Osteoporosis

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

SAN ANTONIO — Monthly denosumab may prove to suppress bone turnover when patients with cancer metastatic to bone do not respond adequately to bisphosphonate therapy, Dr. Allan Lipton said at the Sixth International Meeting on Cancer-Induced Bone Disease.

The drug is a fully human monoclonal antibody to RANK ligand, inhibiting the differentiation and proliferation of osteoclasts, and thus reducing bone turnover. It also is being investigated for the treatment of postmenopausal osteoporosis.

Dr. Lipton presented the interim results of a phase II study in patients in whom zoledronic acid or pamidronate failed to adequately suppress urinary markers of bone turnover.

Adequate suppression is important in these patients not only because it helps prevent fractures, but because it delays tumor progression and improves survival.

The interim analysis included 49 patients who have finished the 25-week trial. Eventually the study will enroll 135 patients.

Of initial patients, 40% had metastatic breast cancer, 40% had metastatic prostate cancer, 10% had multiple myeloma, and the rest had other solid tumors. Most (80%) had been on zoledronic acid; the rest had been on pamidronate. All patients still had urinary N-telopeptide (NTx) levels of more than 50 nmol/mmol creatinine.

Overall, more patients on denosumab than on bisphosphonates experienced a decrease in their urinary NTx levels to less than 50 nmol/mmol creatinine (76% vs. 38%). The difference was still significant when the groups were divided according to baseline NTx levels.

Among those who started with a level of 51–100 nmol/mmol creatinine, 87% of those on denosumab achieved the target compared with 50% of those taking bisphosphonates.

Among those with baseline levels of more than 100 nmol/mmol creatinine, two-thirds of the denosumab group achieved the goal compared with 25% of the bisphosphonate group.

Those who received denosumab every 4 weeks had the longest duration of adequate suppression (a mean of 140 days), followed by patients taking the drug every 12 weeks. Bisphosphonate-treated patients maintained adequate suppression for a mean of 30 days.

The meeting was sponsored by the Cancer and Bone Society. The study was sponsored by Amgen Inc. Dr. Lipton, of the Penn State Milton S. Hershey Medical Center, Hershey, Pa., is a consultant for the company.

CHARLESTON, S.C. — Give breast-feeding women enough vitamin D and you may supplement their babies, too, according to the results of a small but promising pilot study presented at a pediatric meeting sponsored by the Medical University of South Carolina.

“Our question was: 'Would direct vitamin D supplementation meet the needs of both the mother and her nursing infant?' “said Dr. Carol L. Wagner of the department of neonatology at the university, in Charleston.

Insufficient vitamin D causes many problems, primarily a lack of calcium absorption that can lead to bone loss. In addition, recent research suggests a link between insufficient vitamin D and immune system disorders such as diabetes, Dr. Wagner said.

People in the developed world are at risk for vitamin D deficiency because of a primarily indoor lifestyle that has limited adequate vitamin D intake from sunlight, she added.

Data from several recent studies suggest that doses of vitamin D that are significantly higher than the current recommended daily allowance will not cause toxicity and are in fact needed for adequate circulating 25-hydroxyvitamin D concentrations (25[OH]D).

To determine whether giving mothers high doses of vitamin D provides adequate 25(OH)D for both mothers and infants without toxicity to either, Dr. Wagner and colleagues randomized 18 breast-feeding women to receive 400 IU or 6,400 IU of vitamin D3 as a daily pill for 6 months starting at 1 month post partum.

The mothers who were randomized to 6,400 IU of vitamin D3 showed a substantial increase in circulating calcium levels with no adverse effects. In addition, compliance rates were more than 90% because the mothers said that they were more likely to remember to take a pill themselves than to give supplements to their babies.

The infants whose mothers took 400 IU received their own supplement of 300 IU daily, while the infants whose mothers took 6,400 IU received a placebo supplement.

“What we found was a wonderful increase” in infant 25(OH)D levels from breast milk alone, Dr. Wagner said.

After 6 months, the average 25(OH)D level was 47 ng/mL in the mothers who received 6,400 IU and 46 ng/mL in their babies. By comparison, the average 25(OH)D level was 38 ng/mL in the mothers who received 400 IU and 43 ng/mL in their babies. There were no adverse events in either mother or infant related to vitamin D toxicity.

“Supplementing the mom with high-dose vitamin D is still considered unproven,” Dr. Wagner said. “We think it is safe, but we have to study it in large numbers.” A study of 389 lactating women at sites in Charleston, S.C., and Rochester, N.Y., is planned, and the researchers will assess factors including bone mineral density and immune function.

For now, Dr. Wagner encourages physicians to recommend vitamin D supplementation for breast-feeding infants, but if the circulating vitamin D levels in the mothers are 50 ng/mL or higher, the infants are probably getting enough, too. Strive for circulating 25(OH)D levels of at least 30 ng/mL in all patients, she emphasized.

The American Academy of Pediatrics currently recommends vitamin D supplementation for all breast-fed infants because mother's milk is generally deficient in vitamin D. But 25% of the vitamin D in lactating women goes into breast milk, and it seems that increasing vitamin D in mothers results in adequate vitamin D for the breast-fed infant, Dr. Wagner explained. Because a mother is the only source of vitamin D for her developing fetus and the primary source for a breast-feeding infant, more research is needed on whether increasing maternal vitamin D will help infants, too.

CHARLESTON, S.C. — Give breast-feeding women enough vitamin D and you may supplement their babies, too, according to the results of a small but promising pilot study presented at a pediatric meeting sponsored by the Medical University of South Carolina.

“Our question was: 'Would direct vitamin D supplementation meet the needs of both the mother and her nursing infant?' “said Dr. Carol L. Wagner of the department of neonatology at the university, in Charleston.

Insufficient vitamin D causes many problems, primarily a lack of calcium absorption that can lead to bone loss. In addition, recent research suggests a link between insufficient vitamin D and immune system disorders such as diabetes, Dr. Wagner said.

People in the developed world are at risk for vitamin D deficiency because of a primarily indoor lifestyle that has limited adequate vitamin D intake from sunlight, she added.

Data from several recent studies suggest that doses of vitamin D that are significantly higher than the current recommended daily allowance will not cause toxicity and are in fact needed for adequate circulating 25-hydroxyvitamin D concentrations (25[OH]D).

