Kerri Wachter

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., said at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And some studies have suggested that elderly patients with fractures are more likely to be malnourished. Keeping an eye out for malnourished patients could help reduce the risk of falls and fractures, he said.

Although supplements offer an easy solution, food is still the best source of vitamins and minerals. Dr. Binkley shared the following tips:

Phosphorus

Phosphorus insufficiency is generally not a common problem, but it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function.

An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It has also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, Dr. Binkley said. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are.

But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest that the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. But vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, Dr. Binkley said.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD.

The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. But several studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” Dr. Binkley said.

The effect of other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet. “What we've done is taken good food and replaced it with carbonated water. The problem is not what they contain but what they don't.”

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures. In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting that there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., said at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And some studies have suggested that elderly patients with fractures are more likely to be malnourished. Keeping an eye out for malnourished patients could help reduce the risk of falls and fractures, he said.

Although supplements offer an easy solution, food is still the best source of vitamins and minerals. Dr. Binkley shared the following tips:

Phosphorus

Phosphorus insufficiency is generally not a common problem, but it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function.

An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It has also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, Dr. Binkley said. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are.

But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest that the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. But vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, Dr. Binkley said.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD.

The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. But several studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” Dr. Binkley said.

The effect of other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet. “What we've done is taken good food and replaced it with carbonated water. The problem is not what they contain but what they don't.”

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures. In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting that there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., said at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And some studies have suggested that elderly patients with fractures are more likely to be malnourished. Keeping an eye out for malnourished patients could help reduce the risk of falls and fractures, he said.

Although supplements offer an easy solution, food is still the best source of vitamins and minerals. Dr. Binkley shared the following tips:

Phosphorus

Phosphorus insufficiency is generally not a common problem, but it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function.

An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It has also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, Dr. Binkley said. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are.

But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest that the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. But vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, Dr. Binkley said.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD.

The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. But several studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” Dr. Binkley said.

The effect of other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet. “What we've done is taken good food and replaced it with carbonated water. The problem is not what they contain but what they don't.”

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures. In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting that there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short-term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., who is a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Ask patients about long-term glucocorticoids, suppressive doses of thyroid hormone, phenytoin, phenobarbital, GnRH agonists, aromatase inhibitors, cyclosporine, aluminum-containing antacids, long-term heparin, and vitamin A supplementation.

The diagnosis of osteoporosis can be made in premenopausal women if they have low BMD as well as secondary causes of the disorder.

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, according to John Kanis, M.D., who is the director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

Is the risk factor internationally validated? “We need to know that something works as well in Japan as it does in the United States,” Dr. Kanis commented.

Is it feasible for a primary care physician to assess the risk factor? Low calcium intake is a risk factor for hip fracture, but measuring calcium intake is difficult to do.

Is the risk factor intuitive? “Dementia is a very strong risk factor for hip fracture, but it's going to be rather difficult to persuade a primary care physician that if he has a patient with dementia, the first thing he should be thinking about is osteoporosis.

A family history is much more intuitive in medical care,” Dr. Kanis commented at the meeting.

When to Do Vertebral Assessments

Paul Miller, M.D., who is the director of the Colorado Center for Bone Research in Lakewood, recommended that physicians perform a vertebral assessment in patients with any of the following characteristics:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy. The availability of automated assays for a number of the markers allows clinicians to inexpensively assess bone health.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day variability in the results. Clinical markers can vary by the time of collection. “Right now it's suggested that they be collected in the morning, before 9 o'clock,” said Dr. Bauer.

In addition, just how much variability there is between laboratories performing these assays has yet to be studied. There are no standardized cut points available for bone turnover markers.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

“I don't see any reason for a drug holiday, even in the case of depressed bone turnover, because eventually the effects of parathyroid hormone will overcome [depressed bone turnover] … in short order,” he said.

For patients who will be starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

In addition, “Most of us would agree that after teriparatide, we should follow up with an antiresorptive,” Dr. Bilezikian said at the meeting.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short-term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., who is a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Ask patients about long-term glucocorticoids, suppressive doses of thyroid hormone, phenytoin, phenobarbital, GnRH agonists, aromatase inhibitors, cyclosporine, aluminum-containing antacids, long-term heparin, and vitamin A supplementation.

The diagnosis of osteoporosis can be made in premenopausal women if they have low BMD as well as secondary causes of the disorder.

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, according to John Kanis, M.D., who is the director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

Is the risk factor internationally validated? “We need to know that something works as well in Japan as it does in the United States,” Dr. Kanis commented.

Is it feasible for a primary care physician to assess the risk factor? Low calcium intake is a risk factor for hip fracture, but measuring calcium intake is difficult to do.

Is the risk factor intuitive? “Dementia is a very strong risk factor for hip fracture, but it's going to be rather difficult to persuade a primary care physician that if he has a patient with dementia, the first thing he should be thinking about is osteoporosis.

A family history is much more intuitive in medical care,” Dr. Kanis commented at the meeting.

When to Do Vertebral Assessments

Paul Miller, M.D., who is the director of the Colorado Center for Bone Research in Lakewood, recommended that physicians perform a vertebral assessment in patients with any of the following characteristics:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy. The availability of automated assays for a number of the markers allows clinicians to inexpensively assess bone health.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day variability in the results. Clinical markers can vary by the time of collection. “Right now it's suggested that they be collected in the morning, before 9 o'clock,” said Dr. Bauer.

In addition, just how much variability there is between laboratories performing these assays has yet to be studied. There are no standardized cut points available for bone turnover markers.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

“I don't see any reason for a drug holiday, even in the case of depressed bone turnover, because eventually the effects of parathyroid hormone will overcome [depressed bone turnover] … in short order,” he said.

For patients who will be starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

In addition, “Most of us would agree that after teriparatide, we should follow up with an antiresorptive,” Dr. Bilezikian said at the meeting.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short-term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., who is a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Ask patients about long-term glucocorticoids, suppressive doses of thyroid hormone, phenytoin, phenobarbital, GnRH agonists, aromatase inhibitors, cyclosporine, aluminum-containing antacids, long-term heparin, and vitamin A supplementation.

The diagnosis of osteoporosis can be made in premenopausal women if they have low BMD as well as secondary causes of the disorder.

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, according to John Kanis, M.D., who is the director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

Is the risk factor internationally validated? “We need to know that something works as well in Japan as it does in the United States,” Dr. Kanis commented.

Is it feasible for a primary care physician to assess the risk factor? Low calcium intake is a risk factor for hip fracture, but measuring calcium intake is difficult to do.

Is the risk factor intuitive? “Dementia is a very strong risk factor for hip fracture, but it's going to be rather difficult to persuade a primary care physician that if he has a patient with dementia, the first thing he should be thinking about is osteoporosis.

A family history is much more intuitive in medical care,” Dr. Kanis commented at the meeting.

When to Do Vertebral Assessments

Paul Miller, M.D., who is the director of the Colorado Center for Bone Research in Lakewood, recommended that physicians perform a vertebral assessment in patients with any of the following characteristics:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy. The availability of automated assays for a number of the markers allows clinicians to inexpensively assess bone health.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day variability in the results. Clinical markers can vary by the time of collection. “Right now it's suggested that they be collected in the morning, before 9 o'clock,” said Dr. Bauer.

In addition, just how much variability there is between laboratories performing these assays has yet to be studied. There are no standardized cut points available for bone turnover markers.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

“I don't see any reason for a drug holiday, even in the case of depressed bone turnover, because eventually the effects of parathyroid hormone will overcome [depressed bone turnover] … in short order,” he said.

For patients who will be starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

In addition, “Most of us would agree that after teriparatide, we should follow up with an antiresorptive,” Dr. Bilezikian said at the meeting.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, advised John Kanis, M.D., director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

The questions are: Is the risk factor internationally validated? Is it feasible for a primary care physician to assess the risk factor? Is the risk factor intuitive?

