Osteoporosis

SAN ANTONIO — Current American Society of Clinical Oncology guidelines for maintenance of bone health in breast cancer patients are outdated and do not sufficiently protect against fractures, a prominent European expert asserted at the San Antonio Breast Cancer Symposium.

“Nothing against ASCO, but their guidelines were developed in 2002 and published in 2003. Back then people in the osteoporosis field thought bone mineral density was the main contributor to fracture risk, so the ASCO guidelines restrict bisphosphonate therapy to breast cancer patients with a T score of −2.5 or less,” said Dr. Peyman Hadji, professor of endocrinology and reproductive medicine at Philipps University of Marburg (Germany).

“The osteoporosis world has turned around since then. We don't treat T scores anymore, we treat absolute fracture risk. We calculate the absolute risk of a hip or spinal fracture in the next 10 years based on the T score and also using clinical risk factors,” he continued.

Dr. Hadji is the lead author of a contemporary alternative set of evidence-based guidelines developed by expert panel consensus (Ann. Oncol. 2008;19:1407-16).

Those guidelines significantly lower the threshold for bisphosphonate therapy (see sidebar).

“In Europe, these guidelines have had a big uptake. They're very easy for gynecologists and oncologists to use,” he said.

But physicians keep asking me, 'What proportion of breast cancer patients do we have to treat?' Their big fear was they'd have to give [zoledronic acid] to everyone on an aromatase inhi-?bitor. That's why we did this new study,” he explained in an interview.

He reported on 402 postmenopausal women with hormone receptor-positive breast cancer on tamoxifen or an aromatase inhibitor. This group of women had a calculated 10-year fracture risk of about 25%.

Yet under the ASCO guidelines (J. Clin. Oncol. 2003;21:4042-57), which recommend antiresorptive therapy in patients with a T score of −2.5 or lower, only 9% of the women would have qualified. In contrast, under the new guidelines, which call for treatment initiation in the presence of two or more risk factors, 29% of patients were bisphosphonate eligible.

To estimate how many fractures would be prevented in postmenopausal women with hormone receptor-positive breast cancer, Dr. Hadji and his coinvestigators turned to the 150,000-woman-strong database for the National Osteoporosis Risk Assessment study.

Using the ASCO guidelines to initiate bisphosphonate therapy in 9% of patients, only 18% of fractures would be prevented. Using the guidelines developed by Dr. Hadji and his associates, roughly 29% of women would be treated and at least 45% of fractures would be prevented. And that 45% figure is probably an underestimate, since women with breast cancer have a higher fracture risk than do healthy age-matched controls, Dr. Hadji said.

“This again indicates that restricting the risk assessment to bone mineral density is not good enough to identify the women at highest risk of fracture. Until ASCO comes out with new guidelines similar to ours, ours are much superior,” he declared.

The multidisciplinary international panel that joined Dr. Hadji in developing the guidelines for prevention and management of aromatase inhibitor-associated bone loss included Dr. Adam M. Brufsky of the University of Pittsburgh Cancer Institute, Dr. Theresa A. Guise, an endocrinologist at the University of Virginia, Charlottesville, and Dr. Allan Lipton, a medical oncologist at Pennsylvania State University, Hershey.

The guideline-development project was funded by Novartis. Dr. Hadji disclosed that he has received honoraria, unrestricted educational grants, and research funding from Novartis and a dozen other pharmaceutical companies.

'Until ASCO comes out with new guidelines similar to ours, ours are much superior.' DR. HADJI

Who Gets the Bisphosphonate?

The new practical guidelines recommend that all breast cancer patients on an aromatase inhibitor should receive calcium and vitamin D supplements, and that in addition, bisphosphonate therapy is warranted in those with any two of the following validated fracture risk factors:

▸ A T score below −1.5.

▸ Age greater than 65 years.

▸ History of oral corticosteroid use for longer than 6 months.

▸ Body mass index below 20 kg/m

▸ Family history of hip fracture.

▸ Positive smoking history.

▸ Personal history of a fragility fracture after age 50.

Source: Dr. Hadji

SAN ANTONIO — Current American Society of Clinical Oncology guidelines for maintenance of bone health in breast cancer patients are outdated and do not sufficiently protect against fractures, a prominent European expert asserted at the San Antonio Breast Cancer Symposium.

“Nothing against ASCO, but their guidelines were developed in 2002 and published in 2003. Back then people in the osteoporosis field thought bone mineral density was the main contributor to fracture risk, so the ASCO guidelines restrict bisphosphonate therapy to breast cancer patients with a T score of −2.5 or less,” said Dr. Peyman Hadji, professor of endocrinology and reproductive medicine at Philipps University of Marburg (Germany).

“The osteoporosis world has turned around since then. We don't treat T scores anymore, we treat absolute fracture risk. We calculate the absolute risk of a hip or spinal fracture in the next 10 years based on the T score and also using clinical risk factors,” he continued.

Dr. Hadji is the lead author of a contemporary alternative set of evidence-based guidelines developed by expert panel consensus (Ann. Oncol. 2008;19:1407-16).

Those guidelines significantly lower the threshold for bisphosphonate therapy (see sidebar).

“In Europe, these guidelines have had a big uptake. They're very easy for gynecologists and oncologists to use,” he said.