To determine whether giving mothers high doses of vitamin D provides adequate 25(OH)D for both mothers and infants without toxicity to either, Dr. Wagner and colleagues randomized 18 breast-feeding women to receive 400 IU or 6,400 IU of vitamin D3 as a daily pill for 6 months starting at 1 month post partum.

The mothers who were randomized to 6,400 IU of vitamin D3 showed a substantial increase in circulating calcium levels with no adverse effects. In addition, compliance rates were more than 90% because the mothers said that they were more likely to remember to take a pill themselves than to give supplements to their babies.

The infants whose mothers took 400 IU received their own supplement of 300 IU daily, while the infants whose mothers took 6,400 IU received a placebo supplement.

“What we found was a wonderful increase” in infant 25(OH)D levels from breast milk alone, Dr. Wagner said.

After 6 months, the average 25(OH)D level was 47 ng/mL in the mothers who received 6,400 IU and 46 ng/mL in their babies. By comparison, the average 25(OH)D level was 38 ng/mL in the mothers who received 400 IU and 43 ng/mL in their babies. There were no adverse events in either mother or infant related to vitamin D toxicity.

“Supplementing the mom with high-dose vitamin D is still considered unproven,” Dr. Wagner said. “We think it is safe, but we have to study it in large numbers.” A study of 389 lactating women at sites in Charleston, S.C., and Rochester, N.Y., is planned, and the researchers will assess factors including bone mineral density and immune function.

For now, Dr. Wagner encourages physicians to recommend vitamin D supplementation for breast-feeding infants, but if the circulating vitamin D levels in the mothers are 50 ng/mL or higher, the infants are probably getting enough, too. Strive for circulating 25(OH)D levels of at least 30 ng/mL in all patients, she emphasized.

The American Academy of Pediatrics currently recommends vitamin D supplementation for all breast-fed infants because mother's milk is generally deficient in vitamin D. But 25% of the vitamin D in lactating women goes into breast milk, and it seems that increasing vitamin D in mothers results in adequate vitamin D for the breast-fed infant, Dr. Wagner explained. Because a mother is the only source of vitamin D for her developing fetus and the primary source for a breast-feeding infant, more research is needed on whether increasing maternal vitamin D will help infants, too.

CHARLESTON, S.C. — Give breast-feeding women enough vitamin D and you may supplement their babies, too, according to the results of a small but promising pilot study presented at a pediatric meeting sponsored by the Medical University of South Carolina.

“Our question was: 'Would direct vitamin D supplementation meet the needs of both the mother and her nursing infant?' “said Dr. Carol L. Wagner of the department of neonatology at the university, in Charleston.

Insufficient vitamin D causes many problems, primarily a lack of calcium absorption that can lead to bone loss. In addition, recent research suggests a link between insufficient vitamin D and immune system disorders such as diabetes, Dr. Wagner said.

People in the developed world are at risk for vitamin D deficiency because of a primarily indoor lifestyle that has limited adequate vitamin D intake from sunlight, she added.

Data from several recent studies suggest that doses of vitamin D that are significantly higher than the current recommended daily allowance will not cause toxicity and are in fact needed for adequate circulating 25-hydroxyvitamin D concentrations (25[OH]D).

To determine whether giving mothers high doses of vitamin D provides adequate 25(OH)D for both mothers and infants without toxicity to either, Dr. Wagner and colleagues randomized 18 breast-feeding women to receive 400 IU or 6,400 IU of vitamin D3 as a daily pill for 6 months starting at 1 month post partum.

The mothers who were randomized to 6,400 IU of vitamin D3 showed a substantial increase in circulating calcium levels with no adverse effects. In addition, compliance rates were more than 90% because the mothers said that they were more likely to remember to take a pill themselves than to give supplements to their babies.

The infants whose mothers took 400 IU received their own supplement of 300 IU daily, while the infants whose mothers took 6,400 IU received a placebo supplement.

“What we found was a wonderful increase” in infant 25(OH)D levels from breast milk alone, Dr. Wagner said.

After 6 months, the average 25(OH)D level was 47 ng/mL in the mothers who received 6,400 IU and 46 ng/mL in their babies. By comparison, the average 25(OH)D level was 38 ng/mL in the mothers who received 400 IU and 43 ng/mL in their babies. There were no adverse events in either mother or infant related to vitamin D toxicity.

“Supplementing the mom with high-dose vitamin D is still considered unproven,” Dr. Wagner said. “We think it is safe, but we have to study it in large numbers.” A study of 389 lactating women at sites in Charleston, S.C., and Rochester, N.Y., is planned, and the researchers will assess factors including bone mineral density and immune function.

For now, Dr. Wagner encourages physicians to recommend vitamin D supplementation for breast-feeding infants, but if the circulating vitamin D levels in the mothers are 50 ng/mL or higher, the infants are probably getting enough, too. Strive for circulating 25(OH)D levels of at least 30 ng/mL in all patients, she emphasized.

The American Academy of Pediatrics currently recommends vitamin D supplementation for all breast-fed infants because mother's milk is generally deficient in vitamin D. But 25% of the vitamin D in lactating women goes into breast milk, and it seems that increasing vitamin D in mothers results in adequate vitamin D for the breast-fed infant, Dr. Wagner explained. Because a mother is the only source of vitamin D for her developing fetus and the primary source for a breast-feeding infant, more research is needed on whether increasing maternal vitamin D will help infants, too.

ARLINGTON, VA. — People who take sufficiently high supplement doses of vitamin D or those who already have adequate levels of vitamin D were found to have a small but significantly reduced risk of specific fractures, falls, and low bone mineral density, according to an Agency for Healthcare Research and Quality report on the effect of vitamin D supplements on bone health outcomes.

Dr. Ann B. Cranney and her associates at the University of Ottawa Evidence-Based Practice Center extensively reviewed the literature on the effects of 25-hydroxyvitamin D (25[OH]D) concentration or vitamin D supplementation. She presented the results of meta-analyses on studies that met eligibility criteria at a conference sponsored by the American Society for Bone and Mineral Research.

