were randomized to receive 5 mg, 10 mg, 25mg, or 50 mg of daily oral balicatib or placebo, said Dr. Adami, head of gastroenterologic, rheumatologic, and vascular rehabilitation at the University of Verona (Italy). All patients received calcium and vitamin D supplements.

The women were assessed with dual-energy x-ray absorptiometry (DXA) measurements of spine and hip BMD, and levels of bone formation and resorption biomarkers were measured.

At baseline, the average patient age was 62 years. The average lumbar spine and total hip T scores were −2.6 and −1.4, respectively; 87% of the women had no morphometric vertebral fractures.

Following 1 year of treatment with balicatib, “the changes in BMD were quite remarkable,” said Dr. Adami. “With the highest dose [50 mg/day], the change in spine BMD was similar to that which [can be] achieved with bisphosphonate therapy.” Overall there was a dose-related increase in both spine and hip BMD (see table).

In terms of bone resorption, the researchers looked at levels of urinary N-terminal cross-linked telopeptides of type I collagen (normalized with respect to urine creatinine) and serum C-terminal collagen I telopeptide (CTX).

In the first month of treatment, a decrease was observed in serum CTX levels. However, over the next 11 months, there was a trend of rising CTX levels in all patients—even those in the placebo group. “We do not have an explanation,” said Dr. Adami. Overall, there was also a dose-related decrease in serum CTX and urinary NTX levels.

In terms of biomarkers of bone formation, the researchers measured serum osteocalcin and NTX. Serum osteocalcin and NTX decreased somewhat during the early stages but at 12 months, no differences were observed between the treated and placebo patients. Overall, bone resorption markers were decreased, while bone formation markers remained the same.

The numbers of adverse events were very similar between all of the groups. Two patients developed sclerodermic/morphea-like lesions, which improved when the treatment was stopped, Dr. Adami reported.

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — Balicatib, an investigational agent that belongs to a new class of osteoporosis drugs, appears comparable to bisphosphonate therapy in increasing bone mineral density in postmenopausal women, according to trial results presented at the annual meeting of the American Society for Bone and Mineral Research.

“Balicatib was able to increase [bone mineral density] at both the spine and hip, with changes very similar to those seen with bisphosphonates,” said Dr. Silvano Adami.

Balicatib inhibits cathepsin K, a cysteine protease that plays an important role in the pathologic process of bone resorption. Cathepsin K is highly and selectively expressed by osteoclasts. Selective cathepsin K inhibitors provide a new method of action for reducing bone resorption and improving BMD.

In this randomized, placebo-controlled trial, 675 postmenopausal women with lumbar spine BMD T scores of less than −2 were randomized to receive 5 mg, 10 mg, 25mg, or 50 mg of daily oral balicatib or placebo, said Dr. Adami, head of gastroenterologic, rheumatologic, and vascular rehabilitation at the University of Verona (Italy). All patients received calcium and vitamin D supplements.

The women were assessed with dual-energy x-ray absorptiometry (DXA) measurements of spine and hip BMD, and levels of bone formation and resorption biomarkers were measured.

At baseline, the average patient age was 62 years. The average lumbar spine and total hip T scores were −2.6 and −1.4, respectively; 87% of the women had no morphometric vertebral fractures.

Following 1 year of treatment with balicatib, “the changes in BMD were quite remarkable,” said Dr. Adami. “With the highest dose [50 mg/day], the change in spine BMD was similar to that which [can be] achieved with bisphosphonate therapy.” Overall there was a dose-related increase in both spine and hip BMD (see table).

In terms of bone resorption, the researchers looked at levels of urinary N-terminal cross-linked telopeptides of type I collagen (normalized with respect to urine creatinine) and serum C-terminal collagen I telopeptide (CTX).

In the first month of treatment, a decrease was observed in serum CTX levels. However, over the next 11 months, there was a trend of rising CTX levels in all patients—even those in the placebo group. “We do not have an explanation,” said Dr. Adami. Overall, there was also a dose-related decrease in serum CTX and urinary NTX levels.

In terms of biomarkers of bone formation, the researchers measured serum osteocalcin and NTX. Serum osteocalcin and NTX decreased somewhat during the early stages but at 12 months, no differences were observed between the treated and placebo patients. Overall, bone resorption markers were decreased, while bone formation markers remained the same.

The numbers of adverse events were very similar between all of the groups. Two patients developed sclerodermic/morphea-like lesions, which improved when the treatment was stopped, Dr. Adami reported.

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — Balicatib, an investigational agent that belongs to a new class of osteoporosis drugs, appears comparable to bisphosphonate therapy in increasing bone mineral density in postmenopausal women, according to trial results presented at the annual meeting of the American Society for Bone and Mineral Research.

“Balicatib was able to increase [bone mineral density] at both the spine and hip, with changes very similar to those seen with bisphosphonates,” said Dr. Silvano Adami.

Balicatib inhibits cathepsin K, a cysteine protease that plays an important role in the pathologic process of bone resorption. Cathepsin K is highly and selectively expressed by osteoclasts. Selective cathepsin K inhibitors provide a new method of action for reducing bone resorption and improving BMD.

