Osteoporosis

Major Finding: Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (odds ratio = 0.19).

Data Source: The Hip Fracture Intervention Trial (HIPFIT) compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions versus 62 randomized to usual care (6-12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies).

Disclosures: Dr. Singh said she had no relevant financial disclosures.

NEW ORLEANS — Compared with usual care after hip fracture, a comprehensive and targeted intervention that includes high-intensity progressive resistance training over 12 months lowers mortality, decreases nursing home admissions, improves activities of daily living dependency, and decreases the use of assistive devices, according to a randomized, controlled trial.

“It is possible to change the most important outcomes for these people,” Dr. Maria A. Fiatarone Singh said.

Functional dependency, however, did not significantly differ between groups.

Many facets of hip fractures have been studied, from pharmacologic prevention of osteoporosis to acute hospital interventions to fracture rehabilitation. “Although we've done a lot of studies, we still have not figured out how to prevent people from entering a nursing home or dying,” said Dr. Singh, professor of medicine and chair of exercise and sport science at the University of Sydney.

So Dr. Singh and her colleagues launched the Hip Fracture Intervention Trial (HIPFIT). They compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions vs. 62 patients randomized to usual care. She presented results at the meeting.

Intervention was associated with an 84% reduction in the likelihood of nursing home admission (odds ratio, 0.16), compared with usual care, Dr. Singh explained. In absolute numbers, 5 intervention patients (8%) and 12 control patients (19%) were admitted to a nursing home during the 12 months of follow-up.

“Hip fracture is associated with chronic pain, reduced mobility, disability, and increasing degree of dependence. After hip fracture, 10%–20% of formerly community-dwelling people require long-term nursing home care,” Dr. Singh said.

Four intervention patients and eight usual-care patients died. Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (OR = 0.19). Cardiovascular disease, infection, and stroke were among the causes.

Dr. Singh and her associates hypothesized that long-term disability and nursing home utilization after hip fracture would be reduced by targeted, multifactorial intervention aimed at the primary risk factors. They chose modifiable risk factors to make application of their findings more practical, including sarcopenia/muscle weakness, poor balance or gait, malnutrition or weight loss, vitamin D insufficiency, and vision concerns.

All intervention group participants received hip protectors and supervised, high-intensity, progressive resistance training for 12 months. The protocol included seven exercises designed for both upper and lower body strength. A meeting attendee questioned how patients were able to exercise after hip fracture. The intervention began with an isometric measure of strength and actual strength training started about 6 months after fracture, Dr. Singh replied.

Balance training exercises were progressive as well. As tasks were mastered, participants graduated to a more difficult level. For example, if a person could balance holding on to something with two hands, next they progressed to one hand and then to one finger.

Interventions were added for individual participants as needed, up to a total of 13. Treatment of depression, nutritional supplementation, medication management, and vision assessment are examples. Some participants received home assessment and referral to community services. Others received interventions to address risk and/or fear of falling, low self-efficacy, and polypharmacy.

Evaluations were done at baseline and at 4 and 12 months after fracture, with regular review by geriatricians, general practitioners, and ophthalmologists.

Usual care included 6–12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies.

Even though overall functional dependency did not differ significantly, intervention was associated with significantly less decline in some functional dependency KATZ scores (total, continence, and transfer) at 12 months, compared with their prefracture baseline.

In the current study, after the researchers controlled for age, there was less of a decline in function for total KATZ score, transfer change, and continence change if patients were in intervention group vs. usual care, Dr. Singh said.

At baseline, the community-dwelling participants were 69% female; mean age, 79 years; 83% at nutritional risk; 88% vitamin D insufficient; 90% living independently (vs. 10% in nursing homes); and 38% were cognitively impaired. A total 45% were depressed. The mean number of chronic diseases was 3.4. The usual-care group reported worse bodily pain, the only significant difference between groups.

There were no adverse events, except for some musculoskeletal soreness after activity, said Dr. Singh, who is also a senior research associate at Harvard University and a visiting scientist for the Jean Mayer USDA Human Nutrition Research Centre on Aging at Tufts University, all in Boston.

Resistance training was 1 of 13 interventions that kept hip fracture patients out of nursing homes.

Source ©Martinan/Fotolia.com

Major Finding: Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (odds ratio = 0.19).

Data Source: The Hip Fracture Intervention Trial (HIPFIT) compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions versus 62 randomized to usual care (6-12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies).

Disclosures: Dr. Singh said she had no relevant financial disclosures.

NEW ORLEANS — Compared with usual care after hip fracture, a comprehensive and targeted intervention that includes high-intensity progressive resistance training over 12 months lowers mortality, decreases nursing home admissions, improves activities of daily living dependency, and decreases the use of assistive devices, according to a randomized, controlled trial.

“It is possible to change the most important outcomes for these people,” Dr. Maria A. Fiatarone Singh said.

Functional dependency, however, did not significantly differ between groups.

Many facets of hip fractures have been studied, from pharmacologic prevention of osteoporosis to acute hospital interventions to fracture rehabilitation. “Although we've done a lot of studies, we still have not figured out how to prevent people from entering a nursing home or dying,” said Dr. Singh, professor of medicine and chair of exercise and sport science at the University of Sydney.

So Dr. Singh and her colleagues launched the Hip Fracture Intervention Trial (HIPFIT). They compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions vs. 62 patients randomized to usual care. She presented results at the meeting.

Intervention was associated with an 84% reduction in the likelihood of nursing home admission (odds ratio, 0.16), compared with usual care, Dr. Singh explained. In absolute numbers, 5 intervention patients (8%) and 12 control patients (19%) were admitted to a nursing home during the 12 months of follow-up.

“Hip fracture is associated with chronic pain, reduced mobility, disability, and increasing degree of dependence. After hip fracture, 10%–20% of formerly community-dwelling people require long-term nursing home care,” Dr. Singh said.

Four intervention patients and eight usual-care patients died. Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (OR = 0.19). Cardiovascular disease, infection, and stroke were among the causes.

Dr. Singh and her associates hypothesized that long-term disability and nursing home utilization after hip fracture would be reduced by targeted, multifactorial intervention aimed at the primary risk factors. They chose modifiable risk factors to make application of their findings more practical, including sarcopenia/muscle weakness, poor balance or gait, malnutrition or weight loss, vitamin D insufficiency, and vision concerns.

All intervention group participants received hip protectors and supervised, high-intensity, progressive resistance training for 12 months. The protocol included seven exercises designed for both upper and lower body strength. A meeting attendee questioned how patients were able to exercise after hip fracture. The intervention began with an isometric measure of strength and actual strength training started about 6 months after fracture, Dr. Singh replied.

Balance training exercises were progressive as well. As tasks were mastered, participants graduated to a more difficult level. For example, if a person could balance holding on to something with two hands, next they progressed to one hand and then to one finger.

Interventions were added for individual participants as needed, up to a total of 13. Treatment of depression, nutritional supplementation, medication management, and vision assessment are examples. Some participants received home assessment and referral to community services. Others received interventions to address risk and/or fear of falling, low self-efficacy, and polypharmacy.

Evaluations were done at baseline and at 4 and 12 months after fracture, with regular review by geriatricians, general practitioners, and ophthalmologists.

Usual care included 6–12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies.

Even though overall functional dependency did not differ significantly, intervention was associated with significantly less decline in some functional dependency KATZ scores (total, continence, and transfer) at 12 months, compared with their prefracture baseline.

In the current study, after the researchers controlled for age, there was less of a decline in function for total KATZ score, transfer change, and continence change if patients were in intervention group vs. usual care, Dr. Singh said.

At baseline, the community-dwelling participants were 69% female; mean age, 79 years; 83% at nutritional risk; 88% vitamin D insufficient; 90% living independently (vs. 10% in nursing homes); and 38% were cognitively impaired. A total 45% were depressed. The mean number of chronic diseases was 3.4. The usual-care group reported worse bodily pain, the only significant difference between groups.

There were no adverse events, except for some musculoskeletal soreness after activity, said Dr. Singh, who is also a senior research associate at Harvard University and a visiting scientist for the Jean Mayer USDA Human Nutrition Research Centre on Aging at Tufts University, all in Boston.

