Osteoarthritis

WASHINGTON — Endocrinologists and rheumatologists are the most aggressive specialists when it comes to the screening, diagnosis, and treatment of osteoporosis, Tiffany Karas, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Of 122 physicians who responded to an electronic survey, there were 27 geriatricians, 25 endocrinologists, 23 obstetrician/gynecologists, 20 rheumatologists, 19 primary care physicians, and 8 orthopedic surgeons. In screening for osteoporosis, 94% of the entire group said they would order a dual-energy x-ray absorptiometry (DXA) scan for a patient with two or more risk factors, said Dr. Karas and her associates, of Loyola University Medical Center, Maywood, Ill.

The risk factors most likely to prompt DXA scanning were height loss (93%), chronic prednisone use (89%), and menopause (86.6%). Among the risk factors least likely to prompt DXA were low testosterone (60%) and vertebral deformities (74%) in an elderly male patient. In general, all physicians surveyed were much less likely to order DXA for men with indications than for women. “This is one area where continuing education about osteoporosis may improve patient care,” the investigators noted.

Endocrinologists and rheumatologists were more likely to order DXA given any risk factor or patient scenario than were the other specialties, while orthopedic surgeons were the least likely. Rheumatologists were the most likely to initiate treatment in patients, followed by endocrinologists, geriatricians, primary care physicians, and ob.gyns.

Alendronate and risedronate were deemed the most efficacious treatments by more than 98% of all physicians, while calcium/vitamin D and calcitonin were thought to be the least efficacious. Overall, patients were more likely to be screened, diagnosed, and treated for osteoporosis by female physicians who had been in practice more than 6 years and who practice in urban, academic settings, Dr. Karas and her associates reported.

WASHINGTON — Endocrinologists and rheumatologists are the most aggressive specialists when it comes to the screening, diagnosis, and treatment of osteoporosis, Tiffany Karas, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Of 122 physicians who responded to an electronic survey, there were 27 geriatricians, 25 endocrinologists, 23 obstetrician/gynecologists, 20 rheumatologists, 19 primary care physicians, and 8 orthopedic surgeons. In screening for osteoporosis, 94% of the entire group said they would order a dual-energy x-ray absorptiometry (DXA) scan for a patient with two or more risk factors, said Dr. Karas and her associates, of Loyola University Medical Center, Maywood, Ill.

The risk factors most likely to prompt DXA scanning were height loss (93%), chronic prednisone use (89%), and menopause (86.6%). Among the risk factors least likely to prompt DXA were low testosterone (60%) and vertebral deformities (74%) in an elderly male patient. In general, all physicians surveyed were much less likely to order DXA for men with indications than for women. “This is one area where continuing education about osteoporosis may improve patient care,” the investigators noted.

Endocrinologists and rheumatologists were more likely to order DXA given any risk factor or patient scenario than were the other specialties, while orthopedic surgeons were the least likely. Rheumatologists were the most likely to initiate treatment in patients, followed by endocrinologists, geriatricians, primary care physicians, and ob.gyns.

Alendronate and risedronate were deemed the most efficacious treatments by more than 98% of all physicians, while calcium/vitamin D and calcitonin were thought to be the least efficacious. Overall, patients were more likely to be screened, diagnosed, and treated for osteoporosis by female physicians who had been in practice more than 6 years and who practice in urban, academic settings, Dr. Karas and her associates reported.

WASHINGTON — Endocrinologists and rheumatologists are the most aggressive specialists when it comes to the screening, diagnosis, and treatment of osteoporosis, Tiffany Karas, M.D., and her associates reported in a poster at the annual meeting of the American Association of Clinical Endocrinologists.

Of 122 physicians who responded to an electronic survey, there were 27 geriatricians, 25 endocrinologists, 23 obstetrician/gynecologists, 20 rheumatologists, 19 primary care physicians, and 8 orthopedic surgeons. In screening for osteoporosis, 94% of the entire group said they would order a dual-energy x-ray absorptiometry (DXA) scan for a patient with two or more risk factors, said Dr. Karas and her associates, of Loyola University Medical Center, Maywood, Ill.

The risk factors most likely to prompt DXA scanning were height loss (93%), chronic prednisone use (89%), and menopause (86.6%). Among the risk factors least likely to prompt DXA were low testosterone (60%) and vertebral deformities (74%) in an elderly male patient. In general, all physicians surveyed were much less likely to order DXA for men with indications than for women. “This is one area where continuing education about osteoporosis may improve patient care,” the investigators noted.

Endocrinologists and rheumatologists were more likely to order DXA given any risk factor or patient scenario than were the other specialties, while orthopedic surgeons were the least likely. Rheumatologists were the most likely to initiate treatment in patients, followed by endocrinologists, geriatricians, primary care physicians, and ob.gyns.

Alendronate and risedronate were deemed the most efficacious treatments by more than 98% of all physicians, while calcium/vitamin D and calcitonin were thought to be the least efficacious. Overall, patients were more likely to be screened, diagnosed, and treated for osteoporosis by female physicians who had been in practice more than 6 years and who practice in urban, academic settings, Dr. Karas and her associates reported.

VIENNA — Most physicians remain unaware of the factors that motivate women to stay on osteoporosis therapy, according to the results of a new survey released by the International Osteoporosis Foundation.

As a result of this physician/patient disconnect, 85% of surveyed physicians reported having patients who have discontinued bisphosphonate therapy without consulting them, and 71% still didn't know why their patients had stopped, according to the findings, which were presented at the annual European congress of rheumatology.

The goal of the survey was to shed new light on the poorly understood adherence gap in osteoporosis therapy. “Adherence gap” is a term used to describe the phenomenon whereby nearly 80% of women who take a once-daily bisphosphonate and more than half who take a once-weekly agent discontinue therapy within the first year.

The telephone survey, conducted earlier this year in five Western European countries, involved 500 primary care physicians and rheumatologists and 502 postmenopausal women with osteoporosis. Of the women surveyed, 38% were previously on a bisphosphonate but had discontinued it; the rest were currently on a bisphosphonate.

Overall, 64% of women cited a positive motivating factor—such as the desire to do something to help themselves, or a wish to stay independent—as their primary reason for staying on bisphosphonate therapy. But only 13% of physicians said they motivated patients by explaining the benefits of bisphosphonates. Instead, the majority of physicians indicated they emphasized the negative consequences of nonadherence. And 86% of physicians said they were unsure about how best to encourage patients to continue on therapy.

Women cited drug side effects and the inconvenience of bisphosphonate therapy, especially the need to remain upright after taking the oral medication and the necessity of fasting before and after taking the drug, as the main reasons for discontinuing treatment. But lack of understanding on the patient's part was the reason for nonadherence most often cited by physicians. And they had a valid point: Of the women surveyed, 27% said they thought their fracture risk was the same regardless of whether they took their medication. Another 17% didn't think their bisphosphonate had any benefit at all. Also, 51% of women couldn't recall being advised on how long to stay on their medication.