When to Do Vertebral Assessments

Paul Miller, M.D., director of the Colorado Center for Bone Research in Lakewood, recommended performing a vertebral assessment in patients with any of the following:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day and even time-of-day variability in the results, Dr. Bauer said.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

For patients starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, advised John Kanis, M.D., director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

The questions are: Is the risk factor internationally validated? Is it feasible for a primary care physician to assess the risk factor? Is the risk factor intuitive?

When to Do Vertebral Assessments

Paul Miller, M.D., director of the Colorado Center for Bone Research in Lakewood, recommended performing a vertebral assessment in patients with any of the following:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day and even time-of-day variability in the results, Dr. Bauer said.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

For patients starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

NEW ORLEANS — Bone health experts offered their share of helpful clinical insights at the annual meeting of the International Society for Clinical Densitometry.

Here are some of the highlights:

Low Bone Density in the Young

Low bone density is not uncommon in young adults but—at least in the short term—does not carry with it the same relative risk of fracture as in older individuals unless secondary causes of metabolic bone disease are identified, said Andrew J. Laster, M.D., a rheumatologist practicing in North Carolina.

Secondary causes of low BMD include endocrinopathies (hypercalciuria, hypogonadism, hyperparathyroidism, and Cushing's syndrome), some GI disorders (gastrectomy, inflammatory bowel disease, celiac disease, intestinal bypass surgery, primary biliary cirrhosis, and pancreatic insufficiency), genetic disorders (Ehlers-Danlos syndrome, Marfan syndrome, and homocystinuria), and eating disorders (anorexia nervosa, bulimia nervosa, and female athlete triad).

Assessing Fracture Risk Factors

Before experts declare the benefits of addressing a particular risk factor in an individual patient, they should stop and ask some key questions, advised John Kanis, M.D., director of the World Health Organization's Collaborating Centre for Metabolic Bone Diseases in Sheffield, England.

The questions are: Is the risk factor internationally validated? Is it feasible for a primary care physician to assess the risk factor? Is the risk factor intuitive?

When to Do Vertebral Assessments

Paul Miller, M.D., director of the Colorado Center for Bone Research in Lakewood, recommended performing a vertebral assessment in patients with any of the following:

▸ Loss of 1.5 inches or more in height.

▸ Back pain in patients coming to your office for osteoporosis assessment.

▸ Known vertebral deformities or hip fractures.

▸ Kyphosis.

▸ Chronic glucocorticoid therapy.

▸ Age older than 60 years.

Turnover Markers

There are a number of potential advantages to using bone turnover markers, according to Douglas C. Bauer, M.D., of the University of California, San Francisco.

These measurements provide a more dynamic assessment of skeletal metabolism than BMD. More importantly, bone turnover markers rapidly reflect changes as a result of therapy, providing a better means of assessing treatment efficacy.

The most significant disadvantage to using clinical markers is that there is typically very high day-to-day and even time-of-day variability in the results, Dr. Bauer said.

Timing

For a patient who has been on an antiresorptive therapy and who will be taking teriparatide, there is no need for a break between the two therapies, said John Bilezikian, M.D., professor of medicine and pharmacology at Columbia University, New York.

For patients starting therapy for low BMD, Dr. Bilezikian recommends monotherapy with either an antiresorptive or with parathyroid hormone.

NEW ORLEANS — Of all the factors that contribute to bone strength, the rate of turnover may be most clinically relevant, David Dempster, Ph.D., said at the annual meeting of the International Society for Clinical Densitometry.

At the same time, several recent advances may soon transform the way bone is assessed.

Bone turnover affects each and every one of the other variables that factor into bone strength, including structural factors and material properties, said Dr. Dempster, professor of clinical pathology at Columbia University, New York.

High bone turnover increases remodeling space, accelerates bone loss, disrupts the trabecular microarchitecture, increases mechanical stress concentration, decreases mineralization density, and increases cortical porosity, each of which can undermine bone strength, Dr. Dempster said.

When osteoclast activity exceeds osteoblast activity, there's a deficit on the surface of the trabeculae and within the cortex. “This may not amount to much in terms of bone mass … but I think that a small amount of missing bone may be important.”

As bone mass declines, there is an exponential increase in fracture risk. “Simply by preventing a small amount of bone loss, you will prevent that patient from going up a steep slope in terms of fracture risk,” he said.

Another consequence of high turnover is the increase in the destruction of the trabecular microarchitecture. As bone turnover increases, there is a preferential loss of the horizontal trabeculae known as cross-ties, said Dr. Dempster.

“I'm talking about high turnover in a catabolic sense … where resorption exceeds formation.” This type of turnover occurs shortly after menopause or shortly after the introduction of glucocorticoids, said Dr. Dempster, who is also the director of the Regional Bone Center at the Helen Hayes Hospital in West Haverstraw, N.Y.

After menopause, a confluence of three phenomena can occur: a greater number of osteoclasts gather on the bone surface, osteoclasts become more efficient at breaking bone down, and the plates may become thinner. The result is that instead of sweeping across the trabecular surface—as with normal bone turnover—the osteoclasts tend to penetrate through the trabecular plate, leaving osteoblasts without a template for creating new bone. Supportive horizontal trabecular rods eventually become disconnected.

Mechanical stress concentration is another important element of bone strength. Osteoclast resorption cavities are the mechanical stress points. Without these cavities, intact trabeculae bend in response to stress but don't break. When resorption cavities are present, the same force will cause the trabeculae to break.

With high bone turnover, mineral density declines. While measuring bone mineral density (BMD) captures large-scale information on mineralization density, it doesn't provide information on the local distribution of minerals.

Nor do conventional BMD measures provide information on the collagen-to-mineral ratio. Too much mineral makes bones brittle; too much collagen makes them weak.

So far, markers of bone turnover have been shown to be useful in the research setting, by they aren't ready for clinical use, said Dr. Dempster. Still, once they are ready, “I think that a BMD test coupled with a good measure of bone turnover in an individual patient would give you much more information than you currently have.”

Improvements to turnover measurement are imminent, as more of these tests are incorporated into auto-analyzer formats. In addition, progress is being made in defining what the normal premenopausal range is for these markers.

“We [also] have some very good research going on looking at how we can assess microarchitecture noninvasively,” he said. Quantitative CT is starting to be used to assess bone strength in hip structural analysis.

These newer techniques help measure not only BMD but also help assesses the structural geometry of cross sections at specific locations of the hip. The evaluation of bone microarchitecture has benefited from the use of technologies such as peripheral quantitative CT and high-resolution micro MRI.

In the past, bone microarchitecture has been hampered by the need to extract bone samples from volunteers and look at these samples under a powerful microscope. These new technologies give researchers an easier way to study a larger pool of volunteers.

NEW ORLEANS — Of all the factors that contribute to bone strength, the rate of turnover may be most clinically relevant, David Dempster, Ph.D., said at the annual meeting of the International Society for Clinical Densitometry.

At the same time, several recent advances may soon transform the way bone is assessed.

Bone turnover affects each and every one of the other variables that factor into bone strength, including structural factors and material properties, said Dr. Dempster, professor of clinical pathology at Columbia University, New York.

High bone turnover increases remodeling space, accelerates bone loss, disrupts the trabecular microarchitecture, increases mechanical stress concentration, decreases mineralization density, and increases cortical porosity, each of which can undermine bone strength, Dr. Dempster said.

When osteoclast activity exceeds osteoblast activity, there's a deficit on the surface of the trabeculae and within the cortex. “This may not amount to much in terms of bone mass … but I think that a small amount of missing bone may be important.”

As bone mass declines, there is an exponential increase in fracture risk. “Simply by preventing a small amount of bone loss, you will prevent that patient from going up a steep slope in terms of fracture risk,” he said.

Another consequence of high turnover is the increase in the destruction of the trabecular microarchitecture. As bone turnover increases, there is a preferential loss of the horizontal trabeculae known as cross-ties, said Dr. Dempster.

