Osteoarthritis

SAN ANTONIO — Zoledronic acid prevents the profound loss in bone mineral density that often occurs with combined adjuvant endocrine therapy in premenopausal breast cancer patients, Michael Gnant, M.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Based on new data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12), all premenopausal breast cancer patients receiving combination adjuvant therapy with a luteinizing hormone-releasing hormone analogue, such as goserelin, plus either tamoxifen or an aromatase inhibitor, should undergo annual bone mineral density (BMD) testing. Those showing a treatment-related decline should be considered for intravenous zoledronic acid (Zometa) administered once every 6 months, said Dr. Gnant, professor of surgery at the University of Vienna.

In clinical practice, the aromatase inhibitors increasingly are replacing tamoxifen because they provide a greater reduction in recurrence and less risk of endometrial cancer and thromboembolic events. The price has been the greater risk of osteoporosis and fractures associated with aromatase inhibitor use. But prophylactic zoledronic acid appears to erase that downside.

Although it is widely appreciated that postmenopausal breast cancer patients face increased risk of accelerated bone loss, the osseous impact of cancer therapies in premenopausal breast cancer patients was much less clear before ABCSG-12. The primary end point in the 1,315-patient phase III Austrian study will be relapse-free survival, which awaits longer follow-up.

In San Antonio, Dr. Gnant reported on a secondary study end point—change in BMD—in a 401-patient subset.

The ABCSG-12 trial is a four-part study that randomized patients to 3 years of adjuvant goserelin plus either tamoxifen or anastrozole, with or without 3 years of zoledronic acid given at 4 mg IV every 6 months.

After 3 years of goserelin and tamoxifen without zoledronic acid, BMD at the lumbar spine fell an average of 11.6%, compared with baseline. In patients receiving goserelin plus anastrozole but not zoledronic acid, it fell 17.4%. However, patients on either combination who received the potent intravenous bisphosphonate had no significant change in BMD, he said.

In a separate study, Adam Brufsky, M.D., presented preliminary 6-month results from Z-FAST, a 5-year multicenter U.S. trial in which 415 postmenopausal women with early-stage hormone receptor-positive breast cancer receiving adjuvant letrozole (Femara) were randomized to zoledronic acid administered every 6 months either up front or beginning 1 year after the start of the aromatase inhibitor.

BMD at the lumbar spine and hip increased in patients who got zoledronic acid up front and decreased in those assigned to delayed bisphosphonate therapy. Biochemical markers of bone turnover decreased from baseline to 6 months in the up-front zoledronic acid group, while increasing or remaining unchanged in the delayed-treatment arm.

These early findings suggest administration of zoledronic acid from the onset of adjuvant aromatase inhibitor therapy may prevent cancer therapy-induced bone loss in postmenopausal women. However, longer-term follow-up is needed to fully define the effects of zoledronic acid in this population. The Novartis-sponsored Z-FAST trial is scheduled for 5 years of follow-up, said Dr. Brufsky of the University of Pittsburgh. Zoledronic acid is more expensive than pamidronate (Aredia), the other intravenous bisphosphonate, but its infusion time is only 15 minutes, compared with 2 hours or more for pamidronate, and there are some data to suggest zoledronic acid is more effective.

Zoledronic acid does not yet have an indication from the Food and Drug Administration for use in the setting of adjuvant breast cancer therapy, however, many oncologists will continue to follow the American Society of Clinical Oncology's recent guidelines. Those call for increased diligence in screening breast cancer patients for bone loss, advising them on the importance of calcium and vitamin D supplementation and bone-healthy lifestyle measures, and the early use of the clearly less potent oral bisphosphonates in women who show cancer treatment-related decline in BMD.

SAN ANTONIO — Zoledronic acid prevents the profound loss in bone mineral density that often occurs with combined adjuvant endocrine therapy in premenopausal breast cancer patients, Michael Gnant, M.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Based on new data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12), all premenopausal breast cancer patients receiving combination adjuvant therapy with a luteinizing hormone-releasing hormone analogue, such as goserelin, plus either tamoxifen or an aromatase inhibitor, should undergo annual bone mineral density (BMD) testing. Those showing a treatment-related decline should be considered for intravenous zoledronic acid (Zometa) administered once every 6 months, said Dr. Gnant, professor of surgery at the University of Vienna.

In clinical practice, the aromatase inhibitors increasingly are replacing tamoxifen because they provide a greater reduction in recurrence and less risk of endometrial cancer and thromboembolic events. The price has been the greater risk of osteoporosis and fractures associated with aromatase inhibitor use. But prophylactic zoledronic acid appears to erase that downside.

Although it is widely appreciated that postmenopausal breast cancer patients face increased risk of accelerated bone loss, the osseous impact of cancer therapies in premenopausal breast cancer patients was much less clear before ABCSG-12. The primary end point in the 1,315-patient phase III Austrian study will be relapse-free survival, which awaits longer follow-up.

In San Antonio, Dr. Gnant reported on a secondary study end point—change in BMD—in a 401-patient subset.

The ABCSG-12 trial is a four-part study that randomized patients to 3 years of adjuvant goserelin plus either tamoxifen or anastrozole, with or without 3 years of zoledronic acid given at 4 mg IV every 6 months.

After 3 years of goserelin and tamoxifen without zoledronic acid, BMD at the lumbar spine fell an average of 11.6%, compared with baseline. In patients receiving goserelin plus anastrozole but not zoledronic acid, it fell 17.4%. However, patients on either combination who received the potent intravenous bisphosphonate had no significant change in BMD, he said.

In a separate study, Adam Brufsky, M.D., presented preliminary 6-month results from Z-FAST, a 5-year multicenter U.S. trial in which 415 postmenopausal women with early-stage hormone receptor-positive breast cancer receiving adjuvant letrozole (Femara) were randomized to zoledronic acid administered every 6 months either up front or beginning 1 year after the start of the aromatase inhibitor.

BMD at the lumbar spine and hip increased in patients who got zoledronic acid up front and decreased in those assigned to delayed bisphosphonate therapy. Biochemical markers of bone turnover decreased from baseline to 6 months in the up-front zoledronic acid group, while increasing or remaining unchanged in the delayed-treatment arm.

These early findings suggest administration of zoledronic acid from the onset of adjuvant aromatase inhibitor therapy may prevent cancer therapy-induced bone loss in postmenopausal women. However, longer-term follow-up is needed to fully define the effects of zoledronic acid in this population. The Novartis-sponsored Z-FAST trial is scheduled for 5 years of follow-up, said Dr. Brufsky of the University of Pittsburgh. Zoledronic acid is more expensive than pamidronate (Aredia), the other intravenous bisphosphonate, but its infusion time is only 15 minutes, compared with 2 hours or more for pamidronate, and there are some data to suggest zoledronic acid is more effective.