But physicians keep asking me, 'What proportion of breast cancer patients do we have to treat?' Their big fear was they'd have to give [zoledronic acid] to everyone on an aromatase inhi-?bitor. That's why we did this new study,” he explained in an interview.

He reported on 402 postmenopausal women with hormone receptor-positive breast cancer on tamoxifen or an aromatase inhibitor. This group of women had a calculated 10-year fracture risk of about 25%.

Yet under the ASCO guidelines (J. Clin. Oncol. 2003;21:4042-57), which recommend antiresorptive therapy in patients with a T score of −2.5 or lower, only 9% of the women would have qualified. In contrast, under the new guidelines, which call for treatment initiation in the presence of two or more risk factors, 29% of patients were bisphosphonate eligible.

To estimate how many fractures would be prevented in postmenopausal women with hormone receptor-positive breast cancer, Dr. Hadji and his coinvestigators turned to the 150,000-woman-strong database for the National Osteoporosis Risk Assessment study.

Using the ASCO guidelines to initiate bisphosphonate therapy in 9% of patients, only 18% of fractures would be prevented. Using the guidelines developed by Dr. Hadji and his associates, roughly 29% of women would be treated and at least 45% of fractures would be prevented. And that 45% figure is probably an underestimate, since women with breast cancer have a higher fracture risk than do healthy age-matched controls, Dr. Hadji said.

“This again indicates that restricting the risk assessment to bone mineral density is not good enough to identify the women at highest risk of fracture. Until ASCO comes out with new guidelines similar to ours, ours are much superior,” he declared.

The multidisciplinary international panel that joined Dr. Hadji in developing the guidelines for prevention and management of aromatase inhibitor-associated bone loss included Dr. Adam M. Brufsky of the University of Pittsburgh Cancer Institute, Dr. Theresa A. Guise, an endocrinologist at the University of Virginia, Charlottesville, and Dr. Allan Lipton, a medical oncologist at Pennsylvania State University, Hershey.

The guideline-development project was funded by Novartis. Dr. Hadji disclosed that he has received honoraria, unrestricted educational grants, and research funding from Novartis and a dozen other pharmaceutical companies.

'Until ASCO comes out with new guidelines similar to ours, ours are much superior.' DR. HADJI

Who Gets the Bisphosphonate?

The new practical guidelines recommend that all breast cancer patients on an aromatase inhibitor should receive calcium and vitamin D supplements, and that in addition, bisphosphonate therapy is warranted in those with any two of the following validated fracture risk factors:

▸ A T score below −1.5.

▸ Age greater than 65 years.

▸ History of oral corticosteroid use for longer than 6 months.

▸ Body mass index below 20 kg/m

▸ Family history of hip fracture.

▸ Positive smoking history.

▸ Personal history of a fragility fracture after age 50.

Source: Dr. Hadji

SAN ANTONIO — Current American Society of Clinical Oncology guidelines for maintenance of bone health in breast cancer patients are outdated and do not sufficiently protect against fractures, a prominent European expert asserted at the San Antonio Breast Cancer Symposium.

“Nothing against ASCO, but their guidelines were developed in 2002 and published in 2003. Back then people in the osteoporosis field thought bone mineral density was the main contributor to fracture risk, so the ASCO guidelines restrict bisphosphonate therapy to breast cancer patients with a T score of −2.5 or less,” said Dr. Peyman Hadji, professor of endocrinology and reproductive medicine at Philipps University of Marburg (Germany).

“The osteoporosis world has turned around since then. We don't treat T scores anymore, we treat absolute fracture risk. We calculate the absolute risk of a hip or spinal fracture in the next 10 years based on the T score and also using clinical risk factors,” he continued.

Dr. Hadji is the lead author of a contemporary alternative set of evidence-based guidelines developed by expert panel consensus (Ann. Oncol. 2008;19:1407-16).

Those guidelines significantly lower the threshold for bisphosphonate therapy (see sidebar).

“In Europe, these guidelines have had a big uptake. They're very easy for gynecologists and oncologists to use,” he said.

But physicians keep asking me, 'What proportion of breast cancer patients do we have to treat?' Their big fear was they'd have to give [zoledronic acid] to everyone on an aromatase inhi-?bitor. That's why we did this new study,” he explained in an interview.

He reported on 402 postmenopausal women with hormone receptor-positive breast cancer on tamoxifen or an aromatase inhibitor. This group of women had a calculated 10-year fracture risk of about 25%.

Yet under the ASCO guidelines (J. Clin. Oncol. 2003;21:4042-57), which recommend antiresorptive therapy in patients with a T score of −2.5 or lower, only 9% of the women would have qualified. In contrast, under the new guidelines, which call for treatment initiation in the presence of two or more risk factors, 29% of patients were bisphosphonate eligible.

To estimate how many fractures would be prevented in postmenopausal women with hormone receptor-positive breast cancer, Dr. Hadji and his coinvestigators turned to the 150,000-woman-strong database for the National Osteoporosis Risk Assessment study.

Using the ASCO guidelines to initiate bisphosphonate therapy in 9% of patients, only 18% of fractures would be prevented. Using the guidelines developed by Dr. Hadji and his associates, roughly 29% of women would be treated and at least 45% of fractures would be prevented. And that 45% figure is probably an underestimate, since women with breast cancer have a higher fracture risk than do healthy age-matched controls, Dr. Hadji said.

