Alison Palkhivala

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented here at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study also revealed in 2002 that it may increase cardiovascular risk. Experts are therefore exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could be of benefit to postmenopausal women with very low or even undetectable estradiol levels. This group of patients was considered to have a high likelihood of benefiting because, as a group, they have a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or to placebo for 24 months. Bioavailable estradiol levels in these women were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the women's levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), both markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater reductions in osteocalcin and BSAP than women in the highest quintile of bioavailable estrogen in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, compared with women in the highest quintile. There was no evident impact of treatment on spine BMD.

On the basis of these results, the authors concluded that “measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover.”

During a press conference, however, Dr. Huang warned that it is still not clear whether the very women who appear to have most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also have most to lose. That is, these women may be most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented here at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study also revealed in 2002 that it may increase cardiovascular risk. Experts are therefore exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could be of benefit to postmenopausal women with very low or even undetectable estradiol levels. This group of patients was considered to have a high likelihood of benefiting because, as a group, they have a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or to placebo for 24 months. Bioavailable estradiol levels in these women were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the women's levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), both markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater reductions in osteocalcin and BSAP than women in the highest quintile of bioavailable estrogen in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, compared with women in the highest quintile. There was no evident impact of treatment on spine BMD.

On the basis of these results, the authors concluded that “measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover.”

During a press conference, however, Dr. Huang warned that it is still not clear whether the very women who appear to have most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also have most to lose. That is, these women may be most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented here at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study also revealed in 2002 that it may increase cardiovascular risk. Experts are therefore exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could be of benefit to postmenopausal women with very low or even undetectable estradiol levels. This group of patients was considered to have a high likelihood of benefiting because, as a group, they have a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or to placebo for 24 months. Bioavailable estradiol levels in these women were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the women's levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), both markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater reductions in osteocalcin and BSAP than women in the highest quintile of bioavailable estrogen in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, compared with women in the highest quintile. There was no evident impact of treatment on spine BMD.

On the basis of these results, the authors concluded that “measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover.”

During a press conference, however, Dr. Huang warned that it is still not clear whether the very women who appear to have most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also have most to lose. That is, these women may be most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Aromatase inhibitors can wreak havoc on bone mineral density and increase the risk of fracture in patients being treated for breast cancer, Dr. Eugene McCloskey said at the annual meeting of the International Bone and Mineral Society.

Breast cancer has long been known to be linked with poor bone health, said Dr. McCloskey of the metabolic bone center at the University of Sheffield (England). In fact, results of the Women Health Initiative Observation Study revealed that postmenopausal women with a history of breast cancer have a higher risk for clinical fractures than do women with no such cancer history, even after adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle (Arch. Intern. Med. 2005;165:552-8).

Although some of this might be explained by the fact that women with a history of breast cancer avoid hormone replacement therapy (which helps bone but may increase the risk of cancer relapse), it appears that the link between poor bone health and breast cancer is mediated mainly by the treatment used.

In premenopausal women, chemotherapy for breast cancer has been associated with reductions in bone mineral density when it induces ovarian failure, resulting in early menopause. Women who have already undergone menopause naturally do not generally experience ill effects of chemotherapy on bone.

Cancer treatments that induce ovarian failure have the worst effects on bone, Dr. McCloskey said, but these are followed closely by aromatase inhibitors (AIs), which have been shown to worsen the risk for both joint pain and fractures. Because of their superior efficacy and safety, these agents are becoming the standard treatment for early breast cancer, replacing tamoxifen, a drug that may have a beneficial effect on bone.

One solution to the effect of AIs on bone health that has been put forward is to combine these agents with tamoxifen. Unfortunately, adding tamoxifen to an AI has been shown to wipe out the additional cancer-fighting effect of the AI.

It appears that all currently available AIs have at least some negative effect on bone health. Both letrozole and anastrozole have been shown to increase the risk of fracture by about the same amount. There was some hope that the newest AI, exemestane, would have bone-sparing properties because of its androgeniclike metabolite. So far, however, evidence supporting that hope is, at best, weak. In fact, a 2007 update of a clinical trial with exemestane has shown a significantly increased risk of fracture among women taking exemestane, compared with those taking tamoxifen (Lancet Oncol. 2007;8:89–91).