Zoledronic acid does not yet have an indication from the Food and Drug Administration for use in the setting of adjuvant breast cancer therapy, however, many oncologists will continue to follow the American Society of Clinical Oncology's recent guidelines. Those call for increased diligence in screening breast cancer patients for bone loss, advising them on the importance of calcium and vitamin D supplementation and bone-healthy lifestyle measures, and the early use of the clearly less potent oral bisphosphonates in women who show cancer treatment-related decline in BMD.

SAN ANTONIO — Zoledronic acid prevents the profound loss in bone mineral density that often occurs with combined adjuvant endocrine therapy in premenopausal breast cancer patients, Michael Gnant, M.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

Based on new data from the Austrian Breast and Colorectal Cancer Study Group Trial 12 (ABCSG-12), all premenopausal breast cancer patients receiving combination adjuvant therapy with a luteinizing hormone-releasing hormone analogue, such as goserelin, plus either tamoxifen or an aromatase inhibitor, should undergo annual bone mineral density (BMD) testing. Those showing a treatment-related decline should be considered for intravenous zoledronic acid (Zometa) administered once every 6 months, said Dr. Gnant, professor of surgery at the University of Vienna.

In clinical practice, the aromatase inhibitors increasingly are replacing tamoxifen because they provide a greater reduction in recurrence and less risk of endometrial cancer and thromboembolic events. The price has been the greater risk of osteoporosis and fractures associated with aromatase inhibitor use. But prophylactic zoledronic acid appears to erase that downside.

Although it is widely appreciated that postmenopausal breast cancer patients face increased risk of accelerated bone loss, the osseous impact of cancer therapies in premenopausal breast cancer patients was much less clear before ABCSG-12. The primary end point in the 1,315-patient phase III Austrian study will be relapse-free survival, which awaits longer follow-up.

In San Antonio, Dr. Gnant reported on a secondary study end point—change in BMD—in a 401-patient subset.

The ABCSG-12 trial is a four-part study that randomized patients to 3 years of adjuvant goserelin plus either tamoxifen or anastrozole, with or without 3 years of zoledronic acid given at 4 mg IV every 6 months.

After 3 years of goserelin and tamoxifen without zoledronic acid, BMD at the lumbar spine fell an average of 11.6%, compared with baseline. In patients receiving goserelin plus anastrozole but not zoledronic acid, it fell 17.4%. However, patients on either combination who received the potent intravenous bisphosphonate had no significant change in BMD, he said.

In a separate study, Adam Brufsky, M.D., presented preliminary 6-month results from Z-FAST, a 5-year multicenter U.S. trial in which 415 postmenopausal women with early-stage hormone receptor-positive breast cancer receiving adjuvant letrozole (Femara) were randomized to zoledronic acid administered every 6 months either up front or beginning 1 year after the start of the aromatase inhibitor.

BMD at the lumbar spine and hip increased in patients who got zoledronic acid up front and decreased in those assigned to delayed bisphosphonate therapy. Biochemical markers of bone turnover decreased from baseline to 6 months in the up-front zoledronic acid group, while increasing or remaining unchanged in the delayed-treatment arm.

These early findings suggest administration of zoledronic acid from the onset of adjuvant aromatase inhibitor therapy may prevent cancer therapy-induced bone loss in postmenopausal women. However, longer-term follow-up is needed to fully define the effects of zoledronic acid in this population. The Novartis-sponsored Z-FAST trial is scheduled for 5 years of follow-up, said Dr. Brufsky of the University of Pittsburgh. Zoledronic acid is more expensive than pamidronate (Aredia), the other intravenous bisphosphonate, but its infusion time is only 15 minutes, compared with 2 hours or more for pamidronate, and there are some data to suggest zoledronic acid is more effective.

Zoledronic acid does not yet have an indication from the Food and Drug Administration for use in the setting of adjuvant breast cancer therapy, however, many oncologists will continue to follow the American Society of Clinical Oncology's recent guidelines. Those call for increased diligence in screening breast cancer patients for bone loss, advising them on the importance of calcium and vitamin D supplementation and bone-healthy lifestyle measures, and the early use of the clearly less potent oral bisphosphonates in women who show cancer treatment-related decline in BMD.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health-sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users. The increased fracture risk associated with AED use had previously been appreciated, but prior to SOF there was no persuasive evidence that accelerated bone loss played a prominent role. Many people had attributed the increased fracture rate to other causes, such as more frequent falls due to dizziness as an AED side effect, or to the seizure disorder itself.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health-sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users. The increased fracture risk associated with AED use had previously been appreciated, but prior to SOF there was no persuasive evidence that accelerated bone loss played a prominent role. Many people had attributed the increased fracture rate to other causes, such as more frequent falls due to dizziness as an AED side effect, or to the seizure disorder itself.

BRECKENRIDGE, COLO. — Antiepileptic drug usage by older women sharply increases their rate of bone mineral loss, with phenytoin being a particular offender, according to recent data from a landmark American study.

This is a disturbing finding in light of the fact that phenytoin remains the most frequently prescribed antiepileptic drug (AED) in this country, including among older patients, Jose F. Cavazos, M.D., said at a conference on epilepsy syndromes sponsored by the University of Texas at San Antonio.

“If you start a 70-year-old woman on phenytoin and her life expectancy is 15 years, you're going to considerably increase her likelihood of having a hip fracture, compared with women using other anticonvulsants,” added Dr. Cavazos of the university's South Texas Comprehensive Epilepsy Center.

Dr. Cavazos noted that a fuller understanding of the scope of the fracture risk associated with specific AEDs was recently provided by an enormous population-based case-control study led by Peter Vestergaard, M.D., of Aarhus (Denmark) University. The investigators compared rates of AED use in 124,655 patients with any fracture and 373,962 controls.

In an unadjusted analysis, all AEDs—both traditional and newer ones—were associated with increased risk of fracture. However, after adjustment for history of corticosteroid use, prior fractures, diagnosis of epilepsy, comorbid conditions, and other potential confounders, the list of AEDs associated with a significantly increased fracture risk was narrowed to phenobarbital, with a 79% increased risk; clonazepam, 27%; carbamazepine, 18%; valproate, 15%; and oxcarbazepine, 14%.

While phenytoin and topiramate were associated with increased fracture rates of 20% and 39%, these didn't reach significance (Epilepsia 2004;45:1330-7).

The most encouraging finding in this impressive study, according to Dr. Cavazos, was that several newer AEDs emerged as being very unlikely to increase fracture risk. These included tiagabine, with an associated 25% reduced risk of any fracture, compared with non-AED users; vigabatrin, with a 7% decreased risk; and lamotrigine, with a nonsignificant 4% increased risk.

In discussing the overall osteoporosis risk in older women associated with AED use, Dr. Cavazos cited data from the Study of Osteoporotic Fractures (SOF), a National Institutes of Health-sponsored prospective study involving 9,704 elderly community-dwelling women.