Resistance training was 1 of 13 interventions that kept hip fracture patients out of nursing homes.

Source ©Martinan/Fotolia.com

Major Finding: Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (odds ratio = 0.19).

Data Source: The Hip Fracture Intervention Trial (HIPFIT) compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions versus 62 randomized to usual care (6-12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies).

Disclosures: Dr. Singh said she had no relevant financial disclosures.

NEW ORLEANS — Compared with usual care after hip fracture, a comprehensive and targeted intervention that includes high-intensity progressive resistance training over 12 months lowers mortality, decreases nursing home admissions, improves activities of daily living dependency, and decreases the use of assistive devices, according to a randomized, controlled trial.

“It is possible to change the most important outcomes for these people,” Dr. Maria A. Fiatarone Singh said.

Functional dependency, however, did not significantly differ between groups.

Many facets of hip fractures have been studied, from pharmacologic prevention of osteoporosis to acute hospital interventions to fracture rehabilitation. “Although we've done a lot of studies, we still have not figured out how to prevent people from entering a nursing home or dying,” said Dr. Singh, professor of medicine and chair of exercise and sport science at the University of Sydney.

So Dr. Singh and her colleagues launched the Hip Fracture Intervention Trial (HIPFIT). They compared outcomes for 62 hip fracture patients randomized to resistance training and up to 12 other interventions vs. 62 patients randomized to usual care. She presented results at the meeting.

Intervention was associated with an 84% reduction in the likelihood of nursing home admission (odds ratio, 0.16), compared with usual care, Dr. Singh explained. In absolute numbers, 5 intervention patients (8%) and 12 control patients (19%) were admitted to a nursing home during the 12 months of follow-up.

“Hip fracture is associated with chronic pain, reduced mobility, disability, and increasing degree of dependence. After hip fracture, 10%–20% of formerly community-dwelling people require long-term nursing home care,” Dr. Singh said.

Four intervention patients and eight usual-care patients died. Age-adjusted risk of death was significantly reduced in the intervention group, compared with usual care (OR = 0.19). Cardiovascular disease, infection, and stroke were among the causes.

Dr. Singh and her associates hypothesized that long-term disability and nursing home utilization after hip fracture would be reduced by targeted, multifactorial intervention aimed at the primary risk factors. They chose modifiable risk factors to make application of their findings more practical, including sarcopenia/muscle weakness, poor balance or gait, malnutrition or weight loss, vitamin D insufficiency, and vision concerns.

All intervention group participants received hip protectors and supervised, high-intensity, progressive resistance training for 12 months. The protocol included seven exercises designed for both upper and lower body strength. A meeting attendee questioned how patients were able to exercise after hip fracture. The intervention began with an isometric measure of strength and actual strength training started about 6 months after fracture, Dr. Singh replied.

Balance training exercises were progressive as well. As tasks were mastered, participants graduated to a more difficult level. For example, if a person could balance holding on to something with two hands, next they progressed to one hand and then to one finger.

Interventions were added for individual participants as needed, up to a total of 13. Treatment of depression, nutritional supplementation, medication management, and vision assessment are examples. Some participants received home assessment and referral to community services. Others received interventions to address risk and/or fear of falling, low self-efficacy, and polypharmacy.

Evaluations were done at baseline and at 4 and 12 months after fracture, with regular review by geriatricians, general practitioners, and ophthalmologists.

Usual care included 6–12 weeks of physiotherapy, an orthopedic consult at 6 weeks, and any recommended therapies.

Even though overall functional dependency did not differ significantly, intervention was associated with significantly less decline in some functional dependency KATZ scores (total, continence, and transfer) at 12 months, compared with their prefracture baseline.

In the current study, after the researchers controlled for age, there was less of a decline in function for total KATZ score, transfer change, and continence change if patients were in intervention group vs. usual care, Dr. Singh said.

At baseline, the community-dwelling participants were 69% female; mean age, 79 years; 83% at nutritional risk; 88% vitamin D insufficient; 90% living independently (vs. 10% in nursing homes); and 38% were cognitively impaired. A total 45% were depressed. The mean number of chronic diseases was 3.4. The usual-care group reported worse bodily pain, the only significant difference between groups.

There were no adverse events, except for some musculoskeletal soreness after activity, said Dr. Singh, who is also a senior research associate at Harvard University and a visiting scientist for the Jean Mayer USDA Human Nutrition Research Centre on Aging at Tufts University, all in Boston.

Resistance training was 1 of 13 interventions that kept hip fracture patients out of nursing homes.

Source ©Martinan/Fotolia.com

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months, patients who received methotrexate plus intra-articular corticosteroid injections experienced significantly less bone loss in MCP joints 2–5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% in patients who received methotrexate plus injections, compared with −2.42% in those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote. “This may support the view that periarticular osteoporosis results from local production of proinflammatory cytokines which activate osteoclasts to break down bone locally and is not predominantly the result of circulating proinflammatory cytokines.”

They acknowledged certain limitations of the study, including the small sample size and the fact that “the precision of DXA for periarticular regions is poor compared with whole hand measurement. Furthermore, the method is not feasible for clinical use; it has therefore been recommended that assessment of the whole hand be used as a marker for periarticlar bone loss.”

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months, patients who received methotrexate plus intra-articular corticosteroid injections experienced significantly less bone loss in MCP joints 2–5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% in patients who received methotrexate plus injections, compared with −2.42% in those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote. “This may support the view that periarticular osteoporosis results from local production of proinflammatory cytokines which activate osteoclasts to break down bone locally and is not predominantly the result of circulating proinflammatory cytokines.”

They acknowledged certain limitations of the study, including the small sample size and the fact that “the precision of DXA for periarticular regions is poor compared with whole hand measurement. Furthermore, the method is not feasible for clinical use; it has therefore been recommended that assessment of the whole hand be used as a marker for periarticlar bone loss.”

Major Finding: In the first 3 months, the rate of bone loss among patients with early RA who were treated with intra-articular corticosteroid injections plus methotrexate vs. methotrexate alone was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Data Source: A study of 40 patients who were treated for 12 months.

Disclosures: The researchers stated that they had no relevant financial disclosures to make.

Patients with early rheumatoid arthritis who were on methotrexate and received intra-articular corticosteroid injections into inflamed metacarpophalangeal joints for 3 months lost less periarticular density than did those who received methotrexate alone, results from a small study demonstrated.

The finding “supports the concept that, in conditions where inflammation dominates such as early RA, treating inflammation is more important than the negative effect of corticosteroids on bone,” reported researchers led by Dr. Glenn Haugeberg.

Dr. Haugeberg, professor of neuroscience at the Norwegian University of Science and Technology, Trondheim, and a member of the department of rheumatology at Sørlandet Hospital in Kristiansand (Norway), and his associates at two clinical centers in the United Kingdom treated 19 early RA patients with methotrexate alone and 21 with methotrexate plus intra-articular corticosteroid injections for 3 months. Over the next 9 months, all 40 patients received methotrexate plus intra-articular corticosteroid injections.

To assess the effect of treatment on bone loss, the researchers used MRI of the metacarpophalangeal joints of the dominant hand (that is, MCP joints 2-5) at baseline and 3 and 12 months, as well as DXA images of both hands at baseline and 3, 6, and 12 months (Ann. Rheum. Dis. 2011;70:184-7). They used linear regression analysis to determine the association between reduction in bone mineral density and demographic and disease variables, adjusting for treatment group.

The mean age of patients was 54 years, and 55% were women. In the first 3 months, patients who received methotrexate plus intra-articular corticosteroid injections experienced significantly less bone loss in MCP joints 2–5 than did their counterparts in the methotrexate-only group. The rate of bone loss was −0.45% vs. −2.69%, respectively, in digit 2; −0.34% vs. −3.32% in digit 3; −0.39% vs. −2.57% in digit 4, and −0.59% vs. −2.70% in digit 5.

Bone loss in the hand overall was less pronounced over the same time period (−1.53% in patients who received methotrexate plus injections, compared with −2.42% in those in the methotrexate-only group).