Given that the benefits of AIs far outweigh the disadvantages in many women with breast cancer, clinicians must look for ways to treat AI-related bone loss. Dr. McCloskey reviewed the literature on potential treatments and said that bisphosphonates remain the best bet when used at the same doses as those used to treat osteoporosis. Exercise, although associated with an improved quality of life, does not affect bone mineral density in women who are also taking bisphosphonates. Calcium and vitamin D supplementation is also important. Estrogen replacement could also be beneficial, but this therapy is controversial because of its possible association with an increased risk of cancer recurrence.

The question remains, which breast cancer patients require treatment to prevent fracture? Based on guidelines put forth by the American College of Clinical Oncology, women considered at high risk for fracture should receive treatment. Currently, the greatest known risk factors for fracture are age, geographical region, and treatment used. It remains unclear, however, exactly who is “high risk,” and additional guidelines in this area are needed, Dr. McCloskey said.

MONTREAL — Aromatase inhibitors can wreak havoc on bone mineral density and increase the risk of fracture in patients being treated for breast cancer, Dr. Eugene McCloskey said at the annual meeting of the International Bone and Mineral Society.

Breast cancer has long been known to be linked with poor bone health, said Dr. McCloskey of the metabolic bone center at the University of Sheffield (England). In fact, results of the Women Health Initiative Observation Study revealed that postmenopausal women with a history of breast cancer have a higher risk for clinical fractures than do women with no such cancer history, even after adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle (Arch. Intern. Med. 2005;165:552-8).

Although some of this might be explained by the fact that women with a history of breast cancer avoid hormone replacement therapy (which helps bone but may increase the risk of cancer relapse), it appears that the link between poor bone health and breast cancer is mediated mainly by the treatment used.

In premenopausal women, chemotherapy for breast cancer has been associated with reductions in bone mineral density when it induces ovarian failure, resulting in early menopause. Women who have already undergone menopause naturally do not generally experience ill effects of chemotherapy on bone.

Cancer treatments that induce ovarian failure have the worst effects on bone, Dr. McCloskey said, but these are followed closely by aromatase inhibitors (AIs), which have been shown to worsen the risk for both joint pain and fractures. Because of their superior efficacy and safety, these agents are becoming the standard treatment for early breast cancer, replacing tamoxifen, a drug that may have a beneficial effect on bone.

One solution to the effect of AIs on bone health that has been put forward is to combine these agents with tamoxifen. Unfortunately, adding tamoxifen to an AI has been shown to wipe out the additional cancer-fighting effect of the AI.

It appears that all currently available AIs have at least some negative effect on bone health. Both letrozole and anastrozole have been shown to increase the risk of fracture by about the same amount. There was some hope that the newest AI, exemestane, would have bone-sparing properties because of its androgeniclike metabolite. So far, however, evidence supporting that hope is, at best, weak. In fact, a 2007 update of a clinical trial with exemestane has shown a significantly increased risk of fracture among women taking exemestane, compared with those taking tamoxifen (Lancet Oncol. 2007;8:89–91).

Given that the benefits of AIs far outweigh the disadvantages in many women with breast cancer, clinicians must look for ways to treat AI-related bone loss. Dr. McCloskey reviewed the literature on potential treatments and said that bisphosphonates remain the best bet when used at the same doses as those used to treat osteoporosis. Exercise, although associated with an improved quality of life, does not affect bone mineral density in women who are also taking bisphosphonates. Calcium and vitamin D supplementation is also important. Estrogen replacement could also be beneficial, but this therapy is controversial because of its possible association with an increased risk of cancer recurrence.

The question remains, which breast cancer patients require treatment to prevent fracture? Based on guidelines put forth by the American College of Clinical Oncology, women considered at high risk for fracture should receive treatment. Currently, the greatest known risk factors for fracture are age, geographical region, and treatment used. It remains unclear, however, exactly who is “high risk,” and additional guidelines in this area are needed, Dr. McCloskey said.

