Osteoarthritis

WASHINGTON — Teriparatide appeared to increase lumbar spine bone mineral density and showed some promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD increased 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two treatment groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34) and is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. The drug also is indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Currently, only the bisphosphonates risedronate (Actonel, made by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, made by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low BMD.

The trial included men and women at least 21 years of age who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All patients in the trial received calcium and vitamin D supplements. Patients were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis compared with alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures.

BMD was assessed using dual-energy x-ray absorptiometry. Vertebral fractures were assessed using semiquantitative visual scoring of radiographs taken at baseline and at 18 months. Nonvertebral fractures were assessed with radiograph or radiologist report. Both vertebral and nonvertebral fractures were assessed at a central reader site.

In addition, markers of bone turnover were analyzed in roughly half of the patients in each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of patients in both groups had rheumatologic disease. Rheumatoid arthritis was the most common, accounting for 69% of those in the alendronate group and 61% of those in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the researchers measured serum procollagen type 1 N-propeptide (P1NP)–a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)–a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

Adverse event profiles were similar between groups. In the teriparatide group there were 182 adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, and 39 were considered serious.

WASHINGTON — Teriparatide appeared to increase lumbar spine bone mineral density and showed some promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD increased 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two treatment groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34) and is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. The drug also is indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Currently, only the bisphosphonates risedronate (Actonel, made by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, made by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low BMD.

The trial included men and women at least 21 years of age who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All patients in the trial received calcium and vitamin D supplements. Patients were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis compared with alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures.

BMD was assessed using dual-energy x-ray absorptiometry. Vertebral fractures were assessed using semiquantitative visual scoring of radiographs taken at baseline and at 18 months. Nonvertebral fractures were assessed with radiograph or radiologist report. Both vertebral and nonvertebral fractures were assessed at a central reader site.

In addition, markers of bone turnover were analyzed in roughly half of the patients in each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of patients in both groups had rheumatologic disease. Rheumatoid arthritis was the most common, accounting for 69% of those in the alendronate group and 61% of those in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the researchers measured serum procollagen type 1 N-propeptide (P1NP)–a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)–a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

Adverse event profiles were similar between groups. In the teriparatide group there were 182 adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, and 39 were considered serious.

WASHINGTON — Teriparatide appeared to increase lumbar spine bone mineral density and showed some promise in reducing nonvertebral fractures in patients on glucocorticoid therapy with low bone mineral density or a prior fragility fracture, according to data presented at an international symposium sponsored by the National Osteoporosis Foundation.

“In patients with glucocorticoid-induced osteoporosis treated with teriparatide or alendronate for 18 months, teriparatide resulted in significantly greater increases in lumbar spine bone mineral density (BMD) compared with alendronate. Significantly fewer patients had new vertebral fractures with teriparatide, compared with the alendronate group,” said Margaret R. Warner, Ph.D., a researcher with Eli Lilly & Co., which funded this trial.

At 18 months, lumbar spine BMD increased 7.2% for patients treated with teriparatide and 3.4% for those treated with alendronate. Differences could be seen between the two treatment groups as early as 6 months.

Teriparatide (Forteo), made by Eli Lilly, contains recombinant human parathyroid hormone (1–34) and is currently indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for fracture. The drug also is indicated to increase bone mass in men with primary or hypogonadal osteoporosis who are at high risk for fracture. Teriparatide is the only osteoporosis drug shown to stimulate new bone growth.

Glucocorticoid therapy is the most common cause of secondary osteoporosis. Currently, only the bisphosphonates risedronate (Actonel, made by Procter & Gamble Pharmaceuticals) and alendronate (Fosamax, made by Merck & Co.) are indicated for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women receiving glucocorticoids in a daily dosage equivalent to 7.5 mg or greater of prednisone and who have low BMD.

The trial included men and women at least 21 years of age who had taken a minimum dose of 5 mg/day of prednisone (or its equivalent) for 3 months or longer prior to screening. All patients had total hip, femoral neck, or lumbar spine T scores of at most −2.0 or at most −1.0 with a prior fragility fracture. A total of 428 patients (80% women) were randomized to receive 20 mcg/day teriparatide injection and an oral placebo tablet or 10 mg/day oral alendronate and an injectable placebo. All patients in the trial received calcium and vitamin D supplements. Patients were followed for 18 months.

The primary end point was the effect of teriparatide on lumbar spine BMD in patients with glucocorticoid-induced osteoporosis compared with alendronate. The researchers also looked at the effect of teriparatide versus alendronate on total hip and femoral neck BMD, on markers of bone turnover, and on the incidence of vertebral and nonvertebral fractures.

BMD was assessed using dual-energy x-ray absorptiometry. Vertebral fractures were assessed using semiquantitative visual scoring of radiographs taken at baseline and at 18 months. Nonvertebral fractures were assessed with radiograph or radiologist report. Both vertebral and nonvertebral fractures were assessed at a central reader site.

In addition, markers of bone turnover were analyzed in roughly half of the patients in each group. Adverse event data were collected throughout.

At baseline, both groups were fairly evenly matched in terms of gender, race, age, average prednisone dose, and average duration of prednisone use. Both groups were evenly matched in average BMD at the total hip, femoral neck, and lumbar spine, and vertebral and nonvertebral fractures. Three-quarters of patients in both groups had rheumatologic disease. Rheumatoid arthritis was the most common, accounting for 69% of those in the alendronate group and 61% of those in the teriparatide group.

Total hip BMD rose 3.6% for the teriparatide group, versus 2.2% for the alendronate group. Femoral neck BMD rose 3.7% for the teriparatide group, versus 2.1% for the alendronate group.

In terms of biomarkers of bone turnover, the researchers measured serum procollagen type 1 N-propeptide (P1NP)–a marker of bone formation—and serum C-terminal telopeptide of type 1 collagen (CTX)–a marker of bone resorption. “In the teriparatide group, there were increases in serum P1NP and CTX, whereas with the antiresorptive agent there were decreases in serum P1NP and CTX,” said Dr. Warner.

Adverse event profiles were similar between groups. In the teriparatide group there were 182 adverse events, with 45 considered serious. There were 170 adverse events in the alendronate group, and 39 were considered serious.

Alendronate is the only proven cost-effective medication for initiation of primary or secondary prevention of osteoporosis, according to draft assessments issued March 5 by the agency that determines which drugs the National Health Service uses in England and Wales.