“This again indicates that restricting the risk assessment to bone mineral density is not good enough to identify the women at highest risk of fracture. Until ASCO comes out with new guidelines similar to ours, ours are much superior,” he declared.

The multidisciplinary international panel that joined Dr. Hadji in developing the guidelines for prevention and management of aromatase inhibitor-associated bone loss included Dr. Adam M. Brufsky of the University of Pittsburgh Cancer Institute, Dr. Theresa A. Guise, an endocrinologist at the University of Virginia, Charlottesville, and Dr. Allan Lipton, a medical oncologist at Pennsylvania State University, Hershey.

The guideline-development project was funded by Novartis. Dr. Hadji disclosed that he has received honoraria, unrestricted educational grants, and research funding from Novartis and a dozen other pharmaceutical companies.

'Until ASCO comes out with new guidelines similar to ours, ours are much superior.' DR. HADJI

Who Gets the Bisphosphonate?

The new practical guidelines recommend that all breast cancer patients on an aromatase inhibitor should receive calcium and vitamin D supplements, and that in addition, bisphosphonate therapy is warranted in those with any two of the following validated fracture risk factors:

▸ A T score below −1.5.

▸ Age greater than 65 years.

▸ History of oral corticosteroid use for longer than 6 months.

▸ Body mass index below 20 kg/m

▸ Family history of hip fracture.

▸ Positive smoking history.

▸ Personal history of a fragility fracture after age 50.

Source: Dr. Hadji

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, research director of the McLennan County Medical Education and Research Foundation, Waco, Texas.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD, with an average T score of −1.23. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, research director of the McLennan County Medical Education and Research Foundation, Waco, Texas.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD, with an average T score of −1.23. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, research director of the McLennan County Medical Education and Research Foundation, Waco, Texas.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD, with an average T score of −1.23. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

The Food and Drug Administration's recent approval of yearly zoledronic acid infusions for the treatment of low bone mass in men with osteoporosis will give clinicians a treatment option for men other than oral weekly therapy, according to Dr. Nelson Watts.

The agency's decision brings the total number of indications for the intravenous formulation of zoledronic acid (Reclast) to three, including the treatment of postmenopausal osteoporosis (as well as the reduction of new clinical fractures in patients who have experienced a recent low-trauma hip fracture) and the treatment of Paget's disease of bone. It is the only osteoporosis treatment that has been approved for the reduction of fractures of the hip, vertebrae, and other nonvertebral bones.

The other two drugs that are approved to increase bone mass in men with osteoporosis—alendronate (Fosamax) and risedronate (Actonel)—“certainly represent very good therapeutic choices with… evidence in women for spine, hip, and nonvertebral fracture reduction,” said Dr. Watts, director of the University of Cincinnati Bone Health and Osteoporosis Center, which was one of the centers that participated in a randomized, double-blind trial that formed the basis for the FDA's decision. Dr. Watts is a paid consultant to Novartis Pharmaceutical Corp., which manufactures Reclast, and he is on the company's speakers bureau.

Intravenous dosing would be medically indicated for men in three categories: those who can't tolerate an oral agent because of upper GI problems, those with lower GI problems that interfere with drug absorption, and those who can't remember to take an oral agent. “And certainly it can be considered a convenience option for someone who might be a candidate for oral therapy,” Dr. Watts said.

“We don't have fracture reduction data in men, really, with any of these agents in terms of a preplanned primary end point [but] there's no real reason to feel that bisphosphonates work any differently for osteoporosis in men than they do in women,” Dr. Watts said in an interview.

During the 2-year Novartis-sponsored trial that the FDA evaluated, 153 osteoporotic men received a 15-minute infusion of zoledronic acid once per year, and 148 other osteoporotic men received weekly oral alendronate. The men who were treated with zoledronic acid increased their lumbar spine bone mineral density by a mean of 6.1% over 2 years. This change in BMD was similar to the 6.2% increase in the alendronate group. Each patient in the study received 1,000 mg calcium and 800–1,000 IU of vitamin D each day. The men had a mean age of 64 years; some of them had significant osteoporosis secondary to hypogonadism.

In the trial, signs and symptoms of an acute phase reaction occurred in some patients in the first 3 days following the zoledronic acid infusion. Treatment with zoledronic acid was associated with myalgia (17.1%) fever (15.7%), fatigue (12.4%), arthralgia (11.1%), pain (10.5%), chills (9.8%), headache (9.8%), influenza-like illness (8.5%), malaise (5.2%), and back pain (3.3%). No patients developed osteonecrosis of the jaw. There was one death in each group; the two groups had similar rates of serious adverse events.

The FDA has “generally felt” that drugs with proven antifracture efficacy in postmenopausal women can be approved, on the basis of noninferiority “bridging” studies without fracture data, for new dosing regimens or for new populations such as glucocorticoid users or men, Dr. Watts noted. That is why studies in those circumstances have been smaller and not powered to detect a reduction in fractures.”

Zoledronic acid, available as a 5-mg dose in a 100-mL ready-to-infuse solution, has been used by more than 164,000 patients in the United States since it was approved by the FDA in 2007, according to Novartis.

“Intravenous Reclast compares in price with the cost of a year's therapy with a brand-name oral preparation. Medicare has generally covered this for postmenopausal women, and in some states it's already covering it for men,” Dr. Watts said.

