Sherry Boschert

The Food and Drug Administration has backed off from a warning letter it sent to several manufacturers and decided to allow an unapproved version of high-concentrate morphine sulfate oral solution to remain on the market.

Objections from pain specialists, hospice workers, and patients convinced the FDA that there is no good alternative for some patients who need the immediate-release morphine sulfate oral concentrate solution 20 mg/mL for pain control, Dr. Douglas Throckmorton of the FDA's Center for Drug Evaluation and Research said at a press briefing.

The decision will benefit patients at the end of their lives who cannot easily be administered opiates intravenously or through other routes and cannot swallow well. They may need a high morphine dose—several hundred milligrams—and an approved, less-concentrated morphine sulfate elixir would require a large volume of liquid, putting them at risk of aspirating the liquid.

As part of an ongoing crackdown on unapproved drugs in the United States, the FDA on March 30 had written to nine companies warning them to stop making and marketing 14 unapproved narcotic products, believing that acceptable alternatives were available.

The March 30 action alarmed members of four organizations in the Palliative Care Coalition, whose leaders communicate regularly and who quickly drafted a letter apprising the FDA of the medical necessity for the concentrated morphine elixir.

In addition to use in patients near the end of life, the elixir is used to manage pain in “patients who are not dying but [are] going through very traumatic treatment for head and neck cancer, which is likely to be curative but very difficult to get through,” Dr. Diane E. Meier said in an interview. She is director of the Center to Advance Palliative Care at Mount Sinai School of Medicine, New York. The Palliative Care Coalition consists of her organization and the American Academy of Hospice and Palliative Medicine, the Hospice and Palliative Nurses Association, and the National Hospice and Palliative Care Organization.

In response to the outcry, the FDA sent follow-up letters on April 9 to six companies that offer the concentrated morphine sulfate elixir, saying they could continue to market the drug formulation. This should especially help some patients in hospitals and hospices, Dr. Throckmorton acknowledged.

“Both those populations sometimes experience severe pain at the end of life and want to be able to be managed at their homes whenever possible. The use of this elixir enables that,” he said. “That's an important part of the decision that we made today.”

The reversal surprised and delighted observers. “I don't think we expected a response” from the FDA to the coalition's letter, Dr. Meier said, “so to get one was really gratifying and made us very optimistic that this will be the beginning of an effective professional dialogue.”

Mike Cohen, president of the nonprofit Institute for Safe Medication Practices in Horsham, Pa., commented on Twitter.com

The concentrated morphine elixir products were marketed before the 1938 Federal Food, Drug, and Cosmetic Act regulations took effect, and were allowed on the market without formal approval under a grandfather clause. The FDA today believes few drugs are entitled to grandfather status, Mr. Cohen wrote in the institute's April 9 newsletter.

The FDA is willing to fast-track an approval application from any company for the concentrated morphine sulfate elixir, Dr. Throckmorton said. If one gets approved, any companies making unapproved versions will have 180 days to cease manufacturing and marketing their formulations. Until one is approved, however, they can continue to supply the product.

The other unapproved drugs that were targeted in the original warning on March 30 must still be taken off the market within 90 days. These include immediate-release hydromorphone and oxycodone tablets. Failure to comply could result in seizure of these drugs.

Dr. Meier says the coalition remains concerned about those drugs being taken off the market, too. “There is a nationwide shortage of opioids,” she said. “In New York City you can't find many of these drugs, even before this shutdown has taken place. My colleagues report this to be true across the country.”

Dr. Meier and others planned to participate in an invitation-only meeting with FDA officials on May 4 to discuss Risk Evaluation and Mitigation Strategies (REMS) for drugs including opioids. Coalition members are concerned that REMS requirements could further decrease patient access to pain medications, but are hoping that the flexibility shown by the FDA regarding the morphine elixir bode well for future talks.

“I found the responsiveness and timeliness of the FDA to be really wonderful. It reinforced the FDA's obligation to not only reduce harm but [also] to ensure access to beneficial medications,” Dr. Meier said.

The companies that received the April 9 letter allowing them to continue offering morphine sulfate oral solution 20 mg/mL are Lannett Co., Lehigh Valley Technologies, Mallinckrodt Inc. Pharmaceuticals Group, Xanodyne Pharmaceuticals Inc., Boehringer Ingelheim Roxane Inc., and Cody Laboratories Inc.

'I found the responsiveness and timeliness of the FDA to be really wonderful.' DR. MEIER

The Food and Drug Administration has backed off from a warning letter it sent to several manufacturers and decided to allow an unapproved version of high-concentrate morphine sulfate oral solution to remain on the market.

Objections from pain specialists, hospice workers, and patients convinced the FDA that there is no good alternative for some patients who need the immediate-release morphine sulfate oral concentrate solution 20 mg/mL for pain control, Dr. Douglas Throckmorton of the FDA's Center for Drug Evaluation and Research said at a press briefing.

The decision will benefit patients at the end of their lives who cannot easily be administered opiates intravenously or through other routes and cannot swallow well. They may need a high morphine dose—several hundred milligrams—and an approved, less-concentrated morphine sulfate elixir would require a large volume of liquid, putting them at risk of aspirating the liquid.

As part of an ongoing crackdown on unapproved drugs in the United States, the FDA on March 30 had written to nine companies warning them to stop making and marketing 14 unapproved narcotic products, believing that acceptable alternatives were available.