If affirmed later this year, the National Institute for Health and Clinical Effectiveness (NICE) draft document would rule out the use of strontium ranelate, etidronate, risedronate, and raloxifene for primary prevention of osteoporosis in women with at least one clinical risk factor.

For initiation of secondary prevention, a separate NICE document would rule out those four drugs and teriparatide.

NICE found that nonproprietary alendronate, the second-cheapest drug, was as effective as risedronate, etidronate, strontium, and raloxifene. As a result, NICE's drafts ruled that alendronate was the most cost-effective medication. Only etidronate, at £85.65 ($171) a year, could match alendronate on price. However, the committee questioned the evidence regarding etidronate's effectiveness.

At an annual cost of £95.03 ($190) for once-weekly treatment, generic alendronate for primary prevention in patients at high risk of osteoporosis was estimated to cost £17,632 ($35,288) or less per quality-adjusted life year, a measurement of a single year in perfect health, compared with no treatment, according to the NICE committee that appraised the medications.

For initiation of secondary prevention among women with bone mineral density more than 2.5 standard deviations below normal confirmed by bone-density scanning, it was estimated to cost less than £27,422 ($54,881) per quality-adjusted life year, depending on age and treatment strategy, the committee said.

A NICE document on secondary prevention of osteoporosis issued in January 2005 recommended the use of all three bisphosphonates, raloxifene, and teriparatide for secondary prevention in postmenopausal women who have already had an osteoporosis-related fracture.

Alendronate is the only proven cost-effective medication for initiation of primary or secondary prevention of osteoporosis, according to draft assessments issued March 5 by the agency that determines which drugs the National Health Service uses in England and Wales.

If affirmed later this year, the National Institute for Health and Clinical Effectiveness (NICE) draft document would rule out the use of strontium ranelate, etidronate, risedronate, and raloxifene for primary prevention of osteoporosis in women with at least one clinical risk factor.

For initiation of secondary prevention, a separate NICE document would rule out those four drugs and teriparatide.

NICE found that nonproprietary alendronate, the second-cheapest drug, was as effective as risedronate, etidronate, strontium, and raloxifene. As a result, NICE's drafts ruled that alendronate was the most cost-effective medication. Only etidronate, at £85.65 ($171) a year, could match alendronate on price. However, the committee questioned the evidence regarding etidronate's effectiveness.

At an annual cost of £95.03 ($190) for once-weekly treatment, generic alendronate for primary prevention in patients at high risk of osteoporosis was estimated to cost £17,632 ($35,288) or less per quality-adjusted life year, a measurement of a single year in perfect health, compared with no treatment, according to the NICE committee that appraised the medications.

For initiation of secondary prevention among women with bone mineral density more than 2.5 standard deviations below normal confirmed by bone-density scanning, it was estimated to cost less than £27,422 ($54,881) per quality-adjusted life year, depending on age and treatment strategy, the committee said.

A NICE document on secondary prevention of osteoporosis issued in January 2005 recommended the use of all three bisphosphonates, raloxifene, and teriparatide for secondary prevention in postmenopausal women who have already had an osteoporosis-related fracture.

Alendronate is the only proven cost-effective medication for initiation of primary or secondary prevention of osteoporosis, according to draft assessments issued March 5 by the agency that determines which drugs the National Health Service uses in England and Wales.

If affirmed later this year, the National Institute for Health and Clinical Effectiveness (NICE) draft document would rule out the use of strontium ranelate, etidronate, risedronate, and raloxifene for primary prevention of osteoporosis in women with at least one clinical risk factor.

For initiation of secondary prevention, a separate NICE document would rule out those four drugs and teriparatide.

NICE found that nonproprietary alendronate, the second-cheapest drug, was as effective as risedronate, etidronate, strontium, and raloxifene. As a result, NICE's drafts ruled that alendronate was the most cost-effective medication. Only etidronate, at £85.65 ($171) a year, could match alendronate on price. However, the committee questioned the evidence regarding etidronate's effectiveness.

At an annual cost of £95.03 ($190) for once-weekly treatment, generic alendronate for primary prevention in patients at high risk of osteoporosis was estimated to cost £17,632 ($35,288) or less per quality-adjusted life year, a measurement of a single year in perfect health, compared with no treatment, according to the NICE committee that appraised the medications.

For initiation of secondary prevention among women with bone mineral density more than 2.5 standard deviations below normal confirmed by bone-density scanning, it was estimated to cost less than £27,422 ($54,881) per quality-adjusted life year, depending on age and treatment strategy, the committee said.

A NICE document on secondary prevention of osteoporosis issued in January 2005 recommended the use of all three bisphosphonates, raloxifene, and teriparatide for secondary prevention in postmenopausal women who have already had an osteoporosis-related fracture.

At the first follow-up, the patient's BMD, based on a DXA scan, was up 5.3%. However, at the second follow-up, his BMD had dropped by 5.1%. His primary care physician referred the man to determine why he was no longer responding to therapy.

“What is the first thing to do?” asked Dr. Michael Lewiecki, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. Should you “evaluate for adherence to therapy? Ask about calcium and vitamin D intake? Order lab tests to evaluate for factors contributing to bone loss?”

No, the first step is to actually look at the DXA image, said Dr. Lewiecki. In this case, the vertebral bodies were mislabeled on the second follow-up DXA scan.

Typically, the DXA computer program selects the labeling for vertebral bodies on DXA scans. It's not uncommon for mislabeling to occur though, said Dr. Lewiecki. A technologist goes over the labeling to double check the computer. Finally, the image should be reviewed by a physician interpreter as an additional check before the report is generated. In this case, the incorrectly labeled scan was not caught and false BMD measurements were reported to the ordering physician.

“When you have a situation in which BMD changes unexpectedly, it is important to verify that it is a valid comparison,” said Dr. Lewiecki.

Sometimes a left hip is incorrectly compared with the right hip or vice versa when assessing BMD over time. Other times, the lines used by the computer to delineate the edges of bone are misplaced, which can have a big effect on the amount of bone measured.

“Make sure you're comparing apples to apples,” he said. Reanalysis of the image with vertebral bodies correctly labeled showed that the patient's BMD for L1-L4 had been stable since the first follow-up. Response to therapy actually was good, requiring no change in alendronate and hydrochlorothiazide therapy and no laboratory testing for nonresponse to therapy.