MONTREAL — Aromatase inhibitors can wreak havoc on bone mineral density and increase the risk of fracture in patients being treated for breast cancer, Dr. Eugene McCloskey said at the annual meeting of the International Bone and Mineral Society.

Breast cancer has long been known to be linked with poor bone health, said Dr. McCloskey of the metabolic bone center at the University of Sheffield (England). In fact, results of the Women Health Initiative Observation Study revealed that postmenopausal women with a history of breast cancer have a higher risk for clinical fractures than do women with no such cancer history, even after adjusting for factors related to hormone levels, risk of fall, fracture history, medication use, comorbidity, and lifestyle (Arch. Intern. Med. 2005;165:552-8).

Although some of this might be explained by the fact that women with a history of breast cancer avoid hormone replacement therapy (which helps bone but may increase the risk of cancer relapse), it appears that the link between poor bone health and breast cancer is mediated mainly by the treatment used.

In premenopausal women, chemotherapy for breast cancer has been associated with reductions in bone mineral density when it induces ovarian failure, resulting in early menopause. Women who have already undergone menopause naturally do not generally experience ill effects of chemotherapy on bone.

Cancer treatments that induce ovarian failure have the worst effects on bone, Dr. McCloskey said, but these are followed closely by aromatase inhibitors (AIs), which have been shown to worsen the risk for both joint pain and fractures. Because of their superior efficacy and safety, these agents are becoming the standard treatment for early breast cancer, replacing tamoxifen, a drug that may have a beneficial effect on bone.

One solution to the effect of AIs on bone health that has been put forward is to combine these agents with tamoxifen. Unfortunately, adding tamoxifen to an AI has been shown to wipe out the additional cancer-fighting effect of the AI.

It appears that all currently available AIs have at least some negative effect on bone health. Both letrozole and anastrozole have been shown to increase the risk of fracture by about the same amount. There was some hope that the newest AI, exemestane, would have bone-sparing properties because of its androgeniclike metabolite. So far, however, evidence supporting that hope is, at best, weak. In fact, a 2007 update of a clinical trial with exemestane has shown a significantly increased risk of fracture among women taking exemestane, compared with those taking tamoxifen (Lancet Oncol. 2007;8:89–91).

Given that the benefits of AIs far outweigh the disadvantages in many women with breast cancer, clinicians must look for ways to treat AI-related bone loss. Dr. McCloskey reviewed the literature on potential treatments and said that bisphosphonates remain the best bet when used at the same doses as those used to treat osteoporosis. Exercise, although associated with an improved quality of life, does not affect bone mineral density in women who are also taking bisphosphonates. Calcium and vitamin D supplementation is also important. Estrogen replacement could also be beneficial, but this therapy is controversial because of its possible association with an increased risk of cancer recurrence.

The question remains, which breast cancer patients require treatment to prevent fracture? Based on guidelines put forth by the American College of Clinical Oncology, women considered at high risk for fracture should receive treatment. Currently, the greatest known risk factors for fracture are age, geographical region, and treatment used. It remains unclear, however, exactly who is “high risk,” and additional guidelines in this area are needed, Dr. McCloskey said.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

MONTREAL — Three infusions of the bisphophonate ibandronate given a month apart may be all that is needed to significantly lessen clinical symptoms of bone marrow edema in most patients, according to a poster presented here at the 17th Scientific Meeting of the International Bone and Mineral Society. The treatment also improved signs of disease detected via imaging.

In a study conducted in an ambulatory setting, Dr. Christoph Bartl, of the Technical University of Munich, Germany, and colleagues gave an infusion of 6 mg of ibandronate once a month for 3 months to 42 patients with bone marrow edema (BME) confirmed by magnetic resonance imaging (MRI). The average age of patients was 43 years, and they had been experiencing BME symptoms for a mean of 4.2 months. The BME involved the ankle in 18 patients and the knee in 24. Nineteen of the cases of BME were classified as idiopathic, 13 were posttraumatic, and 10 were secondary to active osteoarthritis or mechanical stress.