In a recent secondary analysis of SOF data, Kristine E. Ensrud, M.D., of the University of Minnesota, Minneapolis, and her associates classified the women either as continuous users of AEDs during the study period, intermittent users, or nonusers. Serial measurements showed an adjusted average annual rate of decline in total hip bone mineral density of 0.70% in the nonusers, 0.87% in intermittent users, and 1.16% in continuous AED users.

The same highly significant pattern of increased bone loss with continuous use of AEDs was repeated at the calcaneus.

Extrapolating from the bone mineral density findings, Dr. Ensrud and her colleagues estimated that without intervention, continuous use of AEDs by women aged 65 years and older would increase their risk of hip fracture by 29% over 5 years (Neurology 2004;62:2051-7).

The SOF analysis also demonstrated that continuous use of phenytoin was associated with an adjusted 1.8-fold greater rate of bone loss at the calcaneus and a 1.7-fold greater bone loss at the hip, compared with non-AED users. The increased fracture risk associated with AED use had previously been appreciated, but prior to SOF there was no persuasive evidence that accelerated bone loss played a prominent role. Many people had attributed the increased fracture rate to other causes, such as more frequent falls due to dizziness as an AED side effect, or to the seizure disorder itself.

SAN ANTONIO — Inadequate calcium and vitamin D intake—and outright deficiencies—are even more common among breast cancer patients than in the general population, according to studies presented at the annual breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This is particularly unwelcome because women with a history of breast cancer are at elevated risk for skeletal problems due to treatments that induce early menopause. The breast cancer population is also seeing rapidly rising adjuvant use of aromatase inhibitors, a class of drugs that can accelerate bone mineral loss.

Rachel S. Zinaman, a dietitian at Memorial Sloan-Kettering Cancer Center, New York City, noted that 2003 American Society of Clinical Oncology guidelines call for physicians to make screening for and treatment of osteoporosis in breast cancer patients a greater priority. She said it's time for physicians to step up and implement programs to increase breast cancer patients' awareness of the importance of calcium and vitamin D to bone health.

The increased vulnerability of breast cancer patients to calcium and vitamin D deficiencies was underscored by her retrospective chart review of 100 consecutive patients with early-stage breast cancer. The most disturbing finding was that only 10% of the women consumed the recommended daily minimum of 1,000 mg of calcium and 400 U of vitamin D. Indeed, 63% of the women had no significant dietary calcium intake at all, according to Ms. Zinaman.

That's even worse than in the United States at large. A National Institutes of Health consensus conference has concluded that 50%–60% of the older general population meets the established recommended daily intakes of calcium and vitamin D.

In a separate presentation, Marie E. Taylor, M.D., reported finding vitamin D deficiency in fully two-thirds of 233 patients with a current or past diagnosis of breast cancer who presented with a complaint of moderate to severe generalized musculoskeletal discomfort and stiffness with or without localized musculoskeletal symptoms.

The prevalence of vitamin D deficiency as defined by a serum 25-OH vitamin D level below 30 ng/mL varied by race. It was 57% among 162 white patients—but 91% among African Americans, said Dr. Taylor of Washington University, St. Louis.

A total of 65% of the women were hyperparathyroid as defined by a parathyroid hormone level in excess of 72 pg/mL.

Dr. Taylor speculated that the use of aromatase inhibitors may enhance vitamin D requirements and exacerbate a background vitamin D deficiency, resulting in the clinical symptoms of osteomalacia. She and her coinvestigators have prescribed vitamin D for the deficient women in her study cohort and are now following them to see if this leads to symptomatic improvement and better tolerance of adjuvant therapy.

The vitamin D replacement regimen they are using consists of 50,000 U of 25-OH vitamin D once weekly for 8–12 weeks, then cutting back to once every 2 weeks as maintenance therapy. This is coupled with the standard dietary recommendations for calcium and vitamin D intake via food sources and over-the-counter supplements.

SAN ANTONIO — Inadequate calcium and vitamin D intake—and outright deficiencies—are even more common among breast cancer patients than in the general population, according to studies presented at the annual breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This is particularly unwelcome because women with a history of breast cancer are at elevated risk for skeletal problems due to treatments that induce early menopause. The breast cancer population is also seeing rapidly rising adjuvant use of aromatase inhibitors, a class of drugs that can accelerate bone mineral loss.

Rachel S. Zinaman, a dietitian at Memorial Sloan-Kettering Cancer Center, New York City, noted that 2003 American Society of Clinical Oncology guidelines call for physicians to make screening for and treatment of osteoporosis in breast cancer patients a greater priority. She said it's time for physicians to step up and implement programs to increase breast cancer patients' awareness of the importance of calcium and vitamin D to bone health.

The increased vulnerability of breast cancer patients to calcium and vitamin D deficiencies was underscored by her retrospective chart review of 100 consecutive patients with early-stage breast cancer. The most disturbing finding was that only 10% of the women consumed the recommended daily minimum of 1,000 mg of calcium and 400 U of vitamin D. Indeed, 63% of the women had no significant dietary calcium intake at all, according to Ms. Zinaman.

That's even worse than in the United States at large. A National Institutes of Health consensus conference has concluded that 50%–60% of the older general population meets the established recommended daily intakes of calcium and vitamin D.

In a separate presentation, Marie E. Taylor, M.D., reported finding vitamin D deficiency in fully two-thirds of 233 patients with a current or past diagnosis of breast cancer who presented with a complaint of moderate to severe generalized musculoskeletal discomfort and stiffness with or without localized musculoskeletal symptoms.

The prevalence of vitamin D deficiency as defined by a serum 25-OH vitamin D level below 30 ng/mL varied by race. It was 57% among 162 white patients—but 91% among African Americans, said Dr. Taylor of Washington University, St. Louis.

A total of 65% of the women were hyperparathyroid as defined by a parathyroid hormone level in excess of 72 pg/mL.

Dr. Taylor speculated that the use of aromatase inhibitors may enhance vitamin D requirements and exacerbate a background vitamin D deficiency, resulting in the clinical symptoms of osteomalacia. She and her coinvestigators have prescribed vitamin D for the deficient women in her study cohort and are now following them to see if this leads to symptomatic improvement and better tolerance of adjuvant therapy.

The vitamin D replacement regimen they are using consists of 50,000 U of 25-OH vitamin D once weekly for 8–12 weeks, then cutting back to once every 2 weeks as maintenance therapy. This is coupled with the standard dietary recommendations for calcium and vitamin D intake via food sources and over-the-counter supplements.

SAN ANTONIO — Inadequate calcium and vitamin D intake—and outright deficiencies—are even more common among breast cancer patients than in the general population, according to studies presented at the annual breast cancer symposium sponsored by the Cancer Therapy and Research Center.

This is particularly unwelcome because women with a history of breast cancer are at elevated risk for skeletal problems due to treatments that induce early menopause. The breast cancer population is also seeing rapidly rising adjuvant use of aromatase inhibitors, a class of drugs that can accelerate bone mineral loss.