Baseline DXA scan for L1-L4 (left): DXA at 1-year follow-up shows a 5.3% increase in BMD (center). However, a year later, mislabeling of vertebral bodies showed a 5.1% decrease in BMD (right). The erroneous labeling was clear when compared with the previous DXA images. Photos courtesy Dr. Michael Lewiecki

At the first follow-up, the patient's BMD, based on a DXA scan, was up 5.3%. However, at the second follow-up, his BMD had dropped by 5.1%. His primary care physician referred the man to determine why he was no longer responding to therapy.

“What is the first thing to do?” asked Dr. Michael Lewiecki, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. Should you “evaluate for adherence to therapy? Ask about calcium and vitamin D intake? Order lab tests to evaluate for factors contributing to bone loss?”

No, the first step is to actually look at the DXA image, said Dr. Lewiecki. In this case, the vertebral bodies were mislabeled on the second follow-up DXA scan.

Typically, the DXA computer program selects the labeling for vertebral bodies on DXA scans. It's not uncommon for mislabeling to occur though, said Dr. Lewiecki. A technologist goes over the labeling to double check the computer. Finally, the image should be reviewed by a physician interpreter as an additional check before the report is generated. In this case, the incorrectly labeled scan was not caught and false BMD measurements were reported to the ordering physician.

“When you have a situation in which BMD changes unexpectedly, it is important to verify that it is a valid comparison,” said Dr. Lewiecki.

Sometimes a left hip is incorrectly compared with the right hip or vice versa when assessing BMD over time. Other times, the lines used by the computer to delineate the edges of bone are misplaced, which can have a big effect on the amount of bone measured.

“Make sure you're comparing apples to apples,” he said. Reanalysis of the image with vertebral bodies correctly labeled showed that the patient's BMD for L1-L4 had been stable since the first follow-up. Response to therapy actually was good, requiring no change in alendronate and hydrochlorothiazide therapy and no laboratory testing for nonresponse to therapy.

Baseline DXA scan for L1-L4 (left): DXA at 1-year follow-up shows a 5.3% increase in BMD (center). However, a year later, mislabeling of vertebral bodies showed a 5.1% decrease in BMD (right). The erroneous labeling was clear when compared with the previous DXA images. Photos courtesy Dr. Michael Lewiecki

At the first follow-up, the patient's BMD, based on a DXA scan, was up 5.3%. However, at the second follow-up, his BMD had dropped by 5.1%. His primary care physician referred the man to determine why he was no longer responding to therapy.

“What is the first thing to do?” asked Dr. Michael Lewiecki, director of the New Mexico Clinical Research & Osteoporosis Center in Albuquerque. Should you “evaluate for adherence to therapy? Ask about calcium and vitamin D intake? Order lab tests to evaluate for factors contributing to bone loss?”

No, the first step is to actually look at the DXA image, said Dr. Lewiecki. In this case, the vertebral bodies were mislabeled on the second follow-up DXA scan.

Typically, the DXA computer program selects the labeling for vertebral bodies on DXA scans. It's not uncommon for mislabeling to occur though, said Dr. Lewiecki. A technologist goes over the labeling to double check the computer. Finally, the image should be reviewed by a physician interpreter as an additional check before the report is generated. In this case, the incorrectly labeled scan was not caught and false BMD measurements were reported to the ordering physician.

“When you have a situation in which BMD changes unexpectedly, it is important to verify that it is a valid comparison,” said Dr. Lewiecki.

Sometimes a left hip is incorrectly compared with the right hip or vice versa when assessing BMD over time. Other times, the lines used by the computer to delineate the edges of bone are misplaced, which can have a big effect on the amount of bone measured.

“Make sure you're comparing apples to apples,” he said. Reanalysis of the image with vertebral bodies correctly labeled showed that the patient's BMD for L1-L4 had been stable since the first follow-up. Response to therapy actually was good, requiring no change in alendronate and hydrochlorothiazide therapy and no laboratory testing for nonresponse to therapy.

Baseline DXA scan for L1-L4 (left): DXA at 1-year follow-up shows a 5.3% increase in BMD (center). However, a year later, mislabeling of vertebral bodies showed a 5.1% decrease in BMD (right). The erroneous labeling was clear when compared with the previous DXA images. Photos courtesy Dr. Michael Lewiecki

The benefits of hormone therapy outweigh its risks in healthy perimenopausal and early-postmenopausal women with menopause-related symptoms and a low baseline risk of stroke, according to the revised position statement released by the North American Menopause Society.

However, the paper cautioned, that HT should not be prescribed for the prevention of any disease, with the exception of postmenopausal osteoporosis.

HT can be prescribed for the prevention of postmenopausal osteoporosis in women who require drug therapy to maintain bone. “There is strong evidence of the efficacy of [HT] in reducing the risk of postmenopausal osteoporotic bone fracture,” the statement read.

For women at risk of a fracture during the next 5–10 years, HT can be an option—but only after a careful risk/benefit analysis.

The statement is based on an expert panel's review of HT studies published subsequent to the group's 2004 position paper, said Dr. Wulf Utian, executive director of the North American Menopause Society (NAMS) in Cleveland. “In this day and age, the life span of any position statement is a maximum of 2 or 3 years,” Dr. Utian said in an interview. “In the face of so much new information, we felt an update was due.”

The clinical impacts of HT's short- and long-term effects are becoming clearer, especially as additional subanalyses of the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) begin to emerge, he said.

Results of these and other studies enabled more expert consensus in the new paper than was previously possible—most significantly, Dr. Utian said, in the area of cardiovascular disease risk.

“We have modified our stance on level of risk from 2004,” he explained.

“Apart from the increased risk of stroke in the older woman [taking HT], the absolute risk of stroke and heart attack is rare, and we agreed that any evidence of an increase in heart attack in the perimenopausal woman was poor. We have concluded that for the symptomatic woman without a contraindication, the benefits of HT outweigh the risks, and that these women have less cause to fear than the popular perception,” said Dr. Utian.

Two well-publicized, large studies have precipitated much of the current confusion over the safety of HT, appropriate treatment populations, and timing of therapy, the statement said. “The results of WHI and HERS should not be extrapolated to symptomatic postmenopausal women younger than 50 years of age, who initiate HT at that time, as these women were not studied in those trials.”