The congress was sponsored by the European League Against Rheumatism. The International Osteoporosis Foundation survey was funded by an unrestricted educational grant from GlaxoSmithKline and Roche.

VIENNA — Most physicians remain unaware of the factors that motivate women to stay on osteoporosis therapy, according to the results of a new survey released by the International Osteoporosis Foundation.

As a result of this physician/patient disconnect, 85% of surveyed physicians reported having patients who have discontinued bisphosphonate therapy without consulting them, and 71% still didn't know why their patients had stopped, according to the findings, which were presented at the annual European congress of rheumatology.

The goal of the survey was to shed new light on the poorly understood adherence gap in osteoporosis therapy. “Adherence gap” is a term used to describe the phenomenon whereby nearly 80% of women who take a once-daily bisphosphonate and more than half who take a once-weekly agent discontinue therapy within the first year.

The telephone survey, conducted earlier this year in five Western European countries, involved 500 primary care physicians and rheumatologists and 502 postmenopausal women with osteoporosis. Of the women surveyed, 38% were previously on a bisphosphonate but had discontinued it; the rest were currently on a bisphosphonate.

Overall, 64% of women cited a positive motivating factor—such as the desire to do something to help themselves, or a wish to stay independent—as their primary reason for staying on bisphosphonate therapy. But only 13% of physicians said they motivated patients by explaining the benefits of bisphosphonates. Instead, the majority of physicians indicated they emphasized the negative consequences of nonadherence. And 86% of physicians said they were unsure about how best to encourage patients to continue on therapy.

Women cited drug side effects and the inconvenience of bisphosphonate therapy, especially the need to remain upright after taking the oral medication and the necessity of fasting before and after taking the drug, as the main reasons for discontinuing treatment. But lack of understanding on the patient's part was the reason for nonadherence most often cited by physicians. And they had a valid point: Of the women surveyed, 27% said they thought their fracture risk was the same regardless of whether they took their medication. Another 17% didn't think their bisphosphonate had any benefit at all. Also, 51% of women couldn't recall being advised on how long to stay on their medication.

The congress was sponsored by the European League Against Rheumatism. The International Osteoporosis Foundation survey was funded by an unrestricted educational grant from GlaxoSmithKline and Roche.

VIENNA — Most physicians remain unaware of the factors that motivate women to stay on osteoporosis therapy, according to the results of a new survey released by the International Osteoporosis Foundation.

As a result of this physician/patient disconnect, 85% of surveyed physicians reported having patients who have discontinued bisphosphonate therapy without consulting them, and 71% still didn't know why their patients had stopped, according to the findings, which were presented at the annual European congress of rheumatology.

The goal of the survey was to shed new light on the poorly understood adherence gap in osteoporosis therapy. “Adherence gap” is a term used to describe the phenomenon whereby nearly 80% of women who take a once-daily bisphosphonate and more than half who take a once-weekly agent discontinue therapy within the first year.

The telephone survey, conducted earlier this year in five Western European countries, involved 500 primary care physicians and rheumatologists and 502 postmenopausal women with osteoporosis. Of the women surveyed, 38% were previously on a bisphosphonate but had discontinued it; the rest were currently on a bisphosphonate.

Overall, 64% of women cited a positive motivating factor—such as the desire to do something to help themselves, or a wish to stay independent—as their primary reason for staying on bisphosphonate therapy. But only 13% of physicians said they motivated patients by explaining the benefits of bisphosphonates. Instead, the majority of physicians indicated they emphasized the negative consequences of nonadherence. And 86% of physicians said they were unsure about how best to encourage patients to continue on therapy.

Women cited drug side effects and the inconvenience of bisphosphonate therapy, especially the need to remain upright after taking the oral medication and the necessity of fasting before and after taking the drug, as the main reasons for discontinuing treatment. But lack of understanding on the patient's part was the reason for nonadherence most often cited by physicians. And they had a valid point: Of the women surveyed, 27% said they thought their fracture risk was the same regardless of whether they took their medication. Another 17% didn't think their bisphosphonate had any benefit at all. Also, 51% of women couldn't recall being advised on how long to stay on their medication.

The congress was sponsored by the European League Against Rheumatism. The International Osteoporosis Foundation survey was funded by an unrestricted educational grant from GlaxoSmithKline and Roche.

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

DEDHAM, MASS. — Has the backlash against hormone therapy gone too far? Should doctors take yet another look at the evidence and find selective uses for HT that maximize its benefits and minimize its risks?

The answer to both questions is yes, according to Isaac Schiff, M.D., professor of gynecology at Harvard Medical School and chief of the ob.gyn. service at Massachusetts General Hospital. At a symposium on bone health sponsored by Boston University School of Medicine, Dr. Schiff recommended discussing HT with select patients as a double-duty medication for bone health and menopausal symptoms.

“Just as the pendulum went too far in the early 1990s—when all the retrospective studies suggested estrogens prevented heart disease, osteoporosis, Alzheimer's disease—after the Women's Health Initiative [WHI] the pendulum swung way too far to the other side, suggesting that estrogens are too risky,” Dr. Schiff said.

News reports about the WHI trial tended to focus on the risks of HT and to overlook the benefits. Estrogen therapy is “certainly one of the most potent agents we have available” for preventing hip, vertebral, and wrist fractures, he said. “The problem when dealing with estrogen, of course, is all the other risks that have been identified.”

When the National Institutes of Health announced the landmark findings of the WHI trial, HT prescriptions declined precipitously. “Overall health risks [of HT] exceeded benefits,” investigators concluded after they stopped the trial early (JAMA 2002; 288:321–33).

According to the WHI findings, therapy with estrogen plus progestin was associated with a major increase in the relative risk of several serious health problems. For example, it was tied to a 29% increased risk of coronary heart disease (CHD), a 41% increased risk of stroke, a twofold increased risk of pulmonary embolism (PE), and a 26% increased risk of breast cancer.

Many observers found the absolute risks less alarming, however. According to the WHI data, if 10,000 women took estrogen plus progestin for 1 year, there would be an excess risk of seven more CHD events, eight more strokes, eight more PEs, and eight more invasive breast cancers. There would be no extra deaths. Among women with no uterus taking estrogen only, there would be 12 more strokes (JAMA 2004;291:1701–12).

HT would also confer some benefits among those 10,000 women. There would be six fewer colorectal cancers and five fewer hip fractures.

Among women with no uterus taking estrogen, there would be six fewer hip fractures. The WHI did not state whether HT would relieve menopausal symptoms.