It was not possible to quantitatively summarize the results of 10 randomized controlled trials or 31 observational studies that examined the effect of 25(OH)D levels on bone health outcomes in postmenopausal women and older men, so Dr. Cranney and her colleagues categorized the evidence supporting the effect of the vitamin D metabolite as good, fair, or inconsistent. For serum 25(OH)D levels of at least 50–80 nmol/L, there was good evidence of an association with increased bone mineral density in the hip, fair evidence of an inverse association with the risk of hip fracture, and inconsistent evidence of an association with a reduction in falls and functional measures such as grip strength and body sway.

In 74 randomized controlled trials of supplementation with either vitamin D₃ or vitamin D₂, the investigators found that 25(OH)D levels increased more with supplementation with vitamin D₃ than with vitamin D₂. Data collected from 16 randomized controlled trials provided enough information on 25(OH)D levels in both the control and treatment groups at baseline as well as at the end of the study to enable the investigators to determine that supplementation with 700 IU/day or more of vitamin D₃ was associated with a drop in serum parathyroid hormone levels. The investigators also calculated from the trial results that 1 IU vitamin D₃ raises serum 25(OH)D concentration by 0.016 nmol/L.

Trials that used supplements with either vitamin D₃ or vitamin D₂ did not show a significant effect on reducing the risk of fractures overall or on the risk of hip fractures in particular. Also, supplementation with vitamin D plus calcium or vitamin D alone did not have a significant effect on the risk of nonvertebral fractures. But in eight trials, supplements of 700 IU/day or more vitamin D₃ significantly reduced the risk of nonvertebral fractures by 15%.

This risk reduction was primarily driven by two trials of individuals in an institutional setting, who had a 22% reduction in the risk of nonvertebral fractures. Supplements of 700 IU/day or more vitamin D₃ also significantly lowered the risk of hip fractures; trials in an institutional setting, rather than in the community, factored strongly in the overall results, she noted.

The investigators found that participants in trials of vitamin D₃ supplementation that recorded serum 25(OH)D concentrations of 74 nmol/L or higher had a significant 23% lower risk of nonvertebral fractures than did participants of trials that did not achieve a 25(OH)D level of 74 nmol/L.

Vitamin D supplements did not reduce the risk of falls overall in 12 trials. But vitamin D supplements did significantly lowered the risk of a fall by 11% in six trials in which falls were defined or independently ascertained, Dr. Cranney said.

The Agency for Healthcare Research and Quality requested the report on behalf of the National Institutes of Health Office of Dietary Supplements.

ARLINGTON, VA. — People who take sufficiently high supplement doses of vitamin D or those who already have adequate levels of vitamin D were found to have a small but significantly reduced risk of specific fractures, falls, and low bone mineral density, according to an Agency for Healthcare Research and Quality report on the effect of vitamin D supplements on bone health outcomes.

Dr. Ann B. Cranney and her associates at the University of Ottawa Evidence-Based Practice Center extensively reviewed the literature on the effects of 25-hydroxyvitamin D (25[OH]D) concentration or vitamin D supplementation. She presented the results of meta-analyses on studies that met eligibility criteria at a conference sponsored by the American Society for Bone and Mineral Research.

It was not possible to quantitatively summarize the results of 10 randomized controlled trials or 31 observational studies that examined the effect of 25(OH)D levels on bone health outcomes in postmenopausal women and older men, so Dr. Cranney and her colleagues categorized the evidence supporting the effect of the vitamin D metabolite as good, fair, or inconsistent. For serum 25(OH)D levels of at least 50–80 nmol/L, there was good evidence of an association with increased bone mineral density in the hip, fair evidence of an inverse association with the risk of hip fracture, and inconsistent evidence of an association with a reduction in falls and functional measures such as grip strength and body sway.

In 74 randomized controlled trials of supplementation with either vitamin D₃ or vitamin D₂, the investigators found that 25(OH)D levels increased more with supplementation with vitamin D₃ than with vitamin D₂. Data collected from 16 randomized controlled trials provided enough information on 25(OH)D levels in both the control and treatment groups at baseline as well as at the end of the study to enable the investigators to determine that supplementation with 700 IU/day or more of vitamin D₃ was associated with a drop in serum parathyroid hormone levels. The investigators also calculated from the trial results that 1 IU vitamin D₃ raises serum 25(OH)D concentration by 0.016 nmol/L.

Trials that used supplements with either vitamin D₃ or vitamin D₂ did not show a significant effect on reducing the risk of fractures overall or on the risk of hip fractures in particular. Also, supplementation with vitamin D plus calcium or vitamin D alone did not have a significant effect on the risk of nonvertebral fractures. But in eight trials, supplements of 700 IU/day or more vitamin D₃ significantly reduced the risk of nonvertebral fractures by 15%.

This risk reduction was primarily driven by two trials of individuals in an institutional setting, who had a 22% reduction in the risk of nonvertebral fractures. Supplements of 700 IU/day or more vitamin D₃ also significantly lowered the risk of hip fractures; trials in an institutional setting, rather than in the community, factored strongly in the overall results, she noted.

The investigators found that participants in trials of vitamin D₃ supplementation that recorded serum 25(OH)D concentrations of 74 nmol/L or higher had a significant 23% lower risk of nonvertebral fractures than did participants of trials that did not achieve a 25(OH)D level of 74 nmol/L.

Vitamin D supplements did not reduce the risk of falls overall in 12 trials. But vitamin D supplements did significantly lowered the risk of a fall by 11% in six trials in which falls were defined or independently ascertained, Dr. Cranney said.

The Agency for Healthcare Research and Quality requested the report on behalf of the National Institutes of Health Office of Dietary Supplements.

ARLINGTON, VA. — People who take sufficiently high supplement doses of vitamin D or those who already have adequate levels of vitamin D were found to have a small but significantly reduced risk of specific fractures, falls, and low bone mineral density, according to an Agency for Healthcare Research and Quality report on the effect of vitamin D supplements on bone health outcomes.

Dr. Ann B. Cranney and her associates at the University of Ottawa Evidence-Based Practice Center extensively reviewed the literature on the effects of 25-hydroxyvitamin D (25[OH]D) concentration or vitamin D supplementation. She presented the results of meta-analyses on studies that met eligibility criteria at a conference sponsored by the American Society for Bone and Mineral Research.