“We state very clearly there is no cookbook recipe. Each woman has her own potential indications and risk factors, and only a comprehensive evaluation and discussion is going to decide what is most appropriate for that individual,” Dr. Utian stressed.

The NAMS statement is available at www.menopause.org/aboutmeno/consensus.htm

'There is no cookbook recipe. Each woman has her own potential indications and risk factors.' DR. UTIAN

The benefits of hormone therapy outweigh its risks in healthy perimenopausal and early-postmenopausal women with menopause-related symptoms and a low baseline risk of stroke, according to the revised position statement released by the North American Menopause Society.

However, the paper cautioned, that HT should not be prescribed for the prevention of any disease, with the exception of postmenopausal osteoporosis.

HT can be prescribed for the prevention of postmenopausal osteoporosis in women who require drug therapy to maintain bone. “There is strong evidence of the efficacy of [HT] in reducing the risk of postmenopausal osteoporotic bone fracture,” the statement read.

For women at risk of a fracture during the next 5–10 years, HT can be an option—but only after a careful risk/benefit analysis.

The statement is based on an expert panel's review of HT studies published subsequent to the group's 2004 position paper, said Dr. Wulf Utian, executive director of the North American Menopause Society (NAMS) in Cleveland. “In this day and age, the life span of any position statement is a maximum of 2 or 3 years,” Dr. Utian said in an interview. “In the face of so much new information, we felt an update was due.”

The clinical impacts of HT's short- and long-term effects are becoming clearer, especially as additional subanalyses of the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) begin to emerge, he said.

Results of these and other studies enabled more expert consensus in the new paper than was previously possible—most significantly, Dr. Utian said, in the area of cardiovascular disease risk.

“We have modified our stance on level of risk from 2004,” he explained.

“Apart from the increased risk of stroke in the older woman [taking HT], the absolute risk of stroke and heart attack is rare, and we agreed that any evidence of an increase in heart attack in the perimenopausal woman was poor. We have concluded that for the symptomatic woman without a contraindication, the benefits of HT outweigh the risks, and that these women have less cause to fear than the popular perception,” said Dr. Utian.

Two well-publicized, large studies have precipitated much of the current confusion over the safety of HT, appropriate treatment populations, and timing of therapy, the statement said. “The results of WHI and HERS should not be extrapolated to symptomatic postmenopausal women younger than 50 years of age, who initiate HT at that time, as these women were not studied in those trials.”

“We state very clearly there is no cookbook recipe. Each woman has her own potential indications and risk factors, and only a comprehensive evaluation and discussion is going to decide what is most appropriate for that individual,” Dr. Utian stressed.

The NAMS statement is available at www.menopause.org/aboutmeno/consensus.htm

'There is no cookbook recipe. Each woman has her own potential indications and risk factors.' DR. UTIAN

The benefits of hormone therapy outweigh its risks in healthy perimenopausal and early-postmenopausal women with menopause-related symptoms and a low baseline risk of stroke, according to the revised position statement released by the North American Menopause Society.

However, the paper cautioned, that HT should not be prescribed for the prevention of any disease, with the exception of postmenopausal osteoporosis.

HT can be prescribed for the prevention of postmenopausal osteoporosis in women who require drug therapy to maintain bone. “There is strong evidence of the efficacy of [HT] in reducing the risk of postmenopausal osteoporotic bone fracture,” the statement read.

For women at risk of a fracture during the next 5–10 years, HT can be an option—but only after a careful risk/benefit analysis.

The statement is based on an expert panel's review of HT studies published subsequent to the group's 2004 position paper, said Dr. Wulf Utian, executive director of the North American Menopause Society (NAMS) in Cleveland. “In this day and age, the life span of any position statement is a maximum of 2 or 3 years,” Dr. Utian said in an interview. “In the face of so much new information, we felt an update was due.”

The clinical impacts of HT's short- and long-term effects are becoming clearer, especially as additional subanalyses of the Women's Health Initiative (WHI) and the Heart and Estrogen/Progestin Replacement Study (HERS) begin to emerge, he said.

Results of these and other studies enabled more expert consensus in the new paper than was previously possible—most significantly, Dr. Utian said, in the area of cardiovascular disease risk.

“We have modified our stance on level of risk from 2004,” he explained.

“Apart from the increased risk of stroke in the older woman [taking HT], the absolute risk of stroke and heart attack is rare, and we agreed that any evidence of an increase in heart attack in the perimenopausal woman was poor. We have concluded that for the symptomatic woman without a contraindication, the benefits of HT outweigh the risks, and that these women have less cause to fear than the popular perception,” said Dr. Utian.

Two well-publicized, large studies have precipitated much of the current confusion over the safety of HT, appropriate treatment populations, and timing of therapy, the statement said. “The results of WHI and HERS should not be extrapolated to symptomatic postmenopausal women younger than 50 years of age, who initiate HT at that time, as these women were not studied in those trials.”

“We state very clearly there is no cookbook recipe. Each woman has her own potential indications and risk factors, and only a comprehensive evaluation and discussion is going to decide what is most appropriate for that individual,” Dr. Utian stressed.

The NAMS statement is available at www.menopause.org/aboutmeno/consensus.htm

'There is no cookbook recipe. Each woman has her own potential indications and risk factors.' DR. UTIAN

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

Women considering the risks and benefits of hormone therapy should be informed of the link between hormones and a decreased risk of diabetes, especially if they are at risk for the disorder, according to Dr. Wulf Utian, executive director of the North American Menopause Society in Cleveland.

“While hormone therapy [HT] is not indicated for the prevention of diabetes, women with diabetes risk factors who are considering it for a valid indication should understand the evidence in this area,” Dr. Utian said in an interview. NAMs' newly revised position statement on HT is the group's first to review this evidence.

The paper reviewed three studies on the subject, granting Class I status to the evidence presented in each one: two subanalyses of the Women's Health Initiative (WHI) and one subanalysis of the Heart and Estrogen/Progestin Replacement Study (HERS).

The first of the WHI studies, published in 2004, examined the effect of HT on diabetes development in the 16,600 women included in the estrogen/progestin arm (Diabetologia 2004;47:1175–87). After 5 years of follow-up, women in the active group were 21% less likely to develop diabetes than those in the placebo group (277 cases vs. 324 cases).