Zoledronic acid is covered under Medicare Part B, which applies to medical visits, tests, screenings, and intravenous medications. Part B covers 80% of Medicare-allowable charges, leaving 20% for secondary insurance or self-pay, he noted.

IV dosing would be indicated for men with upper or lower GI problems and those who forget to take pills. DR. WATTS

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, of the McLennan County Medical Education and Research Foundation, Waco, Tex.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, of the McLennan County Medical Education and Research Foundation, Waco, Tex.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

RIO GRANDE, P.R. — Approximately one in four elderly black women have osteoporosis, findings from a small study suggest.

Physicians should not ignore the possibility of osteoporosis in their older black female patients, although these women are not usually considered at high risk, compared with other demographic groups, said Dr. Sally P. Weaver, of the McLennan County Medical Education and Research Foundation, Waco, Tex.

Previous studies of osteoporosis in women have focused mainly on white women because of evidence of an elevated risk for osteoporosis in that population. Yet older women of any ethnicity are prone to age-related fractures if their bone mineral density (BMD) is low, she said in an interview.

Dr. Weaver and her colleagues measured BMD scans from the electronic health records of 44 black women aged 70 years and older. Patients with conditions that could affect bone turnover, vitamin D absorption, or calcium absorption were excluded from the study.

About 50% of the study participants met the criteria for osteopenia and 10% met the criteria for osteoporosis at the left femoral neck. Approximately 25% met criteria for osteopenia or osteoporosis at the lumbar spine. Overall, the left femoral neck had the lowest regional BMD. Dr. Weaver presented the results in a poster at the annual meeting of the North American Primary Care Research Group.

Dr. Weaver had no financial conflicts to disclose.

CHICAGO — CT colonography can screen as reliably for osteoporosis as dual-energy x-ray absorptiometry and can be used to screen simultaneously for bone loss and colorectal cancer, a study of 35 patients suggests.

Of the currently accepted tests for co-lorectal cancer—CT colonography (CTC), flexible sigmoidoscopy or barium enema every 5 years, and colonoscopy every 10 years—“virtual colonoscopy stands out as the only one that can look outside the colon,” study investigator Dr. Aslam Rizwan said at the annual meeting of the Radiological Society of North America.

The study found excellent agreement between retrospectively derived bone mineral density (BMD) and T scores from CTC data sets and BMD and T scores from dual-energy x-ray absorptiometry (DXA) in the same patients, reported Dr. Rizwan of the University of California, San Francisco.

The dual-purpose screening with CTC would provide information on osteoporosis risk with no additional radiation, Dr. Rizwan said. However, he emphasized that he is not suggesting that CTC replace DXA; rather, in patients who already are being screened for colorectal cancer, “the data [on BMD] is there; it's available, and we should use it.” He added that “both techniques have been proven individually. We're showing that it's feasible to do both tests on the same patient at the same time. These patients are going to be screened for polyps, so for no extra cost we can also screen for [bone loss].”

Use of CTC to screen simultaneously for osteoporosis and colorectal cancer offers “added value to a test you're going to give anyway. The added value is that it can give you information on BMD,” said study coauthor Dr. Judy Yee, also of the university. A total of 30 men and 5 women with a mean age of 66 years (age range 54–79) underwent both CTC and DXA. Two experienced readers independently calculated BMD and T scores from CTC data sets. CT bone density measurements were obtained with a bone mineral analysis software package at three vertebral bodies from T12 to L1. Density measurements also were obtained from fat and muscle to provide an internal reference for calculating BMD, T scores, and z scores.

The Centers for Medicare and Medicaid Services (CMS) do not now offer coverage for CTC, other than for diagnosis in symptomatic patients, said Dr. Yee, but “we hope there will be [screening] coverage in 2009.” Dr. Rizwan said that prospective studies are planned. He and Dr. Yee reported no financial conflicts of interest related to this study.

CT colonography was as reliable as DXA at screening for osteoporosis. Radiological Society of North America

CHICAGO — CT colonography can screen as reliably for osteoporosis as dual-energy x-ray absorptiometry and can be used to screen simultaneously for bone loss and colorectal cancer, a study of 35 patients suggests.

Of the currently accepted tests for co-lorectal cancer—CT colonography (CTC), flexible sigmoidoscopy or barium enema every 5 years, and colonoscopy every 10 years—“virtual colonoscopy stands out as the only one that can look outside the colon,” study investigator Dr. Aslam Rizwan said at the annual meeting of the Radiological Society of North America.

The study found excellent agreement between retrospectively derived bone mineral density (BMD) and T scores from CTC data sets and BMD and T scores from dual-energy x-ray absorptiometry (DXA) in the same patients, reported Dr. Rizwan of the University of California, San Francisco.

The dual-purpose screening with CTC would provide information on osteoporosis risk with no additional radiation, Dr. Rizwan said. However, he emphasized that he is not suggesting that CTC replace DXA; rather, in patients who already are being screened for colorectal cancer, “the data [on BMD] is there; it's available, and we should use it.” He added that “both techniques have been proven individually. We're showing that it's feasible to do both tests on the same patient at the same time. These patients are going to be screened for polyps, so for no extra cost we can also screen for [bone loss].”