The Mazur foot score, the Larson knee score, and a 0- to 10-point visual analog scale (VAS) for pain were used for clinical scoring of the effect of the intervention.

After 3 months, patients' mean VAS score dropped from 7.7 to 2.6. It dropped again to 1.8 at 6 months. Reductions in pain were significant both during rest and while the patients were active (P = <0.01).

For patients with affected ankles, Mazur score immediately following surgery was 58; after 3 months of ibandronate therapy, the score increased to 82, and increased to 89.6 after 3 months more (P = <0.05). Similarly, for patients with affected knees, Larson score increased from a preoperative 52 to 88 after 3 months of therapy and to 92 after 6 months of therapy (P = <0.05).

MRI revealed that 70% of patients experienced a significant reduction in BME size or complete normalization of the affected area with ibandronate treatment. Another 21% showed little or no change with MRI. The final 9% of patients did not undergo follow-up MRI, but three of them experienced significant clinical improvement.

Ibandronate therapy was well-tolerated overall, with 17% of patients experiencing mild acute phase reactions consisting of flulike symptoms within 2 days of receiving an infusion. Most patients—a full 86%—reported that their results with ibandronate were good or excellent.

MONTREAL – Antiresorptive drugs help reduce the risk of low-trauma, nonvertebral fractures among women over 50 being treated in a real-world setting, according to a Canadian case-control study presented at the annual meeting of the International Bone and Mineral Society.

Women with a prevalent fracture or with frank osteoporosis appeared to have most to gain from these drugs in terms of fracture risk reduction.

Dr. Suzanne Morin of McGill University in Montreal, and her colleagues, obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over the age of 50 were randomly selected from nine regions across Canada for follow-up. The women in this study underwent a standardized interview that addressed demographics and medical history. They also underwent measurement of their bone mineral density (BMD).

The researchers conducted a case-control analysis of the CaMos data in which women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet, or vertebrae, were matched with up to three controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and availability of baseline BMD.

Overall, 477 cases and 1,377 matched controls were included in the analysis. Among matched cases, 37% were current users of antiresorptive agents, compared with 41% among matched controls. Antiresorptive agents used included estrogen, bisphosphonates, selective estrogen receptor modulators (SERMs), and calcitonin.

Current use of antiresorptive drugs was associated with an adjusted odds ratio of 0.68 for risk of having a low-trauma fracture. Among women with a prevalent fracture or a BMD indicative of osteoporosis, the OR was 0.58, compared with an OR of 0.88 for women with neither of these risk factors.

MONTREAL – Antiresorptive drugs help reduce the risk of low-trauma, nonvertebral fractures among women over 50 being treated in a real-world setting, according to a Canadian case-control study presented at the annual meeting of the International Bone and Mineral Society.

Women with a prevalent fracture or with frank osteoporosis appeared to have most to gain from these drugs in terms of fracture risk reduction.

Dr. Suzanne Morin of McGill University in Montreal, and her colleagues, obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over the age of 50 were randomly selected from nine regions across Canada for follow-up. The women in this study underwent a standardized interview that addressed demographics and medical history. They also underwent measurement of their bone mineral density (BMD).

The researchers conducted a case-control analysis of the CaMos data in which women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet, or vertebrae, were matched with up to three controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and availability of baseline BMD.

Overall, 477 cases and 1,377 matched controls were included in the analysis. Among matched cases, 37% were current users of antiresorptive agents, compared with 41% among matched controls. Antiresorptive agents used included estrogen, bisphosphonates, selective estrogen receptor modulators (SERMs), and calcitonin.

Current use of antiresorptive drugs was associated with an adjusted odds ratio of 0.68 for risk of having a low-trauma fracture. Among women with a prevalent fracture or a BMD indicative of osteoporosis, the OR was 0.58, compared with an OR of 0.88 for women with neither of these risk factors.