It was not possible to quantitatively summarize the results of 10 randomized controlled trials or 31 observational studies that examined the effect of 25(OH)D levels on bone health outcomes in postmenopausal women and older men, so Dr. Cranney and her colleagues categorized the evidence supporting the effect of the vitamin D metabolite as good, fair, or inconsistent. For serum 25(OH)D levels of at least 50–80 nmol/L, there was good evidence of an association with increased bone mineral density in the hip, fair evidence of an inverse association with the risk of hip fracture, and inconsistent evidence of an association with a reduction in falls and functional measures such as grip strength and body sway.

In 74 randomized controlled trials of supplementation with either vitamin D₃ or vitamin D₂, the investigators found that 25(OH)D levels increased more with supplementation with vitamin D₃ than with vitamin D₂. Data collected from 16 randomized controlled trials provided enough information on 25(OH)D levels in both the control and treatment groups at baseline as well as at the end of the study to enable the investigators to determine that supplementation with 700 IU/day or more of vitamin D₃ was associated with a drop in serum parathyroid hormone levels. The investigators also calculated from the trial results that 1 IU vitamin D₃ raises serum 25(OH)D concentration by 0.016 nmol/L.

Trials that used supplements with either vitamin D₃ or vitamin D₂ did not show a significant effect on reducing the risk of fractures overall or on the risk of hip fractures in particular. Also, supplementation with vitamin D plus calcium or vitamin D alone did not have a significant effect on the risk of nonvertebral fractures. But in eight trials, supplements of 700 IU/day or more vitamin D₃ significantly reduced the risk of nonvertebral fractures by 15%.

This risk reduction was primarily driven by two trials of individuals in an institutional setting, who had a 22% reduction in the risk of nonvertebral fractures. Supplements of 700 IU/day or more vitamin D₃ also significantly lowered the risk of hip fractures; trials in an institutional setting, rather than in the community, factored strongly in the overall results, she noted.

The investigators found that participants in trials of vitamin D₃ supplementation that recorded serum 25(OH)D concentrations of 74 nmol/L or higher had a significant 23% lower risk of nonvertebral fractures than did participants of trials that did not achieve a 25(OH)D level of 74 nmol/L.

Vitamin D supplements did not reduce the risk of falls overall in 12 trials. But vitamin D supplements did significantly lowered the risk of a fall by 11% in six trials in which falls were defined or independently ascertained, Dr. Cranney said.

The Agency for Healthcare Research and Quality requested the report on behalf of the National Institutes of Health Office of Dietary Supplements.

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley reported at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, codirector of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said.

But many other conditions that are affected by vitamin D status have been labeled as “age-related” morbidities, including sarcopenia, falling, overactive bladder, swallowing dysfunction, decreased lung function, macular degeneration, and cognitive decline.

“Always consider that perhaps some of these other age-related morbidities are what are causing this dramatic effect of age on fracture,” Dr. Binkley said.

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D.

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, leading to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia. Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after taking a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than in individuals in the lowest quintile of the vitamin.

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, deficient and extremely low levels of vitamin D were found in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley reported at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, codirector of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said.

But many other conditions that are affected by vitamin D status have been labeled as “age-related” morbidities, including sarcopenia, falling, overactive bladder, swallowing dysfunction, decreased lung function, macular degeneration, and cognitive decline.

“Always consider that perhaps some of these other age-related morbidities are what are causing this dramatic effect of age on fracture,” Dr. Binkley said.

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D.

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, leading to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia. Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after taking a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than in individuals in the lowest quintile of the vitamin.

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, deficient and extremely low levels of vitamin D were found in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

ARLINGTON, VA. — Inadequate levels of vitamin D may help to explain not only morbidities such as osteoporosis but also less-appreciated effects of vitamin D insufficiency that worsen bodily functions and are commonly thought to be related to aging alone, Dr. Neil Binkley reported at a conference sponsored by the American Society for Bone and Mineral Research.

“I would like to suggest to you that vitamin D inadequacy might be contributing to what we are currently accepting as old age-related morbidity,” said Dr. Binkley, codirector of the University of Wisconsin Osteoporosis Clinical Center and Research Program, Madison.

The prevalence of densitometric osteopenia markedly increases with advancing age, and at any given bone density, age has a “profound impact” on the risk of fracture, he said.

But many other conditions that are affected by vitamin D status have been labeled as “age-related” morbidities, including sarcopenia, falling, overactive bladder, swallowing dysfunction, decreased lung function, macular degeneration, and cognitive decline.

“Always consider that perhaps some of these other age-related morbidities are what are causing this dramatic effect of age on fracture,” Dr. Binkley said.

▸ Sarcopenia. The expression of vitamin D receptors declines in muscle with aging. In muscle, vitamin D also may be involved with calcium transport and actin-myosin interaction.

A study of 1,008 older adults has suggested that vitamin D inadequacy is associated with sarcopenia. After a 3-year follow-up, men and women with baseline 25(OH)D levels less than 25 nmol/L were more than twice as likely to develop sarcopenia (based on either grip strength or muscle mass) than were those with a higher level of 25(OH)D.

▸ Falling. It is not known whether vitamin D status and muscle strength are causally related, but “it is, however, clear that vitamin D status is related to the risk of falling in both older men and older women,” Dr. Binkley said.

The risk of falling is increased by orthopedic disabilities, visual impairment, central or peripheral neurologic dysfunction, and muscle weakness, which may be the main risk factor, he said. A meta-analysis of double-blind, randomized, trials showed that vitamin D reduced the risk of falling by 22% (JAMA 2004;291:1999–2006).

▸ Overactive bladder. Bladder dysfunction also may be associated with muscle weakness, leading to poorer coordination of the muscles used to control urination. Overactive bladder affects 30%–40% of adults older than 75 years of age and two-thirds of nursing home residents; it is defined as urinary urgency with or without incontinence, usually with frequency and nocturia.

In a study of nearly 6,000 community-dwelling women aged 40 years or older, women in the highest quintiles of vitamin D intake had the lowest risk of developing overactive bladder (Neurourol. Urodyn. 2004;23:204–10).

▸ Difficulty swallowing. Up to 40% of individuals older than 60 years have problems swallowing, which can lead to undernutrition, sarcopenia, and aspiration pneumonia. Dysphagia associated with aging classically has been felt to reflect neurologic disease such as Parkinson's or stroke, but more recent work has shown that even normal healthy adults swallow more slowly and generate lower tongue pressures than do younger adults.