Dr. Schiff termed the findings on fracture prevention “quite impressive.” Citing the reductions in relative risk, he noted that women taking progestin plus estrogen had a 29% reduction in lower forearm fractures and a 33% reduction in hip fractures.

In the estrogen-only arm of the study, there was a 39% decrease in hip fractures and a 38% decrease in vertebral fractures.

Studies of other drugs designed to prevent and treat osteoporosis have had difficulty showing a reduction in hip fractures. The effect of medium-dose HT on fractures “is equivalent to bisphosphonates,” he said.

Hidden amid the WHI data is information on the impact of low-dose estrogens that might help clinicians balance benefits and risks of HT therapy, Dr. Schiff suggested.

At low doses, estrogens increased bone mineral density by 2.4% and 3.9% at the femoral neck and spine, respectively.

Dr. Schiff did not provide evidence from WHI to show that low-dose estrogens were associated with fewer fractures, however.

As the NIH noted in a 2000 consensus statement on osteoporosis, improvements in bone density do not always translate to a decrease in fractures. “The risks for osteoporosis, as reflected by low bone density, and the risks for fracture overlap, but are not identical” (NIH Consens. Statement 2000;17[1]:1–36).

Still, Dr. Schiff said that there is enough evidence to support prescribing low-dose estrogen for the prevention of devastating hip fractures.

Citing data on low-dose OCs in relatively young, healthy women, Dr. Schiff said that, in theory, lower doses of estrogen should yield fewer health risks in the middle-aged and elderly. And “even very-low-dose estrogen is quite effective at maintaining bone density.”

That said, patients must be thoroughly informed about their individual risk profile regarding HT so they can weigh their risks and benefits and make informed decisions.

“A woman of age 50 is not worried about a hip fracture at age 80. She is worried about the potential for breast cancer at age 55,” Dr. Schiff said.

And the data on estrogens and breast cancer are mixed. Some studies show an increased risk, some do not. “I tell my patients I personally have major concerns about the long-term risk” of breast cancer associated with estrogen therapy, he said.

Dr. Schiff said that he prescribes estrogens for the minority of women with very severe hot flashes. For vaginal dryness topical estrogen therapy can help. Very-low-dose estrogen (e.g., an estrogen patch with 0.25-mg Premarin or 0.5-mg estradiol) will also help with urogenital symptoms.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

DEDHAM, MASS. — All calcium supplements are not created equal. The stomach absorbs some better than others, Michael F. Holick, M.D., told a gathering of clinicians at a symposium on bone health sponsored by Boston University School of Medicine.

Dr. Holick said patients can use a simple test to gauge the ability of the GI system to absorb these pills. Toss one in white vinegar and see if the pill dissolves, said the Boston University professor and director of the Bone Healthcare Clinic at Boston Medical Center.

Though there is some controversy about the need for calcium supplements in teenagers and many adults, most experts agree there is one group of individuals who are likely to benefit from them—and also likely to suffer from an indigestible concoction. They are the frail elderly—frequently women, often institutionalized, and occasionally malnourished. The scientific literature and clinical experience generally agree that these individuals are at particular risk for hip fracture.

Healthy people generally get their calcium from their diet, Dr. Holick said. “There's 300 mg in an 8-ounce glass of milk, guaranteed.” Other good sources of calcium include sardines, Tums, and calcium-fortified orange juice, he said.

As with calcium supplements, all sources of dietary calcium are not equal, he noted. At 100 mg calcium per cup, for example, “you'd have to be a cow in order to get enough calcium from broccoli.”

For those individuals who don't get enough calcium in their diet, there are supplements. A huge industry has grown up around them, producing variable results.

A recent ER visit by a 17-year-old woman prompted Dr. Holick to share his calcium pills acid test with his colleagues. The patient arrived with serious abdominal pain. After some investigating, Dr. Holick discovered her calcium supplements were leaving her body in the same state they entered. They were not “bioavailable,” he said.

“Take white vinegar and mix in the calcium preparation,” Dr. Holick said. “In 20 minutes, if it doesn't dissolve in white vinegar, guess what? It's not going to dissolve in your stomach.” In addition, when you find a good calcium supplement, “always take it with your meal,” he advised.

Teenagers need 1,300 mg calcium/day, young and middle-aged adults need 1,000 mg/day, and adults over age 50 require 1,200 mg/day, according to the Institute of Medicine.

BETHESDA, MD. — Calcitonin nasal spray appears to preserve trabecular bone microarchitecture at the distal radius without substantially altering bone mineral density, Charles H. Chestnut III, M.D., said at a meeting on bone quality.

In a 2-year, randomized, double-blind trial involving 91 women with an average age of 67 years, high-resolution MRI analysis of the distal radius showed that calcitonin nasal spray preserved significantly more trabecular bone architecture than placebo.

Calcitonin's effects included preservation of the volume, number, spacing, and thickness of trabecular bone, Dr. Chestnut wrote in a poster presentation at the meeting, which as sponsored by the National Institute for Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

Trabecular bone microarchitecture was significantly preserved—if not reinforced—in calcitonin patients, compared with placebo patients, despite loss in bone mineral density (BMD) at the distal radius or lumbar spine during the same period. In placebo patients, the number of trabeculae declined slightly at those sites even if the women had gained BMD.

The results are consistent with earlier reports showing that calcitonin spray was associated with reductions in osteoporotic fractures in postmenopausal women with a history of vertebral fracture, despite producing minimal increases in BMD, said Dr. Chestnut, professor of medicine and radiology at the University of Washington, Seattle.

Almost none of the measurements of BMD in the lumbar spine or midradius were significantly correlated with measures of trabecular microarchitecture change as shown on high-resolution MRI, suggesting that “BMD is a poor marker for trabecular microarchitecture,” Dr. Chestnut wrote.

In the calcitonin group, trabecular microarchitecture in the lower trochanter was preserved, according to T2-MRI findings, regardless of whether patients lost or gained total hip BMD. By comparison, trabecular microarchitecture deteriorated in the placebo group.

All women in the trial received calcium supplementation.

Dr. Chestnut reported that he has received research grants and consulting fees from Novartis Pharmaceuticals Corp., which funded the trial and manufactures calcitonin-salmon nasal spray (Miacalcin).

BETHESDA, MD. — Calcitonin nasal spray appears to preserve trabecular bone microarchitecture at the distal radius without substantially altering bone mineral density, Charles H. Chestnut III, M.D., said at a meeting on bone quality.

In a 2-year, randomized, double-blind trial involving 91 women with an average age of 67 years, high-resolution MRI analysis of the distal radius showed that calcitonin nasal spray preserved significantly more trabecular bone architecture than placebo.