MONTREAL – Antiresorptive drugs help reduce the risk of low-trauma, nonvertebral fractures among women over 50 being treated in a real-world setting, according to a Canadian case-control study presented at the annual meeting of the International Bone and Mineral Society.

Women with a prevalent fracture or with frank osteoporosis appeared to have most to gain from these drugs in terms of fracture risk reduction.

Dr. Suzanne Morin of McGill University in Montreal, and her colleagues, obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over the age of 50 were randomly selected from nine regions across Canada for follow-up. The women in this study underwent a standardized interview that addressed demographics and medical history. They also underwent measurement of their bone mineral density (BMD).

The researchers conducted a case-control analysis of the CaMos data in which women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet, or vertebrae, were matched with up to three controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and availability of baseline BMD.

Overall, 477 cases and 1,377 matched controls were included in the analysis. Among matched cases, 37% were current users of antiresorptive agents, compared with 41% among matched controls. Antiresorptive agents used included estrogen, bisphosphonates, selective estrogen receptor modulators (SERMs), and calcitonin.

Current use of antiresorptive drugs was associated with an adjusted odds ratio of 0.68 for risk of having a low-trauma fracture. Among women with a prevalent fracture or a BMD indicative of osteoporosis, the OR was 0.58, compared with an OR of 0.88 for women with neither of these risk factors.

MONTREAL — The decreased reliance on brute force and manual labor for human survival during the past few thousand years has taken a toll on bone density, anthropologist Christopher B. Ruff, Ph.D., said at the 17th Scientific Meeting of the International Bone and Mineral Society.

This conclusion comes from a review of archaeological samples of human long bones, reported Dr. Ruff of the center for functional anatomy and evolution, Johns Hopkins University, Baltimore. The modern human genus essentially originated about 2 million years ago. Using cross sections of long bones as a measurement of bone strength reveals that, between 2 million and 8,000 years ago, bone strength relative to body size in humans steadily diminished. Extrapolating the trend to modern times reveals modern humans have bone strength about 30% below what would be expected if the trend had continued. “There are many different possible explanations for this, but my preferred explanation is an environmental one relating to mechanical loading and muscle activity effects,” said Dr. Ruff. Over time but especially in the past few thousand years, modern advances have meant brute force and manual labor are less important for survival. This trend demonstrates how important mechanical loading is for bone strength. The price, of course, is today's increased incidence of osteoporotic fractures.

Archaeological samples also shed light on normal growth and developmental patterns in bone. “Patterns of growth and development are very ancient,” said Dr. Ruff. Computed tomography of the bones of 31 children of various ages who died more than a million years ago reveals a pattern of periosteal expansion, followed, around adolescence, by endosteal expansion and then contraction. Studies of modern tennis players who began practicing the sport at different ages reveal that the same pattern of bone growth persists today.

In addition to revealing these patterns of bone growth, archaeological samples also allow for identifying differences between males and females. For instance, marked endosteal contraction occurs in late adolescence in the female femur but is less apparent in the upper limbs; endosteal contraction occurs equally in upper and lower limbs in men. Both systemic factors, such as hormones, and mechanical factors, such as differences in body size, account for these differences, said Dr. Ruff.

Comparing humans to other species reveals an important difference: Although primates, who use all four limbs for locomotion, have similar bone strength in their upper and lower limbs, bipedal humans have stronger lower limbs than upper limbs. This difference starts to develop after about 1 year of age, because humans are generally quadrupedal in their first year of life. Recognizing this helps archaeologists identify when humans first relied primarily on their lower limbs for locomotion. It also reveals that differences between child and adult skeletons and the growth patterns that lead from one to the other have been maintained for at least 2 million years.

During the past 2 million years, patterns of bone growth and development have remained remarkably stable in humans, allowing for the use of archaeological samples to better understand the bones of modern man. “Archaeological samples tend to be more homogeneous genetically and environmentally, so you get a cleaner signal,” said Dr. Ruff. “They are [from] very similar populations with similar diets, similar activity levels. Skeletal material is available for all ages, as opposed to autopsy samples, where it's very difficult to find younger individuals, and [archaeological samples] can serve as a useful baseline for comparison with really modern samples.”