The March 30 action alarmed members of four organizations in the Palliative Care Coalition, whose leaders communicate regularly and who quickly drafted a letter apprising the FDA of the medical necessity for the concentrated morphine elixir.

In addition to use in patients near the end of life, the elixir is used to manage pain in “patients who are not dying but [are] going through very traumatic treatment for head and neck cancer, which is likely to be curative but very difficult to get through,” Dr. Diane E. Meier said in an interview. She is director of the Center to Advance Palliative Care at Mount Sinai School of Medicine, New York. The Palliative Care Coalition consists of her organization and the American Academy of Hospice and Palliative Medicine, the Hospice and Palliative Nurses Association, and the National Hospice and Palliative Care Organization.

In response to the outcry, the FDA sent follow-up letters on April 9 to six companies that offer the concentrated morphine sulfate elixir, saying they could continue to market the drug formulation. This should especially help some patients in hospitals and hospices, Dr. Throckmorton acknowledged.

“Both those populations sometimes experience severe pain at the end of life and want to be able to be managed at their homes whenever possible. The use of this elixir enables that,” he said. “That's an important part of the decision that we made today.”

The reversal surprised and delighted observers. “I don't think we expected a response” from the FDA to the coalition's letter, Dr. Meier said, “so to get one was really gratifying and made us very optimistic that this will be the beginning of an effective professional dialogue.”

Mike Cohen, president of the nonprofit Institute for Safe Medication Practices in Horsham, Pa., commented on Twitter.com

The concentrated morphine elixir products were marketed before the 1938 Federal Food, Drug, and Cosmetic Act regulations took effect, and were allowed on the market without formal approval under a grandfather clause. The FDA today believes few drugs are entitled to grandfather status, Mr. Cohen wrote in the institute's April 9 newsletter.

The FDA is willing to fast-track an approval application from any company for the concentrated morphine sulfate elixir, Dr. Throckmorton said. If one gets approved, any companies making unapproved versions will have 180 days to cease manufacturing and marketing their formulations. Until one is approved, however, they can continue to supply the product.

The other unapproved drugs that were targeted in the original warning on March 30 must still be taken off the market within 90 days. These include immediate-release hydromorphone and oxycodone tablets. Failure to comply could result in seizure of these drugs.

Dr. Meier says the coalition remains concerned about those drugs being taken off the market, too. “There is a nationwide shortage of opioids,” she said. “In New York City you can't find many of these drugs, even before this shutdown has taken place. My colleagues report this to be true across the country.”

Dr. Meier and others planned to participate in an invitation-only meeting with FDA officials on May 4 to discuss Risk Evaluation and Mitigation Strategies (REMS) for drugs including opioids. Coalition members are concerned that REMS requirements could further decrease patient access to pain medications, but are hoping that the flexibility shown by the FDA regarding the morphine elixir bode well for future talks.

“I found the responsiveness and timeliness of the FDA to be really wonderful. It reinforced the FDA's obligation to not only reduce harm but [also] to ensure access to beneficial medications,” Dr. Meier said.

The companies that received the April 9 letter allowing them to continue offering morphine sulfate oral solution 20 mg/mL are Lannett Co., Lehigh Valley Technologies, Mallinckrodt Inc. Pharmaceuticals Group, Xanodyne Pharmaceuticals Inc., Boehringer Ingelheim Roxane Inc., and Cody Laboratories Inc.

'I found the responsiveness and timeliness of the FDA to be really wonderful.' DR. MEIER

The Food and Drug Administration has backed off from a warning letter it sent to several manufacturers and decided to allow an unapproved version of high-concentrate morphine sulfate oral solution to remain on the market.

Objections from pain specialists, hospice workers, and patients convinced the FDA that there is no good alternative for some patients who need the immediate-release morphine sulfate oral concentrate solution 20 mg/mL for pain control, Dr. Douglas Throckmorton of the FDA's Center for Drug Evaluation and Research said at a press briefing.

The decision will benefit patients at the end of their lives who cannot easily be administered opiates intravenously or through other routes and cannot swallow well. They may need a high morphine dose—several hundred milligrams—and an approved, less-concentrated morphine sulfate elixir would require a large volume of liquid, putting them at risk of aspirating the liquid.

As part of an ongoing crackdown on unapproved drugs in the United States, the FDA on March 30 had written to nine companies warning them to stop making and marketing 14 unapproved narcotic products, believing that acceptable alternatives were available.

The March 30 action alarmed members of four organizations in the Palliative Care Coalition, whose leaders communicate regularly and who quickly drafted a letter apprising the FDA of the medical necessity for the concentrated morphine elixir.

In addition to use in patients near the end of life, the elixir is used to manage pain in “patients who are not dying but [are] going through very traumatic treatment for head and neck cancer, which is likely to be curative but very difficult to get through,” Dr. Diane E. Meier said in an interview. She is director of the Center to Advance Palliative Care at Mount Sinai School of Medicine, New York. The Palliative Care Coalition consists of her organization and the American Academy of Hospice and Palliative Medicine, the Hospice and Palliative Nurses Association, and the National Hospice and Palliative Care Organization.

In response to the outcry, the FDA sent follow-up letters on April 9 to six companies that offer the concentrated morphine sulfate elixir, saying they could continue to market the drug formulation. This should especially help some patients in hospitals and hospices, Dr. Throckmorton acknowledged.

“Both those populations sometimes experience severe pain at the end of life and want to be able to be managed at their homes whenever possible. The use of this elixir enables that,” he said. “That's an important part of the decision that we made today.”