In this randomized, placebo-controlled trial, 675 postmenopausal women with lumbar spine BMD T scores of less than −2 were randomized to receive 5 mg, 10 mg, 25mg, or 50 mg of daily oral balicatib or placebo, said Dr. Adami, head of gastroenterologic, rheumatologic, and vascular rehabilitation at the University of Verona (Italy). All patients received calcium and vitamin D supplements.

The women were assessed with dual-energy x-ray absorptiometry (DXA) measurements of spine and hip BMD, and levels of bone formation and resorption biomarkers were measured.

At baseline, the average patient age was 62 years. The average lumbar spine and total hip T scores were −2.6 and −1.4, respectively; 87% of the women had no morphometric vertebral fractures.

Following 1 year of treatment with balicatib, “the changes in BMD were quite remarkable,” said Dr. Adami. “With the highest dose [50 mg/day], the change in spine BMD was similar to that which [can be] achieved with bisphosphonate therapy.” Overall there was a dose-related increase in both spine and hip BMD (see table).

In terms of bone resorption, the researchers looked at levels of urinary N-terminal cross-linked telopeptides of type I collagen (normalized with respect to urine creatinine) and serum C-terminal collagen I telopeptide (CTX).

In the first month of treatment, a decrease was observed in serum CTX levels. However, over the next 11 months, there was a trend of rising CTX levels in all patients—even those in the placebo group. “We do not have an explanation,” said Dr. Adami. Overall, there was also a dose-related decrease in serum CTX and urinary NTX levels.

In terms of biomarkers of bone formation, the researchers measured serum osteocalcin and NTX. Serum osteocalcin and NTX decreased somewhat during the early stages but at 12 months, no differences were observed between the treated and placebo patients. Overall, bone resorption markers were decreased, while bone formation markers remained the same.

The numbers of adverse events were very similar between all of the groups. Two patients developed sclerodermic/morphea-like lesions, which improved when the treatment was stopped, Dr. Adami reported.

ELSEVIER GLOBAL MEDICAL NEWS

PHILADELPHIA — Once-monthly oral ibandronate (Boniva) increases spine and hip bone mineral density beyond 2 years, Dr. Paul D. Miller reported in a poster presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Miller, of the department of medicine at the University of Colorado, Denver, and medical director of the Colorado Center for Bone Research, Lakewood, and his colleagues presented 1-year results from the long-term extension phase of the MOBILE (Monthly Oral Ibandronate in Ladies) study. In year 3 of treatment with oral ibandronate, lumbar spine bone mineral density (BMD) increased 1.5% for women receiving 150 mg once monthly and 1.1% for women receiving 100 mg once monthly. In the same period, total hip BMD increased 0.3% in the 150-mg group; total hip BMD did not change for the 100-mg group.

In the MOBILE study, 1,609 postmenopausal women with osteoporosis were randomized to receive 100 mg (single dose), 50 mg plus 50 mg (50-mg doses on 2 consecutive days), or 150 mg (single dose) of monthly oral ibandronate, or 2.5 mg of oral daily ibandronate.

At 2 years, once-monthly oral ibandronate provided superior increases in lumbar spine BMD compared with the daily regimen (Ann. Rheum. Dis. 2006;65:654–61). In 2005, the Food and Drug Administration approved the 150-mg, once-monthly dosage of oral ibandronate.

After 2 years, the MOBILE study was extended for another 3 years. In the extension phase, patients in the 100-mg (single dose) or 150-mg oral ibandronate once-monthly groups maintained these regimens. Patients who were originally randomized to daily treatment or the 50 mg plus 50 mg (50-mg doses on 2 consecutive days) per month regimens were rerandomized to receive either 100 mg once monthly or 150 mg once monthly.

All patients received daily calcium (500 mg) and vitamin D (400 IU) supplements.

For 168 women on 150-mg once-monthly oral ibandronate for 3 years (the 2 years of the MOBILE study and 1 year of the extension study), lumbar spine BMD increased 7.6% from baseline.

Likewise, for 173 women on 100 mg ibandronate, lumbar spine BMD increased 6.4% from baseline. Also, total hip BMD increased 4.1% from baseline in women in the 150-mg group, while it increased 3.4% from baseline in the 100-mg group. Over 3 years, there were also gains of 2.5% and 3.5% from baseline at the femoral neck for the 100-mg and 150-mg groups, respectively. In the same period, there were gains of 5.4% and 6.2% from baseline at the trochanter for the 100-mg and 150-mg groups. The long-term extension study was funded by F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline Inc. Dr. Miller reported receiving funding and consulting fees from both companies.

In a separate poster, Dr. Stuart Silverman, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles, and his colleagues reported on adverse events from the MOBILE study.

A total of 719 women—359 in the 100-mg group and 360 in the 150-mg group—were included in the safety analysis.

The rates of drug-related adverse events were generally low and comparable for the two groups (7.8% for the 100-mg group and 7.5% for the 150-mg group). Only one serious adverse event was considered to be possibly related to treatment with 150-mg oral ibandronate once monthly.

The rates of drug-related adverse events leading to withdrawal were also comparable between the two groups (0.3% in the 100-mg group and 0.8% in the 150-mg group).

Gastrointestinal events have often been cited by patients as a reason for discontinuing oral bisphosphonates. The incidence of upper-GI adverse events was 4.5% and 6.9% in the 100-mg and 150-mg groups, respectively. No serious upper-GI adverse events occurred. The five most common upper-GI adverse events reported were dyspepsia, nausea, upper-abdominal pain, gastritis, and vomiting.

