Osteoarthritis

The genetic influence on fracture susceptibility depends on the type of fracture and age at the time of the event, results from a large Swedish twin study suggest.

In addition, the heritability of osteoporotic fractures is stronger than has been previously estimated, especially for early-occurring osteoporotic fractures, according to the study's lead author, Karl Michaëlsson, M.D., Ph.D., of the Uppsala (Sweden) University Hospital and associates.

The investigators identified 33,432 twins born from 1896 to 1944 included in the Swedish Twin Registry, currently the largest twin registry in the world.

Among them, 24,598 agreed to take part in the study.

Computer-assisted telephone interviews and the Swedish Inpatient Registry were used to identify 6,021 twins with any fracture, 3,599 with osteoporotic fractures, and 1,055 with a hip fracture after the age of 50 years.

Just 16% of the overall age-adjusted fracture variance and 27% of the osteoporotic age-adjusted fracture variance were explained by genetic variation (Arch. Intern. Med. 2005;165:1825–30).

The strongest genetic influence was evident for hip fractures. Nearly half (48%) of the variance in liability to these fractures was attributable to genetic factors.

There was a tendency toward lower heritability estimates of fractures among the men, but it was not statistically significant.

If the first hip fracture within a twin pair occurred before age 69 years, 68% of the variance of liability was explained by genetic factors. If the first hip fracture happened between ages 69 and 79 years, 47% of the variance was attributable to genetic variation. After age 79 years, that figure fell to 3%.

The same pattern of attenuated heredity estimates with increasing age also was evident for the other fracture categories.

“A search for genes and gene-environment interactions that affect early osteoporotic fracture risk is likely to be fruitful, but fracture-prevention efforts at older ages should be focused on lifestyle habits,” the authors report.

Finally, they suggest that an assessment of osteoporotic fracture risk by clinical examination may be recommended for relatives of patients with hip fractures before age 80 years.

The genetic influence on fracture susceptibility depends on the type of fracture and age at the time of the event, results from a large Swedish twin study suggest.

In addition, the heritability of osteoporotic fractures is stronger than has been previously estimated, especially for early-occurring osteoporotic fractures, according to the study's lead author, Karl Michaëlsson, M.D., Ph.D., of the Uppsala (Sweden) University Hospital and associates.

The investigators identified 33,432 twins born from 1896 to 1944 included in the Swedish Twin Registry, currently the largest twin registry in the world.

Among them, 24,598 agreed to take part in the study.

Computer-assisted telephone interviews and the Swedish Inpatient Registry were used to identify 6,021 twins with any fracture, 3,599 with osteoporotic fractures, and 1,055 with a hip fracture after the age of 50 years.

Just 16% of the overall age-adjusted fracture variance and 27% of the osteoporotic age-adjusted fracture variance were explained by genetic variation (Arch. Intern. Med. 2005;165:1825–30).

The strongest genetic influence was evident for hip fractures. Nearly half (48%) of the variance in liability to these fractures was attributable to genetic factors.

There was a tendency toward lower heritability estimates of fractures among the men, but it was not statistically significant.

If the first hip fracture within a twin pair occurred before age 69 years, 68% of the variance of liability was explained by genetic factors. If the first hip fracture happened between ages 69 and 79 years, 47% of the variance was attributable to genetic variation. After age 79 years, that figure fell to 3%.

The same pattern of attenuated heredity estimates with increasing age also was evident for the other fracture categories.

“A search for genes and gene-environment interactions that affect early osteoporotic fracture risk is likely to be fruitful, but fracture-prevention efforts at older ages should be focused on lifestyle habits,” the authors report.

Finally, they suggest that an assessment of osteoporotic fracture risk by clinical examination may be recommended for relatives of patients with hip fractures before age 80 years.

The genetic influence on fracture susceptibility depends on the type of fracture and age at the time of the event, results from a large Swedish twin study suggest.

In addition, the heritability of osteoporotic fractures is stronger than has been previously estimated, especially for early-occurring osteoporotic fractures, according to the study's lead author, Karl Michaëlsson, M.D., Ph.D., of the Uppsala (Sweden) University Hospital and associates.

The investigators identified 33,432 twins born from 1896 to 1944 included in the Swedish Twin Registry, currently the largest twin registry in the world.

Among them, 24,598 agreed to take part in the study.

Computer-assisted telephone interviews and the Swedish Inpatient Registry were used to identify 6,021 twins with any fracture, 3,599 with osteoporotic fractures, and 1,055 with a hip fracture after the age of 50 years.

Just 16% of the overall age-adjusted fracture variance and 27% of the osteoporotic age-adjusted fracture variance were explained by genetic variation (Arch. Intern. Med. 2005;165:1825–30).

The strongest genetic influence was evident for hip fractures. Nearly half (48%) of the variance in liability to these fractures was attributable to genetic factors.

There was a tendency toward lower heritability estimates of fractures among the men, but it was not statistically significant.

If the first hip fracture within a twin pair occurred before age 69 years, 68% of the variance of liability was explained by genetic factors. If the first hip fracture happened between ages 69 and 79 years, 47% of the variance was attributable to genetic variation. After age 79 years, that figure fell to 3%.

The same pattern of attenuated heredity estimates with increasing age also was evident for the other fracture categories.

“A search for genes and gene-environment interactions that affect early osteoporotic fracture risk is likely to be fruitful, but fracture-prevention efforts at older ages should be focused on lifestyle habits,” the authors report.

Finally, they suggest that an assessment of osteoporotic fracture risk by clinical examination may be recommended for relatives of patients with hip fractures before age 80 years.

NASHVILLE, TENN. — A school-based exercise program may be one way to head off osteoporosis later in life, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

A school-based exercise program in early school years seems to be followed by a greater increase in bone mineral content (BMC) and bone size than was seen in controls, said Christian Linden, M.D., of Malmö (Sweden) University Hospital.

The finding is from the Pediatric Osteoporosis Prevention (POP) study, a prospective, controlled population-based study assessing the effects of daily exercise in early school years on accrual of bone mineral.

A total of 121 children (73 boys and 48 girls) in grades 1 and 2 (average age 7.7 years) participated in 40 minutes of physical activity during each school day for 4 years. A control group of 100 age-, height-, and weight-matched children (52 boys, 48 girls) in nearby schools followed the standard Swedish curriculum, consisting of 60–90 minutes of physical activity each week.

At baseline there were no differences between the groups with regard to bone mass and size. At follow-up, the boys in the control group had a significantly higher Tanner stage on average; otherwise the children in the two groups were similar.

Boys in the intervention group had significantly greater BMC in the lumbar spine at follow-up after 4 years vs. those in the control group (7.0 g vs. 6.2 g). Girls in the intervention group had significantly higher BMC at the lumbar spine (9.1 g vs. 7.1 g) and femora neck (0.39 g vs. 0.29 g) at follow-up than did those in the control group.

The annual increase in femoral neck width was greater in the intervention group than in the control group for girls (1.23 mm vs. 1.07 mm) and boys (1.45 mm vs. 1.03 mm).

NASHVILLE, TENN. — A school-based exercise program may be one way to head off osteoporosis later in life, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

A school-based exercise program in early school years seems to be followed by a greater increase in bone mineral content (BMC) and bone size than was seen in controls, said Christian Linden, M.D., of Malmö (Sweden) University Hospital.

The finding is from the Pediatric Osteoporosis Prevention (POP) study, a prospective, controlled population-based study assessing the effects of daily exercise in early school years on accrual of bone mineral.

A total of 121 children (73 boys and 48 girls) in grades 1 and 2 (average age 7.7 years) participated in 40 minutes of physical activity during each school day for 4 years. A control group of 100 age-, height-, and weight-matched children (52 boys, 48 girls) in nearby schools followed the standard Swedish curriculum, consisting of 60–90 minutes of physical activity each week.

At baseline there were no differences between the groups with regard to bone mass and size. At follow-up, the boys in the control group had a significantly higher Tanner stage on average; otherwise the children in the two groups were similar.

Boys in the intervention group had significantly greater BMC in the lumbar spine at follow-up after 4 years vs. those in the control group (7.0 g vs. 6.2 g). Girls in the intervention group had significantly higher BMC at the lumbar spine (9.1 g vs. 7.1 g) and femora neck (0.39 g vs. 0.29 g) at follow-up than did those in the control group.

The annual increase in femoral neck width was greater in the intervention group than in the control group for girls (1.23 mm vs. 1.07 mm) and boys (1.45 mm vs. 1.03 mm).

NASHVILLE, TENN. — A school-based exercise program may be one way to head off osteoporosis later in life, according to results from a study presented at the annual meeting of the American Society for Bone and Mineral Research.

A school-based exercise program in early school years seems to be followed by a greater increase in bone mineral content (BMC) and bone size than was seen in controls, said Christian Linden, M.D., of Malmö (Sweden) University Hospital.