The reversal surprised and delighted observers. “I don't think we expected a response” from the FDA to the coalition's letter, Dr. Meier said, “so to get one was really gratifying and made us very optimistic that this will be the beginning of an effective professional dialogue.”

Mike Cohen, president of the nonprofit Institute for Safe Medication Practices in Horsham, Pa., commented on Twitter.com

The concentrated morphine elixir products were marketed before the 1938 Federal Food, Drug, and Cosmetic Act regulations took effect, and were allowed on the market without formal approval under a grandfather clause. The FDA today believes few drugs are entitled to grandfather status, Mr. Cohen wrote in the institute's April 9 newsletter.

The FDA is willing to fast-track an approval application from any company for the concentrated morphine sulfate elixir, Dr. Throckmorton said. If one gets approved, any companies making unapproved versions will have 180 days to cease manufacturing and marketing their formulations. Until one is approved, however, they can continue to supply the product.

The other unapproved drugs that were targeted in the original warning on March 30 must still be taken off the market within 90 days. These include immediate-release hydromorphone and oxycodone tablets. Failure to comply could result in seizure of these drugs.

Dr. Meier says the coalition remains concerned about those drugs being taken off the market, too. “There is a nationwide shortage of opioids,” she said. “In New York City you can't find many of these drugs, even before this shutdown has taken place. My colleagues report this to be true across the country.”

Dr. Meier and others planned to participate in an invitation-only meeting with FDA officials on May 4 to discuss Risk Evaluation and Mitigation Strategies (REMS) for drugs including opioids. Coalition members are concerned that REMS requirements could further decrease patient access to pain medications, but are hoping that the flexibility shown by the FDA regarding the morphine elixir bode well for future talks.

“I found the responsiveness and timeliness of the FDA to be really wonderful. It reinforced the FDA's obligation to not only reduce harm but [also] to ensure access to beneficial medications,” Dr. Meier said.

The companies that received the April 9 letter allowing them to continue offering morphine sulfate oral solution 20 mg/mL are Lannett Co., Lehigh Valley Technologies, Mallinckrodt Inc. Pharmaceuticals Group, Xanodyne Pharmaceuticals Inc., Boehringer Ingelheim Roxane Inc., and Cody Laboratories Inc.

'I found the responsiveness and timeliness of the FDA to be really wonderful.' DR. MEIER

SAN FRANCISCO — A study of 156 patients with systemic sclerosis in two European cities found that vitamin D deficiency was common, present in 28%.

Deficient levels of serum 25-hydroxyvitamin D (25[OH]D)—less than 10 ng/mL—were seen in 29 (32%) of 90 patients in Paris and 15 (23%) of 66 in southern Italy, Dr. Alessandra Vacca and her associates reported in a poster presentation at the annual meeting of the American College of Rheumatology. In addition, 84% of all patients had insufficient vitamin D levels (less than 30 ng/mL), seen in 75 (82%) of the Parisians and 57 (86%) of the Italians.

Overall, patients had a mean age of 57 years, and 97% were female. The mean vitamin D value in the two cohorts was 19 ng/mL, said Dr. Vacca of the University of Cagliari.

The rates of vitamin D deficiency did not differ significantly between cities and so were independent of the different UV radiation levels in the northern and southern cities. Rates of vitamin D deficiency also were independent of usual levels of vitamin D supplementation (800 IU/day), taken by 30% of Parisian patients and 45% of Italian patients.

Because conventional doses of vitamin D supplementation did not prevent vitamin D deficiency, higher-dose supplementation may be needed in patients with systemic sclerosis, especially those with inflammatory activity, she said.

Low vitamin D levels were associated with pulmonary fibrosis (P = .04), systolic pulmonary arterial hypertension (P = .004), and inflammatory activity indicated by acute phase reactants—erythrocyte sedimentation rate (P = .004) and C-reactive protein values (P = .01). There was a significant negative correlation between low vitamin D levels and European disease activity scores (P = −0.04). A mild negative association was seen between vitamin D deficiency and anticentromere antibodies.

Low vitamin D levels may be linked to multiple risk factors, Dr. Vacca suggested, including scarce sun exposure due to disability, insufficient intake and malabsorption of vitamin D due to gastroenteric involvement, or use of drugs that can alter metabolism of vitamin D. There was no association between vitamin D deficiency and other markers of impaired malabsorption such as hemoglobin, ferritin, or albuminemia. No associations were found between vitamin D deficiency and acro-osteolysis, calcinosis, or Medsger's disease severity score.

The investigators reported no conflicts of interest related to this study.

SAN FRANCISCO — A study of 156 patients with systemic sclerosis in two European cities found that vitamin D deficiency was common, present in 28%.

Deficient levels of serum 25-hydroxyvitamin D (25[OH]D)—less than 10 ng/mL—were seen in 29 (32%) of 90 patients in Paris and 15 (23%) of 66 in southern Italy, Dr. Alessandra Vacca and her associates reported in a poster presentation at the annual meeting of the American College of Rheumatology. In addition, 84% of all patients had insufficient vitamin D levels (less than 30 ng/mL), seen in 75 (82%) of the Parisians and 57 (86%) of the Italians.

Overall, patients had a mean age of 57 years, and 97% were female. The mean vitamin D value in the two cohorts was 19 ng/mL, said Dr. Vacca of the University of Cagliari.