There are disadvantages to using archaeological samples, however. These include the need to rely on cross-sectional study designs, the potential bias inherent in only being able to study the skeletons that have survived this long, and the inability to reliably determine the sex of the skeletons of humans who died before adolescence or in old age.

MONTREAL — The decreased reliance on brute force and manual labor for human survival during the past few thousand years has taken a toll on bone density, anthropologist Christopher B. Ruff, Ph.D., said at the 17th Scientific Meeting of the International Bone and Mineral Society.

This conclusion comes from a review of archaeological samples of human long bones, reported Dr. Ruff of the center for functional anatomy and evolution, Johns Hopkins University, Baltimore. The modern human genus essentially originated about 2 million years ago. Using cross sections of long bones as a measurement of bone strength reveals that, between 2 million and 8,000 years ago, bone strength relative to body size in humans steadily diminished. Extrapolating the trend to modern times reveals modern humans have bone strength about 30% below what would be expected if the trend had continued. “There are many different possible explanations for this, but my preferred explanation is an environmental one relating to mechanical loading and muscle activity effects,” said Dr. Ruff. Over time but especially in the past few thousand years, modern advances have meant brute force and manual labor are less important for survival. This trend demonstrates how important mechanical loading is for bone strength. The price, of course, is today's increased incidence of osteoporotic fractures.

Archaeological samples also shed light on normal growth and developmental patterns in bone. “Patterns of growth and development are very ancient,” said Dr. Ruff. Computed tomography of the bones of 31 children of various ages who died more than a million years ago reveals a pattern of periosteal expansion, followed, around adolescence, by endosteal expansion and then contraction. Studies of modern tennis players who began practicing the sport at different ages reveal that the same pattern of bone growth persists today.

In addition to revealing these patterns of bone growth, archaeological samples also allow for identifying differences between males and females. For instance, marked endosteal contraction occurs in late adolescence in the female femur but is less apparent in the upper limbs; endosteal contraction occurs equally in upper and lower limbs in men. Both systemic factors, such as hormones, and mechanical factors, such as differences in body size, account for these differences, said Dr. Ruff.

Comparing humans to other species reveals an important difference: Although primates, who use all four limbs for locomotion, have similar bone strength in their upper and lower limbs, bipedal humans have stronger lower limbs than upper limbs. This difference starts to develop after about 1 year of age, because humans are generally quadrupedal in their first year of life. Recognizing this helps archaeologists identify when humans first relied primarily on their lower limbs for locomotion. It also reveals that differences between child and adult skeletons and the growth patterns that lead from one to the other have been maintained for at least 2 million years.

During the past 2 million years, patterns of bone growth and development have remained remarkably stable in humans, allowing for the use of archaeological samples to better understand the bones of modern man. “Archaeological samples tend to be more homogeneous genetically and environmentally, so you get a cleaner signal,” said Dr. Ruff. “They are [from] very similar populations with similar diets, similar activity levels. Skeletal material is available for all ages, as opposed to autopsy samples, where it's very difficult to find younger individuals, and [archaeological samples] can serve as a useful baseline for comparison with really modern samples.”

There are disadvantages to using archaeological samples, however. These include the need to rely on cross-sectional study designs, the potential bias inherent in only being able to study the skeletons that have survived this long, and the inability to reliably determine the sex of the skeletons of humans who died before adolescence or in old age.

MONTREAL — The decreased reliance on brute force and manual labor for human survival during the past few thousand years has taken a toll on bone density, anthropologist Christopher B. Ruff, Ph.D., said at the 17th Scientific Meeting of the International Bone and Mineral Society.