The finding is from the Pediatric Osteoporosis Prevention (POP) study, a prospective, controlled population-based study assessing the effects of daily exercise in early school years on accrual of bone mineral.

A total of 121 children (73 boys and 48 girls) in grades 1 and 2 (average age 7.7 years) participated in 40 minutes of physical activity during each school day for 4 years. A control group of 100 age-, height-, and weight-matched children (52 boys, 48 girls) in nearby schools followed the standard Swedish curriculum, consisting of 60–90 minutes of physical activity each week.

At baseline there were no differences between the groups with regard to bone mass and size. At follow-up, the boys in the control group had a significantly higher Tanner stage on average; otherwise the children in the two groups were similar.

Boys in the intervention group had significantly greater BMC in the lumbar spine at follow-up after 4 years vs. those in the control group (7.0 g vs. 6.2 g). Girls in the intervention group had significantly higher BMC at the lumbar spine (9.1 g vs. 7.1 g) and femora neck (0.39 g vs. 0.29 g) at follow-up than did those in the control group.

The annual increase in femoral neck width was greater in the intervention group than in the control group for girls (1.23 mm vs. 1.07 mm) and boys (1.45 mm vs. 1.03 mm).

NASHVILLE, TENN. — A little increase in bone mineral density associated with parathyroid hormone use appears to translate into greater vertebral strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

To assess changes in vertebral strength, the researchers used finite element analysis, a technique borrowed from engineering, where it is used to design bridges, skyscrapers, airplanes, and more, said Dennis M. Black, Ph.D., a professor of epidemiology at the University of California, San Francisco.

Starting with a quantitative CT (QCT) scan, the structure of interest is divided into many finite elements—in this case voxels—each of which is assigned material properties based on the bone mineral density (BMD). Computer simulation is then used to apply a set of forces—in this case compressive force—to the model to estimate the mechanical response. One of the responses of the most interest is strength, which in engineering terms means the applied force necessary for the structure to fail—in other words, the force necessary for the vertebra to fracture.

The researchers used the technique in a pilot study to assess vertebral strength changes, using data for 19 randomly selected women enrolled in the Parathyroid Hormone and Alendronate for Osteoporosis study. The postmenopausal women had all been randomized to receive 100 mcg of parathyroid hormone (1–84) daily for 1 year. QCT and dual x-ray absorptiometry (DXA) measurements were performed at baseline and at 1 year. The QCT data was used to look at changes in estimated vertebral strength using finite element analysis.

The average estimated compressive strength was 4,522 N. At 1 year the average estimated compressive strength was 5,715 N—a statistically significant increase in overall vertebral strength of 29%. While overall vertebral strength increased by 29%, overall BMD increased by only 6% based on DXA measurements.

The researchers were also able to virtually “peel away” the outer 2 mm of each vertebra (assumed to be cortical bone), in order to assess changes in the strength of trabecular bone. The increase in trabecular BMD was 29%, as measured by QCT. Trabecular bone accounted for 70% of the increase in total strength over the course of 1 year. At baseline, trabecular bone strength accounted for about half of total bone strength. “From this we inferred that the majority of the increase in strength is attributable to increases in trabecular strength,” Dr. Black explained.

The researchers also compared the increase in strength due to an average increase in bone density with the increase in strength due to a redistribution of bone density in the vertebra. To do this, the researchers assumed that the vertebra has a homogeneous density. So each element in the vertebra is assigned the same density—the average density for the vertebra. “So if we saw that the average density change leads to a strength change that is small, we would then infer that some of the overall increase in strength is due to a redistribution of density,” said Dr. Black.

In fact, they found that the increase in average bone density accounted for most—but not all—of the increase in strength. “This suggests that not all of the increase in strength can be attributed to the average change in bone density,” he said.

Researchers had previously validated the technique for assessing vertebral compressive strength by comparing the results of compression tests on cadaveric vertebra (Bone 2003;33:744–50). The finite element measures of strength correlated well with the test results.

The study was funded in part by NPS Pharmaceuticals Inc., maker of Preos (recombinantly produced, full-length human PTH), which is under development. Dr. Black also receives consulting fees from NPS Pharmaceuticals and is speaker for Merck & Co. Inc., maker of Fosamax (alendronate).

NASHVILLE, TENN. — A little increase in bone mineral density associated with parathyroid hormone use appears to translate into greater vertebral strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

To assess changes in vertebral strength, the researchers used finite element analysis, a technique borrowed from engineering, where it is used to design bridges, skyscrapers, airplanes, and more, said Dennis M. Black, Ph.D., a professor of epidemiology at the University of California, San Francisco.

Starting with a quantitative CT (QCT) scan, the structure of interest is divided into many finite elements—in this case voxels—each of which is assigned material properties based on the bone mineral density (BMD). Computer simulation is then used to apply a set of forces—in this case compressive force—to the model to estimate the mechanical response. One of the responses of the most interest is strength, which in engineering terms means the applied force necessary for the structure to fail—in other words, the force necessary for the vertebra to fracture.

The researchers used the technique in a pilot study to assess vertebral strength changes, using data for 19 randomly selected women enrolled in the Parathyroid Hormone and Alendronate for Osteoporosis study. The postmenopausal women had all been randomized to receive 100 mcg of parathyroid hormone (1–84) daily for 1 year. QCT and dual x-ray absorptiometry (DXA) measurements were performed at baseline and at 1 year. The QCT data was used to look at changes in estimated vertebral strength using finite element analysis.

The average estimated compressive strength was 4,522 N. At 1 year the average estimated compressive strength was 5,715 N—a statistically significant increase in overall vertebral strength of 29%. While overall vertebral strength increased by 29%, overall BMD increased by only 6% based on DXA measurements.

The researchers were also able to virtually “peel away” the outer 2 mm of each vertebra (assumed to be cortical bone), in order to assess changes in the strength of trabecular bone. The increase in trabecular BMD was 29%, as measured by QCT. Trabecular bone accounted for 70% of the increase in total strength over the course of 1 year. At baseline, trabecular bone strength accounted for about half of total bone strength. “From this we inferred that the majority of the increase in strength is attributable to increases in trabecular strength,” Dr. Black explained.

The researchers also compared the increase in strength due to an average increase in bone density with the increase in strength due to a redistribution of bone density in the vertebra. To do this, the researchers assumed that the vertebra has a homogeneous density. So each element in the vertebra is assigned the same density—the average density for the vertebra. “So if we saw that the average density change leads to a strength change that is small, we would then infer that some of the overall increase in strength is due to a redistribution of density,” said Dr. Black.

In fact, they found that the increase in average bone density accounted for most—but not all—of the increase in strength. “This suggests that not all of the increase in strength can be attributed to the average change in bone density,” he said.

Researchers had previously validated the technique for assessing vertebral compressive strength by comparing the results of compression tests on cadaveric vertebra (Bone 2003;33:744–50). The finite element measures of strength correlated well with the test results.

The study was funded in part by NPS Pharmaceuticals Inc., maker of Preos (recombinantly produced, full-length human PTH), which is under development. Dr. Black also receives consulting fees from NPS Pharmaceuticals and is speaker for Merck & Co. Inc., maker of Fosamax (alendronate).

NASHVILLE, TENN. — A little increase in bone mineral density associated with parathyroid hormone use appears to translate into greater vertebral strength, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

To assess changes in vertebral strength, the researchers used finite element analysis, a technique borrowed from engineering, where it is used to design bridges, skyscrapers, airplanes, and more, said Dennis M. Black, Ph.D., a professor of epidemiology at the University of California, San Francisco.

Starting with a quantitative CT (QCT) scan, the structure of interest is divided into many finite elements—in this case voxels—each of which is assigned material properties based on the bone mineral density (BMD). Computer simulation is then used to apply a set of forces—in this case compressive force—to the model to estimate the mechanical response. One of the responses of the most interest is strength, which in engineering terms means the applied force necessary for the structure to fail—in other words, the force necessary for the vertebra to fracture.

The researchers used the technique in a pilot study to assess vertebral strength changes, using data for 19 randomly selected women enrolled in the Parathyroid Hormone and Alendronate for Osteoporosis study. The postmenopausal women had all been randomized to receive 100 mcg of parathyroid hormone (1–84) daily for 1 year. QCT and dual x-ray absorptiometry (DXA) measurements were performed at baseline and at 1 year. The QCT data was used to look at changes in estimated vertebral strength using finite element analysis.

The average estimated compressive strength was 4,522 N. At 1 year the average estimated compressive strength was 5,715 N—a statistically significant increase in overall vertebral strength of 29%. While overall vertebral strength increased by 29%, overall BMD increased by only 6% based on DXA measurements.