“I'm talking about high turnover in a catabolic sense … where resorption exceeds formation.” This type of turnover occurs shortly after menopause or shortly after the introduction of glucocorticoids, said Dr. Dempster, who is also the director of the Regional Bone Center at the Helen Hayes Hospital in West Haverstraw, N.Y.

After menopause, a confluence of three phenomena can occur: a greater number of osteoclasts gather on the bone surface, osteoclasts become more efficient at breaking bone down, and the plates may become thinner. The result is that instead of sweeping across the trabecular surface—as with normal bone turnover—the osteoclasts tend to penetrate through the trabecular plate, leaving osteoblasts without a template for creating new bone. Supportive horizontal trabecular rods eventually become disconnected.

Mechanical stress concentration is another important element of bone strength. Osteoclast resorption cavities are the mechanical stress points. Without these cavities, intact trabeculae bend in response to stress but don't break. When resorption cavities are present, the same force will cause the trabeculae to break.

With high bone turnover, mineral density declines. While measuring bone mineral density (BMD) captures large-scale information on mineralization density, it doesn't provide information on the local distribution of minerals.

Nor do conventional BMD measures provide information on the collagen-to-mineral ratio. Too much mineral makes bones brittle; too much collagen makes them weak.

So far, markers of bone turnover have been shown to be useful in the research setting, by they aren't ready for clinical use, said Dr. Dempster. Still, once they are ready, “I think that a BMD test coupled with a good measure of bone turnover in an individual patient would give you much more information than you currently have.”

Improvements to turnover measurement are imminent, as more of these tests are incorporated into auto-analyzer formats. In addition, progress is being made in defining what the normal premenopausal range is for these markers.

“We [also] have some very good research going on looking at how we can assess microarchitecture noninvasively,” he said. Quantitative CT is starting to be used to assess bone strength in hip structural analysis.

These newer techniques help measure not only BMD but also help assesses the structural geometry of cross sections at specific locations of the hip. The evaluation of bone microarchitecture has benefited from the use of technologies such as peripheral quantitative CT and high-resolution micro MRI.

In the past, bone microarchitecture has been hampered by the need to extract bone samples from volunteers and look at these samples under a powerful microscope. These new technologies give researchers an easier way to study a larger pool of volunteers.

NEW ORLEANS — Of all the factors that contribute to bone strength, the rate of turnover may be most clinically relevant, David Dempster, Ph.D., said at the annual meeting of the International Society for Clinical Densitometry.

At the same time, several recent advances may soon transform the way bone is assessed.

Bone turnover affects each and every one of the other variables that factor into bone strength, including structural factors and material properties, said Dr. Dempster, professor of clinical pathology at Columbia University, New York.

High bone turnover increases remodeling space, accelerates bone loss, disrupts the trabecular microarchitecture, increases mechanical stress concentration, decreases mineralization density, and increases cortical porosity, each of which can undermine bone strength, Dr. Dempster said.

When osteoclast activity exceeds osteoblast activity, there's a deficit on the surface of the trabeculae and within the cortex. “This may not amount to much in terms of bone mass … but I think that a small amount of missing bone may be important.”

As bone mass declines, there is an exponential increase in fracture risk. “Simply by preventing a small amount of bone loss, you will prevent that patient from going up a steep slope in terms of fracture risk,” he said.

Another consequence of high turnover is the increase in the destruction of the trabecular microarchitecture. As bone turnover increases, there is a preferential loss of the horizontal trabeculae known as cross-ties, said Dr. Dempster.

“I'm talking about high turnover in a catabolic sense … where resorption exceeds formation.” This type of turnover occurs shortly after menopause or shortly after the introduction of glucocorticoids, said Dr. Dempster, who is also the director of the Regional Bone Center at the Helen Hayes Hospital in West Haverstraw, N.Y.

After menopause, a confluence of three phenomena can occur: a greater number of osteoclasts gather on the bone surface, osteoclasts become more efficient at breaking bone down, and the plates may become thinner. The result is that instead of sweeping across the trabecular surface—as with normal bone turnover—the osteoclasts tend to penetrate through the trabecular plate, leaving osteoblasts without a template for creating new bone. Supportive horizontal trabecular rods eventually become disconnected.

Mechanical stress concentration is another important element of bone strength. Osteoclast resorption cavities are the mechanical stress points. Without these cavities, intact trabeculae bend in response to stress but don't break. When resorption cavities are present, the same force will cause the trabeculae to break.

With high bone turnover, mineral density declines. While measuring bone mineral density (BMD) captures large-scale information on mineralization density, it doesn't provide information on the local distribution of minerals.

Nor do conventional BMD measures provide information on the collagen-to-mineral ratio. Too much mineral makes bones brittle; too much collagen makes them weak.

So far, markers of bone turnover have been shown to be useful in the research setting, by they aren't ready for clinical use, said Dr. Dempster. Still, once they are ready, “I think that a BMD test coupled with a good measure of bone turnover in an individual patient would give you much more information than you currently have.”

Improvements to turnover measurement are imminent, as more of these tests are incorporated into auto-analyzer formats. In addition, progress is being made in defining what the normal premenopausal range is for these markers.

“We [also] have some very good research going on looking at how we can assess microarchitecture noninvasively,” he said. Quantitative CT is starting to be used to assess bone strength in hip structural analysis.

These newer techniques help measure not only BMD but also help assesses the structural geometry of cross sections at specific locations of the hip. The evaluation of bone microarchitecture has benefited from the use of technologies such as peripheral quantitative CT and high-resolution micro MRI.

In the past, bone microarchitecture has been hampered by the need to extract bone samples from volunteers and look at these samples under a powerful microscope. These new technologies give researchers an easier way to study a larger pool of volunteers.

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., declared at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And studies have suggested that elderly patients with fractures are more likely to be malnourished. Dr. Binkley shared the following tips about diet and nutrition:

Phosphorus

Phosphorus insufficiency is generally not a common problem; however, it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function. An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It's also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, said Dr. Binkley. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are. But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity. If one eats 6 pounds of carotenoids (retinol precursors), the body makes only 1 pound of retinol.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. However, vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, said Dr. Binkley.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD. The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. However, a number of studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” said Dr. Binkley.

The effect of these other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet.

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures.

In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., declared at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And studies have suggested that elderly patients with fractures are more likely to be malnourished. Dr. Binkley shared the following tips about diet and nutrition:

Phosphorus

Phosphorus insufficiency is generally not a common problem; however, it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function. An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It's also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, said Dr. Binkley. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are. But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity. If one eats 6 pounds of carotenoids (retinol precursors), the body makes only 1 pound of retinol.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. However, vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, said Dr. Binkley.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD. The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. However, a number of studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” said Dr. Binkley.

The effect of these other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet.

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures.

In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

NEW ORLEANS — With a virtual alphabet soup of vitamin and mineral supplements available—and a constant barrage of new nutritional advice each week—it's a challenge to know what truly bolsters bone health, Neil Binkley, M.D., declared at the annual meeting of the International Society for Clinical Densitometry.

General malnutrition is actually a common phenomenon in the United States, said Dr. Binkley, of the Institute on Aging at the University of Wisconsin in Madison. According to one study, 11% of patients older than 65 are undernourished. And studies have suggested that elderly patients with fractures are more likely to be malnourished. Dr. Binkley shared the following tips about diet and nutrition:

Phosphorus

Phosphorus insufficiency is generally not a common problem; however, it tends to occur in some of the more vulnerable populations. Phosphorus deficiency decreases mineralization and osteoblast function while increasing osteoclast function. An estimated 15% of women over age 80 receive less than 70% of the U.S. recommended daily allowance (RDA) of phosphorus (1,000 mg). It's also been suggested that patients who fail to respond to calcium supplementation may, in fact, have inadequate phosphorus intake.

Vitamin D

Make sure patients are aware that not all dairy products are fortified with vitamin D. “You can't get vitamin D in food unless you happen to like liver or lots of salmon or mackerel,” Dr. Binkley said.