Rachel S. Zinaman, a dietitian at Memorial Sloan-Kettering Cancer Center, New York City, noted that 2003 American Society of Clinical Oncology guidelines call for physicians to make screening for and treatment of osteoporosis in breast cancer patients a greater priority. She said it's time for physicians to step up and implement programs to increase breast cancer patients' awareness of the importance of calcium and vitamin D to bone health.

The increased vulnerability of breast cancer patients to calcium and vitamin D deficiencies was underscored by her retrospective chart review of 100 consecutive patients with early-stage breast cancer. The most disturbing finding was that only 10% of the women consumed the recommended daily minimum of 1,000 mg of calcium and 400 U of vitamin D. Indeed, 63% of the women had no significant dietary calcium intake at all, according to Ms. Zinaman.

That's even worse than in the United States at large. A National Institutes of Health consensus conference has concluded that 50%–60% of the older general population meets the established recommended daily intakes of calcium and vitamin D.

In a separate presentation, Marie E. Taylor, M.D., reported finding vitamin D deficiency in fully two-thirds of 233 patients with a current or past diagnosis of breast cancer who presented with a complaint of moderate to severe generalized musculoskeletal discomfort and stiffness with or without localized musculoskeletal symptoms.

The prevalence of vitamin D deficiency as defined by a serum 25-OH vitamin D level below 30 ng/mL varied by race. It was 57% among 162 white patients—but 91% among African Americans, said Dr. Taylor of Washington University, St. Louis.

A total of 65% of the women were hyperparathyroid as defined by a parathyroid hormone level in excess of 72 pg/mL.

Dr. Taylor speculated that the use of aromatase inhibitors may enhance vitamin D requirements and exacerbate a background vitamin D deficiency, resulting in the clinical symptoms of osteomalacia. She and her coinvestigators have prescribed vitamin D for the deficient women in her study cohort and are now following them to see if this leads to symptomatic improvement and better tolerance of adjuvant therapy.

The vitamin D replacement regimen they are using consists of 50,000 U of 25-OH vitamin D once weekly for 8–12 weeks, then cutting back to once every 2 weeks as maintenance therapy. This is coupled with the standard dietary recommendations for calcium and vitamin D intake via food sources and over-the-counter supplements.

SAN ANTONIO — Raloxifene continued to markedly reduce breast cancer incidence in postmenopausal osteoporotic women over the course of 8 years in an extension of the landmark Multiple Outcomes of Raloxifene Evaluation trial, according to Silvana Martino, D.O., of the John Wayne Cancer Institute, Santa Monica, Calif.

An attempt to learn in the extended MORE study whether a single baseline serum estradiol measurement might identify subgroups of osteoporotic women who are particularly likely or unlikely to benefit from long-term raloxifene in terms of breast cancer risk reduction proved largely unsuccessful. The magnitude of reduction in invasive breast cancer with raloxifene turned out to be independent of estradiol level, although the absolute benefit was greater in women with a level of at least 5 pmol/L, Dr. Martino said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

MORE was a 4-year randomized double-blind trial in roughly 7,700 women that led to marketing approval of raloxifene (Evista), which is a selective estrogen-receptor modifier (SERM) for prevention and treatment of postmenopausal osteoporosis. Among the predefined secondary end points in MORE was the incidence of invasive breast cancer, which was 72% less with raloxifene, compared with placebo.

Because breast cancer incidence was merely a secondary end point in MORE, however, an extension trial—the Continuing Outcomes Relevant to Evista (CORE) study—was undertaken to evaluate the safety and efficacy of an additional 4 years of raloxifene use, this time with invasive breast cancer prevention as the primary outcome measure. A total of 3,510 postmenopausal osteoporotic women randomized to raloxifene in MORE were assigned to an additional 4 years of the SERM at 60 mg per day. In addition, 1,703 women from the MORE placebo arm continued on placebo.

MORE and CORE were sponsored by Eli Lilly & Co. Dr. Martino serves as a consultant to the company.

During the 4 years of the extended trial, the incidence of invasive breast cancer was reduced 59% in the raloxifene group, compared with the placebo group. Estrogen receptor-positive invasive breast cancer was reduced 66% with raloxifene as well. Thus, the magnitude of risk reduction during the second 4 years of raloxifene therapy was similar to that noted during the initial 4 years.

This is significant because raloxifene for osteoporosis is essentially lifelong therapy. Moreover, the maximal recommended duration for the use of tamoxifen to reduce the incidence of breast cancer in high-risk women is 5 years.

During the 8 years of the combined MORE and CORE studies, the incidence of invasive breast cancer was reduced 66% with raloxifene, compared with placebo, while the rate of estrogen receptor-positive invasive breast cancer was 76% less in the raloxifene arm than the placebo arm.

There was no difference between the two study arms in the incidence of estrogen receptor-negative invasive breast cancer or noninvasive breast cancer in CORE, nor in the full 8-year combined experience, Dr. Martino continued.

In CORE, the incidence of thromboembolism in raloxifene-treated women was 2.9 events per 1,000 woman-years, two times greater than with placebo. The rates in MORE were similar to those in CORE. No new safety concerns emerged with the use of raloxifene during years 4–8 of treatment, she said.

The baseline serum estradiol data suggested the existence of a threshold effect, with women having an estradiol of at least 5 pmol/L—half of all study participants—deriving greater benefit in terms of reduction in invasive breast cancer.

Audience members noted that CORE didn't address the issue of whether raloxifene is beneficial for prevention of breast cancer in at-risk women who don't have osteoporosis.

SAN ANTONIO — Raloxifene continued to markedly reduce breast cancer incidence in postmenopausal osteoporotic women over the course of 8 years in an extension of the landmark Multiple Outcomes of Raloxifene Evaluation trial, according to Silvana Martino, D.O., of the John Wayne Cancer Institute, Santa Monica, Calif.

An attempt to learn in the extended MORE study whether a single baseline serum estradiol measurement might identify subgroups of osteoporotic women who are particularly likely or unlikely to benefit from long-term raloxifene in terms of breast cancer risk reduction proved largely unsuccessful. The magnitude of reduction in invasive breast cancer with raloxifene turned out to be independent of estradiol level, although the absolute benefit was greater in women with a level of at least 5 pmol/L, Dr. Martino said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

MORE was a 4-year randomized double-blind trial in roughly 7,700 women that led to marketing approval of raloxifene (Evista), which is a selective estrogen-receptor modifier (SERM) for prevention and treatment of postmenopausal osteoporosis. Among the predefined secondary end points in MORE was the incidence of invasive breast cancer, which was 72% less with raloxifene, compared with placebo.

Because breast cancer incidence was merely a secondary end point in MORE, however, an extension trial—the Continuing Outcomes Relevant to Evista (CORE) study—was undertaken to evaluate the safety and efficacy of an additional 4 years of raloxifene use, this time with invasive breast cancer prevention as the primary outcome measure. A total of 3,510 postmenopausal osteoporotic women randomized to raloxifene in MORE were assigned to an additional 4 years of the SERM at 60 mg per day. In addition, 1,703 women from the MORE placebo arm continued on placebo.