Use of CTC to screen simultaneously for osteoporosis and colorectal cancer offers “added value to a test you're going to give anyway. The added value is that it can give you information on BMD,” said study coauthor Dr. Judy Yee, also of the university. A total of 30 men and 5 women with a mean age of 66 years (age range 54–79) underwent both CTC and DXA. Two experienced readers independently calculated BMD and T scores from CTC data sets. CT bone density measurements were obtained with a bone mineral analysis software package at three vertebral bodies from T12 to L1. Density measurements also were obtained from fat and muscle to provide an internal reference for calculating BMD, T scores, and z scores.

The Centers for Medicare and Medicaid Services (CMS) do not now offer coverage for CTC, other than for diagnosis in symptomatic patients, said Dr. Yee, but “we hope there will be [screening] coverage in 2009.” Dr. Rizwan said that prospective studies are planned. He and Dr. Yee reported no financial conflicts of interest related to this study.

CT colonography was as reliable as DXA at screening for osteoporosis. Radiological Society of North America

CHICAGO — CT colonography can screen as reliably for osteoporosis as dual-energy x-ray absorptiometry and can be used to screen simultaneously for bone loss and colorectal cancer, a study of 35 patients suggests.

Of the currently accepted tests for co-lorectal cancer—CT colonography (CTC), flexible sigmoidoscopy or barium enema every 5 years, and colonoscopy every 10 years—“virtual colonoscopy stands out as the only one that can look outside the colon,” study investigator Dr. Aslam Rizwan said at the annual meeting of the Radiological Society of North America.

The study found excellent agreement between retrospectively derived bone mineral density (BMD) and T scores from CTC data sets and BMD and T scores from dual-energy x-ray absorptiometry (DXA) in the same patients, reported Dr. Rizwan of the University of California, San Francisco.

The dual-purpose screening with CTC would provide information on osteoporosis risk with no additional radiation, Dr. Rizwan said. However, he emphasized that he is not suggesting that CTC replace DXA; rather, in patients who already are being screened for colorectal cancer, “the data [on BMD] is there; it's available, and we should use it.” He added that “both techniques have been proven individually. We're showing that it's feasible to do both tests on the same patient at the same time. These patients are going to be screened for polyps, so for no extra cost we can also screen for [bone loss].”

Use of CTC to screen simultaneously for osteoporosis and colorectal cancer offers “added value to a test you're going to give anyway. The added value is that it can give you information on BMD,” said study coauthor Dr. Judy Yee, also of the university. A total of 30 men and 5 women with a mean age of 66 years (age range 54–79) underwent both CTC and DXA. Two experienced readers independently calculated BMD and T scores from CTC data sets. CT bone density measurements were obtained with a bone mineral analysis software package at three vertebral bodies from T12 to L1. Density measurements also were obtained from fat and muscle to provide an internal reference for calculating BMD, T scores, and z scores.

The Centers for Medicare and Medicaid Services (CMS) do not now offer coverage for CTC, other than for diagnosis in symptomatic patients, said Dr. Yee, but “we hope there will be [screening] coverage in 2009.” Dr. Rizwan said that prospective studies are planned. He and Dr. Yee reported no financial conflicts of interest related to this study.

CT colonography was as reliable as DXA at screening for osteoporosis. Radiological Society of North America

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use, according to new analysis of data from the Raloxifene Use for the Heart (RUTH)study.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in RUTH. A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors (Am. J. Cardiol. 2002;90:1204–10). Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up (N. Engl. J. Med. 2006:355:125–37).

Investigators launched a second study to see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score.

David Cox, Ph.D., and his associates retrospectively calculated 10-year cumulative risk. He presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

Not surprisingly, risks appeared to congregate in the third and fourth highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score.

Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH. We think the pattern and data would suggest most of the excess risk was among those in the upper half of risk.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline (the median) were at increased risk of stroke death, compared with women who scored lower.

A meeting attendee asked at what age raloxifene should no longer be considered, offering 70 years as an example. “Even at age 70, she might not have enough risk factors,” Dr. Cox said. “But it depends on the risk factor.” For example, he said, “atrial fibrillation would put her over the 13 score.”

Dr. Cox and his colleagues also retrospectively assessed application of the Framingham risk score to 7,705 postmenopausal women with osteoporosis randomized to raloxifene or placebo in the Multiple Outcomes of Raloxifene Evaluation (MORE) study (JAMA 2002;287:847–57). In this study, raloxifene was not associated with an increase in rate of all strokes (hazard ratio, 0.71) or stroke death (HR, 0.57). He noted that the MORE population was generally lower risk than women in RUTH, with baseline Framingham scores of less than 13 in 80%.

Raloxifene's effect on the stroke death rate might differ by baseline stroke risk, Dr. Cox said. Assessing cumulative stroke risk may help target raloxifene treatment to postmenopausal women with the most favorable risk-benefit profile.

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use, according to new analysis of data from the Raloxifene Use for the Heart (RUTH)study.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in RUTH. A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors (Am. J. Cardiol. 2002;90:1204–10). Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up (N. Engl. J. Med. 2006:355:125–37).

Investigators launched a second study to see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score.

David Cox, Ph.D., and his associates retrospectively calculated 10-year cumulative risk. He presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

Not surprisingly, risks appeared to congregate in the third and fourth highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score.

Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH. We think the pattern and data would suggest most of the excess risk was among those in the upper half of risk.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline (the median) were at increased risk of stroke death, compared with women who scored lower.