The researchers were also able to virtually “peel away” the outer 2 mm of each vertebra (assumed to be cortical bone), in order to assess changes in the strength of trabecular bone. The increase in trabecular BMD was 29%, as measured by QCT. Trabecular bone accounted for 70% of the increase in total strength over the course of 1 year. At baseline, trabecular bone strength accounted for about half of total bone strength. “From this we inferred that the majority of the increase in strength is attributable to increases in trabecular strength,” Dr. Black explained.

The researchers also compared the increase in strength due to an average increase in bone density with the increase in strength due to a redistribution of bone density in the vertebra. To do this, the researchers assumed that the vertebra has a homogeneous density. So each element in the vertebra is assigned the same density—the average density for the vertebra. “So if we saw that the average density change leads to a strength change that is small, we would then infer that some of the overall increase in strength is due to a redistribution of density,” said Dr. Black.

In fact, they found that the increase in average bone density accounted for most—but not all—of the increase in strength. “This suggests that not all of the increase in strength can be attributed to the average change in bone density,” he said.

Researchers had previously validated the technique for assessing vertebral compressive strength by comparing the results of compression tests on cadaveric vertebra (Bone 2003;33:744–50). The finite element measures of strength correlated well with the test results.

The study was funded in part by NPS Pharmaceuticals Inc., maker of Preos (recombinantly produced, full-length human PTH), which is under development. Dr. Black also receives consulting fees from NPS Pharmaceuticals and is speaker for Merck & Co. Inc., maker of Fosamax (alendronate).

Women with idiopathic osteoporosis appear to have a low mineralization in trabecular bone, which suggests that alterations in the mineralization processes could be responsible for bone fragility, Jochen G. Hofstätter, M.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Hofstätter and his associates assessed bone mineral density distribution using quantitative backscattered electron imaging, and bone biopsies were collected from nine premenopausal women with idiopathic osteoporosis. Bone mineral density distribution was also evaluated for 15 healthy, age-matched women.

Quantitative backscattered electron imaging is a relatively new technique for studying mineralization patterns, said Dr. Hofstätter of the Ludwig Boltzmann Institute of Osteology in Vienna. The sample is scanned using an electron microscope. The quantity of electrons backscattered from a given surface is proportional to the mean atomic number of the measured material, allowing researchers to identify and quantify minerals present in bone.

To determine the bone mineral density distribution, the researchers measured the mean calcium content, the typical calcium content, the variation of calcium content, and the percentage of low-mineralized matrix.

There were significantly lower levels of mean calcium content (−3.1%) and typical calcium content (−2.7%) among the women with idiopathic osteoporosis, compared with those in the control group.

This is “an interesting finding with respect to the [low] bone turnover situation reported in these patients. One would expect exactly the opposite,” Dr. Hofstätter noted. Low bone turnover typically permits prolonged secondary mineralization in a larger number of bone pockets, resulting in higher mineral content.

There were no significant differences between the two groups in terms of the variation of calcium content and the percentage of low mineralized matrix.

The lower degree of mineralization in women with idiopathic osteoporosis, combined with low bone turnover, suggests that there are differences in their mineralization processes, Dr. Hofstätter said. These changes may be the result of alterations in the extracellular matrix and may in turn contribute to increased fragility.

Women with idiopathic osteoporosis appear to have a low mineralization in trabecular bone, which suggests that alterations in the mineralization processes could be responsible for bone fragility, Jochen G. Hofstätter, M.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Hofstätter and his associates assessed bone mineral density distribution using quantitative backscattered electron imaging, and bone biopsies were collected from nine premenopausal women with idiopathic osteoporosis. Bone mineral density distribution was also evaluated for 15 healthy, age-matched women.

Quantitative backscattered electron imaging is a relatively new technique for studying mineralization patterns, said Dr. Hofstätter of the Ludwig Boltzmann Institute of Osteology in Vienna. The sample is scanned using an electron microscope. The quantity of electrons backscattered from a given surface is proportional to the mean atomic number of the measured material, allowing researchers to identify and quantify minerals present in bone.

To determine the bone mineral density distribution, the researchers measured the mean calcium content, the typical calcium content, the variation of calcium content, and the percentage of low-mineralized matrix.

There were significantly lower levels of mean calcium content (−3.1%) and typical calcium content (−2.7%) among the women with idiopathic osteoporosis, compared with those in the control group.

This is “an interesting finding with respect to the [low] bone turnover situation reported in these patients. One would expect exactly the opposite,” Dr. Hofstätter noted. Low bone turnover typically permits prolonged secondary mineralization in a larger number of bone pockets, resulting in higher mineral content.

There were no significant differences between the two groups in terms of the variation of calcium content and the percentage of low mineralized matrix.

The lower degree of mineralization in women with idiopathic osteoporosis, combined with low bone turnover, suggests that there are differences in their mineralization processes, Dr. Hofstätter said. These changes may be the result of alterations in the extracellular matrix and may in turn contribute to increased fragility.

Women with idiopathic osteoporosis appear to have a low mineralization in trabecular bone, which suggests that alterations in the mineralization processes could be responsible for bone fragility, Jochen G. Hofstätter, M.D., reported at the annual meeting of the American Society for Bone and Mineral Research.

Dr. Hofstätter and his associates assessed bone mineral density distribution using quantitative backscattered electron imaging, and bone biopsies were collected from nine premenopausal women with idiopathic osteoporosis. Bone mineral density distribution was also evaluated for 15 healthy, age-matched women.

Quantitative backscattered electron imaging is a relatively new technique for studying mineralization patterns, said Dr. Hofstätter of the Ludwig Boltzmann Institute of Osteology in Vienna. The sample is scanned using an electron microscope. The quantity of electrons backscattered from a given surface is proportional to the mean atomic number of the measured material, allowing researchers to identify and quantify minerals present in bone.

To determine the bone mineral density distribution, the researchers measured the mean calcium content, the typical calcium content, the variation of calcium content, and the percentage of low-mineralized matrix.

There were significantly lower levels of mean calcium content (−3.1%) and typical calcium content (−2.7%) among the women with idiopathic osteoporosis, compared with those in the control group.

This is “an interesting finding with respect to the [low] bone turnover situation reported in these patients. One would expect exactly the opposite,” Dr. Hofstätter noted. Low bone turnover typically permits prolonged secondary mineralization in a larger number of bone pockets, resulting in higher mineral content.

There were no significant differences between the two groups in terms of the variation of calcium content and the percentage of low mineralized matrix.

The lower degree of mineralization in women with idiopathic osteoporosis, combined with low bone turnover, suggests that there are differences in their mineralization processes, Dr. Hofstätter said. These changes may be the result of alterations in the extracellular matrix and may in turn contribute to increased fragility.

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status, said Benjamin Z. Leder, M.D., of Massachusetts General Hospital in Boston.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All the men underwent 18-hour infusions of parathyroid hormone (PTH) (1–34) at a dose of 0.55 U/kg per hour at baseline and at 6 weeks. Serum levels of the bone turnover markers cross-linked N-telopeptides (NTx) of type I collagen and osteocalcin were measured every 6 hours during the PTH infusions.

Resorption of bone by osteoclasts results in the production of NTx of type I collagen. NTx is specific to bone and is found in serum and urine as a stable end product of bone degradation.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx levels increased during PTH infusion in all groups at all time points.

Serum osteocalcin levels decreased in all groups at all time points during PTH infusion. No differences in serum osteocalcin levels were observed between baseline and week 6 in any of the four groups.

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status, said Benjamin Z. Leder, M.D., of Massachusetts General Hospital in Boston.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All the men underwent 18-hour infusions of parathyroid hormone (PTH) (1–34) at a dose of 0.55 U/kg per hour at baseline and at 6 weeks. Serum levels of the bone turnover markers cross-linked N-telopeptides (NTx) of type I collagen and osteocalcin were measured every 6 hours during the PTH infusions.

Resorption of bone by osteoclasts results in the production of NTx of type I collagen. NTx is specific to bone and is found in serum and urine as a stable end product of bone degradation.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx levels increased during PTH infusion in all groups at all time points.

Serum osteocalcin levels decreased in all groups at all time points during PTH infusion. No differences in serum osteocalcin levels were observed between baseline and week 6 in any of the four groups.

NASHVILLE, TENN. — Suppression of androgens or estrogens increases bone turnover and bone loss in men, according to data presented at the annual meeting of the American Society for Bone and Mineral Research.

A total of 58 men, aged 20–45 years, were assigned to receive combinations of gonadotropin-releasing hormone (GnRH), an aromatase inhibitor, and hormone add-back therapy for 6 weeks, depending on their hormonal status, said Benjamin Z. Leder, M.D., of Massachusetts General Hospital in Boston.

Men in group 1 (16) received a GnRH analog, 3.6-mg goserelin acetate, given subcutaneously every 3 weeks, as well as an aromatase inhibitor, 5-mg anastrozole, given daily. Men in group 2 (12) also received the GnRH analog and aromatase inhibitor, but testosterone was replaced with a testosterone gel (AndroGel), at 5 g daily. Men in group 3 (14) received the GnRH analog and aromatase inhibitor, but estradiol was replaced with an estradiol transdermal patch, applied twice weekly. Men in group 4 (16) received the GnRH analog, aromatase inhibitor, testosterone gel, and estradiol patch. These men were sufficient in both testosterone and estradiol and served as a control group.