Calcitonin's effects included preservation of the volume, number, spacing, and thickness of trabecular bone, Dr. Chestnut wrote in a poster presentation at the meeting, which as sponsored by the National Institute for Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

Trabecular bone microarchitecture was significantly preserved—if not reinforced—in calcitonin patients, compared with placebo patients, despite loss in bone mineral density (BMD) at the distal radius or lumbar spine during the same period. In placebo patients, the number of trabeculae declined slightly at those sites even if the women had gained BMD.

The results are consistent with earlier reports showing that calcitonin spray was associated with reductions in osteoporotic fractures in postmenopausal women with a history of vertebral fracture, despite producing minimal increases in BMD, said Dr. Chestnut, professor of medicine and radiology at the University of Washington, Seattle.

Almost none of the measurements of BMD in the lumbar spine or midradius were significantly correlated with measures of trabecular microarchitecture change as shown on high-resolution MRI, suggesting that “BMD is a poor marker for trabecular microarchitecture,” Dr. Chestnut wrote.

In the calcitonin group, trabecular microarchitecture in the lower trochanter was preserved, according to T2-MRI findings, regardless of whether patients lost or gained total hip BMD. By comparison, trabecular microarchitecture deteriorated in the placebo group.

All women in the trial received calcium supplementation.

Dr. Chestnut reported that he has received research grants and consulting fees from Novartis Pharmaceuticals Corp., which funded the trial and manufactures calcitonin-salmon nasal spray (Miacalcin).

BETHESDA, MD. — Calcitonin nasal spray appears to preserve trabecular bone microarchitecture at the distal radius without substantially altering bone mineral density, Charles H. Chestnut III, M.D., said at a meeting on bone quality.

In a 2-year, randomized, double-blind trial involving 91 women with an average age of 67 years, high-resolution MRI analysis of the distal radius showed that calcitonin nasal spray preserved significantly more trabecular bone architecture than placebo.

Calcitonin's effects included preservation of the volume, number, spacing, and thickness of trabecular bone, Dr. Chestnut wrote in a poster presentation at the meeting, which as sponsored by the National Institute for Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

Trabecular bone microarchitecture was significantly preserved—if not reinforced—in calcitonin patients, compared with placebo patients, despite loss in bone mineral density (BMD) at the distal radius or lumbar spine during the same period. In placebo patients, the number of trabeculae declined slightly at those sites even if the women had gained BMD.

The results are consistent with earlier reports showing that calcitonin spray was associated with reductions in osteoporotic fractures in postmenopausal women with a history of vertebral fracture, despite producing minimal increases in BMD, said Dr. Chestnut, professor of medicine and radiology at the University of Washington, Seattle.

Almost none of the measurements of BMD in the lumbar spine or midradius were significantly correlated with measures of trabecular microarchitecture change as shown on high-resolution MRI, suggesting that “BMD is a poor marker for trabecular microarchitecture,” Dr. Chestnut wrote.

In the calcitonin group, trabecular microarchitecture in the lower trochanter was preserved, according to T2-MRI findings, regardless of whether patients lost or gained total hip BMD. By comparison, trabecular microarchitecture deteriorated in the placebo group.

All women in the trial received calcium supplementation.

Dr. Chestnut reported that he has received research grants and consulting fees from Novartis Pharmaceuticals Corp., which funded the trial and manufactures calcitonin-salmon nasal spray (Miacalcin).

BETHESDA, MD. — New chromosomal regions that possibly contain genes controlling bone quality were recently identified in the first genome-wide linkage scan of cross-sectional bone geometry in humans.

The few reported genetic studies of cross-sectional geometry have shown that the heritability is greater than 50%, “which means that in the general population, more than 50% of the phenotypic variation can be attributable to genetic events,” Hui Shen said at a meeting on bone quality.

In a prospective study of 79 white pedigrees composed of 1,816 individuals, Mr. Shen of Creighton University, Omaha, Neb., and his colleagues calculated logarithmic odds (LOD) scores for bone geometry parameters at the femoral neck, including cross-sectional area, cortical thickness, endocortical diameter, sectional modulus, and buckling ratio in relation to 451 microsatellite markers.

On chromosome 10q26, the researchers calculated an LOD score of 3.29, the highest recorded in the study, for the buckling ratio at the femoral neck. This indicates that the odds are nearly 2,000 to 1 in favor of genetic linkage between the two loci.

Three bone geometry parameters (cross-sectional area, cortical thickness, and buckling ratio) were linked to a broad region on chromosome 20p12-q12 with LOD scores ranging from 1.95 to 2.29. A candidate gene called bone morphogenetic protein 2 (BMP2) is located in that region.

BMP2 is known to regulate bone growth and in a recent study was identified as a genetic determinant of risk for osteoporosis (PLoS Biol. 2003;1:E69).

The researchers also observed some difference in the linkages for buckling ratio and cortical thickness between males and females. “Taken together, this evidence suggests a gene or a group of genes appearing in this area may have significant effects on [bone mineral density], bone geometry, and probably other fracture-related factors,” said Mr. Shen, a doctoral student at Creighton's Osteoporosis Research Center.

The meeting was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

BETHESDA, MD. — New chromosomal regions that possibly contain genes controlling bone quality were recently identified in the first genome-wide linkage scan of cross-sectional bone geometry in humans.

The few reported genetic studies of cross-sectional geometry have shown that the heritability is greater than 50%, “which means that in the general population, more than 50% of the phenotypic variation can be attributable to genetic events,” Hui Shen said at a meeting on bone quality.

In a prospective study of 79 white pedigrees composed of 1,816 individuals, Mr. Shen of Creighton University, Omaha, Neb., and his colleagues calculated logarithmic odds (LOD) scores for bone geometry parameters at the femoral neck, including cross-sectional area, cortical thickness, endocortical diameter, sectional modulus, and buckling ratio in relation to 451 microsatellite markers.

On chromosome 10q26, the researchers calculated an LOD score of 3.29, the highest recorded in the study, for the buckling ratio at the femoral neck. This indicates that the odds are nearly 2,000 to 1 in favor of genetic linkage between the two loci.

Three bone geometry parameters (cross-sectional area, cortical thickness, and buckling ratio) were linked to a broad region on chromosome 20p12-q12 with LOD scores ranging from 1.95 to 2.29. A candidate gene called bone morphogenetic protein 2 (BMP2) is located in that region.

BMP2 is known to regulate bone growth and in a recent study was identified as a genetic determinant of risk for osteoporosis (PLoS Biol. 2003;1:E69).

The researchers also observed some difference in the linkages for buckling ratio and cortical thickness between males and females. “Taken together, this evidence suggests a gene or a group of genes appearing in this area may have significant effects on [bone mineral density], bone geometry, and probably other fracture-related factors,” said Mr. Shen, a doctoral student at Creighton's Osteoporosis Research Center.