A meeting attendee asked at what age raloxifene should no longer be considered, offering 70 years as an example. “Even at age 70, she might not have enough risk factors,” Dr. Cox said. “But it depends on the risk factor.” For example, he said, “atrial fibrillation would put her over the 13 score.”

Dr. Cox and his colleagues also retrospectively assessed application of the Framingham risk score to 7,705 postmenopausal women with osteoporosis randomized to raloxifene or placebo in the Multiple Outcomes of Raloxifene Evaluation (MORE) study (JAMA 2002;287:847–57). In this study, raloxifene was not associated with an increase in rate of all strokes (hazard ratio, 0.71) or stroke death (HR, 0.57). He noted that the MORE population was generally lower risk than women in RUTH, with baseline Framingham scores of less than 13 in 80%.

Raloxifene's effect on the stroke death rate might differ by baseline stroke risk, Dr. Cox said. Assessing cumulative stroke risk may help target raloxifene treatment to postmenopausal women with the most favorable risk-benefit profile.

ORLANDO — The Framingham stroke risk score can predict a high-risk postmenopausal woman's likelihood of a future cerebrovascular event with raloxifene use, according to new analysis of data from the Raloxifene Use for the Heart (RUTH)study.

Investigators in 26 countries enrolled 10,101 women at risk for a major coronary event in RUTH. A total of 5,031 women had documented coronary heart disease and the remaining 5,070 had multiple coronary heart disease risk factors (Am. J. Cardiol. 2002;90:1204–10). Although overall stroke risk was not significantly different between women randomized to raloxifene versus placebo, a higher number of fatal stroke events occurred in the treatment group, 59, compared with 39 in the placebo group during a mean of 5.6 years follow-up (N. Engl. J. Med. 2006:355:125–37).

Investigators launched a second study to see how this increased risk associated with raloxifene (hazard ratio, 1.49; absolute risk increase, 0.7 per 1,000 woman-years) would apply to women stratified by baseline Framingham stroke scale score.

David Cox, Ph.D., and his associates retrospectively calculated 10-year cumulative risk. He presented findings at the annual meeting of the North American Menopause Society. Eli Lilly & Co. supported the study, and Dr. Cox is a clinical research scientist for the company.

Not surprisingly, risks appeared to congregate in the third and fourth highest quartiles of Framingham score risk. However, there were no significant differences between treatment groups in either all strokes or nonfatal strokes, regardless of baseline Framingham score.

Regarding fatal stroke, Dr. Cox said, “after 2 years, you start to see a split between placebo and raloxifene for risk of fatal stroke by Framingham stroke risk score in RUTH. We think the pattern and data would suggest most of the excess risk was among those in the upper half of risk.” Specifically, women who scored a 13 or greater on the Framingham tool at baseline (the median) were at increased risk of stroke death, compared with women who scored lower.

A meeting attendee asked at what age raloxifene should no longer be considered, offering 70 years as an example. “Even at age 70, she might not have enough risk factors,” Dr. Cox said. “But it depends on the risk factor.” For example, he said, “atrial fibrillation would put her over the 13 score.”

Dr. Cox and his colleagues also retrospectively assessed application of the Framingham risk score to 7,705 postmenopausal women with osteoporosis randomized to raloxifene or placebo in the Multiple Outcomes of Raloxifene Evaluation (MORE) study (JAMA 2002;287:847–57). In this study, raloxifene was not associated with an increase in rate of all strokes (hazard ratio, 0.71) or stroke death (HR, 0.57). He noted that the MORE population was generally lower risk than women in RUTH, with baseline Framingham scores of less than 13 in 80%.

Raloxifene's effect on the stroke death rate might differ by baseline stroke risk, Dr. Cox said. Assessing cumulative stroke risk may help target raloxifene treatment to postmenopausal women with the most favorable risk-benefit profile.

Postmenopausal women who discontinue alendronate after 5 years of treatment may experience a moderate decline in bone mineral density but are not at a significantly higher risk for fracture compared with those who continue alendronate for an additional 5 years, reported Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues.

“For many women, discontinuation of alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of clinical vertebral fractures, such as those with vertebral fracture or very low [bone mineral density], may benefit by continuing beyond 5 years,” Dr. Black wrote (JAMA 2006;296:2927–38).

This conclusion was based on findings from a 5-year extension of the Fracture Intervention Trial (FIT), a randomized, placebo-controlled trial designed to evaluate the effect of daily alendronate on bone mineral density (BMD) and fracture risk in postmenopausal women with low BMD.

The FIT Long-Term Extension (FLEX) study was open to women who had been assigned to the alendronate treatment arm in FIT and who had completed at least 3 years of alendronate treatment. Women with a total hip BMD of less than 0.515 g/cm2 (T score less than −3.5) at baseline were ineligible to participate in FLEX.

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary end point was total hip BMD.

Of 1,099 women participating in FLEX, 437 were assigned to placebo, 329 were assigned to 5 mg alendronate, and 333 were assigned to 10 mg alendronate.

After 5 years, total hip BMD declined 3.38% from baseline in the placebo group and 1.02% in the combination of the two alendronate groups. The combined alendronate group experienced a mean 5.26% increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% increase in the placebo group.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study.

Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

Postmenopausal women who discontinue alendronate after 5 years of treatment may experience a moderate decline in bone mineral density but are not at a significantly higher risk for fracture compared with those who continue alendronate for an additional 5 years, reported Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues.