All the men underwent 18-hour infusions of parathyroid hormone (PTH) (1–34) at a dose of 0.55 U/kg per hour at baseline and at 6 weeks. Serum levels of the bone turnover markers cross-linked N-telopeptides (NTx) of type I collagen and osteocalcin were measured every 6 hours during the PTH infusions.

Resorption of bone by osteoclasts results in the production of NTx of type I collagen. NTx is specific to bone and is found in serum and urine as a stable end product of bone degradation.

Mean NTx levels measured prior to PTH infusion did not change between baseline and week 6 in the control group, but NTx levels increased by 24% in group 1, by 16% in group 2, and by 11% in group 3. Serum NTx levels increased during PTH infusion in all groups at all time points.

Serum osteocalcin levels decreased in all groups at all time points during PTH infusion. No differences in serum osteocalcin levels were observed between baseline and week 6 in any of the four groups.

NASHVILLE, TENN. — Three-dimensional, high-resolution peripheral quantitative computed tomography has revealed significant differences in the way that trabecular bone microstructure changes with age in men and women.

The technique allows for in vivo assessment of bone density and trabecular microstructure, Sundeep Khosla, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

He and his associates at the Mayo Clinic, Rochester, Minn., imaged 278 men and 324 women, aged 21–97 years. The nondominant wrist was scanned to obtain 116 views at the distal end of the radius.

The slice thickness was 89 μm.

Differences in the structure of trabecular bone in men and women are evident in young adulthood. Compared with young women, young men have indices of trabecular structure that predict stronger bones and greater resistance to fractures—higher bone volume/tissue volume (BV/TV) and thicker trabeculae, he said.

Over their lifetimes, men and women have similar reductions in BV/TV, but “the structural basis for this parallel decrease in BV/TV seems to be quite different in women and men,” Dr. Khosla said.

In women aged 20–49 years, trabecular number remains stable, then declines at about the same rate as seen in men aged 50 years and older. Men show no long-term net change in trabecular numbers, because decreases from age 50 on are offset by increases from ages 20 to 49.

Trabecular separation increases by 24% over men's lifetimes, but most of this change occurs after age 50. “Trabeculae actually tend to get closer together in men between the ages of 20 and 50, and then separation increases.” The net effect is that there isn't much change, he said.

Trabecular thickness goes down more than twice as much in men than in women over their lifetimes. “Trabecular thickness goes down fairly linearly over life in women. But in men there is a much more dramatic decrease in trabecular thickness from about age 20 to age 50, and then it looks like it doesn't decrease further,” he said. “In women, aging is associated with loss of trabeculae, whereas in men the primary mechanism of the decrease in BV/TV appears to be trabecular thinning.”

“Losing trabeculae is much more detrimental to bone strength than is thinning trabeculae,” Dr. Khosla noted. A 10% drop in BV/TV due to a reduction in trabecular number results in a twofold to fivefold greater loss of bone strength than the same drop in BV/TV caused by a reduction in trabecular thickness.

In a separate study, investigators used MRI-based virtual bone biopsy (VBB) to track trabecular microarchitecture changes in two groups of postmenopausal women aged 45–55 years—one receiving hormone therapy and the other not receiving the therapy.

A 20-patient treatment group received hormone therapy (0.05 mg/day estradiol transdermal patch); a 27-patient control group did not. All women received supplemental calcium (1,500 mg/day), said Glenn A. Ladinsky, M.D., of the University of Pennsylvania, Philadelphia.

In the control group, VBBs collected at the distal radius and the distal tibia showed conversion from trabecular plate to rod structure, indicating a reduction in bone strength during the 24-month study. Platelike trabecular architecture was preserved in patients who received hormone therapy. There was a 3%–4% reduction in bone mineral density in the control group, as measured by DXA. No changes in BMD were noted in the therapy group.

Dr. Ladinsky is a part owner of MicroMRI Inc., which developed the MRI-based VBB technology. The study was funded in part by Novartis Inc.

Differences in trabecular structure are shown here in two 24-year-olds, male (top left) and female (top right), a 73-year-old man (botton left) and a 71-year-old female. Photos courtesy Dr. Sundeep Khosla

NASHVILLE, TENN. — Three-dimensional, high-resolution peripheral quantitative computed tomography has revealed significant differences in the way that trabecular bone microstructure changes with age in men and women.

The technique allows for in vivo assessment of bone density and trabecular microstructure, Sundeep Khosla, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

He and his associates at the Mayo Clinic, Rochester, Minn., imaged 278 men and 324 women, aged 21–97 years. The nondominant wrist was scanned to obtain 116 views at the distal end of the radius.

The slice thickness was 89 μm.

Differences in the structure of trabecular bone in men and women are evident in young adulthood. Compared with young women, young men have indices of trabecular structure that predict stronger bones and greater resistance to fractures—higher bone volume/tissue volume (BV/TV) and thicker trabeculae, he said.

Over their lifetimes, men and women have similar reductions in BV/TV, but “the structural basis for this parallel decrease in BV/TV seems to be quite different in women and men,” Dr. Khosla said.

In women aged 20–49 years, trabecular number remains stable, then declines at about the same rate as seen in men aged 50 years and older. Men show no long-term net change in trabecular numbers, because decreases from age 50 on are offset by increases from ages 20 to 49.

Trabecular separation increases by 24% over men's lifetimes, but most of this change occurs after age 50. “Trabeculae actually tend to get closer together in men between the ages of 20 and 50, and then separation increases.” The net effect is that there isn't much change, he said.

Trabecular thickness goes down more than twice as much in men than in women over their lifetimes. “Trabecular thickness goes down fairly linearly over life in women. But in men there is a much more dramatic decrease in trabecular thickness from about age 20 to age 50, and then it looks like it doesn't decrease further,” he said. “In women, aging is associated with loss of trabeculae, whereas in men the primary mechanism of the decrease in BV/TV appears to be trabecular thinning.”

“Losing trabeculae is much more detrimental to bone strength than is thinning trabeculae,” Dr. Khosla noted. A 10% drop in BV/TV due to a reduction in trabecular number results in a twofold to fivefold greater loss of bone strength than the same drop in BV/TV caused by a reduction in trabecular thickness.

In a separate study, investigators used MRI-based virtual bone biopsy (VBB) to track trabecular microarchitecture changes in two groups of postmenopausal women aged 45–55 years—one receiving hormone therapy and the other not receiving the therapy.

A 20-patient treatment group received hormone therapy (0.05 mg/day estradiol transdermal patch); a 27-patient control group did not. All women received supplemental calcium (1,500 mg/day), said Glenn A. Ladinsky, M.D., of the University of Pennsylvania, Philadelphia.

In the control group, VBBs collected at the distal radius and the distal tibia showed conversion from trabecular plate to rod structure, indicating a reduction in bone strength during the 24-month study. Platelike trabecular architecture was preserved in patients who received hormone therapy. There was a 3%–4% reduction in bone mineral density in the control group, as measured by DXA. No changes in BMD were noted in the therapy group.

Dr. Ladinsky is a part owner of MicroMRI Inc., which developed the MRI-based VBB technology. The study was funded in part by Novartis Inc.

Differences in trabecular structure are shown here in two 24-year-olds, male (top left) and female (top right), a 73-year-old man (botton left) and a 71-year-old female. Photos courtesy Dr. Sundeep Khosla

NASHVILLE, TENN. — Three-dimensional, high-resolution peripheral quantitative computed tomography has revealed significant differences in the way that trabecular bone microstructure changes with age in men and women.

The technique allows for in vivo assessment of bone density and trabecular microstructure, Sundeep Khosla, M.D., said at the annual meeting of the American Society for Bone and Mineral Research.

He and his associates at the Mayo Clinic, Rochester, Minn., imaged 278 men and 324 women, aged 21–97 years. The nondominant wrist was scanned to obtain 116 views at the distal end of the radius.

The slice thickness was 89 μm.

Differences in the structure of trabecular bone in men and women are evident in young adulthood. Compared with young women, young men have indices of trabecular structure that predict stronger bones and greater resistance to fractures—higher bone volume/tissue volume (BV/TV) and thicker trabeculae, he said.

Over their lifetimes, men and women have similar reductions in BV/TV, but “the structural basis for this parallel decrease in BV/TV seems to be quite different in women and men,” Dr. Khosla said.

In women aged 20–49 years, trabecular number remains stable, then declines at about the same rate as seen in men aged 50 years and older. Men show no long-term net change in trabecular numbers, because decreases from age 50 on are offset by increases from ages 20 to 49.