“I think it's at least plausible that this decreased muscle function might be causally related to the increased risk of dysphagia observed with advancing age,” Dr. Binkley suggested.

But no research has been conducted on vitamin D status and the risk of dysphagia of aging, he said.

▸ Pulmonary function. Both the forced expiratory volume in the first second after taking a deep breath and forced vital capacity are known to decline with aging; poor results on such tests are associated with substantial morbidity and mortality.

In a study of people in the National Health and Nutrition Examination Survey III (NHANES III) who were aged 60 years or older, both of those measures of lung function were significantly higher among people in the highest quintile of serum 25(OH)D concentration than in individuals in the lowest quintile of the vitamin.

Biologically plausible ways in which vitamin D might protect against a decline in pulmonary function include the possibility of a decline in respiratory muscle function with inadequate levels of vitamin D, lung tissue remodeling, or a reduction in airway inflammation.

▸ Age-related macular degeneration. In a yet-to-be published study involving 7,752 people who participated in NHANES III, the risk of developing age-related macular degeneration declined steadily from the lowest to the highest quintiles of serum 25(OH)D concentration.

▸ Dementia/cognitive decline. In a small case-control study, deficient and extremely low levels of vitamin D were found in significantly more ambulatory women with Alzheimer's disease than in control women of the same age without Alzheimer's or fractures (Bone 1998;23:555–7).

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day because of a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels, but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000 IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published. This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]₂D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment. Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day because of a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels, but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000 IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published. This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]₂D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment. Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

ARLINGTON, VA. — The currently recommended tolerable upper intake level of vitamin D is too low and is hindering clinical research efforts to determine a more accurate optimal intake of the vitamin, said Reinhold Vieth, Ph.D., at a conference sponsored by the American Society for Bone and Mineral Research.

Preliminary research and case reports on the use of high doses of vitamin D suggest that the tolerable upper intake level (UL) could be much higher than it now is, yet some researchers think that higher doses will cause hypercalcemic toxicity, according to Dr. Vieth, director of the bone and mineral laboratory at Mount Sinai Hospital, Toronto.

The lowest adverse-event level for vitamin D intake was established at 3,800 IU/day because of a 1984 study in which six patients developed hypercalcemia at that level. In the same study, a dosage of 2,400 IU/day of vitamin D resulted in a statistically significant increase in serum calcium levels, but was not regarded as hypercalcemic and was considered safe. But because of an uncertainty factor of about 400 IU/day, the UL—defined as the highest level of daily vitamin D intake likely to pose no risk of adverse effects in almost all individuals in the general population—became 2,000 IU/day (50 mcg/day), Dr. Vieth said (J. Am. Diet. Assoc. 1998;98:699–706).

Research on the effects of vitamin D has been driven by the 2,000 IU/day UL rather than by a more careful dose-finding study of when toxicities begin to appear, he said.

There is no recommended dietary allowance (RDA) for vitamin D because when RDAs were established in 1995, there was perceived to be not enough evidence to recommend one, so an adequate intake level was “guesstimated,” Dr. Vieth said.

Vitamin D and its metabolites are stored at their highest concentration in adipose tissue, but a roughly equal amount overall is stored in muscles, contrary to what has been published. This leaves a large reservoir to store vitamin D. If one extrapolates a study of vitamin D toxicity in rats to humans, the highest dosage that did not cause hypercalcemia was equivalent to 5,000 IU/kg per day; hypercalcemia began to occur when the serum 25-hydroxyvitamin D (25[OH]D) level reached an equivalent of 2,000 nmol/L (Arch. Biochem. Biophys. 1980;202:43–53).

Perhaps the best study of vitamin D toxicity in humans is a report of a family that stole a container from a shipping dock of what they thought was vegetable oil but was actually a concentrate of vitamin D that was for veterinary use, according to Dr. Vieth (Ann. Intern. Med. 1995;122:511–3). In the family, hypercalcemia began to occur at serum 25(OH)D levels that were well above the reference range upper limit of 500 nmol/L; their serum 25(OH)D concentrations ranged from 847 nmol/L to 1,652 nmol/L.

Normally the vitamin D-binding protein binds more than 99% of all 1,25-dihydroxyvitamin D (1,25[OH]₂D) and only a “very small proportion” of vitamin D metabolites. But more than 1% of 1,25(OH)₂D was unbound from the binding protein in the family members and more of it was effectively displaced from the protein than normal because of the relatively high level of vitamin D metabolites in the patients. The levels of total 1,25(OH)₂D were just high-normal in the family members, but most had a high level of unbound 1,25(OH)₂D. This suggests that the likely mechanism through which vitamin D causes toxicity is the displacement of 1,25(OH)₂D from vitamin D-binding protein, Dr. Vieth said.

The capacity of vitamin D-binding protein for all metabolites of vitamin D is 4,000–5,000 nmol/L, but when concentrations of 25(OH)D approach 1,000 nmol/L, vitamin D-binding protein cannot bind as much 1,25(OH)₂D, he said.

“One problem with the vitamin D nutrition story is that we start to think of it as a drug, something to be used in treatment. Unlike any other drug I'm aware of, there's never been a dose-finding study done,” said Dr. Vieth, who is also a professor in the departments of nutritional sciences, pathology, and laboratory medicine at the University of Toronto.

In a preliminary study of 12 patients with active-phase multiple sclerosis, Dr. Vieth and his colleagues studied the safety of using up to 40,000 IU/day of vitamin D₃ in treatment. The dosage of vitamin D₃ in the study increased from 4,000 IU/day up to 40,000 IU/day during the course of the study.

Many of the patients had already been taking vitamin D supplements; they had baseline concentrations of 100 nmol/L of 25(OH)D. The patients also received about 1,000 mg/day of calcium phosphate.

“So if you've got a cohort that's going to be susceptible to vitamin D toxicity in a phase I study, this is it,” he said.

No events of hypercalcemia and no change in urinary calcium levels have occurred. The investigators have received funding to extend the study.

With the results of his study and after a review of the literature, Dr. Vieth concluded that about 1 mg/day or 40,000 IU/day of vitamin D₃ might be the threshold at which toxicity begins.