The meeting was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

BETHESDA, MD. — New chromosomal regions that possibly contain genes controlling bone quality were recently identified in the first genome-wide linkage scan of cross-sectional bone geometry in humans.

The few reported genetic studies of cross-sectional geometry have shown that the heritability is greater than 50%, “which means that in the general population, more than 50% of the phenotypic variation can be attributable to genetic events,” Hui Shen said at a meeting on bone quality.

In a prospective study of 79 white pedigrees composed of 1,816 individuals, Mr. Shen of Creighton University, Omaha, Neb., and his colleagues calculated logarithmic odds (LOD) scores for bone geometry parameters at the femoral neck, including cross-sectional area, cortical thickness, endocortical diameter, sectional modulus, and buckling ratio in relation to 451 microsatellite markers.

On chromosome 10q26, the researchers calculated an LOD score of 3.29, the highest recorded in the study, for the buckling ratio at the femoral neck. This indicates that the odds are nearly 2,000 to 1 in favor of genetic linkage between the two loci.

Three bone geometry parameters (cross-sectional area, cortical thickness, and buckling ratio) were linked to a broad region on chromosome 20p12-q12 with LOD scores ranging from 1.95 to 2.29. A candidate gene called bone morphogenetic protein 2 (BMP2) is located in that region.

BMP2 is known to regulate bone growth and in a recent study was identified as a genetic determinant of risk for osteoporosis (PLoS Biol. 2003;1:E69).

The researchers also observed some difference in the linkages for buckling ratio and cortical thickness between males and females. “Taken together, this evidence suggests a gene or a group of genes appearing in this area may have significant effects on [bone mineral density], bone geometry, and probably other fracture-related factors,” said Mr. Shen, a doctoral student at Creighton's Osteoporosis Research Center.

The meeting was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

BETHESDA, MD. — Testosterone replacement therapy in hypogonadal men appears to significantly improve trabecular bone architecture, according to the results of a small study.

Findings from previous studies suggest that testosterone replacement therapy increases bone mineral density in hypogonadal men, but none of these investigations looked at the effect of the hormone on trabecular architecture.

Maria Benito, M.D., reported at a meeting on bone quality the improvements seen in trabecular architecture in 10 hypogonadal men (median age 51 years) after 2 years of testosterone gel (AndroGel) therapy.

Each patient applied 5 g of a transdermally absorbed gel once per day and then received doses titrated to keep their serum testosterone level within the normal range of 400–900 ng/dL. The men increased their serum testosterone level from a mean of 88 ng/dL at baseline to 468 ng/dL after 2 years, said Dr. Benito of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia.

Using micro MRI scans of the distal tibia taken at baseline, 6, 12, and 24 months, Dr. Benito and her colleagues matched architectural parameters in the images from each subject at each time point to ensure that the same volume was analyzed each time. They measured the ratio of surface voxels (representing trabecular plates) to curve voxels (representing trabecular rods) and the ratio of topologic parameters expected to increase during trabecular deterioration to those expected to decrease (the topologic erosion index).

After 24 months of treatment, the ratio of surface to curve voxels increased significantly by 11% while the topologic erosion index decreased significantly by 8%; both measures indicate that trabecular architecture improved. Bone mineral density also rose significantly in the L1-L4 vertebrae by 7%.

The improvement in trabecular architecture could not be attributed to body mass index or calcium intake during treatment since neither factor changed substantially. Testosterone's effect on trabecular architecture suggests that it may exert an anabolic effect on bone, she said.

Men with a calcium intake of less than 750 mg per day, a history of disease, or on medications that could affect bone, were excluded from the study, Dr. Benito said at the meeting, sponsored by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases and the American Society for Bone and Mineral Research.

Solvay Pharmaceuticals provided the AndroGel used in the study. Dr. Benito had no financial conflicts of interest to report.

BETHESDA, MD. — Testosterone replacement therapy in hypogonadal men appears to significantly improve trabecular bone architecture, according to the results of a small study.

Findings from previous studies suggest that testosterone replacement therapy increases bone mineral density in hypogonadal men, but none of these investigations looked at the effect of the hormone on trabecular architecture.

Maria Benito, M.D., reported at a meeting on bone quality the improvements seen in trabecular architecture in 10 hypogonadal men (median age 51 years) after 2 years of testosterone gel (AndroGel) therapy.

Each patient applied 5 g of a transdermally absorbed gel once per day and then received doses titrated to keep their serum testosterone level within the normal range of 400–900 ng/dL. The men increased their serum testosterone level from a mean of 88 ng/dL at baseline to 468 ng/dL after 2 years, said Dr. Benito of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia.

Using micro MRI scans of the distal tibia taken at baseline, 6, 12, and 24 months, Dr. Benito and her colleagues matched architectural parameters in the images from each subject at each time point to ensure that the same volume was analyzed each time. They measured the ratio of surface voxels (representing trabecular plates) to curve voxels (representing trabecular rods) and the ratio of topologic parameters expected to increase during trabecular deterioration to those expected to decrease (the topologic erosion index).

After 24 months of treatment, the ratio of surface to curve voxels increased significantly by 11% while the topologic erosion index decreased significantly by 8%; both measures indicate that trabecular architecture improved. Bone mineral density also rose significantly in the L1-L4 vertebrae by 7%.

The improvement in trabecular architecture could not be attributed to body mass index or calcium intake during treatment since neither factor changed substantially. Testosterone's effect on trabecular architecture suggests that it may exert an anabolic effect on bone, she said.

Men with a calcium intake of less than 750 mg per day, a history of disease, or on medications that could affect bone, were excluded from the study, Dr. Benito said at the meeting, sponsored by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases and the American Society for Bone and Mineral Research.

Solvay Pharmaceuticals provided the AndroGel used in the study. Dr. Benito had no financial conflicts of interest to report.

BETHESDA, MD. — Testosterone replacement therapy in hypogonadal men appears to significantly improve trabecular bone architecture, according to the results of a small study.

Findings from previous studies suggest that testosterone replacement therapy increases bone mineral density in hypogonadal men, but none of these investigations looked at the effect of the hormone on trabecular architecture.

Maria Benito, M.D., reported at a meeting on bone quality the improvements seen in trabecular architecture in 10 hypogonadal men (median age 51 years) after 2 years of testosterone gel (AndroGel) therapy.

Each patient applied 5 g of a transdermally absorbed gel once per day and then received doses titrated to keep their serum testosterone level within the normal range of 400–900 ng/dL. The men increased their serum testosterone level from a mean of 88 ng/dL at baseline to 468 ng/dL after 2 years, said Dr. Benito of the division of endocrinology, diabetes, and metabolism at the University of Pennsylvania, Philadelphia.