The rates of vitamin D deficiency did not differ significantly between cities and so were independent of the different UV radiation levels in the northern and southern cities. Rates of vitamin D deficiency also were independent of usual levels of vitamin D supplementation (800 IU/day), taken by 30% of Parisian patients and 45% of Italian patients.

Because conventional doses of vitamin D supplementation did not prevent vitamin D deficiency, higher-dose supplementation may be needed in patients with systemic sclerosis, especially those with inflammatory activity, she said.

Low vitamin D levels were associated with pulmonary fibrosis (P = .04), systolic pulmonary arterial hypertension (P = .004), and inflammatory activity indicated by acute phase reactants—erythrocyte sedimentation rate (P = .004) and C-reactive protein values (P = .01). There was a significant negative correlation between low vitamin D levels and European disease activity scores (P = −0.04). A mild negative association was seen between vitamin D deficiency and anticentromere antibodies.

Low vitamin D levels may be linked to multiple risk factors, Dr. Vacca suggested, including scarce sun exposure due to disability, insufficient intake and malabsorption of vitamin D due to gastroenteric involvement, or use of drugs that can alter metabolism of vitamin D. There was no association between vitamin D deficiency and other markers of impaired malabsorption such as hemoglobin, ferritin, or albuminemia. No associations were found between vitamin D deficiency and acro-osteolysis, calcinosis, or Medsger's disease severity score.

The investigators reported no conflicts of interest related to this study.

SAN FRANCISCO — A study of 156 patients with systemic sclerosis in two European cities found that vitamin D deficiency was common, present in 28%.

Deficient levels of serum 25-hydroxyvitamin D (25[OH]D)—less than 10 ng/mL—were seen in 29 (32%) of 90 patients in Paris and 15 (23%) of 66 in southern Italy, Dr. Alessandra Vacca and her associates reported in a poster presentation at the annual meeting of the American College of Rheumatology. In addition, 84% of all patients had insufficient vitamin D levels (less than 30 ng/mL), seen in 75 (82%) of the Parisians and 57 (86%) of the Italians.

Overall, patients had a mean age of 57 years, and 97% were female. The mean vitamin D value in the two cohorts was 19 ng/mL, said Dr. Vacca of the University of Cagliari.

The rates of vitamin D deficiency did not differ significantly between cities and so were independent of the different UV radiation levels in the northern and southern cities. Rates of vitamin D deficiency also were independent of usual levels of vitamin D supplementation (800 IU/day), taken by 30% of Parisian patients and 45% of Italian patients.

Because conventional doses of vitamin D supplementation did not prevent vitamin D deficiency, higher-dose supplementation may be needed in patients with systemic sclerosis, especially those with inflammatory activity, she said.

Low vitamin D levels were associated with pulmonary fibrosis (P = .04), systolic pulmonary arterial hypertension (P = .004), and inflammatory activity indicated by acute phase reactants—erythrocyte sedimentation rate (P = .004) and C-reactive protein values (P = .01). There was a significant negative correlation between low vitamin D levels and European disease activity scores (P = −0.04). A mild negative association was seen between vitamin D deficiency and anticentromere antibodies.

Low vitamin D levels may be linked to multiple risk factors, Dr. Vacca suggested, including scarce sun exposure due to disability, insufficient intake and malabsorption of vitamin D due to gastroenteric involvement, or use of drugs that can alter metabolism of vitamin D. There was no association between vitamin D deficiency and other markers of impaired malabsorption such as hemoglobin, ferritin, or albuminemia. No associations were found between vitamin D deficiency and acro-osteolysis, calcinosis, or Medsger's disease severity score.

The investigators reported no conflicts of interest related to this study.

SAN FRANCISCO — Growth hormone therapy might help adults with a deficiency, but there's no evidence that it helps normal elderly adults or athletes.

Illegal use in antiaging clinics probably accounts for the largest use of growth hormone in the United States today, Dr. Andrew R. Hoffman said.

The therapy is indicated for adults for the treatment of growth hormone deficiency caused by pituitary disease, hypothalamic disease, surgery, radiation, or trauma. It is the only drug in the U.S. that cannot legally be prescribed off label, he said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

What's more, its use in normal elderly people may cause harm by inducing glucose intolerance or increasing the risk for cancer, “although we do not know that” for sure, said Dr. Hoffman, professor of medicine at Stanford (Calif.) University and the Veterans Affairs Palo Alto Health Care System.

Interest in treating normal age-related declines in growth hormone secretion and insulin-like growth factor 1 (IGF-1)—dubbed the “somatopause”—zoomed after a 1999 study reported that giving growth hormone injections to male veterans aged older than 60 years for 6 months increased lean tissue mass by 9%, skin thickness by 7%, and lower-back vertebral density by 2%, while decreasing fatty tissue by 14% (N. Engl. J. Med. 1990;323:1-6). The authors described the effects as equivalent in magnitude to the changes that occur during 10-20 years of aging. “This set up a lot of excitement and was the basis for all the antiaging clinics you can find,” Dr. Hoffman said.

It also generated multiple animal studies by the National Institutes of Health, every one of which showed that longevity is associated with lower growth hormone levels, not higher ones. A systematic review of randomized, controlled trials of growth hormone injections in healthy elderly humans reported small changes in body composition and high rates of adverse events (Ann. Intern. Med. 2007;146:104-15).

One of the potential side effects with growth hormone overtreatment is increased edema. “You can't say it increases muscle,” Dr. Hoffman said. “Much of it might be fluid retention.”