In months 3-12, when all patients received intra-articular corticosteroid injections, only minor, nonsignificant differences in the rate of bone loss were observed between the two groups.

“Data from the current study suggest that bone loss may be arrested by intra-articular corticosteroid injections more effectively in periarticular regions than in the whole hand,” the researchers wrote. “This may support the view that periarticular osteoporosis results from local production of proinflammatory cytokines which activate osteoclasts to break down bone locally and is not predominantly the result of circulating proinflammatory cytokines.”

They acknowledged certain limitations of the study, including the small sample size and the fact that “the precision of DXA for periarticular regions is poor compared with whole hand measurement. Furthermore, the method is not feasible for clinical use; it has therefore been recommended that assessment of the whole hand be used as a marker for periarticlar bone loss.”

The Food and Drug Administration has approved the monoclonal antibody denosumab (Xgeva), which is indicated for fracture prevention in postmenopausal women at high risk, for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said in a written statement on the approval for the new indication.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

Amgen reported that bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer wrote in a statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa).

The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of those data were presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

Xgeva is delivered every 4 weeks as a 120-mg subcutaneous injection.

Because of the drug's expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

The Food and Drug Administration has approved the monoclonal antibody denosumab (Xgeva), which is indicated for fracture prevention in postmenopausal women at high risk, for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said in a written statement on the approval for the new indication.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

Amgen reported that bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer wrote in a statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa).

The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of those data were presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

Xgeva is delivered every 4 weeks as a 120-mg subcutaneous injection.

Because of the drug's expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

The Food and Drug Administration has approved the monoclonal antibody denosumab (Xgeva), which is indicated for fracture prevention in postmenopausal women at high risk, for the prevention of skeletal-related events in patients with bone metastases from solid tumors.

Denosumab maker Amgen made the announcement. The drug was given a 6-month priority review, indicating that it was considered a major advance in treatment.

“Xgeva has a different mechanism of action than currently approved drugs aimed at reducing bone complications from cancer,” Dr. Richard Pazdur, director of the Office of Oncology Drug Products in the FDA's Center for Drug Evaluation and Research, said in a written statement on the approval for the new indication.

A fully human monoclonal antibody with a unique mechanism of action, denosumab specifically targets the receptor activator of the nuclear factor kappa-B (RANK) ligand, the essential mediator of osteoclast fusion. The drug inhibits osteoclast formation, function, and survival, resulting in reduced bone resorption. The RANK ligand pathway was discovered by Amgen scientists in the mid-1990s, according to the company.

Amgen reported that bone metastases occur in 1.5 million cancer patients worldwide. They are most commonly seen in prostate, lung, and breast cancer. Denosumab was not approved for bone metastases related to multiple myeloma.

“A diagnosis of bone metastases is a major event for patients living with cancer, and the consequences can be devastating,” Amgen chairman and CEO Kevin Sharer wrote in a statement. “We are pleased to offer this new advance to patients and their health care providers.”

The approval of denosumab was based on three phase III head-to-head trials comprising 5,700 patients that compared the drug with zoledronic acid (Zometa).

The drug was superior to zoledronic acid in preventing skeletal-related events (SRE) in breast and prostate cancer. Some of those data were presented in June at the annual meeting of the American Society of Clinical Oncology. Denosumab was noninferior in preventing SREs in multiple myeloma and other solid tumors.

Adverse effects include hypocalcemia, fatigue, hypophosphatemia, and nausea. Osteonecrosis of the jaw can also occur.

Xgeva is delivered every 4 weeks as a 120-mg subcutaneous injection.

Because of the drug's expense, Amgen is launching a new patient assistance program. The Xgeva First Step Coupon Program will provide assistance to eligible patients who need help meeting a deductible, copayment, or coinsurance. The first injection would be covered and subsequent injections would cost a maximum of $25.

New federal recommendations on screening for osteoporosis provide more detail on when to screen women younger than age 65 years and – for the first time – point to a lack of data for screening decisions in men.

The U.S. Preventive Services Task Force updated its 2002 recommendations on osteoporosis screening to call for routine screening in all women aged 65 years or older and in any younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors (equivalent to a 9.3% or greater risk of fracture within 10 years). Previously, women younger than 65 would be screened if they were at least 60 years old with risk factors for fracture.

For the first time, the USPSTF evaluated the evidence for osteoporosis screening in men and found insufficient evidence to form any recommendation, Dr. Ned Colange, chair of the USPSTF, said in an interview. There's not enough evidence to recommend screening or treatment in men with no prior osteoporotic fractures, and “there's certainly not enough evidence to say, 'Don't' do it.”

“While there's not a call to action, that's an important call for research,” added Dr. Colange, president and CEO of the Colorado Trust Foundation, Denver.

In women, the recommendations do not say to stop osteoporosis screening at any specific age because the risk of fractures continues to increase with advancing age, and the minimal potential harms of treatment remain small. Clinicians who are considering treating older patients should consider data showing that the benefits of osteoporosis treatment emerge 18–24 months after starting treatment.

To predict an individual's risk for osteoporotic fracture, the USPSTF used the online FRAX tool, developed by the World Health Organization and the National Osteoporosis Foundation.

“The nice thing about the FRAX calculator is, the patient herself can determine that risk. It's available online. It uses measures that the woman should know,” Dr. Colange said.

The FRAX tool estimates 10-year fracture risk based on easily obtained information such as age, body mass index, parental fracture history, and tobacco or alcohol use. It asks about results of dual-energy x-ray absorptiometry scans but does not require this information to calculate fracture risk.

Younger women can reach the new threshold for screening because of various risk factors. For example, a white woman would qualify for screening if she is 50 years old, smokes, drinks alcohol daily, has a BMI less than 21, and has a parental history of fracture. A 55-year-old white woman would need only a parental fracture history to warrant osteoporosis screening. A 60-year-old white woman who smokes and drinks alcohol daily would fit the 10-year-risk profile for screening (Ann. Intern. Med. 2011 Jan. 18 [Epub ahead of print]).

White women are more likely than are nonwhite women to develop osteoporosis and fractures. Although there are fewer data on nonwhite women, the USPSTF recommended screening all women at age 65 years because the consequences of failing to identify and treat low bone-mineral density are considerable and the potential risks of treatment are small.

There aren't enough data to recommend when to rescreen women without osteoporosis on their first screen, the USPSTF stated, but an interval of at least 2 years would be needed to assess a change in bone density, and longer still for better prediction of fracture risk.

The recommendations are based on a 2010 review of studies published since 2002 by a team at the University of Oregon Health and Science University's Evidence-Based Practice Center in Portland.

In a new effort at transparency, the USPSTF first published a draft of the new recommendations online last summer and invited public comment. They received more than 50 comments from individuals, professional organizations, advocates, and drug companies, which led the USPSTF to clarify its approach to fracture risk assessment in the final version, Dr. Colange said.

He said he has no pertinent conflicts of interest.

View on the News

Online Access Will Help Screening Calculations

For clinicians, the biggest change in the new screening recommendations may be the need to calculate the 10-year fracture risk in women aged younger than 65, two experts suggested in interviews.

“They will need to know what tools are out there to be able to figure out whether a younger person is at equal to or greater risk than a 65-year-old woman with no addition risk factors,” Dr. Carolyn J. Crandall said.

The online FRAX calculator that was used by the USPSTF is a “really good tool” for this purpose, said Dr. Crandall. “Clinicians will have to access that tool in their clinics, which means they will either need Internet access at some point, or else they can download versions that are available for iPhone, or print versions that are available.”

Dr. Edward S. Leib also commended inclusion of the FRAX tool in the guidelines, but cautioned that it has some weaknesses that were discussed at a November 2010 “position development conference” conducted jointly by the International Osteoporosis Foundation and the International Society for Clinical Densitometry.

Some important risk factors that could affect the 10-year fracture risk would not necessarily be reflected in the FRAX calculation, he said. In addition, the FRAX tool is based on an international model, and although it included U.S. databases, the calculations may not reflect risks in regional populations.

“For example, in a retrospective review of our population of 15,000 postmenopausal women having bone density studies over the past 10 years, we did not find a correlation between history of fracturing and parental history of hip fractures,” he said.