This conclusion comes from a review of archaeological samples of human long bones, reported Dr. Ruff of the center for functional anatomy and evolution, Johns Hopkins University, Baltimore. The modern human genus essentially originated about 2 million years ago. Using cross sections of long bones as a measurement of bone strength reveals that, between 2 million and 8,000 years ago, bone strength relative to body size in humans steadily diminished. Extrapolating the trend to modern times reveals modern humans have bone strength about 30% below what would be expected if the trend had continued. “There are many different possible explanations for this, but my preferred explanation is an environmental one relating to mechanical loading and muscle activity effects,” said Dr. Ruff. Over time but especially in the past few thousand years, modern advances have meant brute force and manual labor are less important for survival. This trend demonstrates how important mechanical loading is for bone strength. The price, of course, is today's increased incidence of osteoporotic fractures.

Archaeological samples also shed light on normal growth and developmental patterns in bone. “Patterns of growth and development are very ancient,” said Dr. Ruff. Computed tomography of the bones of 31 children of various ages who died more than a million years ago reveals a pattern of periosteal expansion, followed, around adolescence, by endosteal expansion and then contraction. Studies of modern tennis players who began practicing the sport at different ages reveal that the same pattern of bone growth persists today.

In addition to revealing these patterns of bone growth, archaeological samples also allow for identifying differences between males and females. For instance, marked endosteal contraction occurs in late adolescence in the female femur but is less apparent in the upper limbs; endosteal contraction occurs equally in upper and lower limbs in men. Both systemic factors, such as hormones, and mechanical factors, such as differences in body size, account for these differences, said Dr. Ruff.

Comparing humans to other species reveals an important difference: Although primates, who use all four limbs for locomotion, have similar bone strength in their upper and lower limbs, bipedal humans have stronger lower limbs than upper limbs. This difference starts to develop after about 1 year of age, because humans are generally quadrupedal in their first year of life. Recognizing this helps archaeologists identify when humans first relied primarily on their lower limbs for locomotion. It also reveals that differences between child and adult skeletons and the growth patterns that lead from one to the other have been maintained for at least 2 million years.

During the past 2 million years, patterns of bone growth and development have remained remarkably stable in humans, allowing for the use of archaeological samples to better understand the bones of modern man. “Archaeological samples tend to be more homogeneous genetically and environmentally, so you get a cleaner signal,” said Dr. Ruff. “They are [from] very similar populations with similar diets, similar activity levels. Skeletal material is available for all ages, as opposed to autopsy samples, where it's very difficult to find younger individuals, and [archaeological samples] can serve as a useful baseline for comparison with really modern samples.”

There are disadvantages to using archaeological samples, however. These include the need to rely on cross-sectional study designs, the potential bias inherent in only being able to study the skeletons that have survived this long, and the inability to reliably determine the sex of the skeletons of humans who died before adolescence or in old age.

MONTREAL — Antiresorptive drugs reduce the risk of low-trauma, nonvertebral fractures in women over 50, and women with a prevalent fracture or frank osteoporosis have most to gain from these drugs, according to a study presented at the annual meeting of the International Bone and Mineral Society.

Dr. Suzanne Morin, of McGill University, Montreal, and colleagues obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over age 50 were randomly selected from across Canada. Demographics, medical history, and bone mineral density (BMD) were collected.

The researchers conducted a case-control analysis of the data. Women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet or vertebrae, were matched with controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and baseline BMD availability; 477 cases and 1,377 controls were included. Among cases, 37% were current users of antiresorptive agents (estrogen, bisphosphonates, selective estrogen receptor modulators [SERMs], and calcitonin) versus 41% of controls. Antiresorptive drug use was tied to an adjusted odds ratio of 0.68 for risk of a low-trauma fracture. Among those with a prevalent fracture or a BMD indicative of osteoporosis, OR was 0.58, versus 0.88 for women with neither of these risk factors.

MONTREAL — Antiresorptive drugs reduce the risk of low-trauma, nonvertebral fractures in women over 50, and women with a prevalent fracture or frank osteoporosis have most to gain from these drugs, according to a study presented at the annual meeting of the International Bone and Mineral Society.

Dr. Suzanne Morin, of McGill University, Montreal, and colleagues obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over age 50 were randomly selected from across Canada. Demographics, medical history, and bone mineral density (BMD) were collected.