MORE and CORE were sponsored by Eli Lilly & Co. Dr. Martino serves as a consultant to the company.

During the 4 years of the extended trial, the incidence of invasive breast cancer was reduced 59% in the raloxifene group, compared with the placebo group. Estrogen receptor-positive invasive breast cancer was reduced 66% with raloxifene as well. Thus, the magnitude of risk reduction during the second 4 years of raloxifene therapy was similar to that noted during the initial 4 years.

This is significant because raloxifene for osteoporosis is essentially lifelong therapy. Moreover, the maximal recommended duration for the use of tamoxifen to reduce the incidence of breast cancer in high-risk women is 5 years.

During the 8 years of the combined MORE and CORE studies, the incidence of invasive breast cancer was reduced 66% with raloxifene, compared with placebo, while the rate of estrogen receptor-positive invasive breast cancer was 76% less in the raloxifene arm than the placebo arm.

There was no difference between the two study arms in the incidence of estrogen receptor-negative invasive breast cancer or noninvasive breast cancer in CORE, nor in the full 8-year combined experience, Dr. Martino continued.

In CORE, the incidence of thromboembolism in raloxifene-treated women was 2.9 events per 1,000 woman-years, two times greater than with placebo. The rates in MORE were similar to those in CORE. No new safety concerns emerged with the use of raloxifene during years 4–8 of treatment, she said.

The baseline serum estradiol data suggested the existence of a threshold effect, with women having an estradiol of at least 5 pmol/L—half of all study participants—deriving greater benefit in terms of reduction in invasive breast cancer.

Audience members noted that CORE didn't address the issue of whether raloxifene is beneficial for prevention of breast cancer in at-risk women who don't have osteoporosis.

SAN ANTONIO — Raloxifene continued to markedly reduce breast cancer incidence in postmenopausal osteoporotic women over the course of 8 years in an extension of the landmark Multiple Outcomes of Raloxifene Evaluation trial, according to Silvana Martino, D.O., of the John Wayne Cancer Institute, Santa Monica, Calif.

An attempt to learn in the extended MORE study whether a single baseline serum estradiol measurement might identify subgroups of osteoporotic women who are particularly likely or unlikely to benefit from long-term raloxifene in terms of breast cancer risk reduction proved largely unsuccessful. The magnitude of reduction in invasive breast cancer with raloxifene turned out to be independent of estradiol level, although the absolute benefit was greater in women with a level of at least 5 pmol/L, Dr. Martino said at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.

MORE was a 4-year randomized double-blind trial in roughly 7,700 women that led to marketing approval of raloxifene (Evista), which is a selective estrogen-receptor modifier (SERM) for prevention and treatment of postmenopausal osteoporosis. Among the predefined secondary end points in MORE was the incidence of invasive breast cancer, which was 72% less with raloxifene, compared with placebo.

Because breast cancer incidence was merely a secondary end point in MORE, however, an extension trial—the Continuing Outcomes Relevant to Evista (CORE) study—was undertaken to evaluate the safety and efficacy of an additional 4 years of raloxifene use, this time with invasive breast cancer prevention as the primary outcome measure. A total of 3,510 postmenopausal osteoporotic women randomized to raloxifene in MORE were assigned to an additional 4 years of the SERM at 60 mg per day. In addition, 1,703 women from the MORE placebo arm continued on placebo.

MORE and CORE were sponsored by Eli Lilly & Co. Dr. Martino serves as a consultant to the company.

During the 4 years of the extended trial, the incidence of invasive breast cancer was reduced 59% in the raloxifene group, compared with the placebo group. Estrogen receptor-positive invasive breast cancer was reduced 66% with raloxifene as well. Thus, the magnitude of risk reduction during the second 4 years of raloxifene therapy was similar to that noted during the initial 4 years.

This is significant because raloxifene for osteoporosis is essentially lifelong therapy. Moreover, the maximal recommended duration for the use of tamoxifen to reduce the incidence of breast cancer in high-risk women is 5 years.

During the 8 years of the combined MORE and CORE studies, the incidence of invasive breast cancer was reduced 66% with raloxifene, compared with placebo, while the rate of estrogen receptor-positive invasive breast cancer was 76% less in the raloxifene arm than the placebo arm.

There was no difference between the two study arms in the incidence of estrogen receptor-negative invasive breast cancer or noninvasive breast cancer in CORE, nor in the full 8-year combined experience, Dr. Martino continued.

In CORE, the incidence of thromboembolism in raloxifene-treated women was 2.9 events per 1,000 woman-years, two times greater than with placebo. The rates in MORE were similar to those in CORE. No new safety concerns emerged with the use of raloxifene during years 4–8 of treatment, she said.

The baseline serum estradiol data suggested the existence of a threshold effect, with women having an estradiol of at least 5 pmol/L—half of all study participants—deriving greater benefit in terms of reduction in invasive breast cancer.

Audience members noted that CORE didn't address the issue of whether raloxifene is beneficial for prevention of breast cancer in at-risk women who don't have osteoporosis.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Targeted use of bone densitometry in premenopausal women can identify a significant number of patients who would benefit from bone protection, a study has shown.

Of 301 premenopausal women referred to London's Queen Elizabeth Hospital during a 4-year period for dual energy x-ray absorptiometry (DXA) because of possible increased risk of osteoporosis, 41% had abnormal scans, reported said Elizabeth Koshy, M.D., in a presentation at the annual conference of the National Osteoporosis Society.

Premature menopause accounted for 43 (14%) of the patients referred for DXA. Of these, 37% had abnormal scans.

Steroid use accounted for 19% of the referrals, of which 47% of the scans were abnormal. Of the approximately 14% of referrals based on family history, 27% resulted in abnormal scan. Osteopenia or previous fracture was the primary or coexisting indication for 37 or 12% of the patients, and among these, 54% were abnormal. Amenorrhea was the impetus for 11 (3.7%) of the scans, and 64% of these were abnormal, reported Dr. Koshy of Imperial College London.

The medical conditions associated with the highest proportion of abnormal scans were anorexia nervosa (57%) and inflammatory bowel disease (52%), Dr. Koshy noted.

A logistic regression analysis identified low calcium/vitamin D intake, a body mass index of less than 20 kg/m

In most premenopausal women, it may be that the best treatment option remains supplementation with calcium and Vitamin D, Dr. Koshy stated. However, “selective DXA does seem to identify a significant number who could benefit from additional intervention.”

While much attention in recent years has been focused on the importance of routine bone density testing for postmenopausal women, the findings of this study add weight to the argument that younger women who have significant risk factors should be tested as well, “ideally at peak bone mass [between ages 21 and 35],” said Dr. Koshy.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

Approximately half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention. The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures.