Both Dr. Crandall and Dr. Leib also commended the USPSTF for acknowledging the need for more research in men, but Dr. Leib had hoped for more guidance. “It is known that the fracture risk in men who are age 75 is about equivalent to women who are age 65. I would have hoped that the USPSTF would have recommended screening at that age” despite the lack of primary prevention trials, he said.

DR. CRANDALL is professor of medicine at the University of California, Los Angeles. She said she has no pertinent conflicts of interest. DR. LEIB is professor of medicine at the University of Vermont, Burlington. He said he has no pertinent conflicts of interest.

New federal recommendations on screening for osteoporosis provide more detail on when to screen women younger than age 65 years and – for the first time – point to a lack of data for screening decisions in men.

The U.S. Preventive Services Task Force updated its 2002 recommendations on osteoporosis screening to call for routine screening in all women aged 65 years or older and in any younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors (equivalent to a 9.3% or greater risk of fracture within 10 years). Previously, women younger than 65 would be screened if they were at least 60 years old with risk factors for fracture.

For the first time, the USPSTF evaluated the evidence for osteoporosis screening in men and found insufficient evidence to form any recommendation, Dr. Ned Colange, chair of the USPSTF, said in an interview. There's not enough evidence to recommend screening or treatment in men with no prior osteoporotic fractures, and “there's certainly not enough evidence to say, 'Don't' do it.”

“While there's not a call to action, that's an important call for research,” added Dr. Colange, president and CEO of the Colorado Trust Foundation, Denver.

In women, the recommendations do not say to stop osteoporosis screening at any specific age because the risk of fractures continues to increase with advancing age, and the minimal potential harms of treatment remain small. Clinicians who are considering treating older patients should consider data showing that the benefits of osteoporosis treatment emerge 18–24 months after starting treatment.

To predict an individual's risk for osteoporotic fracture, the USPSTF used the online FRAX tool, developed by the World Health Organization and the National Osteoporosis Foundation.

“The nice thing about the FRAX calculator is, the patient herself can determine that risk. It's available online. It uses measures that the woman should know,” Dr. Colange said.

The FRAX tool estimates 10-year fracture risk based on easily obtained information such as age, body mass index, parental fracture history, and tobacco or alcohol use. It asks about results of dual-energy x-ray absorptiometry scans but does not require this information to calculate fracture risk.

Younger women can reach the new threshold for screening because of various risk factors. For example, a white woman would qualify for screening if she is 50 years old, smokes, drinks alcohol daily, has a BMI less than 21, and has a parental history of fracture. A 55-year-old white woman would need only a parental fracture history to warrant osteoporosis screening. A 60-year-old white woman who smokes and drinks alcohol daily would fit the 10-year-risk profile for screening (Ann. Intern. Med. 2011 Jan. 18 [Epub ahead of print]).

White women are more likely than are nonwhite women to develop osteoporosis and fractures. Although there are fewer data on nonwhite women, the USPSTF recommended screening all women at age 65 years because the consequences of failing to identify and treat low bone-mineral density are considerable and the potential risks of treatment are small.

There aren't enough data to recommend when to rescreen women without osteoporosis on their first screen, the USPSTF stated, but an interval of at least 2 years would be needed to assess a change in bone density, and longer still for better prediction of fracture risk.

The recommendations are based on a 2010 review of studies published since 2002 by a team at the University of Oregon Health and Science University's Evidence-Based Practice Center in Portland.

In a new effort at transparency, the USPSTF first published a draft of the new recommendations online last summer and invited public comment. They received more than 50 comments from individuals, professional organizations, advocates, and drug companies, which led the USPSTF to clarify its approach to fracture risk assessment in the final version, Dr. Colange said.

He said he has no pertinent conflicts of interest.

View on the News

Online Access Will Help Screening Calculations

For clinicians, the biggest change in the new screening recommendations may be the need to calculate the 10-year fracture risk in women aged younger than 65, two experts suggested in interviews.

“They will need to know what tools are out there to be able to figure out whether a younger person is at equal to or greater risk than a 65-year-old woman with no addition risk factors,” Dr. Carolyn J. Crandall said.

The online FRAX calculator that was used by the USPSTF is a “really good tool” for this purpose, said Dr. Crandall. “Clinicians will have to access that tool in their clinics, which means they will either need Internet access at some point, or else they can download versions that are available for iPhone, or print versions that are available.”

Dr. Edward S. Leib also commended inclusion of the FRAX tool in the guidelines, but cautioned that it has some weaknesses that were discussed at a November 2010 “position development conference” conducted jointly by the International Osteoporosis Foundation and the International Society for Clinical Densitometry.

Some important risk factors that could affect the 10-year fracture risk would not necessarily be reflected in the FRAX calculation, he said. In addition, the FRAX tool is based on an international model, and although it included U.S. databases, the calculations may not reflect risks in regional populations.

“For example, in a retrospective review of our population of 15,000 postmenopausal women having bone density studies over the past 10 years, we did not find a correlation between history of fracturing and parental history of hip fractures,” he said.

Both Dr. Crandall and Dr. Leib also commended the USPSTF for acknowledging the need for more research in men, but Dr. Leib had hoped for more guidance. “It is known that the fracture risk in men who are age 75 is about equivalent to women who are age 65. I would have hoped that the USPSTF would have recommended screening at that age” despite the lack of primary prevention trials, he said.

DR. CRANDALL is professor of medicine at the University of California, Los Angeles. She said she has no pertinent conflicts of interest. DR. LEIB is professor of medicine at the University of Vermont, Burlington. He said he has no pertinent conflicts of interest.

New federal recommendations on screening for osteoporosis provide more detail on when to screen women younger than age 65 years and – for the first time – point to a lack of data for screening decisions in men.

The U.S. Preventive Services Task Force updated its 2002 recommendations on osteoporosis screening to call for routine screening in all women aged 65 years or older and in any younger women whose fracture risk is equal to or greater than that of a 65-year-old white woman who has no additional risk factors (equivalent to a 9.3% or greater risk of fracture within 10 years). Previously, women younger than 65 would be screened if they were at least 60 years old with risk factors for fracture.

For the first time, the USPSTF evaluated the evidence for osteoporosis screening in men and found insufficient evidence to form any recommendation, Dr. Ned Colange, chair of the USPSTF, said in an interview. There's not enough evidence to recommend screening or treatment in men with no prior osteoporotic fractures, and “there's certainly not enough evidence to say, 'Don't' do it.”

“While there's not a call to action, that's an important call for research,” added Dr. Colange, president and CEO of the Colorado Trust Foundation, Denver.

In women, the recommendations do not say to stop osteoporosis screening at any specific age because the risk of fractures continues to increase with advancing age, and the minimal potential harms of treatment remain small. Clinicians who are considering treating older patients should consider data showing that the benefits of osteoporosis treatment emerge 18–24 months after starting treatment.

To predict an individual's risk for osteoporotic fracture, the USPSTF used the online FRAX tool, developed by the World Health Organization and the National Osteoporosis Foundation.

“The nice thing about the FRAX calculator is, the patient herself can determine that risk. It's available online. It uses measures that the woman should know,” Dr. Colange said.

The FRAX tool estimates 10-year fracture risk based on easily obtained information such as age, body mass index, parental fracture history, and tobacco or alcohol use. It asks about results of dual-energy x-ray absorptiometry scans but does not require this information to calculate fracture risk.

Younger women can reach the new threshold for screening because of various risk factors. For example, a white woman would qualify for screening if she is 50 years old, smokes, drinks alcohol daily, has a BMI less than 21, and has a parental history of fracture. A 55-year-old white woman would need only a parental fracture history to warrant osteoporosis screening. A 60-year-old white woman who smokes and drinks alcohol daily would fit the 10-year-risk profile for screening (Ann. Intern. Med. 2011 Jan. 18 [Epub ahead of print]).

White women are more likely than are nonwhite women to develop osteoporosis and fractures. Although there are fewer data on nonwhite women, the USPSTF recommended screening all women at age 65 years because the consequences of failing to identify and treat low bone-mineral density are considerable and the potential risks of treatment are small.