Dr. Silverman reported receiving funding from F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline.

PHILADELPHIA — Once-monthly oral ibandronate (Boniva) increases spine and hip bone mineral density beyond 2 years, Dr. Paul D. Miller reported in a poster presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Miller, of the department of medicine at the University of Colorado, Denver, and medical director of the Colorado Center for Bone Research, Lakewood, and his colleagues presented 1-year results from the long-term extension phase of the MOBILE (Monthly Oral Ibandronate in Ladies) study. In year 3 of treatment with oral ibandronate, lumbar spine bone mineral density (BMD) increased 1.5% for women receiving 150 mg once monthly and 1.1% for women receiving 100 mg once monthly. In the same period, total hip BMD increased 0.3% in the 150-mg group; total hip BMD did not change for the 100-mg group.

In the MOBILE study, 1,609 postmenopausal women with osteoporosis were randomized to receive 100 mg (single dose), 50 mg plus 50 mg (50-mg doses on 2 consecutive days), or 150 mg (single dose) of monthly oral ibandronate, or 2.5 mg of oral daily ibandronate.

At 2 years, once-monthly oral ibandronate provided superior increases in lumbar spine BMD compared with the daily regimen (Ann. Rheum. Dis. 2006;65:654–61). In 2005, the Food and Drug Administration approved the 150-mg, once-monthly dosage of oral ibandronate.

After 2 years, the MOBILE study was extended for another 3 years. In the extension phase, patients in the 100-mg (single dose) or 150-mg oral ibandronate once-monthly groups maintained these regimens. Patients who were originally randomized to daily treatment or the 50 mg plus 50 mg (50-mg doses on 2 consecutive days) per month regimens were rerandomized to receive either 100 mg once monthly or 150 mg once monthly.

All patients received daily calcium (500 mg) and vitamin D (400 IU) supplements.

For 168 women on 150-mg once-monthly oral ibandronate for 3 years (the 2 years of the MOBILE study and 1 year of the extension study), lumbar spine BMD increased 7.6% from baseline.

Likewise, for 173 women on 100 mg ibandronate, lumbar spine BMD increased 6.4% from baseline. Also, total hip BMD increased 4.1% from baseline in women in the 150-mg group, while it increased 3.4% from baseline in the 100-mg group. Over 3 years, there were also gains of 2.5% and 3.5% from baseline at the femoral neck for the 100-mg and 150-mg groups, respectively. In the same period, there were gains of 5.4% and 6.2% from baseline at the trochanter for the 100-mg and 150-mg groups. The long-term extension study was funded by F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline Inc. Dr. Miller reported receiving funding and consulting fees from both companies.

In a separate poster, Dr. Stuart Silverman, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles, and his colleagues reported on adverse events from the MOBILE study.

A total of 719 women—359 in the 100-mg group and 360 in the 150-mg group—were included in the safety analysis.

The rates of drug-related adverse events were generally low and comparable for the two groups (7.8% for the 100-mg group and 7.5% for the 150-mg group). Only one serious adverse event was considered to be possibly related to treatment with 150-mg oral ibandronate once monthly.

The rates of drug-related adverse events leading to withdrawal were also comparable between the two groups (0.3% in the 100-mg group and 0.8% in the 150-mg group).

Gastrointestinal events have often been cited by patients as a reason for discontinuing oral bisphosphonates. The incidence of upper-GI adverse events was 4.5% and 6.9% in the 100-mg and 150-mg groups, respectively. No serious upper-GI adverse events occurred. The five most common upper-GI adverse events reported were dyspepsia, nausea, upper-abdominal pain, gastritis, and vomiting.

Dr. Silverman reported receiving funding from F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline.

PHILADELPHIA — Once-monthly oral ibandronate (Boniva) increases spine and hip bone mineral density beyond 2 years, Dr. Paul D. Miller reported in a poster presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Miller, of the department of medicine at the University of Colorado, Denver, and medical director of the Colorado Center for Bone Research, Lakewood, and his colleagues presented 1-year results from the long-term extension phase of the MOBILE (Monthly Oral Ibandronate in Ladies) study. In year 3 of treatment with oral ibandronate, lumbar spine bone mineral density (BMD) increased 1.5% for women receiving 150 mg once monthly and 1.1% for women receiving 100 mg once monthly. In the same period, total hip BMD increased 0.3% in the 150-mg group; total hip BMD did not change for the 100-mg group.

In the MOBILE study, 1,609 postmenopausal women with osteoporosis were randomized to receive 100 mg (single dose), 50 mg plus 50 mg (50-mg doses on 2 consecutive days), or 150 mg (single dose) of monthly oral ibandronate, or 2.5 mg of oral daily ibandronate.

At 2 years, once-monthly oral ibandronate provided superior increases in lumbar spine BMD compared with the daily regimen (Ann. Rheum. Dis. 2006;65:654–61). In 2005, the Food and Drug Administration approved the 150-mg, once-monthly dosage of oral ibandronate.

After 2 years, the MOBILE study was extended for another 3 years. In the extension phase, patients in the 100-mg (single dose) or 150-mg oral ibandronate once-monthly groups maintained these regimens. Patients who were originally randomized to daily treatment or the 50 mg plus 50 mg (50-mg doses on 2 consecutive days) per month regimens were rerandomized to receive either 100 mg once monthly or 150 mg once monthly.