The medical literature suggests that treatment probably is helpful for patients with growth hormone deficiency syndrome, Dr. Hoffman said. Treatment produces significant and durable changes in cardiac effects. Bodily fat mass, LDL cholesterol, and total cholesterol levels decrease but insulin and glucose levels tend to increase.

In general, patients treated for growth hormone deficiency syndrome become more physically active, increase their strength and exercise capacity, and slightly increase bone mineral density.

Other data suggest, however, that high levels of IGF-1 over long periods of time could increase the risk for prostate cancer or premenopausal breast cancer.

Dr. Hoffman has received research support, owned stock, or been a consultant to companies that market growth hormone or related products, including Ambryx, LG Life Science, Tercica, Merck Serono, Pfizer, Novo Nordisk, and Teva Pharmaceutical Industries.

SAN FRANCISCO — Growth hormone therapy might help adults with a deficiency, but there's no evidence that it helps normal elderly adults or athletes.

Illegal use in antiaging clinics probably accounts for the largest use of growth hormone in the United States today, Dr. Andrew R. Hoffman said.

The therapy is indicated for adults for the treatment of growth hormone deficiency caused by pituitary disease, hypothalamic disease, surgery, radiation, or trauma. It is the only drug in the U.S. that cannot legally be prescribed off label, he said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

What's more, its use in normal elderly people may cause harm by inducing glucose intolerance or increasing the risk for cancer, “although we do not know that” for sure, said Dr. Hoffman, professor of medicine at Stanford (Calif.) University and the Veterans Affairs Palo Alto Health Care System.

Interest in treating normal age-related declines in growth hormone secretion and insulin-like growth factor 1 (IGF-1)—dubbed the “somatopause”—zoomed after a 1999 study reported that giving growth hormone injections to male veterans aged older than 60 years for 6 months increased lean tissue mass by 9%, skin thickness by 7%, and lower-back vertebral density by 2%, while decreasing fatty tissue by 14% (N. Engl. J. Med. 1990;323:1-6). The authors described the effects as equivalent in magnitude to the changes that occur during 10-20 years of aging. “This set up a lot of excitement and was the basis for all the antiaging clinics you can find,” Dr. Hoffman said.

It also generated multiple animal studies by the National Institutes of Health, every one of which showed that longevity is associated with lower growth hormone levels, not higher ones. A systematic review of randomized, controlled trials of growth hormone injections in healthy elderly humans reported small changes in body composition and high rates of adverse events (Ann. Intern. Med. 2007;146:104-15).

One of the potential side effects with growth hormone overtreatment is increased edema. “You can't say it increases muscle,” Dr. Hoffman said. “Much of it might be fluid retention.”

The medical literature suggests that treatment probably is helpful for patients with growth hormone deficiency syndrome, Dr. Hoffman said. Treatment produces significant and durable changes in cardiac effects. Bodily fat mass, LDL cholesterol, and total cholesterol levels decrease but insulin and glucose levels tend to increase.

In general, patients treated for growth hormone deficiency syndrome become more physically active, increase their strength and exercise capacity, and slightly increase bone mineral density.

Other data suggest, however, that high levels of IGF-1 over long periods of time could increase the risk for prostate cancer or premenopausal breast cancer.

Dr. Hoffman has received research support, owned stock, or been a consultant to companies that market growth hormone or related products, including Ambryx, LG Life Science, Tercica, Merck Serono, Pfizer, Novo Nordisk, and Teva Pharmaceutical Industries.

SAN FRANCISCO — Growth hormone therapy might help adults with a deficiency, but there's no evidence that it helps normal elderly adults or athletes.

Illegal use in antiaging clinics probably accounts for the largest use of growth hormone in the United States today, Dr. Andrew R. Hoffman said.

The therapy is indicated for adults for the treatment of growth hormone deficiency caused by pituitary disease, hypothalamic disease, surgery, radiation, or trauma. It is the only drug in the U.S. that cannot legally be prescribed off label, he said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

What's more, its use in normal elderly people may cause harm by inducing glucose intolerance or increasing the risk for cancer, “although we do not know that” for sure, said Dr. Hoffman, professor of medicine at Stanford (Calif.) University and the Veterans Affairs Palo Alto Health Care System.

Interest in treating normal age-related declines in growth hormone secretion and insulin-like growth factor 1 (IGF-1)—dubbed the “somatopause”—zoomed after a 1999 study reported that giving growth hormone injections to male veterans aged older than 60 years for 6 months increased lean tissue mass by 9%, skin thickness by 7%, and lower-back vertebral density by 2%, while decreasing fatty tissue by 14% (N. Engl. J. Med. 1990;323:1-6). The authors described the effects as equivalent in magnitude to the changes that occur during 10-20 years of aging. “This set up a lot of excitement and was the basis for all the antiaging clinics you can find,” Dr. Hoffman said.

It also generated multiple animal studies by the National Institutes of Health, every one of which showed that longevity is associated with lower growth hormone levels, not higher ones. A systematic review of randomized, controlled trials of growth hormone injections in healthy elderly humans reported small changes in body composition and high rates of adverse events (Ann. Intern. Med. 2007;146:104-15).

One of the potential side effects with growth hormone overtreatment is increased edema. “You can't say it increases muscle,” Dr. Hoffman said. “Much of it might be fluid retention.”

The medical literature suggests that treatment probably is helpful for patients with growth hormone deficiency syndrome, Dr. Hoffman said. Treatment produces significant and durable changes in cardiac effects. Bodily fat mass, LDL cholesterol, and total cholesterol levels decrease but insulin and glucose levels tend to increase.