There aren't enough data to recommend when to rescreen women without osteoporosis on their first screen, the USPSTF stated, but an interval of at least 2 years would be needed to assess a change in bone density, and longer still for better prediction of fracture risk.

The recommendations are based on a 2010 review of studies published since 2002 by a team at the University of Oregon Health and Science University's Evidence-Based Practice Center in Portland.

In a new effort at transparency, the USPSTF first published a draft of the new recommendations online last summer and invited public comment. They received more than 50 comments from individuals, professional organizations, advocates, and drug companies, which led the USPSTF to clarify its approach to fracture risk assessment in the final version, Dr. Colange said.

He said he has no pertinent conflicts of interest.

View on the News

Online Access Will Help Screening Calculations

For clinicians, the biggest change in the new screening recommendations may be the need to calculate the 10-year fracture risk in women aged younger than 65, two experts suggested in interviews.

“They will need to know what tools are out there to be able to figure out whether a younger person is at equal to or greater risk than a 65-year-old woman with no addition risk factors,” Dr. Carolyn J. Crandall said.

The online FRAX calculator that was used by the USPSTF is a “really good tool” for this purpose, said Dr. Crandall. “Clinicians will have to access that tool in their clinics, which means they will either need Internet access at some point, or else they can download versions that are available for iPhone, or print versions that are available.”

Dr. Edward S. Leib also commended inclusion of the FRAX tool in the guidelines, but cautioned that it has some weaknesses that were discussed at a November 2010 “position development conference” conducted jointly by the International Osteoporosis Foundation and the International Society for Clinical Densitometry.

Some important risk factors that could affect the 10-year fracture risk would not necessarily be reflected in the FRAX calculation, he said. In addition, the FRAX tool is based on an international model, and although it included U.S. databases, the calculations may not reflect risks in regional populations.

“For example, in a retrospective review of our population of 15,000 postmenopausal women having bone density studies over the past 10 years, we did not find a correlation between history of fracturing and parental history of hip fractures,” he said.

Both Dr. Crandall and Dr. Leib also commended the USPSTF for acknowledging the need for more research in men, but Dr. Leib had hoped for more guidance. “It is known that the fracture risk in men who are age 75 is about equivalent to women who are age 65. I would have hoped that the USPSTF would have recommended screening at that age” despite the lack of primary prevention trials, he said.

DR. CRANDALL is professor of medicine at the University of California, Los Angeles. She said she has no pertinent conflicts of interest. DR. LEIB is professor of medicine at the University of Vermont, Burlington. He said he has no pertinent conflicts of interest.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

GOTHENBURG, SWEDEN – The popular practice of trying to improve serum vitamin D status through controlled sun exposure is a no-win proposition that's unlikely to result in adequate vitamin D levels year-round without compromising skin health, Brian L. Diffey, Ph.D., asserted in a plenary lecture at the congress.

“Failure to understand the nature of human exposure to sunlight has led to widespread misguided public health advice concerning the sun exposure necessary for adequate vitamin D status. Messages concerning sun exposure should remain focused on the detrimental effects of excessive sun exposure and avoid giving specific advice on what may be thought to be optimal sun exposure,” said Dr. Diffey, professor emeritus of photobiology at the University of Newcastle (England) who has been publishing studies on the relationship between sun exposure and skin cancer for more than 20 years.

“The recommendation for short, casual sun exposure as adequate for a healthy vitamin D status is simply ubiquitous. We read it everywhere. It has become part of our conventional wisdom. Nobody really questions it.

“But there's been a gross oversight in all of these recommendations: These calculations relate only to exposure under a clear sky with no clouds, [while] lying horizontal in the middle of the day in midsummer with no shade and roughly 25% of our body surface exposed,” he explained.

That's simply not how sun exposure occurs in contemporary life. A person walking around in an urban environment with shade from nearby buildings and trees receives a sun exposure on the vertical body surfaces that's typically one-sixth of that of a sunbather lying horizontally, Dr. Diffey continued.

As examples of the widespread public health messages encouraging limited sun exposure to enhance vitamin D levels, he noted that the United Kingdom's National Osteoporosis Society recommends trying to get 10 minutes of sun exposure once or twice a day without sunscreen between May and September for bone health.

Furthermore, the United Kingdom Health Protection Agency states that short periods outdoors will produce sufficient vitamin D. And “The UV Advantage,” by Dr. Michael Holick, professor of medicine at Boston University and winner of the 2009 Linus Pauling prize for health research, containing the “Holick formula for safe sun,” is a brisk seller.

Dr. Diffey pointed to a recent large international study of serum vitamin D levels month-by-month for individuals living at various latitudes in the United Kingdom, which concluded that most people have adequate but suboptimal levels during the summer months, with a mean of 70 nmol/L.

The investigators deemed a level greater than 75 nmol/L to be optimal. In the winter months, most people fall into the “inadequate” range, with a mean serum vitamin D of 48 nmol/L. About 16% have severe deficiency during winter and spring, with higher prevalences in the northernmost latitudes (BMJ 2010;340:b5664. [doi: 10.1136/bmj. b5664].

In light of study data showing that most people in Europe and North America spend an average of 1-2 hours per day outdoors during the summer, they are generally regarded as having suboptimal vitamin D levels during those months and are vitamin D insufficient the rest of the year.

A recommendation for 10-20 minutes of daily casual sun exposure followed by sun avoidance would be “grossly insufficient” to maintain adequate vitamin D levels, he said.

“In fact, if people really did follow the conventional public health advice, we would be much more vitamin D insufficient than we now are,” according to the photobiologist.

The safe and effective ways to raise vitamin D levels, Dr. Diffey said, are more widespread fortification of foods or the use of supplements, especially during the winter months.

For dermatologists, he added, there's another effective option: “Pop into your UVB cabin once a week from November to February when nobody's looking and give yourself 1 SED [standard erythema dose], which is about one-third of the minimal erythema dose.”

His recently published mathematical model (Br. J. Dermatol. 2010;162:1342-8) predicts this modest UVB exposure, adding up to a little over one-tenth of a typical UVB treatment course for psoriasis, would keep the recipient in the adequate range for serum vitamin D throughout the dark months.

Dr. Diffey said he has no relevant financial conflicts of interests.

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER

DENVER – Elderly patients who are placed on a short-acting opioid analgesic for treatment of arthritis pain are twice as likely to experience a fracture during the subsequent year, compared with those on a long-acting opioid, according to a large cohort study.

The increased fracture risk was particularly strong during the first 2 weeks after initiation of therapy, when the relative risk was almost sevenfold higher in patients on a short-acting opioid, such as propoxyphene or oxycodone, than in those who were started on an nonsteroidal anti-inflammatory drug (NSAID) or long-acting opioid, including fentanyl or sustained-release hydrocodone. After that initial 2-week period, the fracture risk associated with short-acting opioid therapy dropped off but remained about threefold greater than with NSAID therapy, Dr. Matthew Miller reported at the meeting.

The fracture risk during the first 2 weeks on a long-acting opioid did not differ significantly from that in patients who were placed on an NSAID.

Over the course of 1 year, however, the difference grew such that the cumulative fracture risk was 2.6-fold greater in the group on a long-acting opioid than in those on an NSAID. In contrast, the relative risk of fracture at 1 year was increased 5.1-fold in elderly arthritis patients on a short-acting opioid, added Dr. Miller, associate director of the Harvard Injury Control Research Center, Boston.

“Our findings indicate that opioids increase the risk of fractures among older patients with arthritis, and suggest that clinicians should be alert to the possibility that short-acting opioids pose a significantly greater risk of fractures among older adults than do equianalgesic doses of long-acting opioids, especially during the first 2 weeks after initiating therapy,” he observed.

These results have the potential to change clinical practice by shifting prescribing in the direction of greater use of long-acting opioids in the elderly. At present, short-acting opioids are prescribed far more often than long-acting ones.

“Our findings, if borne out in other databases, could help inform safer prescribing practices consonant with the latest American Geriatrics Society guidelines on the pharmacological management of pain in older persons, which recommend that all patients with moderate to severe pain, pain-related functional impairment, or diminished quality of life due to pain should be considered for opioid therapy,” the physician continued.