All patients received daily calcium (500 mg) and vitamin D (400 IU) supplements.

For 168 women on 150-mg once-monthly oral ibandronate for 3 years (the 2 years of the MOBILE study and 1 year of the extension study), lumbar spine BMD increased 7.6% from baseline.

Likewise, for 173 women on 100 mg ibandronate, lumbar spine BMD increased 6.4% from baseline. Also, total hip BMD increased 4.1% from baseline in women in the 150-mg group, while it increased 3.4% from baseline in the 100-mg group. Over 3 years, there were also gains of 2.5% and 3.5% from baseline at the femoral neck for the 100-mg and 150-mg groups, respectively. In the same period, there were gains of 5.4% and 6.2% from baseline at the trochanter for the 100-mg and 150-mg groups. The long-term extension study was funded by F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline Inc. Dr. Miller reported receiving funding and consulting fees from both companies.

In a separate poster, Dr. Stuart Silverman, a rheumatologist at Cedars-Sinai Medical Center in Los Angeles, and his colleagues reported on adverse events from the MOBILE study.

A total of 719 women—359 in the 100-mg group and 360 in the 150-mg group—were included in the safety analysis.

The rates of drug-related adverse events were generally low and comparable for the two groups (7.8% for the 100-mg group and 7.5% for the 150-mg group). Only one serious adverse event was considered to be possibly related to treatment with 150-mg oral ibandronate once monthly.

The rates of drug-related adverse events leading to withdrawal were also comparable between the two groups (0.3% in the 100-mg group and 0.8% in the 150-mg group).

Gastrointestinal events have often been cited by patients as a reason for discontinuing oral bisphosphonates. The incidence of upper-GI adverse events was 4.5% and 6.9% in the 100-mg and 150-mg groups, respectively. No serious upper-GI adverse events occurred. The five most common upper-GI adverse events reported were dyspepsia, nausea, upper-abdominal pain, gastritis, and vomiting.

Dr. Silverman reported receiving funding from F. Hoffmann-LaRoche Ltd. and GlaxoSmithKline.

TUCSON, ARIZ. — Customary vitamin D supplementation and springtime sun exposure in the southern United States are inadequate to protect elderly African American women from vitamin D deficiency and osteoporosis, data from a prospective cohort study show.

Not only were most of the women deficient in vitamin D despite 6 weeks of supplementation and nearly 10 hours a week of Texas vernal sunshine, but an unexpectedly high number were osteoporotic or osteopenic, Dr. Sally Weaver and associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Darker skin pigmentation and aging are known to decrease the body's ability to synthesize vitamin D. But it has generally been assumed that sun exposure in southern latitudes is either sufficient to provide adequate vitamin D levels or would reduce the need for supplementation.

The study included 44 African American women living in central Texas who were given 1,000 mg of calcium with 400 IU vitamin D tablets daily for 6 weeks, and told not to make any changes in diet or sun exposure. Clinical evaluations were made at baseline in April and 6 weeks later in June.

That time frame was chosen because, theoretically, 6 weeks is enough time for the body to replenish its supply of vitamin D if it is deficient, and because sun exposure typically increases in the spring, said Dr. Weaver, research director for the McLennan County Medical Education and Research Foundation, in Waco, Tex.

Overall, 36 (82%) of women returned for follow-up. Their average age was 76 years (range 70–88 years) and average BMI (kg/m

The investigators chose 32 ng/mL as the cutoff for “normal” vitamin D levels because there is some work that supports this value as the minimum needed for bone health, Dr. Weaver said. The ideal cutoff is under debate: Many levels use 20–25 ng/mL, but many researchers use higher values, such as 30–32 ng/mL, she said.

No matter which measure was used, the majority of women remained vitamin D deficient. After 6 weeks of supplementation, 23 women (52%) had vitamin D levels lower than 20 ng/mL, 29 (66%) had levels lower than 25 ng/mL, and 37 (84%) had levels lower than 32 ng/mL. Moreover, some women's levels were inexplicably lower after supplementation. Changes in vitamin D levels varied widely, from a loss of 10 ng/mL to a gain of 19 ng/mL over the course of the study. The lower the women's levels at baseline, the more likely they were to show an increase, she said.

Overall, 24 of the women (55%) were osteopenic and 11 (25%) were osteoporotic. The finding was surprising because greater weight is associated with stronger bones, she said. Only 13 (30%) of patients were on medication for the prevention or treatment of osteoporosis or osteopenia.

The average bone mineral density T score was −1.7, with a range of 1.7 to −4.0. Interestingly, T scores were not correlated with vitamin D levels. This could be because of the high number of osteopenic patients in the population, she said.

The amount of sun exposure was not correlated with vitamin D levels or T scores at the beginning or end of the study. “I believe that the combination of darker skin pigmentation and older age is preventing adequate sun conversion of vitamin D to an active form, even in a southern latitude, leading these patients to require much higher doses of oral supplements,” Dr. Weaver said.

TUCSON, ARIZ. — Customary vitamin D supplementation and springtime sun exposure in the southern United States are inadequate to protect elderly African American women from vitamin D deficiency and osteoporosis, data from a prospective cohort study show.