Vitamin D toxicity is less of a concern than it once was. Recommended levels of vitamin D range from 1,200 to 1,500 IU per day. Levels in excess of 10,000 IU per day are now believed toxic, so there is a large margin of error.

Supplements may be necessary to get enough vitamin D. Dr. Binkley noted that to get 1,000 IU vitamin D, you would need to drink half a gallon of milk or eat 40 egg yolks. Getting a little sun is also an option.

The bigger problem with ensuring that patients get enough vitamin D may be in obtaining a good assay, said Dr. Binkley. In one study, he and his colleagues used four different assays to measure patient vitamin D levels. Although the four methods agreed quite well for some patients, there were big differences among the assays for other patients.

Attempts to standardize vitamin D assays are ongoing. High-performance liquid chromatography (HPLC) appears to provide the best results. Dr. Binkley advised that if HPLC and commercial assays agree that a patient's vitamin D levels are low, they probably are. But if commercial assays indicate a patient's levels are not low, consider HPLC. He also noted that if you give your patient very high, prescription-level doses (50,000 IU) of vitamin D, at least one of the commercial 25-hydroxy assays only detects about half of it in the blood.

Vitamin A

A family of about 25 compounds constitute vitamin A, but the active component is retinol. The RDA for vitamin A is 2,600 IU (800 mcg) per day for men and 2,300 IU (700 mcg) per day for women.

The effects of getting too much vitamin A are unclear. Generally, it's been assumed that the body has built-in safeguards to avoid vitamin A toxicity. If one eats 6 pounds of carotenoids (retinol precursors), the body makes only 1 pound of retinol.

Yet it's theorized that excessive vitamin A will suppress osteoblast activity and stimulate bone reabsorption. In addition, epidemiologic data suggest the consumption of more than 5,000 IU daily increases fracture risk—but clinical studies have not confirmed this association.

Dietary sources of vitamin A include liver, fish, and fortified foods such as dairy products; certain fruits and vegetables are high in carotenoids. Vitamin A supplementation is considered necessary only in special situations, and patients should be counseled never to take synthetic retinol.

Vitamin K

Low vitamin K levels have been reported in patients with osteoporotic fractures and epidemiologic data show an increased risk of hip fracture with low levels of vitamin K. However, vitamin K doesn't linger in the blood for very long, so it's difficult to get an accurate measure, said Dr. Binkley.

Most of the existing data come from Japan, where a different form of vitamin K is taken from that used in the United States. The Japanese studies used 45 mg per day and showed sustained levels of bone mineral density (BMD) and vertebral fracture-prevention benefits. Adequate intake of vitamin K in the United States, however, is thought to be about 100 mcg per day. It's probably too early to recommend vitamin K supplementation, he concluded.

Magnesium

Inadequate magnesium is associated with decreased parathyroid hormone. Epidemiologic studies suggest a positive association between increased magnesium intake and BMD. But data from the Women's Health Initiative found that high magnesium intake was not protective of BMD. The bottom line for patients is to eat foods that contain magnesium, including whole grains, vegetables, and nuts. There are no data to support the use of magnesium supplements, Dr. Binkley said.

Caffeine

It's been widely assumed that caffeine is harmful to bone because it leads to increased urinary calcium loss. However, a number of studies have shown that decreased calcium absorption is actually what occurs. “The gist is that for each cup of coffee that we drink, there is a calcium loss of about 5 mg. What does that mean? It means that we need to put about 2 tablespoons of milk in our coffee,” said Dr. Binkley.

The effect of these other caffeinated beverages on calcium absorption is largely negligible. The bigger issue is that soft drinks have replaced milk in the average American's diet.

Protein

One study of elderly patients found that patients getting protein supplements were less likely to have fractures.

In fact, those with higher protein intake and adequate calcium had the best outcomes, suggesting there may be a synergistic effect between protein and calcium. There's no need to restrict protein after hip fractures.

DESTIN, FLA. — The advent of disease-modifying drugs has made magnetic resonance imaging an indispensable tool for diagnosing and monitoring patients with rheumatoid arthritis, Charles G. Peterfy, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

MRI already is the tool of choice for use in clinical trials. Now it's time for clinical practice to incorporate this superior technology, said Dr. Peterfy, a radiologist specializing in musculoskeletal imaging, and chief medical officer of Synarc Inc., which specializes in radiology services for clinical trials. Radiographs have a number of shortcomings. Not only are they relatively insensitive for predicting disease progression and bone erosion, they are not accurate for measuring cartilage loss or for visualizing the synovium.

MRI can provide information on synovitis, tendonitis, and bone edema (or osteitis), all of which improve the predictive accuracy, particularly the negative predictive value. “The absence of these findings on MRI is a very powerful predictor that this patient is not going to progress,” Dr. Peterfy said at the meeting, also sponsored by the International Society for Clinical Densitometry.

MRI of synovitis correlates with histopathology, Doppler ultrasound, PET imaging and “has been found to be more sensitive than clinical examination for swelling and tenderness,” he said.

There are MRI techniques that allow the visualization of preerosive osteitis, which is key because osteitis can progress very rapidly, said Dr. Peterfy, who also is on the advisory board for MagneVu, the maker of portable MRI units. According to one study, baseline osteitis can predict functional disability at 6 years. A number of studies have demonstrated that MRI detects erosions earlier than x-rays, said Dr. Peterfy. In fact, one study demonstrated the ability of baseline MRI to predict bone erosions as much as 2 years later.

The development of a semiquantitative scoring system—such as the Rheumatoid Arthritis MRI Score (RAMRIS) developed by the European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT)—should help standardize the use of MRI to monitor the progression of RA. This system incorporates erosions, osteitis, and synovitis to assess disease changes. The group recently published an MRI atlas intended to improve the performance and generalizability of the MRI scoring system (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i3-i55).

DESTIN, FLA. — The advent of disease-modifying drugs has made magnetic resonance imaging an indispensable tool for diagnosing and monitoring patients with rheumatoid arthritis, Charles G. Peterfy, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

MRI already is the tool of choice for use in clinical trials. Now it's time for clinical practice to incorporate this superior technology, said Dr. Peterfy, a radiologist specializing in musculoskeletal imaging, and chief medical officer of Synarc Inc., which specializes in radiology services for clinical trials. Radiographs have a number of shortcomings. Not only are they relatively insensitive for predicting disease progression and bone erosion, they are not accurate for measuring cartilage loss or for visualizing the synovium.

MRI can provide information on synovitis, tendonitis, and bone edema (or osteitis), all of which improve the predictive accuracy, particularly the negative predictive value. “The absence of these findings on MRI is a very powerful predictor that this patient is not going to progress,” Dr. Peterfy said at the meeting, also sponsored by the International Society for Clinical Densitometry.

MRI of synovitis correlates with histopathology, Doppler ultrasound, PET imaging and “has been found to be more sensitive than clinical examination for swelling and tenderness,” he said.

There are MRI techniques that allow the visualization of preerosive osteitis, which is key because osteitis can progress very rapidly, said Dr. Peterfy, who also is on the advisory board for MagneVu, the maker of portable MRI units. According to one study, baseline osteitis can predict functional disability at 6 years. A number of studies have demonstrated that MRI detects erosions earlier than x-rays, said Dr. Peterfy. In fact, one study demonstrated the ability of baseline MRI to predict bone erosions as much as 2 years later.

The development of a semiquantitative scoring system—such as the Rheumatoid Arthritis MRI Score (RAMRIS) developed by the European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT)—should help standardize the use of MRI to monitor the progression of RA. This system incorporates erosions, osteitis, and synovitis to assess disease changes. The group recently published an MRI atlas intended to improve the performance and generalizability of the MRI scoring system (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i3-i55).