The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82, according to the study findings.

These results are disappointing, noted Ms. Porthouse.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she noted.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

Approximately half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention. The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures.

The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82, according to the study findings.

These results are disappointing, noted Ms. Porthouse.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she noted.

HARROGATE, ENGLAND — Calcium and vitamin D supplementation do not reduce the risk of clinical fracture among women identified as having one or more risk factors for hip fracture, a randomized controlled trial has shown.

Investigators at the University of York (England), in collaboration with community primary care providers, recruited 3,322 women aged 70 years and older, who had at least one of the following risk factors for hip fracture: previous fracture, low body weight, maternal history of hip fracture, a fall in the previous 12 months, or older age (per year increase).

Approximately half of the women were randomized to receive daily oral supplementation of 1,000 mg of calcium and 800 IU vitamin D, along with a patient information leaflet on dietary calcium intake and fall prevention. The remaining patients were randomized to a control group and received only the patient information leaflet, reported York University research fellow Jill Porthouse in a presentation at the annual conference of the National Osteoporosis Society.

After a median follow-up of 25 months, there were no significant differences between the two groups in the rates of all clinical fractures or hip fractures.

The odds ratio for all fractures in the supplement group compared with the control group was 1.03. For hip fractures specifically, the odds ratio was 0.82, according to the study findings.

These results are disappointing, noted Ms. Porthouse.

“Fall-related low-trauma fractures represent a significant burden of illness in older people. Calcium and vitamin D supplementation is a relatively inexpensive intervention, but it does not appear to reduce fracture rates in women at risk,” she noted.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

In patients with rheumatoid arthritis, methotrexate significantly reduces abnormally elevated levels of plasmatic sRANKL, the main cytokine involved in inducing osteoporosis and bone erosions, Doina Baltaru, M.D., reported at the 4th International Congress on Autoimmunity.

Soluble RANKL (receptor activator of nuclear factor-kappa B ligand) is a member of the tumor necrosis factor cytokines and plays a major role in the regulation of bone remodeling, specifically in the stimulation of osteoclast formation, said Dr. Baltaru, of the Emergency Military Hospital in Cluj-Napoca, Romania.

Dr. Baltaru and her colleagues evaluated plasma sRANKL levels of 15 patients with rheumatoid arthritis, who had never received corticosteroids or disease-modifying antirheumatic drugs.

The study participants were assessed before and after 3 months of methotrexate therapy (15 mg/week). sRANKL levels were also evaluated in 7 healthy controls and 10 patients with type I osteoporosis.

Plasma sRANKL values were determined by quantitative enzyme-linked immunosorbent assay. At baseline, the median sRANKL value for RA patients was 467 pg/mL, though there was a wide variation (70-1,500 pg/mL). Levels ranged between 10-30 pg/mL for normal subjects and 20-200 pg/mL in patients with osteoporosis.

Methotrexate therapy significantly reduced plasma sRANKL levels in the rheumatoid arthritis patients, to a median value of 185 pg/mL.

HARROGATE, ENGLAND — A single injection of zoledronic acid can help counteract the loss of bone mass associated with acute stroke and reduce the likelihood of osteoporotic fractures if given soon after the event, a study has shown.

Patients injected with the long-acting, highly potent bisphosphonate within 35 days after suffering a stroke lost significantly less hip bone mineral density than matched control patients who received a placebo, reported Kenneth Poole, B.M., in a presentation at the annual conference of the National Osteoporosis Society.

The findings suggest that taking measures to prevent bone loss as a routine part of stroke management could significantly reduce the high rate of hip fractures among stroke survivors, Dr. Poole said.

“We know that osteoporosis is a significant complication of stroke, particularly when patients become fully or partly immobilized,” said Dr. Poole. “When someone is put to bed and has an immobilized limb, the cells that break down bone are overactive.” The risks are exacerbated by stroke-related lower-limb and vision problems, which lead to more falls and fractures.

Previous studies have shown that stroke survivors are more than four times as likely to suffer hip fractures than individuals in an age-matched reference population.

Most victims of stroke are already at risk for osteoporosis because of their age—more than half of all strokes occur in people older than 70—thus “they can ill afford to lose further bone, said Dr. Poole, who conducted the study with colleagues from the University of Cambridge, England.

The investigators randomly assigned 16 patients to receive 4 mg of zoledronic acid (Zometa) or placebo by intravenous injection within 35 days of acute stroke. All patients also received daily oral calcium and vitamin D supplementation. Bone mineral density (BMD) measurements were obtained in the hemiplegic and unaffected total hip region of all participants at baseline and at months 6 and 12.

At 1 year, patients in the placebo group had a significantly greater reduction of BMD in both hips, compared with those in the zoledronic acid group. The mean percentage decrease in BMD at the hemiplegic and unaffected hips, respectively, of the control patients was 10.2% and 6.0%. By contrast, the patients treated with zoledronic acid group had no decrease in BMD at either site. Zoledronic acid was well tolerated and associated with no serious adverse events. Dr. Poole reported no financial interests relating to zoledronic acid or its manufacturer, Novartis.

HARROGATE, ENGLAND — A single injection of zoledronic acid can help counteract the loss of bone mass associated with acute stroke and reduce the likelihood of osteoporotic fractures if given soon after the event, a study has shown.

Patients injected with the long-acting, highly potent bisphosphonate within 35 days after suffering a stroke lost significantly less hip bone mineral density than matched control patients who received a placebo, reported Kenneth Poole, B.M., in a presentation at the annual conference of the National Osteoporosis Society.

The findings suggest that taking measures to prevent bone loss as a routine part of stroke management could significantly reduce the high rate of hip fractures among stroke survivors, Dr. Poole said.

“We know that osteoporosis is a significant complication of stroke, particularly when patients become fully or partly immobilized,” said Dr. Poole. “When someone is put to bed and has an immobilized limb, the cells that break down bone are overactive.” The risks are exacerbated by stroke-related lower-limb and vision problems, which lead to more falls and fractures.

Previous studies have shown that stroke survivors are more than four times as likely to suffer hip fractures than individuals in an age-matched reference population.

Most victims of stroke are already at risk for osteoporosis because of their age—more than half of all strokes occur in people older than 70—thus “they can ill afford to lose further bone, said Dr. Poole, who conducted the study with colleagues from the University of Cambridge, England.

The investigators randomly assigned 16 patients to receive 4 mg of zoledronic acid (Zometa) or placebo by intravenous injection within 35 days of acute stroke. All patients also received daily oral calcium and vitamin D supplementation. Bone mineral density (BMD) measurements were obtained in the hemiplegic and unaffected total hip region of all participants at baseline and at months 6 and 12.