Not only were most of the women deficient in vitamin D despite 6 weeks of supplementation and nearly 10 hours a week of Texas vernal sunshine, but an unexpectedly high number were osteoporotic or osteopenic, Dr. Sally Weaver and associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Darker skin pigmentation and aging are known to decrease the body's ability to synthesize vitamin D. But it has generally been assumed that sun exposure in southern latitudes is either sufficient to provide adequate vitamin D levels or would reduce the need for supplementation.

The study included 44 African American women living in central Texas who were given 1,000 mg of calcium with 400 IU vitamin D tablets daily for 6 weeks, and told not to make any changes in diet or sun exposure. Clinical evaluations were made at baseline in April and 6 weeks later in June.

That time frame was chosen because, theoretically, 6 weeks is enough time for the body to replenish its supply of vitamin D if it is deficient, and because sun exposure typically increases in the spring, said Dr. Weaver, research director for the McLennan County Medical Education and Research Foundation, in Waco, Tex.

Overall, 36 (82%) of women returned for follow-up. Their average age was 76 years (range 70–88 years) and average BMI (kg/m

The investigators chose 32 ng/mL as the cutoff for “normal” vitamin D levels because there is some work that supports this value as the minimum needed for bone health, Dr. Weaver said. The ideal cutoff is under debate: Many levels use 20–25 ng/mL, but many researchers use higher values, such as 30–32 ng/mL, she said.

No matter which measure was used, the majority of women remained vitamin D deficient. After 6 weeks of supplementation, 23 women (52%) had vitamin D levels lower than 20 ng/mL, 29 (66%) had levels lower than 25 ng/mL, and 37 (84%) had levels lower than 32 ng/mL. Moreover, some women's levels were inexplicably lower after supplementation. Changes in vitamin D levels varied widely, from a loss of 10 ng/mL to a gain of 19 ng/mL over the course of the study. The lower the women's levels at baseline, the more likely they were to show an increase, she said.

Overall, 24 of the women (55%) were osteopenic and 11 (25%) were osteoporotic. The finding was surprising because greater weight is associated with stronger bones, she said. Only 13 (30%) of patients were on medication for the prevention or treatment of osteoporosis or osteopenia.

The average bone mineral density T score was −1.7, with a range of 1.7 to −4.0. Interestingly, T scores were not correlated with vitamin D levels. This could be because of the high number of osteopenic patients in the population, she said.

The amount of sun exposure was not correlated with vitamin D levels or T scores at the beginning or end of the study. “I believe that the combination of darker skin pigmentation and older age is preventing adequate sun conversion of vitamin D to an active form, even in a southern latitude, leading these patients to require much higher doses of oral supplements,” Dr. Weaver said.

TUCSON, ARIZ. — Customary vitamin D supplementation and springtime sun exposure in the southern United States are inadequate to protect elderly African American women from vitamin D deficiency and osteoporosis, data from a prospective cohort study show.

Not only were most of the women deficient in vitamin D despite 6 weeks of supplementation and nearly 10 hours a week of Texas vernal sunshine, but an unexpectedly high number were osteoporotic or osteopenic, Dr. Sally Weaver and associates reported in a poster at the annual meeting of the North American Primary Care Research Group.

Darker skin pigmentation and aging are known to decrease the body's ability to synthesize vitamin D. But it has generally been assumed that sun exposure in southern latitudes is either sufficient to provide adequate vitamin D levels or would reduce the need for supplementation.

The study included 44 African American women living in central Texas who were given 1,000 mg of calcium with 400 IU vitamin D tablets daily for 6 weeks, and told not to make any changes in diet or sun exposure. Clinical evaluations were made at baseline in April and 6 weeks later in June.

That time frame was chosen because, theoretically, 6 weeks is enough time for the body to replenish its supply of vitamin D if it is deficient, and because sun exposure typically increases in the spring, said Dr. Weaver, research director for the McLennan County Medical Education and Research Foundation, in Waco, Tex.

Overall, 36 (82%) of women returned for follow-up. Their average age was 76 years (range 70–88 years) and average BMI (kg/m

The investigators chose 32 ng/mL as the cutoff for “normal” vitamin D levels because there is some work that supports this value as the minimum needed for bone health, Dr. Weaver said. The ideal cutoff is under debate: Many levels use 20–25 ng/mL, but many researchers use higher values, such as 30–32 ng/mL, she said.

No matter which measure was used, the majority of women remained vitamin D deficient. After 6 weeks of supplementation, 23 women (52%) had vitamin D levels lower than 20 ng/mL, 29 (66%) had levels lower than 25 ng/mL, and 37 (84%) had levels lower than 32 ng/mL. Moreover, some women's levels were inexplicably lower after supplementation. Changes in vitamin D levels varied widely, from a loss of 10 ng/mL to a gain of 19 ng/mL over the course of the study. The lower the women's levels at baseline, the more likely they were to show an increase, she said.

Overall, 24 of the women (55%) were osteopenic and 11 (25%) were osteoporotic. The finding was surprising because greater weight is associated with stronger bones, she said. Only 13 (30%) of patients were on medication for the prevention or treatment of osteoporosis or osteopenia.