In general, patients treated for growth hormone deficiency syndrome become more physically active, increase their strength and exercise capacity, and slightly increase bone mineral density.

Other data suggest, however, that high levels of IGF-1 over long periods of time could increase the risk for prostate cancer or premenopausal breast cancer.

Dr. Hoffman has received research support, owned stock, or been a consultant to companies that market growth hormone or related products, including Ambryx, LG Life Science, Tercica, Merck Serono, Pfizer, Novo Nordisk, and Teva Pharmaceutical Industries.

SAN FRANCISCO — Maggot debridement therapy helped clear necrotic tissue from purpura fulminans in a 9-month-old boy who was not responding to standard wound care, according to Dr. Xuan Nguyen.

Reports of maggot debridement therapy in children are scarce. This appears to be the first case of using the therapy in a child with purpura fulminans, Dr. Nguyen said at a meeting of the Society for Pediatric Dermatology.

Maggot debridement therapy—also called biosurgery—was used in the United States in the 1930s and 1940s and reintroduced into medical practice in the 1980s and 1990s. In 2004, the Food and Drug Administration approved the production and marketing of medical maggots for debridement of nonhealing necrotic skin and soft tissue wounds, pressure ulcers, venous stasis ulcers, neuropathic foot ulcers, and nonhealing traumatic or postsurgical wounds.

Although purpura fulminans is not a specific indication, it is a chronic wound infection that seems amenable to maggot debridement therapy, she said.

The previously healthy boy presented to the Phoenix Children's Hospital with mottled skin 24 hours after receiving immunizations. He developed Staphylococcus aureus septicemia that led to extensive purpura fulminans, a diffuse necrosis of the skin and subcutaneous tissue secondary to microvascular thrombosis from transient protein C deficiency. All four extremities and some other areas became necrotic.

Conventional wound management using Dakin's solution, Vaseline petroleum gauze dressing over the ecchymotic wounds, Kerlix wraps, and daily wound dressing changes was applied as some of the wounds and mummified regions started to demarcate. Wounds on the face healed relatively well, but the lower extremities of the patient, in particular, had trouble healing. One patella was exposed after the rotting lower leg slid off, said Dr. Nguyen, a pediatric dermatologist at the hospital.

Dr. Nguyen and her associates applied five rounds (lasting 4-5 days each) of maggot debridement therapy combined with adjunctive daily whirlpool baths to which bleach was added. After five rounds of maggot treatment, whirlpool baths were scheduled three times per week as maintenance.

Maggot therapy serves three functions: It debrides necrotic tissue, acts as an antimicrobial therapy, and stimulates wound healing. Maggots like a moist environment and are relatively contraindicated in dry wounds. “We try not to use them in open wounds of body cavities, because the maggots get lost” when it is time to remove them, she said.

The maggots, which are larvae of the greenbottle blowfly (Lucilia sericata), are applied when 1-2 mm in size and grow to 10 mm after 4-5 days, when they are removed from the wound. The maggots ingest nothing but necrotic tissue, and 200 maggots can consume up to 15 g/day. Mouth hooks on their front ends rake in decaying flesh, making them remarkable eating machines.

The maggots secrete proteolytic enzymes including collagenase, trypsinlike enzymes, and chymotrypsinlike enzymes that facilitate wound healing. Their activity disrupts tissue planes only minimally, and some of their secretions inhibit gram-positive and gram-negative bacteria.

Sterile maggots on gauze were tied over the boy's leg wounds and covered with a Kerlix wrap, netting, and a stocking to keep the maggots in the wound. The boy is healing after amputation of his hands and feet, maggot debridement therapy, and use of maintenance baths, Dr. Nguyen said.

Information about conflicts of interest could not be obtained by press time.

SAN FRANCISCO — Maggot debridement therapy helped clear necrotic tissue from purpura fulminans in a 9-month-old boy who was not responding to standard wound care, according to Dr. Xuan Nguyen.

Reports of maggot debridement therapy in children are scarce. This appears to be the first case of using the therapy in a child with purpura fulminans, Dr. Nguyen said at a meeting of the Society for Pediatric Dermatology.

Maggot debridement therapy—also called biosurgery—was used in the United States in the 1930s and 1940s and reintroduced into medical practice in the 1980s and 1990s. In 2004, the Food and Drug Administration approved the production and marketing of medical maggots for debridement of nonhealing necrotic skin and soft tissue wounds, pressure ulcers, venous stasis ulcers, neuropathic foot ulcers, and nonhealing traumatic or postsurgical wounds.

Although purpura fulminans is not a specific indication, it is a chronic wound infection that seems amenable to maggot debridement therapy, she said.

The previously healthy boy presented to the Phoenix Children's Hospital with mottled skin 24 hours after receiving immunizations. He developed Staphylococcus aureus septicemia that led to extensive purpura fulminans, a diffuse necrosis of the skin and subcutaneous tissue secondary to microvascular thrombosis from transient protein C deficiency. All four extremities and some other areas became necrotic.

Conventional wound management using Dakin's solution, Vaseline petroleum gauze dressing over the ecchymotic wounds, Kerlix wraps, and daily wound dressing changes was applied as some of the wounds and mummified regions started to demarcate. Wounds on the face healed relatively well, but the lower extremities of the patient, in particular, had trouble healing. One patella was exposed after the rotting lower leg slid off, said Dr. Nguyen, a pediatric dermatologist at the hospital.