The researchers conducted a case-control analysis of the data. Women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet or vertebrae, were matched with controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and baseline BMD availability; 477 cases and 1,377 controls were included. Among cases, 37% were current users of antiresorptive agents (estrogen, bisphosphonates, selective estrogen receptor modulators [SERMs], and calcitonin) versus 41% of controls. Antiresorptive drug use was tied to an adjusted odds ratio of 0.68 for risk of a low-trauma fracture. Among those with a prevalent fracture or a BMD indicative of osteoporosis, OR was 0.58, versus 0.88 for women with neither of these risk factors.

MONTREAL — Antiresorptive drugs reduce the risk of low-trauma, nonvertebral fractures in women over 50, and women with a prevalent fracture or frank osteoporosis have most to gain from these drugs, according to a study presented at the annual meeting of the International Bone and Mineral Society.

Dr. Suzanne Morin, of McGill University, Montreal, and colleagues obtained data from the Canadian Multicentre Osteoporosis Study (CaMos), in which more than 6,000 women over age 50 were randomly selected from across Canada. Demographics, medical history, and bone mineral density (BMD) were collected.

The researchers conducted a case-control analysis of the data. Women with self-reported incident low-trauma fractures, excluding fractures of the head, hands, feet or vertebrae, were matched with controls with respect to time in study, age, prevalent osteoporosis, prevalent vertebral deformity, prior clinical low-trauma fracture, and baseline BMD availability; 477 cases and 1,377 controls were included. Among cases, 37% were current users of antiresorptive agents (estrogen, bisphosphonates, selective estrogen receptor modulators [SERMs], and calcitonin) versus 41% of controls. Antiresorptive drug use was tied to an adjusted odds ratio of 0.68 for risk of a low-trauma fracture. Among those with a prevalent fracture or a BMD indicative of osteoporosis, OR was 0.58, versus 0.88 for women with neither of these risk factors.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.

MONTREAL — Postmenopausal women with extremely low levels of bioavailable estradiol may benefit most from the bone-building effects of ultralow-dose hormone therapy, according to a study presented at the annual meeting of the International Bone and Mineral Society.

It remains unclear, however, whether these women are also more vulnerable to the negative effects of hormone therapy. Although estrogen therapy has been shown to suppress bone turnover in postmenopausal women, the Women's Health Study revealed in 2002 that it may increase cardiovascular risk. Experts are exploring the possibility that a dose of estrogen exists, at least for some women, that is high enough to improve bone parameters but too low to affect cardiovascular risk.

Dr. Alison Huang, of the University of California, San Francisco, and colleagues explored whether an ultralow dose of estradiol—only 0.014 mg/day delivered transdermally—could help postmenopausal women with very low or even undetectable estradiol levels. This group has a lower bone mineral density (BMD), increased bone turnover, and are at an increased risk for hip and vertebral fractures.

For the trial, 417 postmenopausal women were randomized to a 0.014- mg/day transdermal estradiol patch or placebo for 2 years. Bioavailable estradiol levels were calculated as the ratio of total estradiol to sex hormone-binding globulin.

The investigators measured the levels of serum osteocalcin and bone-specific alkaline phosphatase (BSAP), markers of bone turnover, at 12 months. They also measured total hip and lumbar spine BMD at 24 months in women who adhered at least 80% to the study protocol.

Women in the lowest quintile of bioavailable estradiol had significantly greater drops in osteocalcin and BSAP than women in the highest quintile of bioavailable estradiol in response to therapy. In women in the lowest quintile, there was also a trend toward greater improvement in total hip BMD, versus women in the highest quintile. Spine BMD was unaffected. “Measurement of bioavailable estradiol levels identifies women for whom the ultralow-dose 0.014-mg/day transdermal estrogen therapy may have significant reductions in bone turnover,” wrote the authors

During a press conference, however, Dr. Huang warned it is still not clear whether the women who appear to have the most to gain from estradiol therapy—those with very low baseline bioavailable estradiol levels—may also be the most vulnerable to the effects of hormone therapy on cardiovascular health.