The average bone mineral density T score was −1.7, with a range of 1.7 to −4.0. Interestingly, T scores were not correlated with vitamin D levels. This could be because of the high number of osteopenic patients in the population, she said.

The amount of sun exposure was not correlated with vitamin D levels or T scores at the beginning or end of the study. “I believe that the combination of darker skin pigmentation and older age is preventing adequate sun conversion of vitamin D to an active form, even in a southern latitude, leading these patients to require much higher doses of oral supplements,” Dr. Weaver said.

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

Neither dehydroepiandrosterone nor testosterone replacement improve body composition, physical performance, bone mineral density, insulin sensitivity, or quality of life in people over age 60 years who have low androgen levels, according to Dr. K. Sreekumarian Nair of the Mayo Clinic, Rochester, Minn., and his associates.

“The search for eternal youth will continue, but the reversal of age-related decreases in the secretion of DHEA [dehydroepiandrosterone] and testosterone through 'physiologic' replacement regimens offers no answer and should not be attempted,” Dr. Paul M. Stewart said in an editorial comment accompanying the report of Dr. Nair's findings, published in the Oct. 19 issue of the New England Journal of Medicine.

Dr. Nair and his associates conducted a 2-year study to assess the effects of full DHEA replacement in 57 women and low-dose testosterone replacement in 87 men whose low hormone levels placed them in the 15th percentile for normal younger men and women. These healthy subjects were randomly assigned to receive either active or placebo tablets and transdermal patches, and were evaluated every 3 months.

Both total and bioavailable levels of the hormones rose significantly in the subjects who received active treatment, to values that would be considered in the high-normal range for young adults. However, neither treatment “had any detectable effect on physical performance, insulin sensitivity, or the physical and mental components of the quality of life,” the investigators said (N. Engl. J. Med. 2006;355:1647–59).

Testosterone replacement caused a small but significant increase in fat-free mass, but no change in muscle area, muscle strength, or overall fitness.

Similarly, both DHEA and testosterone caused a small but significant increase in bone mineral density at the ultradistal radius in women and at the femoral neck in men. However, there were no bone mass changes at several other sites, and the magnitude of the beneficial effect was less than that reported with conventional osteoporosis therapies.

The findings confirm that neither DHEA nor testosterone is “an effective antiaging hormone supplement and argue strongly against the use of these agents for this purpose,” they noted.

In his editorial comment, Dr. Stewart observed that “another 'negative' study on the efficacy of DHEA is unlikely to have much effect on its use in Western societies.” Legally, it is classified as a dietary supplement rather than a drug, and as such it will continue to be used inappropriately, “and quackery will prevail,” he said (N. Engl. J. Med. 2006;255:1724–6).

“Companies that sell supplements may not claim that the products prevent, treat, cure, mitigate, or diagnose disease, but these guidelines are often ignored or circumvented, as appears to be the case with many current providers of DHEA,” said Dr. Stewart of the University of Birmingham (England).

PHILADELPHIA — Bone geometry appears to confer femoral strength to older black men and may account for some of the differences seen in fracture risk and bone mineral density between older black and white men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Marc C. Hochberg, professor of medicine and epidemiology at the University of Maryland, Baltimore, and his colleagues used hip structural analysis based on dual-energy x-ray absorptiometry (DXA) scan data to assess parameters of structural geometry of the proximal femur in older black and white men, in an attempt to account for reported differences in hip fracture and hip bone mineral density (BMD).

The researchers used data collected as part of the Baltimore Men's Osteoporosis Study, which recruited 503 white men and 191 black men aged 65 years and older. Black men were slightly heavier (mean weight 87 kg vs. 83 kg for white men) and slightly younger (mean age 72 years vs. 75 years for white men).

The researchers used hip structural analysis to calculate several measures of bone geometry, including the outer diameter, the bone cross-sectional area, the section modulus (an indicator of bending strength), the estimated mean cortical thickness, and the estimated buckling ratio (an estimate of cortical stability in buckling) from DXA hip scans.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the angle bisecting neck and shaft axes), and across the shaft (at a distance of 1.5 times the minimum neck width distal to the axes of intersection).

The geometric parameters were compared between racial groups, using age, height, lean mass, and lean mass fraction as covariates.

BMD was greater for black men at the narrow neck, intertrochanteric, and shaft regions. “Black men had more bone tissue and the bone was narrower, so the tissue was enclosed in a smaller volume,” said Dr. Hochberg.

However, there was no difference in the calculated section modulus (a measure of resistance to axial bending) between white and black men at any of the three sites.

“Since there were no differences in femur bending resistance between the black and the white men, narrower bone, therefore, requires more bone tissue to achieve the same bending strength,” said Dr. Hochberg. Narrower bone with thicker cortices would have a lower buckling ratio and, therefore, higher buckling strength.

Cortical thickness was significantly greater in black men than in white men at all three sites. This did correlate to lower buckling ratios, providing greater protection against buckling failure.

Overall, black men had greater cross-sectional area, which reflects more bone mass. They also had a narrower outer diameter (reflecting smaller bone), thicker cortices, and lower buckling ratios, which reduce the risk of failure on bending at all three sites within the hip. “These geometric factors may explain the lower rate of hip fracture in older black men than in older white men,” said Dr. Hochberg.