Trabecular separation increases by 24% over men's lifetimes, but most of this change occurs after age 50. “Trabeculae actually tend to get closer together in men between the ages of 20 and 50, and then separation increases.” The net effect is that there isn't much change, he said.

Trabecular thickness goes down more than twice as much in men than in women over their lifetimes. “Trabecular thickness goes down fairly linearly over life in women. But in men there is a much more dramatic decrease in trabecular thickness from about age 20 to age 50, and then it looks like it doesn't decrease further,” he said. “In women, aging is associated with loss of trabeculae, whereas in men the primary mechanism of the decrease in BV/TV appears to be trabecular thinning.”

“Losing trabeculae is much more detrimental to bone strength than is thinning trabeculae,” Dr. Khosla noted. A 10% drop in BV/TV due to a reduction in trabecular number results in a twofold to fivefold greater loss of bone strength than the same drop in BV/TV caused by a reduction in trabecular thickness.

In a separate study, investigators used MRI-based virtual bone biopsy (VBB) to track trabecular microarchitecture changes in two groups of postmenopausal women aged 45–55 years—one receiving hormone therapy and the other not receiving the therapy.

A 20-patient treatment group received hormone therapy (0.05 mg/day estradiol transdermal patch); a 27-patient control group did not. All women received supplemental calcium (1,500 mg/day), said Glenn A. Ladinsky, M.D., of the University of Pennsylvania, Philadelphia.

In the control group, VBBs collected at the distal radius and the distal tibia showed conversion from trabecular plate to rod structure, indicating a reduction in bone strength during the 24-month study. Platelike trabecular architecture was preserved in patients who received hormone therapy. There was a 3%–4% reduction in bone mineral density in the control group, as measured by DXA. No changes in BMD were noted in the therapy group.

Dr. Ladinsky is a part owner of MicroMRI Inc., which developed the MRI-based VBB technology. The study was funded in part by Novartis Inc.

Differences in trabecular structure are shown here in two 24-year-olds, male (top left) and female (top right), a 73-year-old man (botton left) and a 71-year-old female. Photos courtesy Dr. Sundeep Khosla

DENVER — The conventional wisdom holding that prescribing hypnotic agents for nursing home patients increases their risk of falling and hip fracture may not be correct.

A recent study involving more than 34,000 Michigan nursing home residents suggests an alternative explanation: The increased risk of falls may be attributable to the insomnia for which hypnotic agents are so often prescribed, rather than to the drugs themselves, W. Vaughn McCall, M.D., said at a satellite symposium held in conjunction with the annual meeting of the Associated Professional Sleep Societies.

He cited an analysis of a Michigan Medicare database by Alon Y. Avidan, M.D., and coinvestigators at the University of Michigan and the Veterans Affairs Medical Center in Ann Arbor. They examined the risk of falls and hip fracture over roughly 6 months of follow-up in 34,163 elderly residents in 437 Michigan nursing homes.

During follow-up, 42.9% of patients fell and 2.5% sustained a hip fracture. After adjusting for numerous potential confounders in a multiple logistic regression analysis, including age, gender, functional status, illness burden, number of medications being taken, cognitive status, and intensity of resource utilization, the investigators concluded that insomnia—but not hypnotic use per se—was predictive of future falls, noted Dr. McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C.

Dr. Avidan and colleagues went on to speculate that the use of hypnotics to treat insomnia in the frail elderly might actually protect against falls. Dr. McCall called that “a very provocative statement.” And while he is intrigued by the Michigan findings, it will take more than a single observational study, however large, to convince him.

“I'm not ready to state this as the final word on the subject. I'm personally not prepared to go that far, even though this is a large study of debilitated nursing home patients. But I do think the study opens the door to looking at this issue more carefully,” he said at the symposium, sponsored by Sepracor.

In the Michigan study, supported by the National Institute on Aging, the 259 insomniac nursing home residents on a hypnotic agent had an adjusted 32% greater risk of falls than did the 31,391 who did not have insomnia and were not on a hypnotic. Particularly noteworthy was the finding that the 1,890 individuals with insomnia who were not taking a hypnotic agent had a 55% greater risk of falls. Among the nursing home population who did not have insomnia, the 632 on a hypnotic agent did not have a significantly greater risk of falling than did those who were not on this class of medication (J. Am. Geriatr. Soc. 2005;53:955–62).

There is no doubt that sleep problems are more common in the elderly than in any other age group, and that those sleep difficulties produce next-day impairments in cognitive ability that can be confused with dementia. This underscores the importance of appropriately assessing and treating elderly patients with sleep problems using the behavioral therapies and/or medications, particularly the newer short-acting nonbenzodiazepines—zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta)—with demonstrated efficacy in this setting, he said.

Of interest is a recent multicenter double-blind randomized trial in which Dr. McCall was a coinvestigator. It involved 231 patients aged 65–85 years with primary insomnia randomized to nightly 1- or 2-mg eszopiclone or placebo for 2 weeks.

While the lower dose induced sleep compared with placebo, the higher dose induced and maintained sleep. The 2-mg dose was accompanied by significantly higher patient-reported ratings of daytime alertness, sense of physical well-being, and quality of life (Sleep 2005;28:720–7).

The trial also was sponsored by Sepracor. Dr. McCall serves as a consultant to the company.

DENVER — The conventional wisdom holding that prescribing hypnotic agents for nursing home patients increases their risk of falling and hip fracture may not be correct.

A recent study involving more than 34,000 Michigan nursing home residents suggests an alternative explanation: The increased risk of falls may be attributable to the insomnia for which hypnotic agents are so often prescribed, rather than to the drugs themselves, W. Vaughn McCall, M.D., said at a satellite symposium held in conjunction with the annual meeting of the Associated Professional Sleep Societies.

He cited an analysis of a Michigan Medicare database by Alon Y. Avidan, M.D., and coinvestigators at the University of Michigan and the Veterans Affairs Medical Center in Ann Arbor. They examined the risk of falls and hip fracture over roughly 6 months of follow-up in 34,163 elderly residents in 437 Michigan nursing homes.

During follow-up, 42.9% of patients fell and 2.5% sustained a hip fracture. After adjusting for numerous potential confounders in a multiple logistic regression analysis, including age, gender, functional status, illness burden, number of medications being taken, cognitive status, and intensity of resource utilization, the investigators concluded that insomnia—but not hypnotic use per se—was predictive of future falls, noted Dr. McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C.

Dr. Avidan and colleagues went on to speculate that the use of hypnotics to treat insomnia in the frail elderly might actually protect against falls. Dr. McCall called that “a very provocative statement.” And while he is intrigued by the Michigan findings, it will take more than a single observational study, however large, to convince him.

“I'm not ready to state this as the final word on the subject. I'm personally not prepared to go that far, even though this is a large study of debilitated nursing home patients. But I do think the study opens the door to looking at this issue more carefully,” he said at the symposium, sponsored by Sepracor.

In the Michigan study, supported by the National Institute on Aging, the 259 insomniac nursing home residents on a hypnotic agent had an adjusted 32% greater risk of falls than did the 31,391 who did not have insomnia and were not on a hypnotic. Particularly noteworthy was the finding that the 1,890 individuals with insomnia who were not taking a hypnotic agent had a 55% greater risk of falls. Among the nursing home population who did not have insomnia, the 632 on a hypnotic agent did not have a significantly greater risk of falling than did those who were not on this class of medication (J. Am. Geriatr. Soc. 2005;53:955–62).

There is no doubt that sleep problems are more common in the elderly than in any other age group, and that those sleep difficulties produce next-day impairments in cognitive ability that can be confused with dementia. This underscores the importance of appropriately assessing and treating elderly patients with sleep problems using the behavioral therapies and/or medications, particularly the newer short-acting nonbenzodiazepines—zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta)—with demonstrated efficacy in this setting, he said.

Of interest is a recent multicenter double-blind randomized trial in which Dr. McCall was a coinvestigator. It involved 231 patients aged 65–85 years with primary insomnia randomized to nightly 1- or 2-mg eszopiclone or placebo for 2 weeks.

While the lower dose induced sleep compared with placebo, the higher dose induced and maintained sleep. The 2-mg dose was accompanied by significantly higher patient-reported ratings of daytime alertness, sense of physical well-being, and quality of life (Sleep 2005;28:720–7).

The trial also was sponsored by Sepracor. Dr. McCall serves as a consultant to the company.

DENVER — The conventional wisdom holding that prescribing hypnotic agents for nursing home patients increases their risk of falling and hip fracture may not be correct.

A recent study involving more than 34,000 Michigan nursing home residents suggests an alternative explanation: The increased risk of falls may be attributable to the insomnia for which hypnotic agents are so often prescribed, rather than to the drugs themselves, W. Vaughn McCall, M.D., said at a satellite symposium held in conjunction with the annual meeting of the Associated Professional Sleep Societies.