The numbers achieved greater significance when the analysis was restricted to the small subgroup of women who remained compliant with therapy throughout the follow-up period. In this group, the decreased risk was 33%. The difference seemed to be driven by steady improvements in fasting glucose and insulin resistance in the active group, the authors wrote. The risk ratios remained unchanged after adjusting for body mass index (BMI) and waist circumference.

Insulin resistance and glucose level were also the driving forces behind the smaller risk reductions seen among women in WHI's estrogen-only arm (Diabetologia 2006;49:459–68). This study included 9,712 women. At year 6, women in the active group were 12% less likely to have developed diabetes than those in the placebo group (a rate of 8.3% vs. a rate of 9.3%). This difference was not significant in the overall group, but became highly so in the smaller group of women who were compliant with therapy through the study's end. These women were 27% less likely to develop diabetes than the placebo group.

Again, adjusting for BMI and waist circumference did not account for the difference, the authors said. Instead, the risk reduction seemed to be related to improvements in fasting glucose and insulin resistance. These were significant within the first year of therapy and then waned in the overall group, but remained significant in the compliant group.

The final study, a subanalysis of the HERS data, confirmed HT's beneficial effect on diabetes development in women with preexisting coronary heart disease. The subanalysis followed 2,029 patients who did not have diabetes at baseline (Ann. Intern. Med. 2003;138:1–9).

At 4 years' follow-up, the incidence of diabetes in the active group was 6.2%, compared with 9.5% in the placebo group—a significant risk reduction of 35%. The risk differential was related to significantly higher fasting glucose levels in the placebo group; these levels remained stable in the active group. There was no association of decreased diabetes with the active group's modest decreases in BMI or waist circumference.

More research is necessary to further define HT's impact on diabetes, Dr. Utian said.

Moderate renal impairment raises the risk of hip fracture, particularly trochanter fracture, in older white women, reported Dr. Kristine E. Ensrud, and her associates in the Study of Osteoporotic Fractures.

“These findings suggest that clinicians should consider including renal function as part of the risk assessment for hip fracture in elderly women,” the researchers reported. An increased rate of hip fractures has been reported in patients with end-stage renal disease, those undergoing dialysis, and those who have received a renal transplant. However, this is the first longitudinal study of the link between hip fracture and mild to moderate renal insufficiency, according to Dr. Ensrud of the Veterans Affairs Medical Center, Minneapolis, and her associates.

They conducted a case-cohort study within the Study of Osteoporotic Fractures, a prospective study of over 9,700 women living in four U.S. regions that were aged 65 and older when enrolled in 1986–1988. The investigators assessed 149 white patients randomly selected from among those who sustained hip fractures during a mean follow-up of 6 years, and 377 without hip fractures.

A decreased estimated glomerular filtration (GFR) rate was significantly associated with an increased risk for hip fracture, even after the data were adjusted to account for traditional risk factors, the researchers reported (Arch. Intern. Med. 2007;167:133–9). In patients with a mildly decreased GFR the hazard ratio for hip fracture was 1.7, and in those with a moderately decreased GFR the hazard ratio was 2.3, compared with subjects who had a normal GFR.

Similarly, in subjects with a mildly decreased GFR the risk of trochanteric fracture in particular was increased nearly fourfold, and in those with moderately decreased GFR it was increased fivefold, compared with those who had a normal GFR. The underlying mechanisms for these associations are not yet understood. Abnormalities in phosphorous, calcium, and vitamin D metabolism occur in even mild renal insufficiency. And moderate renal dysfunction has been linked with increased inflammation, impaired coagulation, anemia, and malnutrition, Dr. Ensrud and her associates noted.

In an editorial comment accompanying the report, Dr. Stuart M. Sprague of Northwestern University, Chicago, said that “a staggering 19.2 million Americans, or 11% of the adult population,” currently have chronic kidney disease (CKD).

The study findings “are potentially very important, as they support the concept that a diagnosis of osteoporosis based on [bmd] criteria should not be made in patients with CKD and used as a predictor of fracture outcome,” Dr. Sprague wrote (Arch. Intern Med. 2007;167:115–6).

Moderate renal impairment raises the risk of hip fracture, particularly trochanter fracture, in older white women, reported Dr. Kristine E. Ensrud, and her associates in the Study of Osteoporotic Fractures.

“These findings suggest that clinicians should consider including renal function as part of the risk assessment for hip fracture in elderly women,” the researchers reported. An increased rate of hip fractures has been reported in patients with end-stage renal disease, those undergoing dialysis, and those who have received a renal transplant. However, this is the first longitudinal study of the link between hip fracture and mild to moderate renal insufficiency, according to Dr. Ensrud of the Veterans Affairs Medical Center, Minneapolis, and her associates.

They conducted a case-cohort study within the Study of Osteoporotic Fractures, a prospective study of over 9,700 women living in four U.S. regions that were aged 65 and older when enrolled in 1986–1988. The investigators assessed 149 white patients randomly selected from among those who sustained hip fractures during a mean follow-up of 6 years, and 377 without hip fractures.

A decreased estimated glomerular filtration (GFR) rate was significantly associated with an increased risk for hip fracture, even after the data were adjusted to account for traditional risk factors, the researchers reported (Arch. Intern. Med. 2007;167:133–9). In patients with a mildly decreased GFR the hazard ratio for hip fracture was 1.7, and in those with a moderately decreased GFR the hazard ratio was 2.3, compared with subjects who had a normal GFR.

Similarly, in subjects with a mildly decreased GFR the risk of trochanteric fracture in particular was increased nearly fourfold, and in those with moderately decreased GFR it was increased fivefold, compared with those who had a normal GFR. The underlying mechanisms for these associations are not yet understood. Abnormalities in phosphorous, calcium, and vitamin D metabolism occur in even mild renal insufficiency. And moderate renal dysfunction has been linked with increased inflammation, impaired coagulation, anemia, and malnutrition, Dr. Ensrud and her associates noted.

In an editorial comment accompanying the report, Dr. Stuart M. Sprague of Northwestern University, Chicago, said that “a staggering 19.2 million Americans, or 11% of the adult population,” currently have chronic kidney disease (CKD).

The study findings “are potentially very important, as they support the concept that a diagnosis of osteoporosis based on [bmd] criteria should not be made in patients with CKD and used as a predictor of fracture outcome,” Dr. Sprague wrote (Arch. Intern Med. 2007;167:115–6).