PHILADELPHIA — Bone geometry appears to confer femoral strength to older black men and may account for some of the differences seen in fracture risk and bone mineral density between older black and white men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Marc C. Hochberg, professor of medicine and epidemiology at the University of Maryland, Baltimore, and his colleagues used hip structural analysis based on dual-energy x-ray absorptiometry (DXA) scan data to assess parameters of structural geometry of the proximal femur in older black and white men, in an attempt to account for reported differences in hip fracture and hip bone mineral density (BMD).

The researchers used data collected as part of the Baltimore Men's Osteoporosis Study, which recruited 503 white men and 191 black men aged 65 years and older. Black men were slightly heavier (mean weight 87 kg vs. 83 kg for white men) and slightly younger (mean age 72 years vs. 75 years for white men).

The researchers used hip structural analysis to calculate several measures of bone geometry, including the outer diameter, the bone cross-sectional area, the section modulus (an indicator of bending strength), the estimated mean cortical thickness, and the estimated buckling ratio (an estimate of cortical stability in buckling) from DXA hip scans.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the angle bisecting neck and shaft axes), and across the shaft (at a distance of 1.5 times the minimum neck width distal to the axes of intersection).

The geometric parameters were compared between racial groups, using age, height, lean mass, and lean mass fraction as covariates.

BMD was greater for black men at the narrow neck, intertrochanteric, and shaft regions. “Black men had more bone tissue and the bone was narrower, so the tissue was enclosed in a smaller volume,” said Dr. Hochberg.

However, there was no difference in the calculated section modulus (a measure of resistance to axial bending) between white and black men at any of the three sites.

“Since there were no differences in femur bending resistance between the black and the white men, narrower bone, therefore, requires more bone tissue to achieve the same bending strength,” said Dr. Hochberg. Narrower bone with thicker cortices would have a lower buckling ratio and, therefore, higher buckling strength.

Cortical thickness was significantly greater in black men than in white men at all three sites. This did correlate to lower buckling ratios, providing greater protection against buckling failure.

Overall, black men had greater cross-sectional area, which reflects more bone mass. They also had a narrower outer diameter (reflecting smaller bone), thicker cortices, and lower buckling ratios, which reduce the risk of failure on bending at all three sites within the hip. “These geometric factors may explain the lower rate of hip fracture in older black men than in older white men,” said Dr. Hochberg.

PHILADELPHIA — Bone geometry appears to confer femoral strength to older black men and may account for some of the differences seen in fracture risk and bone mineral density between older black and white men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Marc C. Hochberg, professor of medicine and epidemiology at the University of Maryland, Baltimore, and his colleagues used hip structural analysis based on dual-energy x-ray absorptiometry (DXA) scan data to assess parameters of structural geometry of the proximal femur in older black and white men, in an attempt to account for reported differences in hip fracture and hip bone mineral density (BMD).

The researchers used data collected as part of the Baltimore Men's Osteoporosis Study, which recruited 503 white men and 191 black men aged 65 years and older. Black men were slightly heavier (mean weight 87 kg vs. 83 kg for white men) and slightly younger (mean age 72 years vs. 75 years for white men).

The researchers used hip structural analysis to calculate several measures of bone geometry, including the outer diameter, the bone cross-sectional area, the section modulus (an indicator of bending strength), the estimated mean cortical thickness, and the estimated buckling ratio (an estimate of cortical stability in buckling) from DXA hip scans.

Hip structural analysis is an investigational technique used to assess bone geometry in cross-sections of three regions of the proximal femur: across the femoral neck at its narrowest point, in the intertrochanteric region (along the angle bisecting neck and shaft axes), and across the shaft (at a distance of 1.5 times the minimum neck width distal to the axes of intersection).

The geometric parameters were compared between racial groups, using age, height, lean mass, and lean mass fraction as covariates.

BMD was greater for black men at the narrow neck, intertrochanteric, and shaft regions. “Black men had more bone tissue and the bone was narrower, so the tissue was enclosed in a smaller volume,” said Dr. Hochberg.

However, there was no difference in the calculated section modulus (a measure of resistance to axial bending) between white and black men at any of the three sites.

“Since there were no differences in femur bending resistance between the black and the white men, narrower bone, therefore, requires more bone tissue to achieve the same bending strength,” said Dr. Hochberg. Narrower bone with thicker cortices would have a lower buckling ratio and, therefore, higher buckling strength.

Cortical thickness was significantly greater in black men than in white men at all three sites. This did correlate to lower buckling ratios, providing greater protection against buckling failure.

Overall, black men had greater cross-sectional area, which reflects more bone mass. They also had a narrower outer diameter (reflecting smaller bone), thicker cortices, and lower buckling ratios, which reduce the risk of failure on bending at all three sites within the hip. “These geometric factors may explain the lower rate of hip fracture in older black men than in older white men,” said Dr. Hochberg.

PHILADELPHIA — Antiresorptive therapy reduces the risk of recurrent hip fracture by more than 25%, according to one analysis presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients exposed to bisphosphonate therapy following a first hip fracture had a 26% reduction in recurrent hip fracture (hazard ratio [HR] 0.74), after adjusting for age, sex, comorbidity, and medication, said Dr. Suzanne N. Morin, an internist at the McGill University Health Centre in Montreal.

Dr. Morin and her colleagues performed a retrospective cohort study, using administrative databases to identify patients aged 65 years and older who had been hospitalized for a first hip fracture between 1996 and 2003.