Dr. Nguyen and her associates applied five rounds (lasting 4-5 days each) of maggot debridement therapy combined with adjunctive daily whirlpool baths to which bleach was added. After five rounds of maggot treatment, whirlpool baths were scheduled three times per week as maintenance.

Maggot therapy serves three functions: It debrides necrotic tissue, acts as an antimicrobial therapy, and stimulates wound healing. Maggots like a moist environment and are relatively contraindicated in dry wounds. “We try not to use them in open wounds of body cavities, because the maggots get lost” when it is time to remove them, she said.

The maggots, which are larvae of the greenbottle blowfly (Lucilia sericata), are applied when 1-2 mm in size and grow to 10 mm after 4-5 days, when they are removed from the wound. The maggots ingest nothing but necrotic tissue, and 200 maggots can consume up to 15 g/day. Mouth hooks on their front ends rake in decaying flesh, making them remarkable eating machines.

The maggots secrete proteolytic enzymes including collagenase, trypsinlike enzymes, and chymotrypsinlike enzymes that facilitate wound healing. Their activity disrupts tissue planes only minimally, and some of their secretions inhibit gram-positive and gram-negative bacteria.

Sterile maggots on gauze were tied over the boy's leg wounds and covered with a Kerlix wrap, netting, and a stocking to keep the maggots in the wound. The boy is healing after amputation of his hands and feet, maggot debridement therapy, and use of maintenance baths, Dr. Nguyen said.

Information about conflicts of interest could not be obtained by press time.

SAN FRANCISCO — Maggot debridement therapy helped clear necrotic tissue from purpura fulminans in a 9-month-old boy who was not responding to standard wound care, according to Dr. Xuan Nguyen.

Reports of maggot debridement therapy in children are scarce. This appears to be the first case of using the therapy in a child with purpura fulminans, Dr. Nguyen said at a meeting of the Society for Pediatric Dermatology.

Maggot debridement therapy—also called biosurgery—was used in the United States in the 1930s and 1940s and reintroduced into medical practice in the 1980s and 1990s. In 2004, the Food and Drug Administration approved the production and marketing of medical maggots for debridement of nonhealing necrotic skin and soft tissue wounds, pressure ulcers, venous stasis ulcers, neuropathic foot ulcers, and nonhealing traumatic or postsurgical wounds.

Although purpura fulminans is not a specific indication, it is a chronic wound infection that seems amenable to maggot debridement therapy, she said.

The previously healthy boy presented to the Phoenix Children's Hospital with mottled skin 24 hours after receiving immunizations. He developed Staphylococcus aureus septicemia that led to extensive purpura fulminans, a diffuse necrosis of the skin and subcutaneous tissue secondary to microvascular thrombosis from transient protein C deficiency. All four extremities and some other areas became necrotic.

Conventional wound management using Dakin's solution, Vaseline petroleum gauze dressing over the ecchymotic wounds, Kerlix wraps, and daily wound dressing changes was applied as some of the wounds and mummified regions started to demarcate. Wounds on the face healed relatively well, but the lower extremities of the patient, in particular, had trouble healing. One patella was exposed after the rotting lower leg slid off, said Dr. Nguyen, a pediatric dermatologist at the hospital.

Dr. Nguyen and her associates applied five rounds (lasting 4-5 days each) of maggot debridement therapy combined with adjunctive daily whirlpool baths to which bleach was added. After five rounds of maggot treatment, whirlpool baths were scheduled three times per week as maintenance.

Maggot therapy serves three functions: It debrides necrotic tissue, acts as an antimicrobial therapy, and stimulates wound healing. Maggots like a moist environment and are relatively contraindicated in dry wounds. “We try not to use them in open wounds of body cavities, because the maggots get lost” when it is time to remove them, she said.

The maggots, which are larvae of the greenbottle blowfly (Lucilia sericata), are applied when 1-2 mm in size and grow to 10 mm after 4-5 days, when they are removed from the wound. The maggots ingest nothing but necrotic tissue, and 200 maggots can consume up to 15 g/day. Mouth hooks on their front ends rake in decaying flesh, making them remarkable eating machines.

The maggots secrete proteolytic enzymes including collagenase, trypsinlike enzymes, and chymotrypsinlike enzymes that facilitate wound healing. Their activity disrupts tissue planes only minimally, and some of their secretions inhibit gram-positive and gram-negative bacteria.

Sterile maggots on gauze were tied over the boy's leg wounds and covered with a Kerlix wrap, netting, and a stocking to keep the maggots in the wound. The boy is healing after amputation of his hands and feet, maggot debridement therapy, and use of maintenance baths, Dr. Nguyen said.

Information about conflicts of interest could not be obtained by press time.

SAN FRANCISCO — As director of the University of Colorado Hospital's dermatopathology services, Dr. James Fitzpatrick manages the handling of 70,000 skin specimens each year, with about 3,000 of those being pediatric specimens.

Those numbers posed a problem for Dr. Fitzpatrick, whose staff (including him) at the Aurora, Colo., hospital numbered only four dermatopathologists, the equivalent of 2.6 full-time employees, none of whom were trained specifically to handle pediatric cases. They got little quality support from the general pathologists, he said.

"General pathologists as a rule are not very good at dermatopathology, particularly in pediatric dermatopathology," he said at a meeting of the Society for Pediatric Dermatology. "There are a lot of glaring omissions" in their reports.