“For many women, discontinuation of alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of clinical vertebral fractures, such as those with vertebral fracture or very low [bone mineral density], may benefit by continuing beyond 5 years,” Dr. Black wrote (JAMA 2006;296:2927–38).

This conclusion was based on findings from a 5-year extension of the Fracture Intervention Trial (FIT), a randomized, placebo-controlled trial designed to evaluate the effect of daily alendronate on bone mineral density (BMD) and fracture risk in postmenopausal women with low BMD.

The FIT Long-Term Extension (FLEX) study was open to women who had been assigned to the alendronate treatment arm in FIT and who had completed at least 3 years of alendronate treatment. Women with a total hip BMD of less than 0.515 g/cm2 (T score less than −3.5) at baseline were ineligible to participate in FLEX.

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary end point was total hip BMD.

Of 1,099 women participating in FLEX, 437 were assigned to placebo, 329 were assigned to 5 mg alendronate, and 333 were assigned to 10 mg alendronate.

After 5 years, total hip BMD declined 3.38% from baseline in the placebo group and 1.02% in the combination of the two alendronate groups. The combined alendronate group experienced a mean 5.26% increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% increase in the placebo group.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study.

Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

Postmenopausal women who discontinue alendronate after 5 years of treatment may experience a moderate decline in bone mineral density but are not at a significantly higher risk for fracture compared with those who continue alendronate for an additional 5 years, reported Dennis M. Black, Ph.D., of the University of California, San Francisco, and his colleagues.

“For many women, discontinuation of alendronate after 5 years for up to 5 more years does not significantly increase fracture risk, but women at high risk of clinical vertebral fractures, such as those with vertebral fracture or very low [bone mineral density], may benefit by continuing beyond 5 years,” Dr. Black wrote (JAMA 2006;296:2927–38).

This conclusion was based on findings from a 5-year extension of the Fracture Intervention Trial (FIT), a randomized, placebo-controlled trial designed to evaluate the effect of daily alendronate on bone mineral density (BMD) and fracture risk in postmenopausal women with low BMD.

The FIT Long-Term Extension (FLEX) study was open to women who had been assigned to the alendronate treatment arm in FIT and who had completed at least 3 years of alendronate treatment. Women with a total hip BMD of less than 0.515 g/cm2 (T score less than −3.5) at baseline were ineligible to participate in FLEX.

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary end point was total hip BMD.

Of 1,099 women participating in FLEX, 437 were assigned to placebo, 329 were assigned to 5 mg alendronate, and 333 were assigned to 10 mg alendronate.

After 5 years, total hip BMD declined 3.38% from baseline in the placebo group and 1.02% in the combination of the two alendronate groups. The combined alendronate group experienced a mean 5.26% increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% increase in the placebo group.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study.

Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m2 and a mean age of 44 years. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry.

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

It had been thought that obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures. The authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m2 and a mean age of 44 years. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry.

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

It had been thought that obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures. The authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

VERONA, ITALY — Contrary to conventional wisdom, obese patients may not be protected against osteoporosis and could present with significant bone loss, new data show.

In a study of 233 morbidly obese patients, 34% showed a significant decrease in bone mineral density at the lumbar spine with a median T score of −1.98 (range −1.1 to −4.2), Dr. Carlo Lubrano and his colleagues reported in a poster at a joint meeting of the Italian Association of Clinical Endocrinologists and the American Association of Clinical Endocrinologists.

Low bone mass is defined as a bone density at the spine or hip between 1.0 and 2.4 standard deviations below the average for healthy young adults, which translates to a T score of −1 to −2.5, according to the World Health Organization. Bone density 2.5 standard deviations or more below the young adult mean is categorized as osteoporosis.

The 195 women and 38 men in the study had an average body mass index of 37 kg/m2 and a mean age of 44 years. Bone mineral density (BMD) was measured by dual-energy x-ray absorptiometry.

Overall, 31.5% of the women showed a median BMD of 0.971 g/cm

It had been thought that obesity might protect the skeleton against osteoporosis. Recent evidence suggests that obesity may actually weaken the skeleton and increase the risk of fractures. The authors concluded that a “specific and careful characterization of skeletal metabolism might be useful in both female and male obese subjects.”

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

Hip fracture risk was increased with long-term use of proton pump inhibitors in a study published recently in the Journal of the American Medical Association, and the findings have led to concerns and questions among physicians, as well as among patients who take these frequently prescribed drugs.

Dr. Yu-Xiao Yang of the division of gastroenterology at the University of Pennsylvania and his colleagues analyzed data on 1.8 million patients in the General Practice Research Database, a national database of patients in the United Kingdom, to assess a possible association between proton pump inhibitor (PPI) therapy and the risk of hip fracture (JAMA 2006;296:2947–53).

The adjusted odds ratio (AOR) for hip fracture associated with more than 1 year of PPI use was significantly increased at 1.44 (95% confidence interval [CI], 1.30–1.59; P less than .001). In addition, patients who were prescribed long-term, high-dose PPI therapy had a markedly increased risk of hip fracture, with an AOR of 2.65 (95% CI, 1.80–3.90; P less than .001).