A total of 20,644 patients were identified and classified based on whether they had been exposed to antiresorptive therapy following hospital discharge for hip fracture. Exposure was defined as being dispensed a prescription for bisphosphonates, raloxifene, calcitonin, or hormone replacement therapy.

Of those patients, 6,779 were exposed to antiresorptive therapy (mean time to first exposure after hospital discharge was 3 months) and 13,865 were not. Most of the patients—90% of those exposed and 73% of those not exposed—were women.

“In general, the exposed patients tended to be younger and to have less comorbidities than the nonexposed,” Dr. Morin said. The antiresorptive-exposed patients were also more likely to take calcium and vitamin D supplements and to use corticosteroids. Bisphosphonates were prescribed the most frequently.

For exposed patients, follow-up began on the day that the prescription for an antiresorptive was filled. Unexposed patients were assigned starting dates that were frequency matched to those of the exposed patients. Mean follow-up was 2.2 years, during which time 9,146 patients died and 992 recurrent fractures occurred. The refracture rate was 2.2 per 100 person-years for the exposed group and 2.9 per 100 person-years for the nonexposed group.

Men were also less likely to have a recurrent hip fracture (HR 0.75). For each 1-year increase in age, the risk increased 3%. The presence of osteoporosis was associated with a twofold increase in the risk of recurrent hip fracture.

PHILADELPHIA — Antiresorptive therapy reduces the risk of recurrent hip fracture by more than 25%, according to one analysis presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients exposed to bisphosphonate therapy following a first hip fracture had a 26% reduction in recurrent hip fracture (hazard ratio [HR] 0.74), after adjusting for age, sex, comorbidity, and medication, said Dr. Suzanne N. Morin, an internist at the McGill University Health Centre in Montreal.

Dr. Morin and her colleagues performed a retrospective cohort study, using administrative databases to identify patients aged 65 years and older who had been hospitalized for a first hip fracture between 1996 and 2003.

A total of 20,644 patients were identified and classified based on whether they had been exposed to antiresorptive therapy following hospital discharge for hip fracture. Exposure was defined as being dispensed a prescription for bisphosphonates, raloxifene, calcitonin, or hormone replacement therapy.

Of those patients, 6,779 were exposed to antiresorptive therapy (mean time to first exposure after hospital discharge was 3 months) and 13,865 were not. Most of the patients—90% of those exposed and 73% of those not exposed—were women.

“In general, the exposed patients tended to be younger and to have less comorbidities than the nonexposed,” Dr. Morin said. The antiresorptive-exposed patients were also more likely to take calcium and vitamin D supplements and to use corticosteroids. Bisphosphonates were prescribed the most frequently.

For exposed patients, follow-up began on the day that the prescription for an antiresorptive was filled. Unexposed patients were assigned starting dates that were frequency matched to those of the exposed patients. Mean follow-up was 2.2 years, during which time 9,146 patients died and 992 recurrent fractures occurred. The refracture rate was 2.2 per 100 person-years for the exposed group and 2.9 per 100 person-years for the nonexposed group.

Men were also less likely to have a recurrent hip fracture (HR 0.75). For each 1-year increase in age, the risk increased 3%. The presence of osteoporosis was associated with a twofold increase in the risk of recurrent hip fracture.

PHILADELPHIA — Antiresorptive therapy reduces the risk of recurrent hip fracture by more than 25%, according to one analysis presented at the annual meeting of the American Society for Bone and Mineral Research.

Patients exposed to bisphosphonate therapy following a first hip fracture had a 26% reduction in recurrent hip fracture (hazard ratio [HR] 0.74), after adjusting for age, sex, comorbidity, and medication, said Dr. Suzanne N. Morin, an internist at the McGill University Health Centre in Montreal.

Dr. Morin and her colleagues performed a retrospective cohort study, using administrative databases to identify patients aged 65 years and older who had been hospitalized for a first hip fracture between 1996 and 2003.

A total of 20,644 patients were identified and classified based on whether they had been exposed to antiresorptive therapy following hospital discharge for hip fracture. Exposure was defined as being dispensed a prescription for bisphosphonates, raloxifene, calcitonin, or hormone replacement therapy.

Of those patients, 6,779 were exposed to antiresorptive therapy (mean time to first exposure after hospital discharge was 3 months) and 13,865 were not. Most of the patients—90% of those exposed and 73% of those not exposed—were women.

“In general, the exposed patients tended to be younger and to have less comorbidities than the nonexposed,” Dr. Morin said. The antiresorptive-exposed patients were also more likely to take calcium and vitamin D supplements and to use corticosteroids. Bisphosphonates were prescribed the most frequently.

For exposed patients, follow-up began on the day that the prescription for an antiresorptive was filled. Unexposed patients were assigned starting dates that were frequency matched to those of the exposed patients. Mean follow-up was 2.2 years, during which time 9,146 patients died and 992 recurrent fractures occurred. The refracture rate was 2.2 per 100 person-years for the exposed group and 2.9 per 100 person-years for the nonexposed group.

Men were also less likely to have a recurrent hip fracture (HR 0.75). For each 1-year increase in age, the risk increased 3%. The presence of osteoporosis was associated with a twofold increase in the risk of recurrent hip fracture.