At 1 year, patients in the placebo group had a significantly greater reduction of BMD in both hips, compared with those in the zoledronic acid group. The mean percentage decrease in BMD at the hemiplegic and unaffected hips, respectively, of the control patients was 10.2% and 6.0%. By contrast, the patients treated with zoledronic acid group had no decrease in BMD at either site. Zoledronic acid was well tolerated and associated with no serious adverse events. Dr. Poole reported no financial interests relating to zoledronic acid or its manufacturer, Novartis.

HARROGATE, ENGLAND — A single injection of zoledronic acid can help counteract the loss of bone mass associated with acute stroke and reduce the likelihood of osteoporotic fractures if given soon after the event, a study has shown.

Patients injected with the long-acting, highly potent bisphosphonate within 35 days after suffering a stroke lost significantly less hip bone mineral density than matched control patients who received a placebo, reported Kenneth Poole, B.M., in a presentation at the annual conference of the National Osteoporosis Society.

The findings suggest that taking measures to prevent bone loss as a routine part of stroke management could significantly reduce the high rate of hip fractures among stroke survivors, Dr. Poole said.

“We know that osteoporosis is a significant complication of stroke, particularly when patients become fully or partly immobilized,” said Dr. Poole. “When someone is put to bed and has an immobilized limb, the cells that break down bone are overactive.” The risks are exacerbated by stroke-related lower-limb and vision problems, which lead to more falls and fractures.

Previous studies have shown that stroke survivors are more than four times as likely to suffer hip fractures than individuals in an age-matched reference population.

Most victims of stroke are already at risk for osteoporosis because of their age—more than half of all strokes occur in people older than 70—thus “they can ill afford to lose further bone, said Dr. Poole, who conducted the study with colleagues from the University of Cambridge, England.

The investigators randomly assigned 16 patients to receive 4 mg of zoledronic acid (Zometa) or placebo by intravenous injection within 35 days of acute stroke. All patients also received daily oral calcium and vitamin D supplementation. Bone mineral density (BMD) measurements were obtained in the hemiplegic and unaffected total hip region of all participants at baseline and at months 6 and 12.

At 1 year, patients in the placebo group had a significantly greater reduction of BMD in both hips, compared with those in the zoledronic acid group. The mean percentage decrease in BMD at the hemiplegic and unaffected hips, respectively, of the control patients was 10.2% and 6.0%. By contrast, the patients treated with zoledronic acid group had no decrease in BMD at either site. Zoledronic acid was well tolerated and associated with no serious adverse events. Dr. Poole reported no financial interests relating to zoledronic acid or its manufacturer, Novartis.

HARROGATE, ENGLAND — Low serum albumin and T3 levels are independently predictive of vertebral fractures in women older than 50 years, a 10-year prospective study has shown.

Because albumin and T3 deficiencies are considered markers of frailty and sickness, the findings suggest that chronic poor health may itself be a risk factor for vertebral fracture, said Judith Finigan, principal investigator and research nurse in the bone metabolism group at the University of Sheffield (England).

To identify predictors of fracture in women between ages 50 and 85, the Sheffield investigators acquired baseline bone mineral density (BMD) measures and medical and lifestyle information from a population-based group of 375 women. They also collected fasting blood samples for measuring serum calcium, alkaline phosphatase, parathyroid hormone, creatinine, phosphate, albumin, and thyroid hormones.

All participants had spinal radiographs taken at baseline and at years 2, 5, 7, and 10, which were reviewed for incident vertebral fractures by a single radiologist. Nonvertebral fractures were confirmed by radiologist reports.

Cox regression analysis showed that numerous risk factors—including age; BMD at the lumbar spine, hip, or total body; years of estrogen exposure; and prevalent vertebral fracture—predicted fractures overall.

Low serum T3, low serum albumin, and low body fat were specifically predictive of vertebral fractures but not nonvertebral fractures. These measures remained significantly predictive, even after adjusting for age, Ms. Finigan reported at the annual conference of the National Osteoporosis Society. Neither TSH nor T4 predicted fracture, she noted.

The age-adjusted relative risks per standard deviation decrease for T3, albumin, and body fat were 1.71, 1.74, and 1.55, respectively. “T3 and albumin also predicted vertebral fracture independently of spine or hip BMD,” said Ms. Finigan.

In a separate analysis of a larger cohort, the investigators examined the relationship between serum albumin and vertebral fractures in postmenopausal women from the placebo arms of the Hip Intervention Program (HIP) trial and the Vertebral Efficacy with Risedronate Therapy (VERT) trial.

At 3 years, 381 of 2,720 subjects had experienced one or more incident vertebral fractures. A multiple stepwise logistic regression analysis showed a 1.23 relative risk of vertebral fracture for each standard deviation decrease in serum albumin, after adjusting for femoral neck BMD, weight, and age.

As in the smaller study, low serum albumin was not associated with an increased risk of incident nonvertebral fractures in the larger population.

The findings of the second analysis “confirm the association between low baseline albumin levels and incident vertebral fractures,” Ms. Finigan said.

Serum albumin and thyroid hormone measurements are recommended as part of a routine evaluation for osteoporosis in postmenopausal women. Patients with deficiencies in these may be candidates for antiresorptive treatment to reduce their risk of vertebral fractures, Ms. Finigan concluded.

HARROGATE, ENGLAND — Low serum albumin and T3 levels are independently predictive of vertebral fractures in women older than 50 years, a 10-year prospective study has shown.

Because albumin and T3 deficiencies are considered markers of frailty and sickness, the findings suggest that chronic poor health may itself be a risk factor for vertebral fracture, said Judith Finigan, principal investigator and research nurse in the bone metabolism group at the University of Sheffield (England).

To identify predictors of fracture in women between ages 50 and 85, the Sheffield investigators acquired baseline bone mineral density (BMD) measures and medical and lifestyle information from a population-based group of 375 women. They also collected fasting blood samples for measuring serum calcium, alkaline phosphatase, parathyroid hormone, creatinine, phosphate, albumin, and thyroid hormones.

All participants had spinal radiographs taken at baseline and at years 2, 5, 7, and 10, which were reviewed for incident vertebral fractures by a single radiologist. Nonvertebral fractures were confirmed by radiologist reports.

Cox regression analysis showed that numerous risk factors—including age; BMD at the lumbar spine, hip, or total body; years of estrogen exposure; and prevalent vertebral fracture—predicted fractures overall.

Low serum T3, low serum albumin, and low body fat were specifically predictive of vertebral fractures but not nonvertebral fractures. These measures remained significantly predictive, even after adjusting for age, Ms. Finigan reported at the annual conference of the National Osteoporosis Society. Neither TSH nor T4 predicted fracture, she noted.

The age-adjusted relative risks per standard deviation decrease for T3, albumin, and body fat were 1.71, 1.74, and 1.55, respectively. “T3 and albumin also predicted vertebral fracture independently of spine or hip BMD,” said Ms. Finigan.

In a separate analysis of a larger cohort, the investigators examined the relationship between serum albumin and vertebral fractures in postmenopausal women from the placebo arms of the Hip Intervention Program (HIP) trial and the Vertebral Efficacy with Risedronate Therapy (VERT) trial.