He cited an analysis of a Michigan Medicare database by Alon Y. Avidan, M.D., and coinvestigators at the University of Michigan and the Veterans Affairs Medical Center in Ann Arbor. They examined the risk of falls and hip fracture over roughly 6 months of follow-up in 34,163 elderly residents in 437 Michigan nursing homes.

During follow-up, 42.9% of patients fell and 2.5% sustained a hip fracture. After adjusting for numerous potential confounders in a multiple logistic regression analysis, including age, gender, functional status, illness burden, number of medications being taken, cognitive status, and intensity of resource utilization, the investigators concluded that insomnia—but not hypnotic use per se—was predictive of future falls, noted Dr. McCall, professor and chairman of the department of psychiatry and behavioral medicine at Wake Forest University, Winston-Salem, N.C.

Dr. Avidan and colleagues went on to speculate that the use of hypnotics to treat insomnia in the frail elderly might actually protect against falls. Dr. McCall called that “a very provocative statement.” And while he is intrigued by the Michigan findings, it will take more than a single observational study, however large, to convince him.

“I'm not ready to state this as the final word on the subject. I'm personally not prepared to go that far, even though this is a large study of debilitated nursing home patients. But I do think the study opens the door to looking at this issue more carefully,” he said at the symposium, sponsored by Sepracor.

In the Michigan study, supported by the National Institute on Aging, the 259 insomniac nursing home residents on a hypnotic agent had an adjusted 32% greater risk of falls than did the 31,391 who did not have insomnia and were not on a hypnotic. Particularly noteworthy was the finding that the 1,890 individuals with insomnia who were not taking a hypnotic agent had a 55% greater risk of falls. Among the nursing home population who did not have insomnia, the 632 on a hypnotic agent did not have a significantly greater risk of falling than did those who were not on this class of medication (J. Am. Geriatr. Soc. 2005;53:955–62).

There is no doubt that sleep problems are more common in the elderly than in any other age group, and that those sleep difficulties produce next-day impairments in cognitive ability that can be confused with dementia. This underscores the importance of appropriately assessing and treating elderly patients with sleep problems using the behavioral therapies and/or medications, particularly the newer short-acting nonbenzodiazepines—zolpidem (Ambien), zaleplon (Sonata), and eszopiclone (Lunesta)—with demonstrated efficacy in this setting, he said.

Of interest is a recent multicenter double-blind randomized trial in which Dr. McCall was a coinvestigator. It involved 231 patients aged 65–85 years with primary insomnia randomized to nightly 1- or 2-mg eszopiclone or placebo for 2 weeks.

While the lower dose induced sleep compared with placebo, the higher dose induced and maintained sleep. The 2-mg dose was accompanied by significantly higher patient-reported ratings of daytime alertness, sense of physical well-being, and quality of life (Sleep 2005;28:720–7).

The trial also was sponsored by Sepracor. Dr. McCall serves as a consultant to the company.

Prophylactic use of calcitonin prevents the rapid initial bone loss commonly associated with high-dose steroids early after heart transplant surgery in adults, although bone mass eventually reaches normal levels after 7 years even without treatment, according to Emmanouil I. Kapetanakis, M.D., and colleagues.

Triple-drug immunosuppression treatment after cardiac transplantation usually combines cyclosporine, azathioprine, and prednisone. The long-term administration of the steroid is generally blamed for the associated bone loss and fractures seen as a complication after transplant.

In a small study of 23 patients, age-adjusted bone mineral density (BMD) values 1 year after cardiac transplant were significantly different for the 11 control group patients (BMD 61%), compared with the 12 calcitonin-treated patients (BMD 89%).

During the first 3 years of follow-up, these values reached 69% for the no-calcitonin group, compared with 90% in the treated group—also a significant difference. The calcitonin group maintained BMD within normal ranges during the entire time of follow-up.

Calcitonin is a salmon-derived polypeptide hormone approved for the treatment of osteoporosis.

However, “the BMD decline in the no-calcitonin group stabilized and was reversed during subsequent follow-up so that BMD values during the intermediate (4–6 years) and late (7+ years) follow-up periods were not statistically different,” according to Dr. Kapetanakis of Washington Hospital Center and colleagues (J. Heart Lung Transplant. 2005;24:526–32).

The researchers believe their work indicates the benefits of using intranasal salmon calcitonin to prevent rapid bone loss associated with high-dose steroids early after heart transplantation. But they also said that long-term use does not seem warranted, given the natural reestablishment of BMD over lengthier periods of time.

A related small study examined the rate and etiology of osteoporosis in nine adult transplant survivors who received their new heart in adolescence. These patients were compared with an equal number of control subjects matched for age (21–32 years), sex (seven men, two women), and race (six white, one black, one Hispanic, one other), reported Adi Cohen, M.D., and colleagues (J. Heart Lung Transplant. 2005;24:696–702).

Hyperparathyroidism, mild renal insufficiency, and increased bone turnover appeared to be the key factors involved in the high rate of long-term osteoporosis seen in the transplant subjects, according to Dr. Cohen of Columbia University, New York, and associates.

BMD was measured in the lumbar spine, femoral neck, and the forearm one-third radius (DR).

Osteoporosis was present in 56% of the transplant subjects at the lumbar spine, in 33% at the femoral neck, and in 100% at the DR. Only two control subjects showed osteoporosis, and only in the lumbar spine.

Biochemically, serum parathyroid hormone (PTH) levels were threefold higher in transplant subjects than in controls.

All serum markers for bone turnover were higher in subjects than in controls, with statistically significant differences for bone-specific alkaline phosphatase and N-telopeptide. Serum calcium levels, although in the normal range, were significantly lower in the subjects than in the controls.

“Although the precise etiology of the osteoporosis remains unclear … biochemical studies suggest slightly impaired renal function and documented secondary hyperparathyroidism and increased bone turnover,” Dr. Cohen and associates reported.

“This is the first study of pediatric transplant recipients to evaluate the forearm … [that is] sensitive to the catabolic effects of PTH,” they added. Because the radius was also the most severely affected site, “these findings suggest a role for PTH in the pathogenesis of osteoporosis in this population.”

Because survival rates after pediatric cardiac transplantation have increased dramatically, long-term consequences, such as osteoporosis, will become more evident and must be properly managed, according to the researchers. Understanding the etiology of these complications is the first step to developing treatments, Dr. Cohen and his associates said.

Prophylactic use of calcitonin prevents the rapid initial bone loss commonly associated with high-dose steroids early after heart transplant surgery in adults, although bone mass eventually reaches normal levels after 7 years even without treatment, according to Emmanouil I. Kapetanakis, M.D., and colleagues.

Triple-drug immunosuppression treatment after cardiac transplantation usually combines cyclosporine, azathioprine, and prednisone. The long-term administration of the steroid is generally blamed for the associated bone loss and fractures seen as a complication after transplant.

In a small study of 23 patients, age-adjusted bone mineral density (BMD) values 1 year after cardiac transplant were significantly different for the 11 control group patients (BMD 61%), compared with the 12 calcitonin-treated patients (BMD 89%).

During the first 3 years of follow-up, these values reached 69% for the no-calcitonin group, compared with 90% in the treated group—also a significant difference. The calcitonin group maintained BMD within normal ranges during the entire time of follow-up.

Calcitonin is a salmon-derived polypeptide hormone approved for the treatment of osteoporosis.

However, “the BMD decline in the no-calcitonin group stabilized and was reversed during subsequent follow-up so that BMD values during the intermediate (4–6 years) and late (7+ years) follow-up periods were not statistically different,” according to Dr. Kapetanakis of Washington Hospital Center and colleagues (J. Heart Lung Transplant. 2005;24:526–32).

The researchers believe their work indicates the benefits of using intranasal salmon calcitonin to prevent rapid bone loss associated with high-dose steroids early after heart transplantation. But they also said that long-term use does not seem warranted, given the natural reestablishment of BMD over lengthier periods of time.

A related small study examined the rate and etiology of osteoporosis in nine adult transplant survivors who received their new heart in adolescence. These patients were compared with an equal number of control subjects matched for age (21–32 years), sex (seven men, two women), and race (six white, one black, one Hispanic, one other), reported Adi Cohen, M.D., and colleagues (J. Heart Lung Transplant. 2005;24:696–702).

Hyperparathyroidism, mild renal insufficiency, and increased bone turnover appeared to be the key factors involved in the high rate of long-term osteoporosis seen in the transplant subjects, according to Dr. Cohen of Columbia University, New York, and associates.

BMD was measured in the lumbar spine, femoral neck, and the forearm one-third radius (DR).

Osteoporosis was present in 56% of the transplant subjects at the lumbar spine, in 33% at the femoral neck, and in 100% at the DR. Only two control subjects showed osteoporosis, and only in the lumbar spine.

Biochemically, serum parathyroid hormone (PTH) levels were threefold higher in transplant subjects than in controls.