His study involved 12,436 Medicare beneficiaries with arthritis who initiated monotherapy with an opioid analgesic, and 4,874 who started on an NSAID. Participants averaged 81 years of age, and 85% were women. Osteoarthritis was the diagnosis in 90%; the rest had rheumatoid arthritis. None of the subjects had been on an opioid within the previous 6 months.

Not surprisingly, patients who were started on an opioid tended to be somewhat sicker, with a mean baseline Charlson comorbidity index score of 2.2 in the short-acting opioid group, 2.1 in those on a long-acting opioid, and 1.6 in the NSAID group.

The primary study end point was the 1-year incidence of fractures of the hip, radius, ulna, or wrist. The incidence rate was 25 fractures per 1,000 person-years in the NSAID group, 128 per 1,000 person-years in those on short-acting opioids, and 53 per 1,000 person-years in the group on long-acting opioids.

A dose effect was evident. Patients on a low-dose opioid had a 2.2-fold greater fracture risk than did those on an NSAID, after adjustment for comorbid conditions and other potential confounding variables. Patients on a moderate-dose opioid had a 4.6-fold increased risk. And those on high-dose opioid therapy had a 5.1-fold increased risk.

Among high-dose opioid users, patients who were placed on a short-acting opioid had an adjusted 2.1-fold greater risk of a fracture than did those on a high-dose, long-acting opioid.

Asked why he thought short-acting opioids were prescribed 13-times more frequently than long-acting ones in the study population, Dr. Miller replied that although the study didn't address this question, it's his impression that many physicians believe that if they place a patient on a long-acting opioid, the patient may not get pain relief quickly enough. Hence, the patient might take another dose, and then another, perhaps getting into the overdose range. This belief about long-acting opioids' sluggish onset of action, he added, is erroneous.

“It's important to recognize that the modern formulations of these long-acting drugs can actually provide adequate analgesia in a time scale that's similar to that for short-acting drugs, because of the long-acting agents' biphasic distribution in the blood stream. Yet 90% of the drugs that we're prescribing when we're prescribing opioids in an elderly population are short-acting drugs, raising the question of whether we're putting people at unnecessary risk,” Dr. Miller said.

The Food and Drug Administration recently removed from the U.S. market one of the short-acting opioids in this study – propoxyphene – because of an increased risk for fatal heart rhythm abnormalities associated with its use.

Dr. Miller declared having no relevant financial interests.

When 90% of opioids prescribed to the elderly are short-acting, we may be putting people at unnecessary risk.

Source DR. MILLER

CHICAGO – Visceral obesity was associated with low bone mineral density in a study of premenopausal women, indicating that abdominal fat is a risk factor for osteoporosis.

The finding indicates that “obesity does not always protect against osteoporosis,” study investigator Dr. Miriam A. Bredella said in a press briefing at the meeting.

“Excessive visceral fat is not only a risk factor for heart disease and diabetes, but also for bone loss,” she said.

The study flies in the face of current thinking that obesity actually protects against osteoporosis. Previous studies suggesting a link between fat and bone health focused primarily on body mass index (BMI), which incorporates measures of muscle and bone mass and subcutaneous fat as well as visceral fat.

The present study zeroed in specifically on visceral fat, Dr. Bredella explained.

She described “disturbing pictures emerging from the obesity epidemic, because the number of forearm fractures among young patients has increased dramatically over the last year, and the strongest risk factor in that group … was actually increased body weight.” This finding prompted the investigators to see whether there was a connection between osteoporosis and fat, said Dr. Bredella of Massachusetts General Hospital and Harvard Medical School, both in Boston.

In the present study, 50 premenopausal women with a BMI of 19-46 kg/m

The results showed a positive correlation between visceral fat and BM fat (r = 0.28) and an inverse association between visceral fat and BMD (r = −0.31) and between vertebral BM fat and BMD (r = −0.45). These results were statistically significant. There was no correlation between either subcutaneous fat (fat concentrated around the hips and thighs) or total body fat and either BM fat or BMD.

These results reveal the distinctly detrimental effect of abdominal obesity on bone health, Dr. Bredella said.

The study is among the first to explore the relationship between body fat and bone marrow fat, and the dynamic appears to be complex, she said in an interview.

According to recent research, “the amount of fat within your bones could predict if you will develop a fracture independent of bone mineral density,” she noted. A recent study by Dr. Bredella and her colleagues found that women with anorexia nervosa had three times the amount of bone marrow fat as did normal-weight women.

Dr. Bredella had no financial disclosures.

CT scan of the abdomen through the L4 in an obese woman (left) shows high levels of visceral fat. Further analysis (right) showed high bone marrow fat content.

Source Images courtesy Radiological Society of North America

CHICAGO – Visceral obesity was associated with low bone mineral density in a study of premenopausal women, indicating that abdominal fat is a risk factor for osteoporosis.

The finding indicates that “obesity does not always protect against osteoporosis,” study investigator Dr. Miriam A. Bredella said in a press briefing at the meeting.

“Excessive visceral fat is not only a risk factor for heart disease and diabetes, but also for bone loss,” she said.

The study flies in the face of current thinking that obesity actually protects against osteoporosis. Previous studies suggesting a link between fat and bone health focused primarily on body mass index (BMI), which incorporates measures of muscle and bone mass and subcutaneous fat as well as visceral fat.

The present study zeroed in specifically on visceral fat, Dr. Bredella explained.

She described “disturbing pictures emerging from the obesity epidemic, because the number of forearm fractures among young patients has increased dramatically over the last year, and the strongest risk factor in that group … was actually increased body weight.” This finding prompted the investigators to see whether there was a connection between osteoporosis and fat, said Dr. Bredella of Massachusetts General Hospital and Harvard Medical School, both in Boston.

In the present study, 50 premenopausal women with a BMI of 19-46 kg/m

The results showed a positive correlation between visceral fat and BM fat (r = 0.28) and an inverse association between visceral fat and BMD (r = −0.31) and between vertebral BM fat and BMD (r = −0.45). These results were statistically significant. There was no correlation between either subcutaneous fat (fat concentrated around the hips and thighs) or total body fat and either BM fat or BMD.

These results reveal the distinctly detrimental effect of abdominal obesity on bone health, Dr. Bredella said.

The study is among the first to explore the relationship between body fat and bone marrow fat, and the dynamic appears to be complex, she said in an interview.

According to recent research, “the amount of fat within your bones could predict if you will develop a fracture independent of bone mineral density,” she noted. A recent study by Dr. Bredella and her colleagues found that women with anorexia nervosa had three times the amount of bone marrow fat as did normal-weight women.

Dr. Bredella had no financial disclosures.

CT scan of the abdomen through the L4 in an obese woman (left) shows high levels of visceral fat. Further analysis (right) showed high bone marrow fat content.

Source Images courtesy Radiological Society of North America

CHICAGO – Visceral obesity was associated with low bone mineral density in a study of premenopausal women, indicating that abdominal fat is a risk factor for osteoporosis.

The finding indicates that “obesity does not always protect against osteoporosis,” study investigator Dr. Miriam A. Bredella said in a press briefing at the meeting.

“Excessive visceral fat is not only a risk factor for heart disease and diabetes, but also for bone loss,” she said.

The study flies in the face of current thinking that obesity actually protects against osteoporosis. Previous studies suggesting a link between fat and bone health focused primarily on body mass index (BMI), which incorporates measures of muscle and bone mass and subcutaneous fat as well as visceral fat.

The present study zeroed in specifically on visceral fat, Dr. Bredella explained.

She described “disturbing pictures emerging from the obesity epidemic, because the number of forearm fractures among young patients has increased dramatically over the last year, and the strongest risk factor in that group … was actually increased body weight.” This finding prompted the investigators to see whether there was a connection between osteoporosis and fat, said Dr. Bredella of Massachusetts General Hospital and Harvard Medical School, both in Boston.

In the present study, 50 premenopausal women with a BMI of 19-46 kg/m

The results showed a positive correlation between visceral fat and BM fat (r = 0.28) and an inverse association between visceral fat and BMD (r = −0.31) and between vertebral BM fat and BMD (r = −0.45). These results were statistically significant. There was no correlation between either subcutaneous fat (fat concentrated around the hips and thighs) or total body fat and either BM fat or BMD.