But the actual UL for vitamin D should be about 10,000 IU/day, or 250 mcg/day, Dr. Vieth suggested. This is not an RDA, but it is a level not likely to cause harm in most individuals.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, Dr. Lewiecki noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Among patients who chose intravenous administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, Dr. Lewiecki noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Among patients who chose intravenous administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

TORONTO — Women with postmenopausal osteoporosis who had previously discontinued oral bisphosphonate therapy because of gastrointestinal intolerance preferred an intravenous, every-3-month regimen of ibandronate over a monthly oral regimen, Dr. E. Michael Lewiecki reported at a world congress on osteoporosis.

Complex dosing instructions designed to maximize bioavailability and address tolerability concerns may affect adherence to oral bisphosphonate therapy, and adherence is crucial to clinical efficacy and fracture prevention, Dr. Lewiecki noted.

Adherence was addressed in a 12-month, open-label multicenter study that included 542 patients with osteoporosis or osteopenia who had stopped daily or weekly treatment with oral alendronate or risedronate because of perceived or actual symptoms such as heartburn and acid reflux. All received supplemental vitamin D (400 IU/day) and elemental calcium (1,000 mg/day).

Patients were given the choice of oral ibandronate, 150 mg once monthly, or 3 mg by intravenous injection every 3 months. A total of 396 (73%) of patients chose the intravenous regimen, while 146 (27%) chose the oral route.

They were permitted to switch treatment groups once during the study if they experienced adverse effects, he noted.

Severity and frequency of gastrointestinal symptoms and other side effects were evaluated with surveys administered at baseline and at months 1, 4, 7, and 10.

Available data indicate that adherence to both regimens at 6 months was high, at 94.5%. Actual duration of study medication intake divided by maximum duration of intake and a threshold of 75% or more was used to define adherence, according to Dr. Lewiecki of New Mexico Clinical Research and Osteoporosis Center, Albuquerque.

Among patients receiving the oral drug, adherence was 87.7%, while adherence was 94.9% among those receiving the intravenous formulation, Dr. Lewiecki wrote in a poster session at the meeting, which was sponsored by the International Osteoporosis Foundation.

Among patients who chose intravenous administration, 147 (37.1%) had a history of fracture as an adult, compared with 36 (24.7%) of those who chose the oral drug.

Thus far, 26 patients have switched their route of administration. Eleven switched from oral to intravenous ibandronate because of gastrointestinal intolerance, while 15 switched from intravenous to oral for reasons including influenzalike symptoms and injection-site reactions.

By month 4, 28.1% and 36.6% of patients on the oral and intravenous drugs, respectively, reported improved gastrointestinal tolerance, compared with baseline.

“Based on these findings, it appears that patients who had previously discontinued weekly or daily oral bisphosphonates because of gastrointestinal intolerance prefer intravenous dosing, and that patients with a previous fracture are even more likely to do so than patients without a previous fracture,” Dr. Lewiecki concluded.

The study was sponsored by Roche Laboratories.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Whereas previous studies have documented an association between type 1 diabetes and osteoporotic fractures, the data on patients with type 2 diabetes have conflicted. Those studies have mostly been small and limited to women. Moreover, bone density is typically normal or high in type 2 diabetes, whereas it is reduced in type 1, leading some to believe that people with type 2 diabetes are somehow “protected,” said Dr. Lipscome, of the University of Toronto.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. After excluding those with prior hip fractures or hip replacements and those on oral corticosteroid treatment, the study population comprised 207,252 diabetics and 414,504 nondiabetics, with an overall mean age of 71.7 years. Information about diabetes type was not available, but it was presumed that most were type 2 because of the age group involved, Dr. Lipscome said in an interview.

After a mean of 6.1 years, the risk for hip fractures was significantly higher among those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Compared with nondiabetics, those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age; comorbidity; prior stroke; visual impairment; neuropathy; amputation; treatment with nitrates, statins, anticonvulsants, inhaled corticosteroids, thiazides, or fall-promoting medications; history of a bone mineral density test; estrogen treatment in women; and income quintile in men, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men, compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Whereas previous studies have documented an association between type 1 diabetes and osteoporotic fractures, the data on patients with type 2 diabetes have conflicted. Those studies have mostly been small and limited to women. Moreover, bone density is typically normal or high in type 2 diabetes, whereas it is reduced in type 1, leading some to believe that people with type 2 diabetes are somehow “protected,” said Dr. Lipscome, of the University of Toronto.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. After excluding those with prior hip fractures or hip replacements and those on oral corticosteroid treatment, the study population comprised 207,252 diabetics and 414,504 nondiabetics, with an overall mean age of 71.7 years. Information about diabetes type was not available, but it was presumed that most were type 2 because of the age group involved, Dr. Lipscome said in an interview.

After a mean of 6.1 years, the risk for hip fractures was significantly higher among those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Compared with nondiabetics, those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age; comorbidity; prior stroke; visual impairment; neuropathy; amputation; treatment with nitrates, statins, anticonvulsants, inhaled corticosteroids, thiazides, or fall-promoting medications; history of a bone mineral density test; estrogen treatment in women; and income quintile in men, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men, compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

TORONTO — The risk for hip fractures appears to be elevated in elderly men and women with diabetes, Dr. Lorraine L. Lipscome reported in a poster at the joint annual meeting of the Canadian Diabetes Association and the Canadian Society of Endocrinology and Metabolism.

Whereas previous studies have documented an association between type 1 diabetes and osteoporotic fractures, the data on patients with type 2 diabetes have conflicted. Those studies have mostly been small and limited to women. Moreover, bone density is typically normal or high in type 2 diabetes, whereas it is reduced in type 1, leading some to believe that people with type 2 diabetes are somehow “protected,” said Dr. Lipscome, of the University of Toronto.

In a retrospective cohort study using population-based Ontario health care databases from 1994 to 2003, researchers compared the risk of hip fractures between individuals older than 65 years of age with and without diabetes. After excluding those with prior hip fractures or hip replacements and those on oral corticosteroid treatment, the study population comprised 207,252 diabetics and 414,504 nondiabetics, with an overall mean age of 71.7 years. Information about diabetes type was not available, but it was presumed that most were type 2 because of the age group involved, Dr. Lipscome said in an interview.

After a mean of 6.1 years, the risk for hip fractures was significantly higher among those with diabetes, at 7.21 per 1,000 person-years, compared with 6.15 per 1,000 person-years among those without diabetes.