All serum markers for bone turnover were higher in subjects than in controls, with statistically significant differences for bone-specific alkaline phosphatase and N-telopeptide. Serum calcium levels, although in the normal range, were significantly lower in the subjects than in the controls.

“Although the precise etiology of the osteoporosis remains unclear … biochemical studies suggest slightly impaired renal function and documented secondary hyperparathyroidism and increased bone turnover,” Dr. Cohen and associates reported.

“This is the first study of pediatric transplant recipients to evaluate the forearm … [that is] sensitive to the catabolic effects of PTH,” they added. Because the radius was also the most severely affected site, “these findings suggest a role for PTH in the pathogenesis of osteoporosis in this population.”

Because survival rates after pediatric cardiac transplantation have increased dramatically, long-term consequences, such as osteoporosis, will become more evident and must be properly managed, according to the researchers. Understanding the etiology of these complications is the first step to developing treatments, Dr. Cohen and his associates said.

Prophylactic use of calcitonin prevents the rapid initial bone loss commonly associated with high-dose steroids early after heart transplant surgery in adults, although bone mass eventually reaches normal levels after 7 years even without treatment, according to Emmanouil I. Kapetanakis, M.D., and colleagues.

Triple-drug immunosuppression treatment after cardiac transplantation usually combines cyclosporine, azathioprine, and prednisone. The long-term administration of the steroid is generally blamed for the associated bone loss and fractures seen as a complication after transplant.

In a small study of 23 patients, age-adjusted bone mineral density (BMD) values 1 year after cardiac transplant were significantly different for the 11 control group patients (BMD 61%), compared with the 12 calcitonin-treated patients (BMD 89%).

During the first 3 years of follow-up, these values reached 69% for the no-calcitonin group, compared with 90% in the treated group—also a significant difference. The calcitonin group maintained BMD within normal ranges during the entire time of follow-up.

Calcitonin is a salmon-derived polypeptide hormone approved for the treatment of osteoporosis.

However, “the BMD decline in the no-calcitonin group stabilized and was reversed during subsequent follow-up so that BMD values during the intermediate (4–6 years) and late (7+ years) follow-up periods were not statistically different,” according to Dr. Kapetanakis of Washington Hospital Center and colleagues (J. Heart Lung Transplant. 2005;24:526–32).

The researchers believe their work indicates the benefits of using intranasal salmon calcitonin to prevent rapid bone loss associated with high-dose steroids early after heart transplantation. But they also said that long-term use does not seem warranted, given the natural reestablishment of BMD over lengthier periods of time.

A related small study examined the rate and etiology of osteoporosis in nine adult transplant survivors who received their new heart in adolescence. These patients were compared with an equal number of control subjects matched for age (21–32 years), sex (seven men, two women), and race (six white, one black, one Hispanic, one other), reported Adi Cohen, M.D., and colleagues (J. Heart Lung Transplant. 2005;24:696–702).

Hyperparathyroidism, mild renal insufficiency, and increased bone turnover appeared to be the key factors involved in the high rate of long-term osteoporosis seen in the transplant subjects, according to Dr. Cohen of Columbia University, New York, and associates.

BMD was measured in the lumbar spine, femoral neck, and the forearm one-third radius (DR).

Osteoporosis was present in 56% of the transplant subjects at the lumbar spine, in 33% at the femoral neck, and in 100% at the DR. Only two control subjects showed osteoporosis, and only in the lumbar spine.

Biochemically, serum parathyroid hormone (PTH) levels were threefold higher in transplant subjects than in controls.

All serum markers for bone turnover were higher in subjects than in controls, with statistically significant differences for bone-specific alkaline phosphatase and N-telopeptide. Serum calcium levels, although in the normal range, were significantly lower in the subjects than in the controls.

“Although the precise etiology of the osteoporosis remains unclear … biochemical studies suggest slightly impaired renal function and documented secondary hyperparathyroidism and increased bone turnover,” Dr. Cohen and associates reported.

“This is the first study of pediatric transplant recipients to evaluate the forearm … [that is] sensitive to the catabolic effects of PTH,” they added. Because the radius was also the most severely affected site, “these findings suggest a role for PTH in the pathogenesis of osteoporosis in this population.”

Because survival rates after pediatric cardiac transplantation have increased dramatically, long-term consequences, such as osteoporosis, will become more evident and must be properly managed, according to the researchers. Understanding the etiology of these complications is the first step to developing treatments, Dr. Cohen and his associates said.

ST. LOUIS — Bisphosphonates remain underutilized in the prevention of glucocorticoid-induced osteoporosis, despite national clinical guidelines that recommend their use in patients on long-term oral steroid therapy, Rosemarie Liu, M.D., said at the annual meeting of the Society of Investigative Dermatology.

“In 2001, the American College of Rheumatology published guidelines recommending that all patients beginning long-term oral steroid therapy of at least 5 mg/day should receive a prescription for a bisphosphonate, if not contraindicated,” said Dr. Liu of Eastern Virginia Medical School, Norfolk. “Despite these guidelines, the vast majority of patients in our study did not receive appropriate prophylaxis for glucocorticoid-induced osteoporosis.”

Dr. Liu and her colleagues conducted a cross-sectional study of 35 patients referred to the tertiary dermatology clinic at the Hospital of the University of Pennsylvania, Philadelphia, from 1995 to 2004. Of that group, 60% (21) were female and 83% (29) were white. Their mean age was 54 years (29–86). The mean daily dose of prednisone was 53 mg, with a range of 10–150 mg/day. The patients had been on steroids for a mean of 17 months, with the longest duration of use, 102 months.

Twenty-eight (80%) of the patients were taking prednisone for pemphigus vulgaris; other indications were lupus erythematosus (4), dermatomyositis (2), and arthritis with interstitial granulomatous dermatitis (1). The majority of the patients (80%) were not on any bisphosphonates at the time of their referral. The investigators found that the 2001 publication of the ACR Guidelines for Prevention and Treatment of Glucocorticoid-Induced Osteoporosis had no effect on bisphosphonate prescriptions in this group.

“The guidelines were published in July 2001, but we used January 2002 as the cut-off date, because we wanted to give adequate time for them to be incorporated into clinical practice,” Dr. Liu said. Among those referred before 2002, 75% were not on bisphosphonates; among these referred after 2002 (1 year after the guidelines were published), 81% were not on bisphosphonates.

Dual energy x-ray absorptiometry scans were available for 18 patients. The mean time on steroids before DXA scan was 13 months. Seven of those patients had a normal scan, eight had evidence of osteopenia, and three had evidence of osteoporosis. One patient had a vertebral fracture within 5 months of beginning prednisone.

“When patients are started on long-term oral steroids, a bisphosphonate should be prescribed unless contraindicated, Dr. Liu said. Also, a baseline DXA scan should be ordered to provide information about baseline bone health, and should be repeated whenever clinically indicated.”

ST. LOUIS — Bisphosphonates remain underutilized in the prevention of glucocorticoid-induced osteoporosis, despite national clinical guidelines that recommend their use in patients on long-term oral steroid therapy, Rosemarie Liu, M.D., said at the annual meeting of the Society of Investigative Dermatology.

“In 2001, the American College of Rheumatology published guidelines recommending that all patients beginning long-term oral steroid therapy of at least 5 mg/day should receive a prescription for a bisphosphonate, if not contraindicated,” said Dr. Liu of Eastern Virginia Medical School, Norfolk. “Despite these guidelines, the vast majority of patients in our study did not receive appropriate prophylaxis for glucocorticoid-induced osteoporosis.”

Dr. Liu and her colleagues conducted a cross-sectional study of 35 patients referred to the tertiary dermatology clinic at the Hospital of the University of Pennsylvania, Philadelphia, from 1995 to 2004. Of that group, 60% (21) were female and 83% (29) were white. Their mean age was 54 years (29–86). The mean daily dose of prednisone was 53 mg, with a range of 10–150 mg/day. The patients had been on steroids for a mean of 17 months, with the longest duration of use, 102 months.

Twenty-eight (80%) of the patients were taking prednisone for pemphigus vulgaris; other indications were lupus erythematosus (4), dermatomyositis (2), and arthritis with interstitial granulomatous dermatitis (1). The majority of the patients (80%) were not on any bisphosphonates at the time of their referral. The investigators found that the 2001 publication of the ACR Guidelines for Prevention and Treatment of Glucocorticoid-Induced Osteoporosis had no effect on bisphosphonate prescriptions in this group.

“The guidelines were published in July 2001, but we used January 2002 as the cut-off date, because we wanted to give adequate time for them to be incorporated into clinical practice,” Dr. Liu said. Among those referred before 2002, 75% were not on bisphosphonates; among these referred after 2002 (1 year after the guidelines were published), 81% were not on bisphosphonates.