These results reveal the distinctly detrimental effect of abdominal obesity on bone health, Dr. Bredella said.

The study is among the first to explore the relationship between body fat and bone marrow fat, and the dynamic appears to be complex, she said in an interview.

According to recent research, “the amount of fat within your bones could predict if you will develop a fracture independent of bone mineral density,” she noted. A recent study by Dr. Bredella and her colleagues found that women with anorexia nervosa had three times the amount of bone marrow fat as did normal-weight women.

Dr. Bredella had no financial disclosures.

CT scan of the abdomen through the L4 in an obese woman (left) shows high levels of visceral fat. Further analysis (right) showed high bone marrow fat content.

Source Images courtesy Radiological Society of North America

Major Finding: The annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%–2.3% in the lumbar spine and 1.0%–1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%–10% drop in BMD at the spine in the average woman, along with a 5%–7% decline at the hip.

Data Source: SWAN, a long-term, longitudinal, observational study of 3,302 women from five ethnic groups at seven U.S. sites who were pre- or early perimenopausal at enrollment.

Disclosures: Dr. Santoro declared having no financial interests relevant to the National Institutes of Health–funded study.

DENVER – The Study of Women's Health Across the Nation has filled important knowledge gaps regarding bone loss rates at various stages of the menopausal transition, enabling physicians for the first time to make informed decisions about the appropriate time to screen for osteoporosis.

“Hypoestrogenic bone loss does not occur until the late transition. Duration of amenorrhea is the best predictor of when this process begins. There's no rationale to measure bone mineral density prior to 90 days of amenorrhea if postmenopausal osteoporosis is the clinical issue,” Dr. Nanette F. Santoro explained at the meeting.

“Bone mineral density at the lumbar spine and total hip starts dropping like a stone as soon as the women get to late menopause, so 3-11 months of amenorrhea is the tipping point for bone density. There is no point in assessing it sooner if you think they may have bone loss related to the menopause transition, because it's not going to be estrogen-related prior to this point,” said Dr. Santoro, a long-time SWAN (Study of Women's Health Across the Nation) investigator and chair of obstetrics and gynecology at the University of Colorado at Denver.

The SWAN findings have important clinical implications because most guidelines don't recommend routine screening of women for osteoporosis until age 65. That's too late. Since the rate of BMD loss accelerates markedly in late menopause, accompanied by an attendant increase in fracture risk, it makes sense to measure bone mineral density after a women has experienced 3 months of amenorrhea, and to intervene if she is beginning to lose bone rapidly, she continued.

SWAN showed that the annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%-2.3% in the lumbar spine and 1.0%-1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%-10% drop in BMD at the spine in the average woman, along with a 5%-7% decline at the hip. And that in turn foretells a 50%-100% higher fracture rate.

Another key SWAN finding regarding BMD changes during the menopausal transition is that rates of bone loss are markedly greater in women who are in the lowest tertile of body weight. Indeed, women in the top tertile for body weight had a 33%-55% slower rate of bone loss than did those in the lightest tertile. The apparent large ethnic differences in bone loss rates observed in SWAN turned out on closer inspection to be explained chiefly by ethnic differences in body weight.

SWAN is a long-term, longitudinal, observational study involving 3,302 women who were pre- or early perimenopausal at enrollment.

Participants were recruited from five ethnic groups – white, black, Hispanic, Japanese, and Chinese – at seven U.S. sites. The BMD substudy included 1,902 SWAN participants with BMD measurements obtained at up to six annual visits. The key findings of the BMD substudy have already been published (J. Clin. Endocrinol. Metab. 2008;93:861-8). Dr. Santoro, in her plenary lecture at the meeting, sought to spread the word.

Major Finding: The annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%–2.3% in the lumbar spine and 1.0%–1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%–10% drop in BMD at the spine in the average woman, along with a 5%–7% decline at the hip.

Data Source: SWAN, a long-term, longitudinal, observational study of 3,302 women from five ethnic groups at seven U.S. sites who were pre- or early perimenopausal at enrollment.

Disclosures: Dr. Santoro declared having no financial interests relevant to the National Institutes of Health–funded study.

DENVER – The Study of Women's Health Across the Nation has filled important knowledge gaps regarding bone loss rates at various stages of the menopausal transition, enabling physicians for the first time to make informed decisions about the appropriate time to screen for osteoporosis.

“Hypoestrogenic bone loss does not occur until the late transition. Duration of amenorrhea is the best predictor of when this process begins. There's no rationale to measure bone mineral density prior to 90 days of amenorrhea if postmenopausal osteoporosis is the clinical issue,” Dr. Nanette F. Santoro explained at the meeting.

“Bone mineral density at the lumbar spine and total hip starts dropping like a stone as soon as the women get to late menopause, so 3-11 months of amenorrhea is the tipping point for bone density. There is no point in assessing it sooner if you think they may have bone loss related to the menopause transition, because it's not going to be estrogen-related prior to this point,” said Dr. Santoro, a long-time SWAN (Study of Women's Health Across the Nation) investigator and chair of obstetrics and gynecology at the University of Colorado at Denver.

The SWAN findings have important clinical implications because most guidelines don't recommend routine screening of women for osteoporosis until age 65. That's too late. Since the rate of BMD loss accelerates markedly in late menopause, accompanied by an attendant increase in fracture risk, it makes sense to measure bone mineral density after a women has experienced 3 months of amenorrhea, and to intervene if she is beginning to lose bone rapidly, she continued.

SWAN showed that the annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%-2.3% in the lumbar spine and 1.0%-1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%-10% drop in BMD at the spine in the average woman, along with a 5%-7% decline at the hip. And that in turn foretells a 50%-100% higher fracture rate.

Another key SWAN finding regarding BMD changes during the menopausal transition is that rates of bone loss are markedly greater in women who are in the lowest tertile of body weight. Indeed, women in the top tertile for body weight had a 33%-55% slower rate of bone loss than did those in the lightest tertile. The apparent large ethnic differences in bone loss rates observed in SWAN turned out on closer inspection to be explained chiefly by ethnic differences in body weight.

SWAN is a long-term, longitudinal, observational study involving 3,302 women who were pre- or early perimenopausal at enrollment.

Participants were recruited from five ethnic groups – white, black, Hispanic, Japanese, and Chinese – at seven U.S. sites. The BMD substudy included 1,902 SWAN participants with BMD measurements obtained at up to six annual visits. The key findings of the BMD substudy have already been published (J. Clin. Endocrinol. Metab. 2008;93:861-8). Dr. Santoro, in her plenary lecture at the meeting, sought to spread the word.

Major Finding: The annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%–2.3% in the lumbar spine and 1.0%–1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%–10% drop in BMD at the spine in the average woman, along with a 5%–7% decline at the hip.

Data Source: SWAN, a long-term, longitudinal, observational study of 3,302 women from five ethnic groups at seven U.S. sites who were pre- or early perimenopausal at enrollment.

Disclosures: Dr. Santoro declared having no financial interests relevant to the National Institutes of Health–funded study.

DENVER – The Study of Women's Health Across the Nation has filled important knowledge gaps regarding bone loss rates at various stages of the menopausal transition, enabling physicians for the first time to make informed decisions about the appropriate time to screen for osteoporosis.

“Hypoestrogenic bone loss does not occur until the late transition. Duration of amenorrhea is the best predictor of when this process begins. There's no rationale to measure bone mineral density prior to 90 days of amenorrhea if postmenopausal osteoporosis is the clinical issue,” Dr. Nanette F. Santoro explained at the meeting.

“Bone mineral density at the lumbar spine and total hip starts dropping like a stone as soon as the women get to late menopause, so 3-11 months of amenorrhea is the tipping point for bone density. There is no point in assessing it sooner if you think they may have bone loss related to the menopause transition, because it's not going to be estrogen-related prior to this point,” said Dr. Santoro, a long-time SWAN (Study of Women's Health Across the Nation) investigator and chair of obstetrics and gynecology at the University of Colorado at Denver.