DESTIN, FLA. — The advent of disease-modifying drugs has made magnetic resonance imaging an indispensable tool for diagnosing and monitoring patients with rheumatoid arthritis, Charles G. Peterfy, M.D., said at a rheumatology meeting sponsored by Virginia Commonwealth University.

MRI already is the tool of choice for use in clinical trials. Now it's time for clinical practice to incorporate this superior technology, said Dr. Peterfy, a radiologist specializing in musculoskeletal imaging, and chief medical officer of Synarc Inc., which specializes in radiology services for clinical trials. Radiographs have a number of shortcomings. Not only are they relatively insensitive for predicting disease progression and bone erosion, they are not accurate for measuring cartilage loss or for visualizing the synovium.

MRI can provide information on synovitis, tendonitis, and bone edema (or osteitis), all of which improve the predictive accuracy, particularly the negative predictive value. “The absence of these findings on MRI is a very powerful predictor that this patient is not going to progress,” Dr. Peterfy said at the meeting, also sponsored by the International Society for Clinical Densitometry.

MRI of synovitis correlates with histopathology, Doppler ultrasound, PET imaging and “has been found to be more sensitive than clinical examination for swelling and tenderness,” he said.

There are MRI techniques that allow the visualization of preerosive osteitis, which is key because osteitis can progress very rapidly, said Dr. Peterfy, who also is on the advisory board for MagneVu, the maker of portable MRI units. According to one study, baseline osteitis can predict functional disability at 6 years. A number of studies have demonstrated that MRI detects erosions earlier than x-rays, said Dr. Peterfy. In fact, one study demonstrated the ability of baseline MRI to predict bone erosions as much as 2 years later.

The development of a semiquantitative scoring system—such as the Rheumatoid Arthritis MRI Score (RAMRIS) developed by the European League Against Rheumatism-Outcome Measures in Rheumatoid Arthritis Clinical Trials (EULAR-OMERACT)—should help standardize the use of MRI to monitor the progression of RA. This system incorporates erosions, osteitis, and synovitis to assess disease changes. The group recently published an MRI atlas intended to improve the performance and generalizability of the MRI scoring system (Ann. Rheum. Dis. 2005;64 [suppl. 1]:i3-i55).

DESTIN, FLA. — Oral desensitization appears to be a safe and effective alternative for patients who are allergic to allopurinol and who cannot take other urate-lowering drugs for gout, Adel G. Fam, M.D., reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

While 1%-3% of patients experience a pruritic maculopapular rash in response to allopurinol, severe allopurinol hypersensitivity syndrome (AHS) occurs in only about 0.4% of patients, said Dr. Fam, a professor of rheumatology at the University of Toronto.

Dr. Fam suggested that allopurinol desensitization be considered in gout patients with any of the following circumstances:

▸ Renal impairment, which renders uricosuric drugs ineffective.

▸ Underexcretion hyperuricemia; and allergy, intolerance, or contraindications to both probenecid and sulfinpyrazone.

▸ Overproduction/overexcretion hyperuricemia, which coupled with uricosurics can increase the risk of renal stones.

▸ History of transplantation, renal insufficiency, and severe and debilitating gout.

▸ The patient requires prevention of malignancy-associated hyperuricemia and tumor lysis syndrome due to cytolytic therapy for hematologic malignancies; the resulting massive uricosuria precludes the use of uricosuric drugs.

The standard allopurinol desensitization protocol starts patients at a 50-mcg dose of allopurinol in suspension. The dose is gradually increased at 3-day intervals up to a target dose of 50-100 mg/day (in tablet form). The dosage can be adjusted if a rash occurs, Dr. Fam said at the meeting, also sponsored by the International Society for Clinical Densitometry.

For high-risk patients, a modified protocol is recommended. This protocol begins with allopurinol, 10 mcg or 25 mcg, in suspension. The dosage is titrated every 5-10 days.

In a retrospective study of 32 patients, 78% were able to tolerate long-term allopurinol therapy following desensitization (Arthritis Rheum. 2001;44:231-8).

The diagnostic criteria for AHS includes a definite history of exposure to allopurinol, lack of exposure to another drug that may have caused similar symptoms, and the fulfillment of either two major criteria or one major and one minor criterion. Major criteria include: worsening renal function, acute hepatocellular injury, and rash (toxic epidermal necrosis, erythema multiforme, diffuse maculopapular rash, or exfoliative dermatitis). Minor criteria include: fever, eosinophilia, and leukocytosis.

DESTIN, FLA. — Oral desensitization appears to be a safe and effective alternative for patients who are allergic to allopurinol and who cannot take other urate-lowering drugs for gout, Adel G. Fam, M.D., reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

While 1%-3% of patients experience a pruritic maculopapular rash in response to allopurinol, severe allopurinol hypersensitivity syndrome (AHS) occurs in only about 0.4% of patients, said Dr. Fam, a professor of rheumatology at the University of Toronto.

Dr. Fam suggested that allopurinol desensitization be considered in gout patients with any of the following circumstances:

▸ Renal impairment, which renders uricosuric drugs ineffective.

▸ Underexcretion hyperuricemia; and allergy, intolerance, or contraindications to both probenecid and sulfinpyrazone.

▸ Overproduction/overexcretion hyperuricemia, which coupled with uricosurics can increase the risk of renal stones.

▸ History of transplantation, renal insufficiency, and severe and debilitating gout.

▸ The patient requires prevention of malignancy-associated hyperuricemia and tumor lysis syndrome due to cytolytic therapy for hematologic malignancies; the resulting massive uricosuria precludes the use of uricosuric drugs.

The standard allopurinol desensitization protocol starts patients at a 50-mcg dose of allopurinol in suspension. The dose is gradually increased at 3-day intervals up to a target dose of 50-100 mg/day (in tablet form). The dosage can be adjusted if a rash occurs, Dr. Fam said at the meeting, also sponsored by the International Society for Clinical Densitometry.

For high-risk patients, a modified protocol is recommended. This protocol begins with allopurinol, 10 mcg or 25 mcg, in suspension. The dosage is titrated every 5-10 days.

In a retrospective study of 32 patients, 78% were able to tolerate long-term allopurinol therapy following desensitization (Arthritis Rheum. 2001;44:231-8).

The diagnostic criteria for AHS includes a definite history of exposure to allopurinol, lack of exposure to another drug that may have caused similar symptoms, and the fulfillment of either two major criteria or one major and one minor criterion. Major criteria include: worsening renal function, acute hepatocellular injury, and rash (toxic epidermal necrosis, erythema multiforme, diffuse maculopapular rash, or exfoliative dermatitis). Minor criteria include: fever, eosinophilia, and leukocytosis.

DESTIN, FLA. — Oral desensitization appears to be a safe and effective alternative for patients who are allergic to allopurinol and who cannot take other urate-lowering drugs for gout, Adel G. Fam, M.D., reported at a rheumatology meeting sponsored by Virginia Commonwealth University.

While 1%-3% of patients experience a pruritic maculopapular rash in response to allopurinol, severe allopurinol hypersensitivity syndrome (AHS) occurs in only about 0.4% of patients, said Dr. Fam, a professor of rheumatology at the University of Toronto.

Dr. Fam suggested that allopurinol desensitization be considered in gout patients with any of the following circumstances:

▸ Renal impairment, which renders uricosuric drugs ineffective.

▸ Underexcretion hyperuricemia; and allergy, intolerance, or contraindications to both probenecid and sulfinpyrazone.

▸ Overproduction/overexcretion hyperuricemia, which coupled with uricosurics can increase the risk of renal stones.

▸ History of transplantation, renal insufficiency, and severe and debilitating gout.

▸ The patient requires prevention of malignancy-associated hyperuricemia and tumor lysis syndrome due to cytolytic therapy for hematologic malignancies; the resulting massive uricosuria precludes the use of uricosuric drugs.

The standard allopurinol desensitization protocol starts patients at a 50-mcg dose of allopurinol in suspension. The dose is gradually increased at 3-day intervals up to a target dose of 50-100 mg/day (in tablet form). The dosage can be adjusted if a rash occurs, Dr. Fam said at the meeting, also sponsored by the International Society for Clinical Densitometry.