Compared with nondiabetics, those with diabetes had more comorbidity, were less likely to have had a bone mineral density test, and were more likely to be taking drugs that affected fall risk and bone density.

Women had a significantly higher risk for fracture than did men, but diabetes increased the risk in both genders, with hazard ratios of 1.22 for men and 1.19 for women. The increased risk remained significant (1.18 in men and 1.11 in women) after adjustment for age; comorbidity; prior stroke; visual impairment; neuropathy; amputation; treatment with nitrates, statins, anticonvulsants, inhaled corticosteroids, thiazides, or fall-promoting medications; history of a bone mineral density test; estrogen treatment in women; and income quintile in men, Dr. Lipscome reported.

Insulin use among the patients with diabetes increased the fracture risk, with hazard ratios of 1.34 in women and 1.64 in men, compared with those not using insulin.

Until the phenomenon is better understood, bone fracture risk assessment and enhanced prevention strategies are warranted in all patients with diabetes, she said.

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are available to patients, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study. Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m2.

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are available to patients, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study. Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m2.

ARLINGTON, VA. — Fish oil capsules and multivitamin tablets that contain 10 mcg of vitamin D₃ provide the same increase in stored levels of the vitamin when taken daily during a 4-week period, Kristin Holvik reported at a conference sponsored by the American Society for Bone and Mineral Research.

Even though many types of vitamin supplements are available to patients, little is known about whether the bioavailability of vitamin D₃ (cholecalciferol) differs when it is sequestered in fat-containing capsules as opposed to solid tablets, noted Ms. Holvik, a Ph.D. student at the Institute of General Practice and Community Medicine at the University of Oslo.

In a randomized trial, 55 healthy young adults (34 females and 21 males) received 28 days of supplementation with either fish oil capsules or multivitamin tablets, each of which was taken once daily and contained 10 mcg vitamin D₃ (an amount equivalent to 400 IU).

The participants completed a self-administered questionnaire about diet and sun exposure and had a nonfasting venous blood sample drawn at the beginning and end of the study, which took place in Oslo in late winter 2005, according to Ms. Holvik. She won an ASBMR Young Investigator Award for her research, which she presented during a poster session at the conference.

Serum 25-hydroxyvitamin D levels in individuals who took fish oil capsules increased from an average of 48.5 nmol/L to 80.4 nmol/L at the end of the study. Multivitamin users had a similar rise in serum 25-hydroxyvitamin D levels from a mean of 40.3 nmol/L to 76.5 nmol/L. On average, the participants were aged about 28 years and had a body mass index of about 24 kg/m2.

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

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

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

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

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said.

As a consequence of high PTH levels, blacks have generally been measured with higher 1–25dihydroxyvitamin D [1,25(OH)₂D] levels than have whites.

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

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said.

However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

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

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

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

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

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

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

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

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said.

As a consequence of high PTH levels, blacks have generally been measured with higher 1–25dihydroxyvitamin D [1,25(OH)₂D] levels than have whites.

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

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said.

However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

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

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

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

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

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

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

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

In many studies, parathyroid hormone (PTH) levels are higher, on average, in blacks than in whites. The PTH levels found in blacks occur within the context of low calcium intake in addition to low 25(OH)D levels, which may be related to “real or perceived” lactose intolerance, Dr. Cosman said.

As a consequence of high PTH levels, blacks have generally been measured with higher 1–25dihydroxyvitamin D [1,25(OH)₂D] levels than have whites.

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

One also would expect blacks to have higher bone turnover levels because of high PTH levels, but in general this has not been true, Dr. Cosman said.

However, nearly all studies of the kidney have found that blacks have lower urinary calcium excretion than whites.

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

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

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

PHILADELPHIA — White men and black women are at an increased risk for cardiovascular disease for each standard deviation decrease in volumetric bone mineral density, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

White men have an almost 40% increased risk for each standard deviation decrease in volumetric spine bone mineral density (BMD), while black women appear to have up to a 44% increased risk for each standard deviation decrease in areal BMD, presenting a complicated picture of how bone mass and cardiovascular disease interact with gender and race, said Ghada N. Farhat, Ph.D., an epidemiology research associate at the University of Pittsburgh.

Previous studies have linked low bone mass with increased cardiovascular mortality and morbidity and clinical measures of atherosclerosis. However, many of these studies primarily have involved white women. Less is known about the associations between bone mass and cardiovascular disease (CVD) in men and other races, Dr. Farhat said.

Dr. Farhat and her colleagues performed a longitudinal analysis looking at CVD incidence and bone mass using data from the Health, Aging and Body Composition (Health ABC) study. The Health ABC study was designed to assess the association between changes in body composition and functional decline.

This analysis involved 2,310 adults aged 68–80 years who were included if CVD-free at baseline. The cohort was composed of slightly more men (55%) and white patients (58%). Study participants had to be free of disability in activities of daily living and free of functional limitations (defined as any difficulty walking a quarter of a mile or walking up 10 steps without resting) at baseline.

Incidence of CVD was defined as the onset of one or more of the following conditions between study entry and mean follow-up of 5.4 years: coronary heart disease, cerebrovascular disease, peripheral artery disease, and coronary artery disease.

Baseline areal BMD data (obtained by dual-energy x-ray absorptiometry) was available for the total hip, femoral neck, and trochanter in all patients. Baseline volumetric BMD data (obtained by quantitative CT) was available for the trabecular, integral, and cortical spine in a subset of 1,095 patients.

Regression analysis was used to assess associations of BMD measures (per standard deviation decrease) with CVD. The researchers controlled for body mass index, physical activity level, lipids, blood pressure, and other covariates in their analysis models.

During follow-up, 23% of the men and 14% of the women developed CVD. White men had the highest incidence, followed by black men, black women, and white women.

Significant interactions were observed between race and spine volumetric BMD in men. “In black men, no associations were observed between volumetric BMD measures and CVD,” Dr. Farhat said. However, in white men, significant associations were observed between spine volumetric BMD measures and CVD. White men had an increased risk of 39% and 38% for each decrease of one standard deviation for integral and cortical spine BMD, respectively.

Significant interactions were also observed between race and all of the areal BMD hip measures among women. “In black women, we observed that all of the areal BMD measures of the hip showed significant associations with CVD,” Dr. Farhat said. In black women, the risk of CVD was increased by 36%, 44%, and 34% for each decrease of one standard deviation in areal BMD of the total hip, femoral neck, and trochanter, respectively.