Moderate renal impairment raises the risk of hip fracture, particularly trochanter fracture, in older white women, reported Dr. Kristine E. Ensrud, and her associates in the Study of Osteoporotic Fractures.

“These findings suggest that clinicians should consider including renal function as part of the risk assessment for hip fracture in elderly women,” the researchers reported. An increased rate of hip fractures has been reported in patients with end-stage renal disease, those undergoing dialysis, and those who have received a renal transplant. However, this is the first longitudinal study of the link between hip fracture and mild to moderate renal insufficiency, according to Dr. Ensrud of the Veterans Affairs Medical Center, Minneapolis, and her associates.

They conducted a case-cohort study within the Study of Osteoporotic Fractures, a prospective study of over 9,700 women living in four U.S. regions that were aged 65 and older when enrolled in 1986–1988. The investigators assessed 149 white patients randomly selected from among those who sustained hip fractures during a mean follow-up of 6 years, and 377 without hip fractures.

A decreased estimated glomerular filtration (GFR) rate was significantly associated with an increased risk for hip fracture, even after the data were adjusted to account for traditional risk factors, the researchers reported (Arch. Intern. Med. 2007;167:133–9). In patients with a mildly decreased GFR the hazard ratio for hip fracture was 1.7, and in those with a moderately decreased GFR the hazard ratio was 2.3, compared with subjects who had a normal GFR.

Similarly, in subjects with a mildly decreased GFR the risk of trochanteric fracture in particular was increased nearly fourfold, and in those with moderately decreased GFR it was increased fivefold, compared with those who had a normal GFR. The underlying mechanisms for these associations are not yet understood. Abnormalities in phosphorous, calcium, and vitamin D metabolism occur in even mild renal insufficiency. And moderate renal dysfunction has been linked with increased inflammation, impaired coagulation, anemia, and malnutrition, Dr. Ensrud and her associates noted.

In an editorial comment accompanying the report, Dr. Stuart M. Sprague of Northwestern University, Chicago, said that “a staggering 19.2 million Americans, or 11% of the adult population,” currently have chronic kidney disease (CKD).

The study findings “are potentially very important, as they support the concept that a diagnosis of osteoporosis based on [bmd] criteria should not be made in patients with CKD and used as a predictor of fracture outcome,” Dr. Sprague wrote (Arch. Intern Med. 2007;167:115–6).

Repeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

Repeat BMD testing is done “commonly” in clinical practice, even though “there is little evidence evaluating the additional value of repeat BMD testing for fracture risk,” the investigators reported (Arch. Intern. Med. 2007;167:155–60).

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates.

The subjects were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, intertrochanter, trochanter, femoral neck, and Ward's triangle. The 513 subjects who sustained a fracture between the initial and the repeat BMD assessments were excluded from the study.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. “Each standard deviation lower in either initial or repeat BMD was associated with a 55%–61% increased risk of incident nonspine fracture, a 102%–121% increased risk of incident hip fracture, and a 75%–86% increased risk of spine fracture,” Dr. Hillier and her associates reported.

However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

Their findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” Dr. Hillier and her associates noted.

“However, our results do suggest that, for the average healthy older woman…a repeat BMD measurement has little or no value in classifying risk for future fracture—even for the average older woman who has osteoporosis by initial BMD measure, or high BMD loss,” they wrote, noting this study did not address BMD testing to monitor osteoporosis treatment response. These results may not be generalizable to men, nonwhite women, or women younger than 65.

Repeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

Repeat BMD testing is done “commonly” in clinical practice, even though “there is little evidence evaluating the additional value of repeat BMD testing for fracture risk,” the investigators reported (Arch. Intern. Med. 2007;167:155–60).

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates.

The subjects were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, intertrochanter, trochanter, femoral neck, and Ward's triangle. The 513 subjects who sustained a fracture between the initial and the repeat BMD assessments were excluded from the study.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. “Each standard deviation lower in either initial or repeat BMD was associated with a 55%–61% increased risk of incident nonspine fracture, a 102%–121% increased risk of incident hip fracture, and a 75%–86% increased risk of spine fracture,” Dr. Hillier and her associates reported.

However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

Their findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” Dr. Hillier and her associates noted.

“However, our results do suggest that, for the average healthy older woman…a repeat BMD measurement has little or no value in classifying risk for future fracture—even for the average older woman who has osteoporosis by initial BMD measure, or high BMD loss,” they wrote, noting this study did not address BMD testing to monitor osteoporosis treatment response. These results may not be generalizable to men, nonwhite women, or women younger than 65.

Repeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

Repeat BMD testing is done “commonly” in clinical practice, even though “there is little evidence evaluating the additional value of repeat BMD testing for fracture risk,” the investigators reported (Arch. Intern. Med. 2007;167:155–60).

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates.

The subjects were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, intertrochanter, trochanter, femoral neck, and Ward's triangle. The 513 subjects who sustained a fracture between the initial and the repeat BMD assessments were excluded from the study.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. “Each standard deviation lower in either initial or repeat BMD was associated with a 55%–61% increased risk of incident nonspine fracture, a 102%–121% increased risk of incident hip fracture, and a 75%–86% increased risk of spine fracture,” Dr. Hillier and her associates reported.

However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

Their findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” Dr. Hillier and her associates noted.

“However, our results do suggest that, for the average healthy older woman…a repeat BMD measurement has little or no value in classifying risk for future fracture—even for the average older woman who has osteoporosis by initial BMD measure, or high BMD loss,” they wrote, noting this study did not address BMD testing to monitor osteoporosis treatment response. These results may not be generalizable to men, nonwhite women, or women younger than 65.

ARLINGTON, VA. — African Americans may have a lower rate of osteoporosis-related fractures than whites because of adaptations in calcium homeostasis, bone turnover and resorption, and response to parathyroid hormone, Dr. Felicia Cosman said at a conference sponsored by the American Society for Bone and Mineral Research.

It is “very surprising” that at all ages, black individuals have a lower rate of fractures and higher bone mineral density (BMD) than white individuals, even though blacks generally have higher rates of vitamin D deficiency or insufficiency, said Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital, West Haverstraw, N.Y.