At 3 years, 381 of 2,720 subjects had experienced one or more incident vertebral fractures. A multiple stepwise logistic regression analysis showed a 1.23 relative risk of vertebral fracture for each standard deviation decrease in serum albumin, after adjusting for femoral neck BMD, weight, and age.

As in the smaller study, low serum albumin was not associated with an increased risk of incident nonvertebral fractures in the larger population.

The findings of the second analysis “confirm the association between low baseline albumin levels and incident vertebral fractures,” Ms. Finigan said.

Serum albumin and thyroid hormone measurements are recommended as part of a routine evaluation for osteoporosis in postmenopausal women. Patients with deficiencies in these may be candidates for antiresorptive treatment to reduce their risk of vertebral fractures, Ms. Finigan concluded.

HARROGATE, ENGLAND — Low serum albumin and T3 levels are independently predictive of vertebral fractures in women older than 50 years, a 10-year prospective study has shown.

Because albumin and T3 deficiencies are considered markers of frailty and sickness, the findings suggest that chronic poor health may itself be a risk factor for vertebral fracture, said Judith Finigan, principal investigator and research nurse in the bone metabolism group at the University of Sheffield (England).

To identify predictors of fracture in women between ages 50 and 85, the Sheffield investigators acquired baseline bone mineral density (BMD) measures and medical and lifestyle information from a population-based group of 375 women. They also collected fasting blood samples for measuring serum calcium, alkaline phosphatase, parathyroid hormone, creatinine, phosphate, albumin, and thyroid hormones.

All participants had spinal radiographs taken at baseline and at years 2, 5, 7, and 10, which were reviewed for incident vertebral fractures by a single radiologist. Nonvertebral fractures were confirmed by radiologist reports.

Cox regression analysis showed that numerous risk factors—including age; BMD at the lumbar spine, hip, or total body; years of estrogen exposure; and prevalent vertebral fracture—predicted fractures overall.

Low serum T3, low serum albumin, and low body fat were specifically predictive of vertebral fractures but not nonvertebral fractures. These measures remained significantly predictive, even after adjusting for age, Ms. Finigan reported at the annual conference of the National Osteoporosis Society. Neither TSH nor T4 predicted fracture, she noted.

The age-adjusted relative risks per standard deviation decrease for T3, albumin, and body fat were 1.71, 1.74, and 1.55, respectively. “T3 and albumin also predicted vertebral fracture independently of spine or hip BMD,” said Ms. Finigan.

In a separate analysis of a larger cohort, the investigators examined the relationship between serum albumin and vertebral fractures in postmenopausal women from the placebo arms of the Hip Intervention Program (HIP) trial and the Vertebral Efficacy with Risedronate Therapy (VERT) trial.

At 3 years, 381 of 2,720 subjects had experienced one or more incident vertebral fractures. A multiple stepwise logistic regression analysis showed a 1.23 relative risk of vertebral fracture for each standard deviation decrease in serum albumin, after adjusting for femoral neck BMD, weight, and age.

As in the smaller study, low serum albumin was not associated with an increased risk of incident nonvertebral fractures in the larger population.

The findings of the second analysis “confirm the association between low baseline albumin levels and incident vertebral fractures,” Ms. Finigan said.

Serum albumin and thyroid hormone measurements are recommended as part of a routine evaluation for osteoporosis in postmenopausal women. Patients with deficiencies in these may be candidates for antiresorptive treatment to reduce their risk of vertebral fractures, Ms. Finigan concluded.

SEATTLE — Calcium supplementation appears to reduce by 34% the 5-year risk of fracture in elderly women, according to a population-based study presented at the annual meeting of the American Society for Bone and Mineral Research.

The benefit was seen as early as 13 months, even though women were deemed at baseline to be getting adequate calcium—a mean of 960 mg/day, said Richard Prince, M.D., of Sir Charles Gairdner Hospital, Perth, Australia.

The 1,460 healthy ambulatory women, aged 70 or older, were randomly assigned to receive 600 mg calcium carbonate twice daily or placebo. Calcium intake was assessed and dual x-ray absorptiometry (DXA) scans were taken at baseline and again at least 1 year later. During the 5-year study, the rates of death, withdrawal, and treatment cessation were similar between the two groups. In all, 235 individuals sustained 296 fractures; 118 in those taking calcium and 178 in those taking placebo, for an overall 34% reduction in fractures in patients in the calcium group who stuck to the protocol for the entire study period.

Calcium appeared to improve bone mineral density at cortical bone sites, according to DXA findings. At 13 months, there were early indications of a reduction in fracture rates among patients in the calcium group.

SEATTLE — Calcium supplementation appears to reduce by 34% the 5-year risk of fracture in elderly women, according to a population-based study presented at the annual meeting of the American Society for Bone and Mineral Research.

The benefit was seen as early as 13 months, even though women were deemed at baseline to be getting adequate calcium—a mean of 960 mg/day, said Richard Prince, M.D., of Sir Charles Gairdner Hospital, Perth, Australia.

The 1,460 healthy ambulatory women, aged 70 or older, were randomly assigned to receive 600 mg calcium carbonate twice daily or placebo. Calcium intake was assessed and dual x-ray absorptiometry (DXA) scans were taken at baseline and again at least 1 year later. During the 5-year study, the rates of death, withdrawal, and treatment cessation were similar between the two groups. In all, 235 individuals sustained 296 fractures; 118 in those taking calcium and 178 in those taking placebo, for an overall 34% reduction in fractures in patients in the calcium group who stuck to the protocol for the entire study period.

Calcium appeared to improve bone mineral density at cortical bone sites, according to DXA findings. At 13 months, there were early indications of a reduction in fracture rates among patients in the calcium group.

SEATTLE — Calcium supplementation appears to reduce by 34% the 5-year risk of fracture in elderly women, according to a population-based study presented at the annual meeting of the American Society for Bone and Mineral Research.

The benefit was seen as early as 13 months, even though women were deemed at baseline to be getting adequate calcium—a mean of 960 mg/day, said Richard Prince, M.D., of Sir Charles Gairdner Hospital, Perth, Australia.

The 1,460 healthy ambulatory women, aged 70 or older, were randomly assigned to receive 600 mg calcium carbonate twice daily or placebo. Calcium intake was assessed and dual x-ray absorptiometry (DXA) scans were taken at baseline and again at least 1 year later. During the 5-year study, the rates of death, withdrawal, and treatment cessation were similar between the two groups. In all, 235 individuals sustained 296 fractures; 118 in those taking calcium and 178 in those taking placebo, for an overall 34% reduction in fractures in patients in the calcium group who stuck to the protocol for the entire study period.

Calcium appeared to improve bone mineral density at cortical bone sites, according to DXA findings. At 13 months, there were early indications of a reduction in fracture rates among patients in the calcium group.