For high-risk patients, a modified protocol is recommended. This protocol begins with allopurinol, 10 mcg or 25 mcg, in suspension. The dosage is titrated every 5-10 days.

In a retrospective study of 32 patients, 78% were able to tolerate long-term allopurinol therapy following desensitization (Arthritis Rheum. 2001;44:231-8).

The diagnostic criteria for AHS includes a definite history of exposure to allopurinol, lack of exposure to another drug that may have caused similar symptoms, and the fulfillment of either two major criteria or one major and one minor criterion. Major criteria include: worsening renal function, acute hepatocellular injury, and rash (toxic epidermal necrosis, erythema multiforme, diffuse maculopapular rash, or exfoliative dermatitis). Minor criteria include: fever, eosinophilia, and leukocytosis.

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

DESTIN, FLA. — Rheumatologists are probably missing the diagnosis of joint hypermobility syndrome on a regular basis, Alan J. Hakim, M.D., proposed at a rheumatology meeting sponsored by Virginia Commonwealth University.

Joint hypermobility syndrome (JHS) shares a number of features with related disorders, making it difficult to identify, but the correct diagnosis will make all the difference in patients' lives, said Dr. Hakim, a rheumatologist at Whipps Cross University Hospital in London.

JHS is thought to be related to Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta. In addition, JHS mimics fibromyalgia and chronic fatigue syndrome, and it can be difficult to distinguish JHS from these other conditions, he said.

JHS can involve a variety of musculoskeletal symptoms, from chronic pain and fatigue to soft-tissue and visceral injury, all in the presence of general joint laxity.

Of the musculoskeletal symptoms, chronic noninflammatory joint pain or spinal pain is a key complaint. Other musculoskeletal symptoms include dislocation or subluxation of joints; ligament, tendon, or muscle overuse injuries; and deconditioning as a result of kinesphobia.

The other key clinical components include skin abnormalities such as excessive stretching of the skin and abnormal scarring, and psychosocial problems. This overall symptom complex can manifest in childhood, adolescence, or even early adulthood.

The prevalence of JHS in the general population ranges from 10% to 30%; the disorder is three times more common in women.

JHS is more commonly seen in people of African and Asian ethnicity than in whites. There appears to be a strong genetic component, with approximately a 75% heritability rate of the phenotype.

Psychologic aspects are typical, because patients tend to feel anxious or depressed as a result of their chronic pain and disability.

Panic disorders and phobias are four times more common in JHS patients. They may not be able work, adding to their sense of isolation. They avoid relationships and social activities. Sexual difficulties and reproductive concerns are common.

These patients may feel frustrated with a medical system that has been unable to correctly diagnose them, Dr. Hakim explained.

Cardiorespiratory and bowel disturbances are also frequent and often disabling.

Related symptoms include palpitations, chest discomfort, lightheadedness, and presyncope. Bowel disturbances include nausea, dyspepsia, constipation, and diarrhea. All these symptoms are strongly associated with fatigue and anxiety.

There also appear to be proprioception and autonomic-nervous system disturbances.

Proprioceptive deficits have been shown to create a vicious cycle, whereby diminished proprioception leads to altered neuromuscular control, causing altered mechanical loading, which leads to joint capsule and ligament damage, which in turn creates more of a tendency toward poor proprioception.

The Beighton nine-point scoring system, the conventional means of detecting hypermobility, assesses a patient's ability to perform five maneuvers on the right and left side of the body.

Maneuvers include passive dorsiflexion of the fifth metacarpophalangeal joint to at least 90 degrees, opposition of the thumb to the volar aspect of the ipsilateral forearm, hyperextension of the elbow to at least 10 degrees, hyperextension of the knee to at least 10 degrees, and the ability to place the hands flat on the floor without bending the knees.

More recently, Dr. Hakim and colleagues have developed a simple five-item questionnaire to use as an adjunct for screening individuals with diffuse or localized musculoskeletal symptoms, in whom no clear-cut degenerative or inflammatory disease can be found. (See box.) The questionnaire is 80%-85% sensitive and 80%-90% specific, Dr. Hakim said.

Caring for these patients likewise requires a multidisciplinary approach, involving the patient, a physiotherapist, an occupational therapist, a psychologist, a nurse specialist, and a physician specialist, Dr. Hakim said at the meeting, also sponsored by the International Society for Clinical Densitometry.

The goals of rehabilitation are to reassure and educate these patients; develop core stability; enhance joint stability and proprioception; restore normal mobility, which for these patients may still mean hypermobility; reverse deconditioning, by improving fitness and stamina; and develop behavioral strategies for coping and pain control.

Acute pain often responds to simple analgesics, NSAIDs, and local steroid injections. Chronic pain is more challenging to treat, in that anecdotal evidence suggests that simple analgesics are ineffective. Alternatives include serotonin/norepinephrine reuptake inhibitors, amitriptyline, tramadol, and gabapentin, Dr. Hakim said.

Cognitive behavior therapy has been shown to be helpful for improving quality of life and reducing pain and depression severity.

Physiotherapy alone does not appear effective, with JHS patients often reporting failure of this treatment.

In a study of 100 patients with back pain who participated in a rehabilitation program, Dr. Hakim and a colleague retrospectively assessed patients for JHS. Patients who had been diagnosed with JHS were then matched for age and gender with patients not diagnosed with the disorder. Although both groups showed the same ability to walk prior to rehabilitation, those with JHS showed much less improvement immediately following the program and up to 3 months afterward.

The ability to stand from a sitting position improved to a lesser extent in JHS patients, compared with those without the disorder.

However, the JHS patients had returned to baseline at 3 months' follow-up. The same was true for the ability to step up. Likewise, pain scores had not improved in the JHS group at 3 months, and those without the disorder showed marked improvement.

But physiotherapy can still be an important component of JHS treatment, he said.

The ideal program would focus on developing core and peripheral stability, improving general posture, and improving proprioception. The pace of physiotherapy should take tissue fragility into account, because injuries in JHS patients can take longer to heal, and many patients need special care to overcome their fear of movement.

JHS can involve various symptoms, all in the presence of general joint laxity.

Skin abnormalities such as excessive stretching of the skin are typical. Photos courtesy Dr. Alan J. Hakim

Five Questions Identify JHS

Can you now (or could you ever) place your hands flat on the floor without bending your knees?

Can you now (or could you ever) bend your thumb to touch your forearm?

As a child, did you amuse your friends by contorting your body into strange shapes, or could you do the splits?

As a child or teenager, did your shoulder or kneecap dislocate on more than one occasion?

Do you consider yourself double-jointed?

Source: Dr. Hakim

WASHINGTON — Methylphenidate appears to be effective and safe for the treatment of attention-deficit hyperactivity disorder in preschool-age children, according to preliminary data presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The results come from Treatment of Attention Deficit Hyperactivity Disorder in Preschool-Age Children study (PATS), sponsored by the National Institute of Mental Health.

Several studies have previously suggested that preschool-age children with ADHD would respond to and tolerate methylphenidate, and this multisite study is the first major effort aimed at directly assessing the safety and efficacy of a stimulant for attention-deficit hyperactivity disorder in children aged 3-5 years.

“The take-home message is that 85% of the children responded to the methylphenidate,” during the 5-week crossover period to determine the optimal dosing for each of the children, said study investigator Howard B. Abikoff, Ph.D., of the New York (N.Y.) University Child Study Center.

The optimal dose for each child was determined during a 5-week period. Over that period, all of the children were given a placebo or a dose of 1.25 mg, 2.5 mg, 5 mg, or 7.5 mg three times daily for 1 week each. Overall, 144 children completed this 5-week trial. Each week, a composite score of symptom severity was assigned based on parent and teacher responses to the Conners, Loney, and Milich (CLAM) Questionnaire and the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale.