The SWAN findings have important clinical implications because most guidelines don't recommend routine screening of women for osteoporosis until age 65. That's too late. Since the rate of BMD loss accelerates markedly in late menopause, accompanied by an attendant increase in fracture risk, it makes sense to measure bone mineral density after a women has experienced 3 months of amenorrhea, and to intervene if she is beginning to lose bone rapidly, she continued.

SWAN showed that the annual rate of bone loss during the late perimenopausal and early postmenopausal years is 1.8%-2.3% in the lumbar spine and 1.0%-1.4% in the hip. At those rates, 5 years of bone loss would translate to a 7%-10% drop in BMD at the spine in the average woman, along with a 5%-7% decline at the hip. And that in turn foretells a 50%-100% higher fracture rate.

Another key SWAN finding regarding BMD changes during the menopausal transition is that rates of bone loss are markedly greater in women who are in the lowest tertile of body weight. Indeed, women in the top tertile for body weight had a 33%-55% slower rate of bone loss than did those in the lightest tertile. The apparent large ethnic differences in bone loss rates observed in SWAN turned out on closer inspection to be explained chiefly by ethnic differences in body weight.

SWAN is a long-term, longitudinal, observational study involving 3,302 women who were pre- or early perimenopausal at enrollment.

Participants were recruited from five ethnic groups – white, black, Hispanic, Japanese, and Chinese – at seven U.S. sites. The BMD substudy included 1,902 SWAN participants with BMD measurements obtained at up to six annual visits. The key findings of the BMD substudy have already been published (J. Clin. Endocrinol. Metab. 2008;93:861-8). Dr. Santoro, in her plenary lecture at the meeting, sought to spread the word.

Major Finding: The Women's Health Initiative reported in May 2002 that risks of coronary heart disease and cancer were associated with HT. Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustment for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture.

Data Source: A study of 80,995 patients in the Kaiser Permanente Southern California database.

Disclosures: Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women's Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles, at the meeting.

“The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use,” she said.

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data were collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients' HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

“Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy,” she said.

Women at risk of hip fracture should consider carefully before they stop using hormone therapy.

Source DR. KARIM

Major Finding: The Women's Health Initiative reported in May 2002 that risks of coronary heart disease and cancer were associated with HT. Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustment for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture.

Data Source: A study of 80,995 patients in the Kaiser Permanente Southern California database.

Disclosures: Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women's Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles, at the meeting.

“The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use,” she said.

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data were collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients' HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

“Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy,” she said.

Women at risk of hip fracture should consider carefully before they stop using hormone therapy.

Source DR. KARIM

Major Finding: The Women's Health Initiative reported in May 2002 that risks of coronary heart disease and cancer were associated with HT. Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustment for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture.

Data Source: A study of 80,995 patients in the Kaiser Permanente Southern California database.

Disclosures: Dr. Karim said she had no financial conflicts of interest. The study was supported by the University of Southern California.

CHICAGO – Prescriptions for hormone therapy for elderly postmenopausal women declined significantly after the results of the Women's Health Initiative were reported in May 2002, and it now appears that there has been a correspondingly steep rise in hip fracture rates, said Roksana Karim, Ph.D., of the University of Southern California, Los Angeles, at the meeting.

“The rise in hip fracture rates in elderly postmenopausal women may be partially attributed to the continued decline in hormone therapy use,” she said.

This was the conclusion of a longitudinal observational study of 80,995 postmenopausal women aged 60 years or older using data from 11 Kaiser Permanente medical centers in southern California. The study was designed to assess the risk of hip fracture for women who stopped taking hormone therapy (HT), compared with those who continued the therapy. It was also designed to evaluate the risk of hip fracture over time after stopping HT, and to measure bone mineral density (BMD) over time after stopping HT.

Data were collected on hip fracture, HT use, and the use of antiosteoporotic medication from June 2002 through December 2008. All hip fractures were verified by chart review by an orthopedic surgeon who was blinded to patients' HT status. Exclusion criteria included fractures secondary to tumors or high-energy trauma, and periprosthetic fractures. Patients were considered to be HT users if they had filled at least two prescriptions in a given year, as each prescription provides a 3-month supply of medication. HT was defined as estrogen alone or estrogen plus progesterone.

BMD data of the hip and lumbar regions were available for 54,209 women (67%). The 80,955 women had a mean age of 68.8 years and a mean body mass index of 26.9 kg/m

Between July 2002 and December 2008, HT use in this population decreased from 85% to 18%. After adjustments for age and race, women who did not use HT in the previous year had a 55% increased risk of hip fracture (hazard ratio, 1.55), said Dr. Karim. She also said that hip fracture risk significantly increased with 2 or more years of HT cessation. Mean BMD was significantly and inversely associated with cumulative years of HT nonuse, she said.

Dr. Karim acknowledged that the study was limited by lack of body mass index data in 47% of the population, or information on history of past HT use or on previous fractures.

“Women at risk of hip fracture should consider carefully before making a decision of stopping using hormone therapy,” she said.

Women at risk of hip fracture should consider carefully before they stop using hormone therapy.

Source DR. KARIM

Bone metabolism appears to change before patients show clinical signs of rheumatoid arthritis and could ultimately serve as an early marker of disease, based on a study of 79 patients.

“There appears to be an alteration in bone metabolism parallel to inflammation and autoimmunity in the asymptomatic preclinical phase of RA, which may reflect the beginning of joint destruction,” according to Dr. Dirkjan van Schaardenburg, a rheumatologist at Jan van Breemen Institute in Amsterdam, and his coinvestigators.

They found significantly increased average levels of only P1NP (procollagen type I intact N-terminal propeptide) and osteoprotegerin in the group of preclinical RA patients, compared with a control group of healthy individuals. Specifically, P1NP increased by 5 ng/mL and osteoprotegerin increased by 4 pmol/L (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.135723]).

Three blood samples taken 1, 2, and 5 years prior to the onset of symptoms were identified for 47 patients with RA; two samples were collected from 18 patients and one sample was collected from 14 patients. The individuals had been blood donors prior to developing the disease.

The study was funded by the Dutch Arthritis Association. The authors reported that they had no competing interests.

Bone metabolism appears to change before patients show clinical signs of rheumatoid arthritis and could ultimately serve as an early marker of disease, based on a study of 79 patients.

“There appears to be an alteration in bone metabolism parallel to inflammation and autoimmunity in the asymptomatic preclinical phase of RA, which may reflect the beginning of joint destruction,” according to Dr. Dirkjan van Schaardenburg, a rheumatologist at Jan van Breemen Institute in Amsterdam, and his coinvestigators.

They found significantly increased average levels of only P1NP (procollagen type I intact N-terminal propeptide) and osteoprotegerin in the group of preclinical RA patients, compared with a control group of healthy individuals. Specifically, P1NP increased by 5 ng/mL and osteoprotegerin increased by 4 pmol/L (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.135723]).

Three blood samples taken 1, 2, and 5 years prior to the onset of symptoms were identified for 47 patients with RA; two samples were collected from 18 patients and one sample was collected from 14 patients. The individuals had been blood donors prior to developing the disease.

The study was funded by the Dutch Arthritis Association. The authors reported that they had no competing interests.

Bone metabolism appears to change before patients show clinical signs of rheumatoid arthritis and could ultimately serve as an early marker of disease, based on a study of 79 patients.

“There appears to be an alteration in bone metabolism parallel to inflammation and autoimmunity in the asymptomatic preclinical phase of RA, which may reflect the beginning of joint destruction,” according to Dr. Dirkjan van Schaardenburg, a rheumatologist at Jan van Breemen Institute in Amsterdam, and his coinvestigators.

They found significantly increased average levels of only P1NP (procollagen type I intact N-terminal propeptide) and osteoprotegerin in the group of preclinical RA patients, compared with a control group of healthy individuals. Specifically, P1NP increased by 5 ng/mL and osteoprotegerin increased by 4 pmol/L (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.135723]).

Three blood samples taken 1, 2, and 5 years prior to the onset of symptoms were identified for 47 patients with RA; two samples were collected from 18 patients and one sample was collected from 14 patients. The individuals had been blood donors prior to developing the disease.

The study was funded by the Dutch Arthritis Association. The authors reported that they had no competing interests.