Using micro MRI scans of the distal tibia taken at baseline, 6, 12, and 24 months, Dr. Benito and her colleagues matched architectural parameters in the images from each subject at each time point to ensure that the same volume was analyzed each time. They measured the ratio of surface voxels (representing trabecular plates) to curve voxels (representing trabecular rods) and the ratio of topologic parameters expected to increase during trabecular deterioration to those expected to decrease (the topologic erosion index).

After 24 months of treatment, the ratio of surface to curve voxels increased significantly by 11% while the topologic erosion index decreased significantly by 8%; both measures indicate that trabecular architecture improved. Bone mineral density also rose significantly in the L1-L4 vertebrae by 7%.

The improvement in trabecular architecture could not be attributed to body mass index or calcium intake during treatment since neither factor changed substantially. Testosterone's effect on trabecular architecture suggests that it may exert an anabolic effect on bone, she said.

Men with a calcium intake of less than 750 mg per day, a history of disease, or on medications that could affect bone, were excluded from the study, Dr. Benito said at the meeting, sponsored by the National Institute for Arthritis, Musculoskeletal, and Skin Diseases and the American Society for Bone and Mineral Research.

Solvay Pharmaceuticals provided the AndroGel used in the study. Dr. Benito had no financial conflicts of interest to report.

BETHESDA, MD. — Fracture will continue to be the primary end point in clinical trials of treatments for osteoporosis until new biomarkers can stand in as surrogates for fracture, according to speakers at a meeting on bone quality.

The large number of factors that need to be tested to validate a single biomarker as a surrogate end point make it unlikely that any single biomarker will adequately predict the risk of fracture, said Henry Bone, M.D., of the Michigan Bone and Mineral Clinic, Detroit. Researchers may need to combine a set of biomarkers into a model to produce the best surrogate.

Many new potential biomarkers of bone quality are being evaluated in small subgroups in clinical trials, but no single study has compared a set of bone quality measurements with bone mineral density (BMD) and radiographs for prediction of fractures and the effect of treatment, Dr. Bone said. “We really haven't considered using combined models integrating a number of different kinds of these intermediate end points or biomarkers.”

“For something as complicated as fracture risk, I think this is where we're going to end up—that we use combinations of anatomical and more dynamic measurements in order to explain the effects of treatment,” added Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute in San Francisco.

Surrogate end points, which may be faster and easier to measure than clinical outcomes such as fracture, could allow researchers to speed up clinical trials, enroll fewer patients into studies, and lower the cost of drug development, said Theresa Kehoe, M.D., of the division of metabolic and endocrine drug products at the Food and Drug Administration's Center for Drug Evaluation and Research.

A surrogate end point in a clinical trial is a laboratory or radiologic measurement or physical sign—a biomarker—used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. The changes induced by a therapy on this surrogate end point are expected to reflect changes in a clinically meaningful end point, such as fracture, Dr. Kehoe said.

In osteoporosis clinical trials involving the prevention of postmenopausal osteoporosis with estrogens, current regulatory practice permits the use of BMD data alone to act as a surrogate end point, Dr. Kehoe said at the meeting, which was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

But data on the rate of fracture are necessary for clinical trials of the prevention or treatment of postmenopausal osteoporosis with selective estrogen receptor modulators or nonestrogen products. In those trials, Dr. Kehoe said the FDA “tends not to accept” BMD data as a surrogate for prevention of postmenopausal osteoporosis before it has data on the rate of fracture.

BMD is still the primary end point for efficacy in noninferiority trials that compare a once-daily formulation of a drug that has already been approved based on its ability to reduce the rate of fracture with a new formulation of the same drug, she said.

Dr. Kehoe raised additional questions to consider about surrogate end points:

▸ Should the surrogate show consistent sensitivity and specificity in more than one therapeutic class of drugs? A single negative therapeutic example has the potential to undermine the biological plausibility of the proposed surrogate, she noted.

▸ What type of fracture should the surrogate be tested against? This could be an asymptomatic morphometric vertebral fracture, which some already consider to be a surrogate for a symptomatic fracture.

▸ Should the surrogate have equal sensitivity and specificity for mild, moderate, and severe vertebral fractures?

▸ What sensitivity, specificity, positive and negative predictive values, or other relevant statistics should be required to prove that a surrogate is valid?

BETHESDA, MD. — Fracture will continue to be the primary end point in clinical trials of treatments for osteoporosis until new biomarkers can stand in as surrogates for fracture, according to speakers at a meeting on bone quality.

The large number of factors that need to be tested to validate a single biomarker as a surrogate end point make it unlikely that any single biomarker will adequately predict the risk of fracture, said Henry Bone, M.D., of the Michigan Bone and Mineral Clinic, Detroit. Researchers may need to combine a set of biomarkers into a model to produce the best surrogate.

Many new potential biomarkers of bone quality are being evaluated in small subgroups in clinical trials, but no single study has compared a set of bone quality measurements with bone mineral density (BMD) and radiographs for prediction of fractures and the effect of treatment, Dr. Bone said. “We really haven't considered using combined models integrating a number of different kinds of these intermediate end points or biomarkers.”

“For something as complicated as fracture risk, I think this is where we're going to end up—that we use combinations of anatomical and more dynamic measurements in order to explain the effects of treatment,” added Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute in San Francisco.

Surrogate end points, which may be faster and easier to measure than clinical outcomes such as fracture, could allow researchers to speed up clinical trials, enroll fewer patients into studies, and lower the cost of drug development, said Theresa Kehoe, M.D., of the division of metabolic and endocrine drug products at the Food and Drug Administration's Center for Drug Evaluation and Research.

A surrogate end point in a clinical trial is a laboratory or radiologic measurement or physical sign—a biomarker—used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. The changes induced by a therapy on this surrogate end point are expected to reflect changes in a clinically meaningful end point, such as fracture, Dr. Kehoe said.

In osteoporosis clinical trials involving the prevention of postmenopausal osteoporosis with estrogens, current regulatory practice permits the use of BMD data alone to act as a surrogate end point, Dr. Kehoe said at the meeting, which was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

But data on the rate of fracture are necessary for clinical trials of the prevention or treatment of postmenopausal osteoporosis with selective estrogen receptor modulators or nonestrogen products. In those trials, Dr. Kehoe said the FDA “tends not to accept” BMD data as a surrogate for prevention of postmenopausal osteoporosis before it has data on the rate of fracture.

BMD is still the primary end point for efficacy in noninferiority trials that compare a once-daily formulation of a drug that has already been approved based on its ability to reduce the rate of fracture with a new formulation of the same drug, she said.