Dual energy x-ray absorptiometry scans were available for 18 patients. The mean time on steroids before DXA scan was 13 months. Seven of those patients had a normal scan, eight had evidence of osteopenia, and three had evidence of osteoporosis. One patient had a vertebral fracture within 5 months of beginning prednisone.

“When patients are started on long-term oral steroids, a bisphosphonate should be prescribed unless contraindicated, Dr. Liu said. Also, a baseline DXA scan should be ordered to provide information about baseline bone health, and should be repeated whenever clinically indicated.”

ST. LOUIS — Bisphosphonates remain underutilized in the prevention of glucocorticoid-induced osteoporosis, despite national clinical guidelines that recommend their use in patients on long-term oral steroid therapy, Rosemarie Liu, M.D., said at the annual meeting of the Society of Investigative Dermatology.

“In 2001, the American College of Rheumatology published guidelines recommending that all patients beginning long-term oral steroid therapy of at least 5 mg/day should receive a prescription for a bisphosphonate, if not contraindicated,” said Dr. Liu of Eastern Virginia Medical School, Norfolk. “Despite these guidelines, the vast majority of patients in our study did not receive appropriate prophylaxis for glucocorticoid-induced osteoporosis.”

Dr. Liu and her colleagues conducted a cross-sectional study of 35 patients referred to the tertiary dermatology clinic at the Hospital of the University of Pennsylvania, Philadelphia, from 1995 to 2004. Of that group, 60% (21) were female and 83% (29) were white. Their mean age was 54 years (29–86). The mean daily dose of prednisone was 53 mg, with a range of 10–150 mg/day. The patients had been on steroids for a mean of 17 months, with the longest duration of use, 102 months.

Twenty-eight (80%) of the patients were taking prednisone for pemphigus vulgaris; other indications were lupus erythematosus (4), dermatomyositis (2), and arthritis with interstitial granulomatous dermatitis (1). The majority of the patients (80%) were not on any bisphosphonates at the time of their referral. The investigators found that the 2001 publication of the ACR Guidelines for Prevention and Treatment of Glucocorticoid-Induced Osteoporosis had no effect on bisphosphonate prescriptions in this group.

“The guidelines were published in July 2001, but we used January 2002 as the cut-off date, because we wanted to give adequate time for them to be incorporated into clinical practice,” Dr. Liu said. Among those referred before 2002, 75% were not on bisphosphonates; among these referred after 2002 (1 year after the guidelines were published), 81% were not on bisphosphonates.

Dual energy x-ray absorptiometry scans were available for 18 patients. The mean time on steroids before DXA scan was 13 months. Seven of those patients had a normal scan, eight had evidence of osteopenia, and three had evidence of osteoporosis. One patient had a vertebral fracture within 5 months of beginning prednisone.

“When patients are started on long-term oral steroids, a bisphosphonate should be prescribed unless contraindicated, Dr. Liu said. Also, a baseline DXA scan should be ordered to provide information about baseline bone health, and should be repeated whenever clinically indicated.”

CHICAGO — In one of the first studies to examine the long-term endocrine effects of gastric bypass surgery, it appears that after a loss in the first year post procedure, bone mineral density recovers in succeeding years, researchers reported at the annual meeting of the Society for Surgery of the Alimentary Tract.

Surgeons at Virginia Commonwealth University in Richmond prospectively collected data on 233 patients who were undergoing gastric bypass surgery. Of those, 82% had a Roux-en-Y procedure, 12% laparoscopically. The average age was 40 years, and the average body mass index was 50 kg/m

Dr. Johnson and his colleagues obtained preoperative bone mineral density (BMD) scans and found that most patients were normal at baseline, and remained at normal levels, even after surgery. Fifteen patients were osteopenic at baseline. Three developed osteopenia at 1 year post procedure. One patient with preoperative osteopenia actually had an increase in BMD after surgery.

At 1 year, for all patients, total forearm BMD decreased by 0.55%, and radius BMD increased by 1.85%. Total hip and lumbar spine BMD declined by 9.27% and 4.53%, respectively. These seem like fairly large decreases, but none of the patients developed osteoporosis during this period, Dr. Johnson said. The figures suggest a decline in the first year after gastric bypass, but the clinical significance of this is not yet known, he added.

At 2 years, forearm BMD decreased by 3.62%, but radius BMD remained steady. Both total hip and lumbar spine BMD recovered somewhat in the second year, bringing them to almost the same levels as preoperatively.

At 3 and 4 years after surgery, BMD trended up, but there were too few patients at those time points to determine if the increases were statistically significant, Dr. Johnson said.

About 50%–60% of patients had calcium, parathyroid hormone, and vitamin D levels taken before surgery; all had those elements measured annually thereafter.

The mean serum calcium decreased from 9.8 mg/dL at baseline to 9.2 mg/dL in the first year, and to 8.8 mg/dL in the second year.

Although the study backed other reports showing an initial decline in BMD, the clinical significance is not known, Dr. Johnson said. “We have shown it's not an ongoing process,” he added.

CHICAGO — In one of the first studies to examine the long-term endocrine effects of gastric bypass surgery, it appears that after a loss in the first year post procedure, bone mineral density recovers in succeeding years, researchers reported at the annual meeting of the Society for Surgery of the Alimentary Tract.

Surgeons at Virginia Commonwealth University in Richmond prospectively collected data on 233 patients who were undergoing gastric bypass surgery. Of those, 82% had a Roux-en-Y procedure, 12% laparoscopically. The average age was 40 years, and the average body mass index was 50 kg/m

Dr. Johnson and his colleagues obtained preoperative bone mineral density (BMD) scans and found that most patients were normal at baseline, and remained at normal levels, even after surgery. Fifteen patients were osteopenic at baseline. Three developed osteopenia at 1 year post procedure. One patient with preoperative osteopenia actually had an increase in BMD after surgery.

At 1 year, for all patients, total forearm BMD decreased by 0.55%, and radius BMD increased by 1.85%. Total hip and lumbar spine BMD declined by 9.27% and 4.53%, respectively. These seem like fairly large decreases, but none of the patients developed osteoporosis during this period, Dr. Johnson said. The figures suggest a decline in the first year after gastric bypass, but the clinical significance of this is not yet known, he added.

At 2 years, forearm BMD decreased by 3.62%, but radius BMD remained steady. Both total hip and lumbar spine BMD recovered somewhat in the second year, bringing them to almost the same levels as preoperatively.

At 3 and 4 years after surgery, BMD trended up, but there were too few patients at those time points to determine if the increases were statistically significant, Dr. Johnson said.

About 50%–60% of patients had calcium, parathyroid hormone, and vitamin D levels taken before surgery; all had those elements measured annually thereafter.

The mean serum calcium decreased from 9.8 mg/dL at baseline to 9.2 mg/dL in the first year, and to 8.8 mg/dL in the second year.

Although the study backed other reports showing an initial decline in BMD, the clinical significance is not known, Dr. Johnson said. “We have shown it's not an ongoing process,” he added.

CHICAGO — In one of the first studies to examine the long-term endocrine effects of gastric bypass surgery, it appears that after a loss in the first year post procedure, bone mineral density recovers in succeeding years, researchers reported at the annual meeting of the Society for Surgery of the Alimentary Tract.

Surgeons at Virginia Commonwealth University in Richmond prospectively collected data on 233 patients who were undergoing gastric bypass surgery. Of those, 82% had a Roux-en-Y procedure, 12% laparoscopically. The average age was 40 years, and the average body mass index was 50 kg/m

Dr. Johnson and his colleagues obtained preoperative bone mineral density (BMD) scans and found that most patients were normal at baseline, and remained at normal levels, even after surgery. Fifteen patients were osteopenic at baseline. Three developed osteopenia at 1 year post procedure. One patient with preoperative osteopenia actually had an increase in BMD after surgery.

At 1 year, for all patients, total forearm BMD decreased by 0.55%, and radius BMD increased by 1.85%. Total hip and lumbar spine BMD declined by 9.27% and 4.53%, respectively. These seem like fairly large decreases, but none of the patients developed osteoporosis during this period, Dr. Johnson said. The figures suggest a decline in the first year after gastric bypass, but the clinical significance of this is not yet known, he added.

At 2 years, forearm BMD decreased by 3.62%, but radius BMD remained steady. Both total hip and lumbar spine BMD recovered somewhat in the second year, bringing them to almost the same levels as preoperatively.

At 3 and 4 years after surgery, BMD trended up, but there were too few patients at those time points to determine if the increases were statistically significant, Dr. Johnson said.

About 50%–60% of patients had calcium, parathyroid hormone, and vitamin D levels taken before surgery; all had those elements measured annually thereafter.

The mean serum calcium decreased from 9.8 mg/dL at baseline to 9.2 mg/dL in the first year, and to 8.8 mg/dL in the second year.

Although the study backed other reports showing an initial decline in BMD, the clinical significance is not known, Dr. Johnson said. “We have shown it's not an ongoing process,” he added.