Two blinded assessors were then asked to identify the best dose for each child. A full panel of all investigators decided upon the appropriate dose when the two assessors did not agree. Just over half (51%) of the children were referred to the full panel of investigators to determine the optimal dose.

Children also could be evaluated at a 10-mg dose if investigators agreed that there was a good chance that the child would have an even better response with a higher dose. This happened in 15 cases.

“First of all, we got a very significant effect per dose relative to placebo,” said Dr. Abikoff. For the 2.5-mg, 5-mg, and 7.5-mg doses, the children's composite scores were significantly lower than for placebo.

“We got small to moderate effect sizes at the intermediate doses [2.5 mg and 5 mg] and a reasonably robust effect size at the 7.5-mg dose,” Dr. Abikoff said. There was also a trend toward significantly lower scores for children in the 1.25-mg group.

After the 5-week crossover period, 113 children were randomized to receive either the optimal dose (61 children) or placebo (52 children) for 4 weeks. In the analysis of this portion of the trial, all children were included even if they left the trial early, with the last observation for that child carried through.

In the second portion of the study, a statistically significant difference was found in the composite scores—1.79 points for those in the placebo group and 1.49 points for those receiving the optimum dose of methylphenidate. “The effect sizes are linear from 1.25 mg up to 7.5 mg. … The effect size for 10 mg was somewhat lower,” said Dr. Abikoff.

Over the course of the trial there were 39 adverse events, including difficulty falling asleep, decreased appetite, emotional outbursts, and stomach discomfort.

Safety was a significant concern, given the age group involved. The researchers worked closely with the Food and Drug Administration in designing the trial to ensure safety. In fact, the original study design was altered to account for the concern that children in this age group might be uniquely sensitive to stimulants and have a number of adverse events. Originally, the lowest dose of methylphenidate was planned to be 2.5 mg three times a day, but the dose was lowered to 1.25 mg three times daily to ease FDA concerns about adverse reactions.

There was also a 40-week open-label maintenance phase, with children receiving a mean total daily dose of 14 mg. During this phase, the child was given the dose that the clinician thought was appropriate. “What's interesting is that we see a noticeable increase of 23% in absolute dose,” Dr. Abikoff said.

At the end of this maintenance period, the optimal dose had increased to 20 mg/day. This suggests “the doses used here were a bit low in terms of clinical optimization,” he said.

WASHINGTON — Methylphenidate appears to be effective and safe for the treatment of attention-deficit hyperactivity disorder in preschool-age children, according to preliminary data presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The results come from Treatment of Attention Deficit Hyperactivity Disorder in Preschool-Age Children study (PATS), sponsored by the National Institute of Mental Health.

Several studies have previously suggested that preschool-age children with ADHD would respond to and tolerate methylphenidate, and this multisite study is the first major effort aimed at directly assessing the safety and efficacy of a stimulant for attention-deficit hyperactivity disorder in children aged 3-5 years.

“The take-home message is that 85% of the children responded to the methylphenidate,” during the 5-week crossover period to determine the optimal dosing for each of the children, said study investigator Howard B. Abikoff, Ph.D., of the New York (N.Y.) University Child Study Center.

The optimal dose for each child was determined during a 5-week period. Over that period, all of the children were given a placebo or a dose of 1.25 mg, 2.5 mg, 5 mg, or 7.5 mg three times daily for 1 week each. Overall, 144 children completed this 5-week trial. Each week, a composite score of symptom severity was assigned based on parent and teacher responses to the Conners, Loney, and Milich (CLAM) Questionnaire and the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale.

Two blinded assessors were then asked to identify the best dose for each child. A full panel of all investigators decided upon the appropriate dose when the two assessors did not agree. Just over half (51%) of the children were referred to the full panel of investigators to determine the optimal dose.

Children also could be evaluated at a 10-mg dose if investigators agreed that there was a good chance that the child would have an even better response with a higher dose. This happened in 15 cases.

“First of all, we got a very significant effect per dose relative to placebo,” said Dr. Abikoff. For the 2.5-mg, 5-mg, and 7.5-mg doses, the children's composite scores were significantly lower than for placebo.

“We got small to moderate effect sizes at the intermediate doses [2.5 mg and 5 mg] and a reasonably robust effect size at the 7.5-mg dose,” Dr. Abikoff said. There was also a trend toward significantly lower scores for children in the 1.25-mg group.

After the 5-week crossover period, 113 children were randomized to receive either the optimal dose (61 children) or placebo (52 children) for 4 weeks. In the analysis of this portion of the trial, all children were included even if they left the trial early, with the last observation for that child carried through.

In the second portion of the study, a statistically significant difference was found in the composite scores—1.79 points for those in the placebo group and 1.49 points for those receiving the optimum dose of methylphenidate. “The effect sizes are linear from 1.25 mg up to 7.5 mg. … The effect size for 10 mg was somewhat lower,” said Dr. Abikoff.

Over the course of the trial there were 39 adverse events, including difficulty falling asleep, decreased appetite, emotional outbursts, and stomach discomfort.

Safety was a significant concern, given the age group involved. The researchers worked closely with the Food and Drug Administration in designing the trial to ensure safety. In fact, the original study design was altered to account for the concern that children in this age group might be uniquely sensitive to stimulants and have a number of adverse events. Originally, the lowest dose of methylphenidate was planned to be 2.5 mg three times a day, but the dose was lowered to 1.25 mg three times daily to ease FDA concerns about adverse reactions.

There was also a 40-week open-label maintenance phase, with children receiving a mean total daily dose of 14 mg. During this phase, the child was given the dose that the clinician thought was appropriate. “What's interesting is that we see a noticeable increase of 23% in absolute dose,” Dr. Abikoff said.

At the end of this maintenance period, the optimal dose had increased to 20 mg/day. This suggests “the doses used here were a bit low in terms of clinical optimization,” he said.

WASHINGTON — Methylphenidate appears to be effective and safe for the treatment of attention-deficit hyperactivity disorder in preschool-age children, according to preliminary data presented at the annual meeting of the American Academy of Child and Adolescent Psychiatry.

The results come from Treatment of Attention Deficit Hyperactivity Disorder in Preschool-Age Children study (PATS), sponsored by the National Institute of Mental Health.

Several studies have previously suggested that preschool-age children with ADHD would respond to and tolerate methylphenidate, and this multisite study is the first major effort aimed at directly assessing the safety and efficacy of a stimulant for attention-deficit hyperactivity disorder in children aged 3-5 years.

“The take-home message is that 85% of the children responded to the methylphenidate,” during the 5-week crossover period to determine the optimal dosing for each of the children, said study investigator Howard B. Abikoff, Ph.D., of the New York (N.Y.) University Child Study Center.

The optimal dose for each child was determined during a 5-week period. Over that period, all of the children were given a placebo or a dose of 1.25 mg, 2.5 mg, 5 mg, or 7.5 mg three times daily for 1 week each. Overall, 144 children completed this 5-week trial. Each week, a composite score of symptom severity was assigned based on parent and teacher responses to the Conners, Loney, and Milich (CLAM) Questionnaire and the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) rating scale.

Two blinded assessors were then asked to identify the best dose for each child. A full panel of all investigators decided upon the appropriate dose when the two assessors did not agree. Just over half (51%) of the children were referred to the full panel of investigators to determine the optimal dose.

Children also could be evaluated at a 10-mg dose if investigators agreed that there was a good chance that the child would have an even better response with a higher dose. This happened in 15 cases.

“First of all, we got a very significant effect per dose relative to placebo,” said Dr. Abikoff. For the 2.5-mg, 5-mg, and 7.5-mg doses, the children's composite scores were significantly lower than for placebo.

“We got small to moderate effect sizes at the intermediate doses [2.5 mg and 5 mg] and a reasonably robust effect size at the 7.5-mg dose,” Dr. Abikoff said. There was also a trend toward significantly lower scores for children in the 1.25-mg group.