Dr. Kehoe raised additional questions to consider about surrogate end points:

▸ Should the surrogate show consistent sensitivity and specificity in more than one therapeutic class of drugs? A single negative therapeutic example has the potential to undermine the biological plausibility of the proposed surrogate, she noted.

▸ What type of fracture should the surrogate be tested against? This could be an asymptomatic morphometric vertebral fracture, which some already consider to be a surrogate for a symptomatic fracture.

▸ Should the surrogate have equal sensitivity and specificity for mild, moderate, and severe vertebral fractures?

▸ What sensitivity, specificity, positive and negative predictive values, or other relevant statistics should be required to prove that a surrogate is valid?

BETHESDA, MD. — Fracture will continue to be the primary end point in clinical trials of treatments for osteoporosis until new biomarkers can stand in as surrogates for fracture, according to speakers at a meeting on bone quality.

The large number of factors that need to be tested to validate a single biomarker as a surrogate end point make it unlikely that any single biomarker will adequately predict the risk of fracture, said Henry Bone, M.D., of the Michigan Bone and Mineral Clinic, Detroit. Researchers may need to combine a set of biomarkers into a model to produce the best surrogate.

Many new potential biomarkers of bone quality are being evaluated in small subgroups in clinical trials, but no single study has compared a set of bone quality measurements with bone mineral density (BMD) and radiographs for prediction of fractures and the effect of treatment, Dr. Bone said. “We really haven't considered using combined models integrating a number of different kinds of these intermediate end points or biomarkers.”

“For something as complicated as fracture risk, I think this is where we're going to end up—that we use combinations of anatomical and more dynamic measurements in order to explain the effects of treatment,” added Steven R. Cummings, M.D., of the California Pacific Medical Center Research Institute in San Francisco.

Surrogate end points, which may be faster and easier to measure than clinical outcomes such as fracture, could allow researchers to speed up clinical trials, enroll fewer patients into studies, and lower the cost of drug development, said Theresa Kehoe, M.D., of the division of metabolic and endocrine drug products at the Food and Drug Administration's Center for Drug Evaluation and Research.

A surrogate end point in a clinical trial is a laboratory or radiologic measurement or physical sign—a biomarker—used as a substitute for a clinically meaningful end point that measures directly how a patient feels, functions, or survives. The changes induced by a therapy on this surrogate end point are expected to reflect changes in a clinically meaningful end point, such as fracture, Dr. Kehoe said.

In osteoporosis clinical trials involving the prevention of postmenopausal osteoporosis with estrogens, current regulatory practice permits the use of BMD data alone to act as a surrogate end point, Dr. Kehoe said at the meeting, which was sponsored by the National Institute of Arthritis and Musculoskeletal and Skin Diseases and the American Society for Bone and Mineral Research.

But data on the rate of fracture are necessary for clinical trials of the prevention or treatment of postmenopausal osteoporosis with selective estrogen receptor modulators or nonestrogen products. In those trials, Dr. Kehoe said the FDA “tends not to accept” BMD data as a surrogate for prevention of postmenopausal osteoporosis before it has data on the rate of fracture.

BMD is still the primary end point for efficacy in noninferiority trials that compare a once-daily formulation of a drug that has already been approved based on its ability to reduce the rate of fracture with a new formulation of the same drug, she said.

Dr. Kehoe raised additional questions to consider about surrogate end points:

▸ Should the surrogate show consistent sensitivity and specificity in more than one therapeutic class of drugs? A single negative therapeutic example has the potential to undermine the biological plausibility of the proposed surrogate, she noted.

▸ What type of fracture should the surrogate be tested against? This could be an asymptomatic morphometric vertebral fracture, which some already consider to be a surrogate for a symptomatic fracture.

▸ Should the surrogate have equal sensitivity and specificity for mild, moderate, and severe vertebral fractures?

▸ What sensitivity, specificity, positive and negative predictive values, or other relevant statistics should be required to prove that a surrogate is valid?

WASHINGTON — Osteoporosis patients demonstrate greater compliance with weekly bisphosphonate therapy than with daily medication, but the numbers are still suboptimal, Deborah T. Gold, Ph.D., reported in a poster she presented at an international symposium sponsored by the National Osteoporosis Foundation.

Patients often resist taking bisphosphonates because of their inconvenient and complex dosing procedures, explained Dr. Gold of Duke University Medical Center, Durham, N.C.

Dr. Gold and her associates analyzed data on 214,060 women aged 50 years and older who received bisphosphonate therapy; the information had been collected for two health claims and retail pharmacy databases. Overall, weekly doses led to improved compliance after 1 year, compared with daily doses (44%–55% vs. 32%–40%), but 42%–67% of the patients on the weekly regimen had discontinued the medication within a year.

In addition, the level of compliance with either a weekly or daily dose was often too low to benefit many patients. Sufficient compliance was defined as a “medication possession ratio” of at least 80%. At most, only 53% of patients who received weekly medication were deemed compliant enough to derive antifracture benefits from it, which was still significantly better than the up to 40% rate of sufficient compliance among patients who received daily medication. Dr. Gold serves as a consultant for multiple pharmaceutical companies.

WASHINGTON — Osteoporosis patients demonstrate greater compliance with weekly bisphosphonate therapy than with daily medication, but the numbers are still suboptimal, Deborah T. Gold, Ph.D., reported in a poster she presented at an international symposium sponsored by the National Osteoporosis Foundation.

Patients often resist taking bisphosphonates because of their inconvenient and complex dosing procedures, explained Dr. Gold of Duke University Medical Center, Durham, N.C.

Dr. Gold and her associates analyzed data on 214,060 women aged 50 years and older who received bisphosphonate therapy; the information had been collected for two health claims and retail pharmacy databases. Overall, weekly doses led to improved compliance after 1 year, compared with daily doses (44%–55% vs. 32%–40%), but 42%–67% of the patients on the weekly regimen had discontinued the medication within a year.

In addition, the level of compliance with either a weekly or daily dose was often too low to benefit many patients. Sufficient compliance was defined as a “medication possession ratio” of at least 80%. At most, only 53% of patients who received weekly medication were deemed compliant enough to derive antifracture benefits from it, which was still significantly better than the up to 40% rate of sufficient compliance among patients who received daily medication. Dr. Gold serves as a consultant for multiple pharmaceutical companies.

WASHINGTON — Osteoporosis patients demonstrate greater compliance with weekly bisphosphonate therapy than with daily medication, but the numbers are still suboptimal, Deborah T. Gold, Ph.D., reported in a poster she presented at an international symposium sponsored by the National Osteoporosis Foundation.

Patients often resist taking bisphosphonates because of their inconvenient and complex dosing procedures, explained Dr. Gold of Duke University Medical Center, Durham, N.C.