Mean serum levels of 25-hydroxyvitamin D [25(OH)D] are known at all ages and in both genders to be generally lower in blacks than in whites. This is the result of reduced skin production of vitamin D and a lower dietary intake of vitamin D, Dr. Cosman said.

An alteration in the vitamin D-endocrine system in blacks was first proposed by Dr. Norman Bell; it was based on evidence that blacks have a greater prevalence of vitamin D deficiency and relative secondary hyperparathyroidism, lower levels of bone turnover, and increased urinary calcium retention as an adaptive means to maintain calcium homeostasis without sacrificing the skeleton (J. Clin. Invest. 1985;76:470–3).

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said. As a consequence of high PTH levels, blacks have generally been measured with higher 1–25 dihydroxyvitamin D [1,25(OH)2D] levels than have whites.

“We would expect that with higher 1,25(OH)2D levels, you would see greater [dietary] calcium absorption in black individuals compared to whites,” but studies have reported inconsistent data, many of which have shown no significant interracial differences, she said.

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said. However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

In addition, supplementation of 1,25(OH)2D has been shown to cause a significantly greater decrease in urinary calcium excretion in blacks than in whites. Markers of bone formation also increased more among blacks than among whites, whereas bone resorption indices showed no racial differences (Osteoporos. Int. 2000;11:271–7). In a separate study, administration of PTH also caused blacks to retain urinary calcium to a greater degree than it did in whites, but it did not cause any racial differences in bone formation markers. After receipt of PTH, blacks also did not have as great an increase in bone resorption markers (J. Bone Miner. Res. 1997;12:958–66). This finding directly confirms “the hypothesis that the black skeleton could be resistant to the acute bone resorptive effects of PTH,” she said.

Studies of histomorphometric differences in bone have shown significantly reduced bone formation rates and a longer total bone formation period in blacks, compared with whites. The results of those studies are consistent with evidence that blacks have a lower level of serum osteocalcin—which has been the most sensitive indicator of a racial difference in bone turnover levels—and that blacks respond more slowly to bone remodeling therapies.

“The bottom line message … for these measurements is that in a relative secondary hyperparathyroid state you really expect to see high [bone] turnover,” Dr. Cosman said. “We never see that. We see either the same or, in most cases, lower turnover in blacks.”

ARLINGTON, VA. — African Americans may have a lower rate of osteoporosis-related fractures than whites because of adaptations in calcium homeostasis, bone turnover and resorption, and response to parathyroid hormone, Dr. Felicia Cosman said at a conference sponsored by the American Society for Bone and Mineral Research.

It is “very surprising” that at all ages, black individuals have a lower rate of fractures and higher bone mineral density (BMD) than white individuals, even though blacks generally have higher rates of vitamin D deficiency or insufficiency, said Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital, West Haverstraw, N.Y.

Mean serum levels of 25-hydroxyvitamin D [25(OH)D] are known at all ages and in both genders to be generally lower in blacks than in whites. This is the result of reduced skin production of vitamin D and a lower dietary intake of vitamin D, Dr. Cosman said.

An alteration in the vitamin D-endocrine system in blacks was first proposed by Dr. Norman Bell; it was based on evidence that blacks have a greater prevalence of vitamin D deficiency and relative secondary hyperparathyroidism, lower levels of bone turnover, and increased urinary calcium retention as an adaptive means to maintain calcium homeostasis without sacrificing the skeleton (J. Clin. Invest. 1985;76:470–3).

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said. As a consequence of high PTH levels, blacks have generally been measured with higher 1–25 dihydroxyvitamin D [1,25(OH)2D] levels than have whites.

“We would expect that with higher 1,25(OH)2D levels, you would see greater [dietary] calcium absorption in black individuals compared to whites,” but studies have reported inconsistent data, many of which have shown no significant interracial differences, she said.

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said. However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

In addition, supplementation of 1,25(OH)2D has been shown to cause a significantly greater decrease in urinary calcium excretion in blacks than in whites. Markers of bone formation also increased more among blacks than among whites, whereas bone resorption indices showed no racial differences (Osteoporos. Int. 2000;11:271–7). In a separate study, administration of PTH also caused blacks to retain urinary calcium to a greater degree than it did in whites, but it did not cause any racial differences in bone formation markers. After receipt of PTH, blacks also did not have as great an increase in bone resorption markers (J. Bone Miner. Res. 1997;12:958–66). This finding directly confirms “the hypothesis that the black skeleton could be resistant to the acute bone resorptive effects of PTH,” she said.

Studies of histomorphometric differences in bone have shown significantly reduced bone formation rates and a longer total bone formation period in blacks, compared with whites. The results of those studies are consistent with evidence that blacks have a lower level of serum osteocalcin—which has been the most sensitive indicator of a racial difference in bone turnover levels—and that blacks respond more slowly to bone remodeling therapies.

“The bottom line message … for these measurements is that in a relative secondary hyperparathyroid state you really expect to see high [bone] turnover,” Dr. Cosman said. “We never see that. We see either the same or, in most cases, lower turnover in blacks.”

ARLINGTON, VA. — African Americans may have a lower rate of osteoporosis-related fractures than whites because of adaptations in calcium homeostasis, bone turnover and resorption, and response to parathyroid hormone, Dr. Felicia Cosman said at a conference sponsored by the American Society for Bone and Mineral Research.

It is “very surprising” that at all ages, black individuals have a lower rate of fractures and higher bone mineral density (BMD) than white individuals, even though blacks generally have higher rates of vitamin D deficiency or insufficiency, said Dr. Cosman, medical director of the clinical research center at Helen Hayes Hospital, West Haverstraw, N.Y.

Mean serum levels of 25-hydroxyvitamin D [25(OH)D] are known at all ages and in both genders to be generally lower in blacks than in whites. This is the result of reduced skin production of vitamin D and a lower dietary intake of vitamin D, Dr. Cosman said.

An alteration in the vitamin D-endocrine system in blacks was first proposed by Dr. Norman Bell; it was based on evidence that blacks have a greater prevalence of vitamin D deficiency and relative secondary hyperparathyroidism, lower levels of bone turnover, and increased urinary calcium retention as an adaptive means to maintain calcium homeostasis without sacrificing the skeleton (J. Clin. Invest. 1985;76:470–3).

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said. As a consequence of high PTH levels, blacks have generally been measured with higher 1–25 dihydroxyvitamin D [1,25(OH)2D] levels than have whites.