After the 5-week crossover period, 113 children were randomized to receive either the optimal dose (61 children) or placebo (52 children) for 4 weeks. In the analysis of this portion of the trial, all children were included even if they left the trial early, with the last observation for that child carried through.

In the second portion of the study, a statistically significant difference was found in the composite scores—1.79 points for those in the placebo group and 1.49 points for those receiving the optimum dose of methylphenidate. “The effect sizes are linear from 1.25 mg up to 7.5 mg. … The effect size for 10 mg was somewhat lower,” said Dr. Abikoff.

Over the course of the trial there were 39 adverse events, including difficulty falling asleep, decreased appetite, emotional outbursts, and stomach discomfort.

Safety was a significant concern, given the age group involved. The researchers worked closely with the Food and Drug Administration in designing the trial to ensure safety. In fact, the original study design was altered to account for the concern that children in this age group might be uniquely sensitive to stimulants and have a number of adverse events. Originally, the lowest dose of methylphenidate was planned to be 2.5 mg three times a day, but the dose was lowered to 1.25 mg three times daily to ease FDA concerns about adverse reactions.

There was also a 40-week open-label maintenance phase, with children receiving a mean total daily dose of 14 mg. During this phase, the child was given the dose that the clinician thought was appropriate. “What's interesting is that we see a noticeable increase of 23% in absolute dose,” Dr. Abikoff said.

At the end of this maintenance period, the optimal dose had increased to 20 mg/day. This suggests “the doses used here were a bit low in terms of clinical optimization,” he said.

WASHINGTON – Chronic benzodiazepine use by the elderly does not necessarily lead to an increased risk of death, hospital readmission, institutionalization, or functional decline, Christophe J. Bula, M.D., said at the annual meeting of the Gerontological Society of America.

Dr. Bula of Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his colleagues studied 304 patients admitted from the emergency department to the internal medicine department of an academic hospital over a 6-month period.

They found that the patients who were chronic users of benzodiazepines were no more likely to die, to be readmitted to the hospital, to be admitted to a nursing home, or to experience functional decline than were the nonchronic users.

Patients were included in the study if they were 75 years or older, lived in the community, had a hospital stay of at least 12 hours, and had basic insurance. At baseline, patients underwent a bedside interview and a geriatric assessment–including cognitive, affective, and physical components–by a trained research nurse. Utilization data (hospital and nursing home admissions) were obtained from the state centralized billing office records.

The patients were followed with a phone interview at 3 months and a home visit at 6 months. The home visit involved the same interview and assessment as at baseline, Dr. Bula said.

For this study, benzodiazepines included any drug from groups N05B (anxiolytics) and N05C (hypnotics and sedatives) of the Anatomical Therapeutic Chemical classification system. Chronic use was defined as self-reported use at least three times per week in the previous month. The validity of this definition was assessed in a small subgroup by repeating the drug use portion of the interview and by urine analysis. Both showed good agreement.

Almost half (45%) of the patients were chronic users of benzodiazepines. Following multivariate analysis, chronic users were more likely to be women (OR 2.4), to have a high school education (OR 1.9), to have in-home help (OR 2.3), and to have depressive symptoms (OR 1.7).

“We think that the baseline differences between chronic benzodiazepine users and the others suggest a strong prescribing bias, where practitioners seem to avoid prescribing benzodiazepines to the frailest elderly,” Dr. Bula said at the meeting.

Interestingly, chronic users were more likely to improve their cognitive performance at 6 months (adjusted OR 2.4). Improved cognition among chronic users suggests a temporary impairment in cognitive performance at hospitalization, he said.

“This could be consistent with what we know about the increased risk of chronic users to become delirious when they are hospitalized,” he noted.

WASHINGTON – Chronic benzodiazepine use by the elderly does not necessarily lead to an increased risk of death, hospital readmission, institutionalization, or functional decline, Christophe J. Bula, M.D., said at the annual meeting of the Gerontological Society of America.

Dr. Bula of Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his colleagues studied 304 patients admitted from the emergency department to the internal medicine department of an academic hospital over a 6-month period.

They found that the patients who were chronic users of benzodiazepines were no more likely to die, to be readmitted to the hospital, to be admitted to a nursing home, or to experience functional decline than were the nonchronic users.

Patients were included in the study if they were 75 years or older, lived in the community, had a hospital stay of at least 12 hours, and had basic insurance. At baseline, patients underwent a bedside interview and a geriatric assessment–including cognitive, affective, and physical components–by a trained research nurse. Utilization data (hospital and nursing home admissions) were obtained from the state centralized billing office records.

The patients were followed with a phone interview at 3 months and a home visit at 6 months. The home visit involved the same interview and assessment as at baseline, Dr. Bula said.

For this study, benzodiazepines included any drug from groups N05B (anxiolytics) and N05C (hypnotics and sedatives) of the Anatomical Therapeutic Chemical classification system. Chronic use was defined as self-reported use at least three times per week in the previous month. The validity of this definition was assessed in a small subgroup by repeating the drug use portion of the interview and by urine analysis. Both showed good agreement.

Almost half (45%) of the patients were chronic users of benzodiazepines. Following multivariate analysis, chronic users were more likely to be women (OR 2.4), to have a high school education (OR 1.9), to have in-home help (OR 2.3), and to have depressive symptoms (OR 1.7).

“We think that the baseline differences between chronic benzodiazepine users and the others suggest a strong prescribing bias, where practitioners seem to avoid prescribing benzodiazepines to the frailest elderly,” Dr. Bula said at the meeting.

Interestingly, chronic users were more likely to improve their cognitive performance at 6 months (adjusted OR 2.4). Improved cognition among chronic users suggests a temporary impairment in cognitive performance at hospitalization, he said.

“This could be consistent with what we know about the increased risk of chronic users to become delirious when they are hospitalized,” he noted.

WASHINGTON – Chronic benzodiazepine use by the elderly does not necessarily lead to an increased risk of death, hospital readmission, institutionalization, or functional decline, Christophe J. Bula, M.D., said at the annual meeting of the Gerontological Society of America.

Dr. Bula of Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, and his colleagues studied 304 patients admitted from the emergency department to the internal medicine department of an academic hospital over a 6-month period.

They found that the patients who were chronic users of benzodiazepines were no more likely to die, to be readmitted to the hospital, to be admitted to a nursing home, or to experience functional decline than were the nonchronic users.

Patients were included in the study if they were 75 years or older, lived in the community, had a hospital stay of at least 12 hours, and had basic insurance. At baseline, patients underwent a bedside interview and a geriatric assessment–including cognitive, affective, and physical components–by a trained research nurse. Utilization data (hospital and nursing home admissions) were obtained from the state centralized billing office records.

The patients were followed with a phone interview at 3 months and a home visit at 6 months. The home visit involved the same interview and assessment as at baseline, Dr. Bula said.

For this study, benzodiazepines included any drug from groups N05B (anxiolytics) and N05C (hypnotics and sedatives) of the Anatomical Therapeutic Chemical classification system. Chronic use was defined as self-reported use at least three times per week in the previous month. The validity of this definition was assessed in a small subgroup by repeating the drug use portion of the interview and by urine analysis. Both showed good agreement.

Almost half (45%) of the patients were chronic users of benzodiazepines. Following multivariate analysis, chronic users were more likely to be women (OR 2.4), to have a high school education (OR 1.9), to have in-home help (OR 2.3), and to have depressive symptoms (OR 1.7).

“We think that the baseline differences between chronic benzodiazepine users and the others suggest a strong prescribing bias, where practitioners seem to avoid prescribing benzodiazepines to the frailest elderly,” Dr. Bula said at the meeting.

Interestingly, chronic users were more likely to improve their cognitive performance at 6 months (adjusted OR 2.4). Improved cognition among chronic users suggests a temporary impairment in cognitive performance at hospitalization, he said.

“This could be consistent with what we know about the increased risk of chronic users to become delirious when they are hospitalized,” he noted.