Dr. Gold and her associates analyzed data on 214,060 women aged 50 years and older who received bisphosphonate therapy; the information had been collected for two health claims and retail pharmacy databases. Overall, weekly doses led to improved compliance after 1 year, compared with daily doses (44%–55% vs. 32%–40%), but 42%–67% of the patients on the weekly regimen had discontinued the medication within a year.

In addition, the level of compliance with either a weekly or daily dose was often too low to benefit many patients. Sufficient compliance was defined as a “medication possession ratio” of at least 80%. At most, only 53% of patients who received weekly medication were deemed compliant enough to derive antifracture benefits from it, which was still significantly better than the up to 40% rate of sufficient compliance among patients who received daily medication. Dr. Gold serves as a consultant for multiple pharmaceutical companies.

CHICAGO — Long-term use of proton pump inhibitors, histamine2-receptor antagonists, and other acid suppressors increases the risk of hip fracture, Yu-Xiao Yang, M.D., reported at the annual Digestive Disease Week.

Physicians turning to a combination of NSAIDs and protein pump inhibitors (PPIs) in place of cyclooxygenase-2 (COX-2) inhibitors should be aware of this effect in patients who are at increased risk of osteoporosis, but they should not deny this therapy to patients with appropriate indications, said Dr. Yang of the division of gastroenterology at the University of Pennsylvania, Philadelphia.

PPIs interfere with calcium absorption, leading to an increased risk of hip fracture.

“Do patients with more than 1 year of PPI therapy have more hip fractures? Up until now, there has been no epidemiological study to address this,” said Dr. Yang.

His conclusions came from a retrospective cohort study of 518,096 patients older than 40 years who were included in the U.K. General Practice Research Database between May 1987 and April 2002. Of these, 47,631 had more than 1 year of exposure to a PPI; the remaining 470,465 patients had no exposure to either a PPI or histamine2-receptor antagonist (H2RA).

By looking at complete prescription information and validated hip fracture reports, the researchers discovered that taking a PPI long term was associated with an increased risk of hip fracture, with a relative risk of 1.9 associated with at least 1 year of PPI use.

The relationship had both a dose-response effect and a duration-response effect. H2RA use also increased the relative risk of hip fracture, but to a lesser extent, Dr. Yang noted.

In general, the PPI-exposed patients were sicker and took more medications, so potential confounders were considered and adjusted for if they represented markers of comorbidity status or if they had an effect on the central nervous system that would increase the risk of falling, Dr. Yang noted in his presentation.

After adjustment for potential confounders, there was still a significantly increased risk of hip fracture among long-term PPI users. Significant confounders included antidepressant use and an increased number of office visits.

The study was limited by the assumption of 100% compliance with therapy and the lack of information on use of over-the-counter drugs, Dr. Yang said.

CHICAGO — Long-term use of proton pump inhibitors, histamine2-receptor antagonists, and other acid suppressors increases the risk of hip fracture, Yu-Xiao Yang, M.D., reported at the annual Digestive Disease Week.

Physicians turning to a combination of NSAIDs and protein pump inhibitors (PPIs) in place of cyclooxygenase-2 (COX-2) inhibitors should be aware of this effect in patients who are at increased risk of osteoporosis, but they should not deny this therapy to patients with appropriate indications, said Dr. Yang of the division of gastroenterology at the University of Pennsylvania, Philadelphia.

PPIs interfere with calcium absorption, leading to an increased risk of hip fracture.

“Do patients with more than 1 year of PPI therapy have more hip fractures? Up until now, there has been no epidemiological study to address this,” said Dr. Yang.

His conclusions came from a retrospective cohort study of 518,096 patients older than 40 years who were included in the U.K. General Practice Research Database between May 1987 and April 2002. Of these, 47,631 had more than 1 year of exposure to a PPI; the remaining 470,465 patients had no exposure to either a PPI or histamine2-receptor antagonist (H2RA).

By looking at complete prescription information and validated hip fracture reports, the researchers discovered that taking a PPI long term was associated with an increased risk of hip fracture, with a relative risk of 1.9 associated with at least 1 year of PPI use.

The relationship had both a dose-response effect and a duration-response effect. H2RA use also increased the relative risk of hip fracture, but to a lesser extent, Dr. Yang noted.

In general, the PPI-exposed patients were sicker and took more medications, so potential confounders were considered and adjusted for if they represented markers of comorbidity status or if they had an effect on the central nervous system that would increase the risk of falling, Dr. Yang noted in his presentation.

After adjustment for potential confounders, there was still a significantly increased risk of hip fracture among long-term PPI users. Significant confounders included antidepressant use and an increased number of office visits.

The study was limited by the assumption of 100% compliance with therapy and the lack of information on use of over-the-counter drugs, Dr. Yang said.

CHICAGO — Long-term use of proton pump inhibitors, histamine2-receptor antagonists, and other acid suppressors increases the risk of hip fracture, Yu-Xiao Yang, M.D., reported at the annual Digestive Disease Week.

Physicians turning to a combination of NSAIDs and protein pump inhibitors (PPIs) in place of cyclooxygenase-2 (COX-2) inhibitors should be aware of this effect in patients who are at increased risk of osteoporosis, but they should not deny this therapy to patients with appropriate indications, said Dr. Yang of the division of gastroenterology at the University of Pennsylvania, Philadelphia.

PPIs interfere with calcium absorption, leading to an increased risk of hip fracture.

“Do patients with more than 1 year of PPI therapy have more hip fractures? Up until now, there has been no epidemiological study to address this,” said Dr. Yang.

His conclusions came from a retrospective cohort study of 518,096 patients older than 40 years who were included in the U.K. General Practice Research Database between May 1987 and April 2002. Of these, 47,631 had more than 1 year of exposure to a PPI; the remaining 470,465 patients had no exposure to either a PPI or histamine2-receptor antagonist (H2RA).

By looking at complete prescription information and validated hip fracture reports, the researchers discovered that taking a PPI long term was associated with an increased risk of hip fracture, with a relative risk of 1.9 associated with at least 1 year of PPI use.

The relationship had both a dose-response effect and a duration-response effect. H2RA use also increased the relative risk of hip fracture, but to a lesser extent, Dr. Yang noted.

In general, the PPI-exposed patients were sicker and took more medications, so potential confounders were considered and adjusted for if they represented markers of comorbidity status or if they had an effect on the central nervous system that would increase the risk of falling, Dr. Yang noted in his presentation.

After adjustment for potential confounders, there was still a significantly increased risk of hip fracture among long-term PPI users. Significant confounders included antidepressant use and an increased number of office visits.

The study was limited by the assumption of 100% compliance with therapy and the lack of information on use of over-the-counter drugs, Dr. Yang said.