“We would expect that with higher 1,25(OH)2D levels, you would see greater [dietary] calcium absorption in black individuals compared to whites,” but studies have reported inconsistent data, many of which have shown no significant interracial differences, she said.

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said. However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

In addition, supplementation of 1,25(OH)2D has been shown to cause a significantly greater decrease in urinary calcium excretion in blacks than in whites. Markers of bone formation also increased more among blacks than among whites, whereas bone resorption indices showed no racial differences (Osteoporos. Int. 2000;11:271–7). In a separate study, administration of PTH also caused blacks to retain urinary calcium to a greater degree than it did in whites, but it did not cause any racial differences in bone formation markers. After receipt of PTH, blacks also did not have as great an increase in bone resorption markers (J. Bone Miner. Res. 1997;12:958–66). This finding directly confirms “the hypothesis that the black skeleton could be resistant to the acute bone resorptive effects of PTH,” she said.

Studies of histomorphometric differences in bone have shown significantly reduced bone formation rates and a longer total bone formation period in blacks, compared with whites. The results of those studies are consistent with evidence that blacks have a lower level of serum osteocalcin—which has been the most sensitive indicator of a racial difference in bone turnover levels—and that blacks respond more slowly to bone remodeling therapies.

“The bottom line message … for these measurements is that in a relative secondary hyperparathyroid state you really expect to see high [bone] turnover,” Dr. Cosman said. “We never see that. We see either the same or, in most cases, lower turnover in blacks.”

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/cm

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary study 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.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study, and no cases of osteonecrosis were observed.

After 5 years, total hip bone mineral density declined 3.38% (0.22) from baseline values in the placebo group and 1.02% (0.18) in the combination of the two alendronate groups for a mean difference of 2.36% (95% CI: 1.81%–2.90%; P less than .001). The combined alendronate group experienced a mean 5.26% (0.24) increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% (0.29) increase in the placebo group (mean difference of 3.74%; 95% CI: 3.03%–4.45%, P less than .001). Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

The two alendronate groups did not differ significantly in their incidence of total clinical fractures or nonvertebral fractures.

However, the risk of clinical vertebral fractures was significantly higher in the placebo group (5.3%) than in the combined alendronate group (2.4%).

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/cm

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary study 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.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study, and no cases of osteonecrosis were observed.

After 5 years, total hip bone mineral density declined 3.38% (0.22) from baseline values in the placebo group and 1.02% (0.18) in the combination of the two alendronate groups for a mean difference of 2.36% (95% CI: 1.81%–2.90%; P less than .001). The combined alendronate group experienced a mean 5.26% (0.24) increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% (0.29) increase in the placebo group (mean difference of 3.74%; 95% CI: 3.03%–4.45%, P less than .001). Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

The two alendronate groups did not differ significantly in their incidence of total clinical fractures or nonvertebral fractures.

However, the risk of clinical vertebral fractures was significantly higher in the placebo group (5.3%) than in the combined alendronate group (2.4%).

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/cm

Participants were randomly assigned to receive daily treatment with 10 mg alendronate (30%), 5 mg alendronate (30%), or placebo (40%). The primary study 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.

The treatment groups did not significantly differ in adverse events or other safety parameters during the study, and no cases of osteonecrosis were observed.

After 5 years, total hip bone mineral density declined 3.38% (0.22) from baseline values in the placebo group and 1.02% (0.18) in the combination of the two alendronate groups for a mean difference of 2.36% (95% CI: 1.81%–2.90%; P less than .001). The combined alendronate group experienced a mean 5.26% (0.24) increase from FLEX baseline in lumbar spine BMD compared with a mean 1.52% (0.29) increase in the placebo group (mean difference of 3.74%; 95% CI: 3.03%–4.45%, P less than .001). Notably, mean BMD levels remained at or above FIT baseline levels in all treatment groups after 5 years.

The two alendronate groups did not differ significantly in their incidence of total clinical fractures or nonvertebral fractures.

However, the risk of clinical vertebral fractures was significantly higher in the placebo group (5.3%) than in the combined alendronate group (2.4%).

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS

SAN ANTONIO — Monthly ibandronate appears to prevent, and perhaps even reverse, bone loss in women who are taking anastrozole for estrogen receptor-positive breast cancers, Dr. J.E. Lester reported in a poster at the Sixth International Meeting on Cancer-Induced Bone Disease.

While she said that further follow-up is required, her randomized placebo-controlled trial showed that after 1 year, women taking the bisphosphonate showed a significant increase in bone mineral density (BMD) at both the hip and spine, while those taking the placebo experienced a significant decrease at both sites.

Dr. Lester, of the Cancer Research Centre of Weston Park Hospital, Sheffield, England, examined ibandronate's effects in 131 postmenopausal women with estrogen receptor-positive breast cancers. The women were grouped according to baseline BMD: 68 had normal BMD (mean age 63 years), 50 were osteopenic (mean age 67 years), and 13 were osteoporotic (mean age 71 years).

All patients were taking calcium and vitamin D supplements in addition to anastrozole. Those with normal BMD continued on the supplements. Osteopenic patients were randomized to either 150 mg oral ibandronate every 28 days (25 patients) or placebo (25 patients). All osteoporotic women received the same monthly ibandronate treatment.

Ibandronate significantly increased BMD at the hip and spine in both treated groups. At 1 year, osteopenic women had a mean increase of 2.8% at the lumbar spine and 1.4% at the hip. After 1 year, five of the previously osteopenic women were found to have normal BMD.

Women in the placebo group had a decrease of BMD at both sites (mean −2.6% at the lumbar spine and −2.3% at the hip).

During the blinded period, two osteopenic patients lost more than 10% of their BMD at either the spine or hip. They were withdrawn and unblinded; both had been taking the placebo and both were offered open-label ibandronate.

Among the osteoporotic women, the mean increase in BMD was 2.6% at the lumbar spine and 2.6% at the hip. Seven previously osteoporotic patients were found to be osteopenic at 1-year follow-up.

Of the 68 women with initially normal BMD untreated with ibandronate, 20 were followed for 2 years. Follow-up scans showed a mean BMD decrease of −4% at the lumbar spine and −3% at the hip. Despite these changes, however, none of the women developed osteoporosis.

ELSEVIER GLOBAL MEDICAL NEWS