Dr. Colin W. Howden, professor of gastroenterology at Northwestern University, Chicago, said while the study indicates that PPIs increase the risk of hip fracture, physicians and patients should avoid becoming overly concerned about the findings. “The risk needs to be put in context,” he said.

All patients were at least 50 years old and had no documented hip fracture before the study started or during the first year of follow-up; all started follow-up between May 1987 and March 2003. The cohort included 192,028 people who had received at least one prescription for a PPI during the follow-up period; 187,686 people who received at least one prescription for a histamine2 receptor antagonist (H2RA) during the follow-up period but had not used a PPI; and 1.4 million people who had no documented use of either a PPI or H2RA, and were thus classified as acid-suppression nonusers.

The authors matched cases of those who had a hip fracture during the study period with controls who did not. Cases and matched controls (up to 10 controls for each case) were similar in terms of sex, age, and both the calendar period and duration of follow-up before the index date.

The results revealed that 13,556 incident hip fractures—10,834 among acid suppression nonusers and 2,722 among PPI users—occurred during the study period. These hip fracture cases were matched with a total of 135,386 controls (at least 1 control per case).

In addition to an increased adjusted odds ratio for hip fracture after more than 1 year of PPI use, the data showed that the strength of the association between hip fracture and PPI use increased with each cumulative year of use. The AOR was 1.22 for 1 year of PPI therapy, 1.41 for 2 years, 1.54 for 3 years, and 1.59 for 4 years, with P less than .001 for all comparisons.

Dr. Howden commented that this study should remind physicians to review their patients' medication lists, particularly those of older patients who are at higher risk for hip fractures. “The bottom line is that if [patients need] to be on a PPI for a valid reason, they should be on a PPI,” he said. Clinicians who are concerned about the hip fracture risk in patients who may not need to take a PPI continually could discontinue the drug and see how the patient fares.

The study did not determine the mechanism behind the increased risk of hip fracture in PPI users, but the authors noted that these drugs may decrease calcium absorption via induction of hypochlorhydria, and may reduce bone resorption by inhibiting the osteoclastic proton transport system.

Currently, there are no guidelines for intensifying osteoporosis screening in patients on long-term PPI therapy. Until guidelines are published, physicians should consider the needs of individual patients and make diagnostic and treatment recommendations accordingly.

Dr. Howden cautioned against taking an alarmist approach to this study. “I think the absolute risk is quite small, but it's not zero,” he said.

Dr. George Sachs, professor of medicine and physiology at the University of California, Los Angeles, agreed that the study shows only a small excess risk of hip fracture in the group taking PPIs. These medications have only a small effect on stomach pH levels and hence calcium absorption, according to Dr. Sachs. Increasing calcium supplements or milk intake is the best method of decreasing the risk of hip fracture, he said.

“The findings are not surprising,” commented Dr. Steven Petak, president of the American Association of Clinical Endocrinologists. “Vitamin D and calcium insufficiency are very common in the population and it is likely [that] using a PPI only adds to an already significant problem.”

He recommends that patients consume 1,200–1,400 mg of calcium and 600–1,000 IU of vitamin D3 (cholecalciferol) daily; supplements should be taken in divided doses with food to help absorption.

“If PPI drugs are needed, then certainly they should be used, but with additional evaluation of the bone and calcium status,” Dr. Petak said.

ELSEVIER GLOBAL MEDICAL NEWS

CHICAGO — Low bone mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From, of the Mayo Clinic in Rochester, Minn., and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

The analysis included all patients who underwent dual-energy x-ray absorptiometry of the femoral neck at the Mayo Clinic during August 1998-October 2003 who also had an exercise echocardiography examination soon after the bone scan. The researchers identified 1,142 patients who fulfilled these criteria.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score, a statistically significant difference, Dr. From and his associates reported in the poster.

CHICAGO — Low bone mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From, of the Mayo Clinic in Rochester, Minn., and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

The analysis included all patients who underwent dual-energy x-ray absorptiometry of the femoral neck at the Mayo Clinic during August 1998-October 2003 who also had an exercise echocardiography examination soon after the bone scan. The researchers identified 1,142 patients who fulfilled these criteria.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score, a statistically significant difference, Dr. From and his associates reported in the poster.

CHICAGO — Low bone mineral density was associated with exercise-induced myocardial ischemia in a retrospective analysis of more than 1,000 patients.

These are the first study results to show a link between bone mineral density (BMD) and exercise-induced ischemia using exercise echocardiography, Dr. Aaron M. From, of the Mayo Clinic in Rochester, Minn., and his associates said in a poster presented at the annual scientific sessions of the American Heart Association.

The analysis included all patients who underwent dual-energy x-ray absorptiometry of the femoral neck at the Mayo Clinic during August 1998-October 2003 who also had an exercise echocardiography examination soon after the bone scan. The researchers identified 1,142 patients who fulfilled these criteria.

The group included a total of 643 patients with low BMD, including 126 with osteoporosis and 517 with osteopenia. The remaining 499 patients had BMDs in the normal range.

The analysis showed that patients with the lowest BMD (a T score of −4 to −3) had the shortest exercise duration, 5.8 minutes, while patients with the highest T scores (+1 to +2) had the longest exercise duration, 8.9 minutes.

In a multivariate analysis, the risk of having exercise-induced ischemia rose by 22% for every one-point decrease in T score, a statistically significant difference, Dr. From and his associates reported in the poster.