Neither IL-6 nor TNF-α nor oxidized LDL cholesterol levels could explain the association of BMD with the incidence of CVD, she said.

Dr. Farhat reported that she had no conflicts of interest.

PHILADELPHIA — White men and black women are at an increased risk for cardiovascular disease for each standard deviation decrease in volumetric bone mineral density, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

White men have an almost 40% increased risk for each standard deviation decrease in volumetric spine bone mineral density (BMD), while black women appear to have up to a 44% increased risk for each standard deviation decrease in areal BMD, presenting a complicated picture of how bone mass and cardiovascular disease interact with gender and race, said Ghada N. Farhat, Ph.D., an epidemiology research associate at the University of Pittsburgh.

Previous studies have linked low bone mass with increased cardiovascular mortality and morbidity and clinical measures of atherosclerosis. However, many of these studies primarily have involved white women. Less is known about the associations between bone mass and cardiovascular disease (CVD) in men and other races, Dr. Farhat said.

Dr. Farhat and her colleagues performed a longitudinal analysis looking at CVD incidence and bone mass using data from the Health, Aging and Body Composition (Health ABC) study. The Health ABC study was designed to assess the association between changes in body composition and functional decline.

This analysis involved 2,310 adults aged 68–80 years who were included if CVD-free at baseline. The cohort was composed of slightly more men (55%) and white patients (58%). Study participants had to be free of disability in activities of daily living and free of functional limitations (defined as any difficulty walking a quarter of a mile or walking up 10 steps without resting) at baseline.

Incidence of CVD was defined as the onset of one or more of the following conditions between study entry and mean follow-up of 5.4 years: coronary heart disease, cerebrovascular disease, peripheral artery disease, and coronary artery disease.

Baseline areal BMD data (obtained by dual-energy x-ray absorptiometry) was available for the total hip, femoral neck, and trochanter in all patients. Baseline volumetric BMD data (obtained by quantitative CT) was available for the trabecular, integral, and cortical spine in a subset of 1,095 patients.

Regression analysis was used to assess associations of BMD measures (per standard deviation decrease) with CVD. The researchers controlled for body mass index, physical activity level, lipids, blood pressure, and other covariates in their analysis models.

During follow-up, 23% of the men and 14% of the women developed CVD. White men had the highest incidence, followed by black men, black women, and white women.

Significant interactions were observed between race and spine volumetric BMD in men. “In black men, no associations were observed between volumetric BMD measures and CVD,” Dr. Farhat said. However, in white men, significant associations were observed between spine volumetric BMD measures and CVD. White men had an increased risk of 39% and 38% for each decrease of one standard deviation for integral and cortical spine BMD, respectively.

Significant interactions were also observed between race and all of the areal BMD hip measures among women. “In black women, we observed that all of the areal BMD measures of the hip showed significant associations with CVD,” Dr. Farhat said. In black women, the risk of CVD was increased by 36%, 44%, and 34% for each decrease of one standard deviation in areal BMD of the total hip, femoral neck, and trochanter, respectively.

Neither IL-6 nor TNF-α nor oxidized LDL cholesterol levels could explain the association of BMD with the incidence of CVD, she said.

Dr. Farhat reported that she had no conflicts of interest.

PHILADELPHIA — White men and black women are at an increased risk for cardiovascular disease for each standard deviation decrease in volumetric bone mineral density, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

White men have an almost 40% increased risk for each standard deviation decrease in volumetric spine bone mineral density (BMD), while black women appear to have up to a 44% increased risk for each standard deviation decrease in areal BMD, presenting a complicated picture of how bone mass and cardiovascular disease interact with gender and race, said Ghada N. Farhat, Ph.D., an epidemiology research associate at the University of Pittsburgh.

Previous studies have linked low bone mass with increased cardiovascular mortality and morbidity and clinical measures of atherosclerosis. However, many of these studies primarily have involved white women. Less is known about the associations between bone mass and cardiovascular disease (CVD) in men and other races, Dr. Farhat said.

Dr. Farhat and her colleagues performed a longitudinal analysis looking at CVD incidence and bone mass using data from the Health, Aging and Body Composition (Health ABC) study. The Health ABC study was designed to assess the association between changes in body composition and functional decline.

This analysis involved 2,310 adults aged 68–80 years who were included if CVD-free at baseline. The cohort was composed of slightly more men (55%) and white patients (58%). Study participants had to be free of disability in activities of daily living and free of functional limitations (defined as any difficulty walking a quarter of a mile or walking up 10 steps without resting) at baseline.

Incidence of CVD was defined as the onset of one or more of the following conditions between study entry and mean follow-up of 5.4 years: coronary heart disease, cerebrovascular disease, peripheral artery disease, and coronary artery disease.

Baseline areal BMD data (obtained by dual-energy x-ray absorptiometry) was available for the total hip, femoral neck, and trochanter in all patients. Baseline volumetric BMD data (obtained by quantitative CT) was available for the trabecular, integral, and cortical spine in a subset of 1,095 patients.

Regression analysis was used to assess associations of BMD measures (per standard deviation decrease) with CVD. The researchers controlled for body mass index, physical activity level, lipids, blood pressure, and other covariates in their analysis models.

During follow-up, 23% of the men and 14% of the women developed CVD. White men had the highest incidence, followed by black men, black women, and white women.

Significant interactions were observed between race and spine volumetric BMD in men. “In black men, no associations were observed between volumetric BMD measures and CVD,” Dr. Farhat said. However, in white men, significant associations were observed between spine volumetric BMD measures and CVD. White men had an increased risk of 39% and 38% for each decrease of one standard deviation for integral and cortical spine BMD, respectively.

Significant interactions were also observed between race and all of the areal BMD hip measures among women. “In black women, we observed that all of the areal BMD measures of the hip showed significant associations with CVD,” Dr. Farhat said. In black women, the risk of CVD was increased by 36%, 44%, and 34% for each decrease of one standard deviation in areal BMD of the total hip, femoral neck, and trochanter, respectively.

Neither IL-6 nor TNF-α nor oxidized LDL cholesterol levels could explain the association of BMD with the incidence of CVD, she said.

Dr. Farhat reported that she had no conflicts of interest.