What he needed, he decided, was a pediatric dermatopathologist who also could help with the adult dermatopathology workload.

Dr. Fiztpatrick made his case to the chair of the university's dermatology department and to the Children's Hospital in Aurora, and managed to get funding from the Children's Hospital for a pediatric dermatology fellow to learn dermatopathology from him and his staff.

Some physicians criticized the plan, claiming that anyone could do pediatric dermatopathology.

Dr. Fitzpatrick disagreed: "There are a lot of issues that are unique to pediatric dermatopathology."

For example, there was one skin specimen from a 2-year-old that looked exactly like Sweet's syndrome on histology. Clinically, however, the child had osteomyelitis and anemia, two of the clinical features of genetic Majeed syndrome. Further confusing the diagnosis was the fact that Majeed syndrome, like Sweet's syndrome, can cause fever.

"What's the likelihood of your general pathologist or adult dermatopathologist, like me, getting it right? You really need someone with the proper background" to put the clinical and histologic picture together to make the right diagnosis, he said.

The ideal background for pediatric dermatopathology probably should include knowledge of pediatrics and of genetic syndromes, Dr. Fitzpatrick suggested. Training a dermatology resident or pediatric dermatology fellow to become a dermatopathologist probably makes more sense than trying to teach pediatrics to a dermatopathologist or a pathologist, who lacks clinical expertise.

The department chair wanted to know how the position would pay for itself.

"It's actually an easy sell, because you make more money in dermatopathology than you do seeing a bunch of kids" in clinic as a dermatology fellow, he noted.

The plan has worked out beautifully, Dr. Fitzpatrick said.

Dr. Lori Prok, who is the new pediatric dermatopathologist, works in an office right next to his. "When a clinician calls up and says, 'I have a 3-year-old,' I say, 'Hold on a second.'" He can then transfer the call to Dr. Prok for better care.

Those who were resistant at first to the idea of a pediatric dermatopathologist have since come around. "Now, if Lori's gone for 2 days, they hold everything until she gets back," Dr. Fitzpatrick said. Every other week, a case conference brings Dr. Prok together with pathologists, dermatopathologists, and pediatric dermatologists from several departments.

Dr. Fitzpatrick and Dr. Prok have expanded her role since she started to fill another void—research in pediatric dermatopathology.

She is involved in multiple research projects dealing with Spitz nevi, the role of Polyomavirus in Langerhans cell histiocytosis, and varicella zoster virus, to name a few.

Pediatric dermatopathology is a niche whose time has come, but so far it has been discovered by only a few physicians, said Dr. Fitzpatrick. If you search the Internet for pediatric dermatopathologists, you'll find a grand total of two, one of whom is Dr. Prok, he noted.

SAN FRANCISCO — As director of the University of Colorado Hospital's dermatopathology services, Dr. James Fitzpatrick manages the handling of 70,000 skin specimens each year, with about 3,000 of those being pediatric specimens.

Those numbers posed a problem for Dr. Fitzpatrick, whose staff (including him) at the Aurora, Colo., hospital numbered only four dermatopathologists, the equivalent of 2.6 full-time employees, none of whom were trained specifically to handle pediatric cases. They got little quality support from the general pathologists, he said.

"General pathologists as a rule are not very good at dermatopathology, particularly in pediatric dermatopathology," he said at a meeting of the Society for Pediatric Dermatology. "There are a lot of glaring omissions" in their reports.

What he needed, he decided, was a pediatric dermatopathologist who also could help with the adult dermatopathology workload.

Dr. Fiztpatrick made his case to the chair of the university's dermatology department and to the Children's Hospital in Aurora, and managed to get funding from the Children's Hospital for a pediatric dermatology fellow to learn dermatopathology from him and his staff.

Some physicians criticized the plan, claiming that anyone could do pediatric dermatopathology.

Dr. Fitzpatrick disagreed: "There are a lot of issues that are unique to pediatric dermatopathology."

For example, there was one skin specimen from a 2-year-old that looked exactly like Sweet's syndrome on histology. Clinically, however, the child had osteomyelitis and anemia, two of the clinical features of genetic Majeed syndrome. Further confusing the diagnosis was the fact that Majeed syndrome, like Sweet's syndrome, can cause fever.

"What's the likelihood of your general pathologist or adult dermatopathologist, like me, getting it right? You really need someone with the proper background" to put the clinical and histologic picture together to make the right diagnosis, he said.

The ideal background for pediatric dermatopathology probably should include knowledge of pediatrics and of genetic syndromes, Dr. Fitzpatrick suggested. Training a dermatology resident or pediatric dermatology fellow to become a dermatopathologist probably makes more sense than trying to teach pediatrics to a dermatopathologist or a pathologist, who lacks clinical expertise.

The department chair wanted to know how the position would pay for itself.

"It's actually an easy sell, because you make more money in dermatopathology than you do seeing a bunch of kids" in clinic as a dermatology fellow, he noted.

The plan has worked out beautifully, Dr. Fitzpatrick said.

Dr. Lori Prok, who is the new pediatric dermatopathologist, works in an office right next to his. "When a clinician calls up and says, 'I have a 3-year-old,' I say, 'Hold on a second.'" He can then transfer the call to Dr. Prok for better care.

Those who were resistant at first to the idea of a pediatric dermatopathologist have since come around. "Now, if Lori's gone for 2 days, they hold everything until she gets back," Dr. Fitzpatrick said. Every other week, a case conference brings Dr. Prok together with pathologists, dermatopathologists, and pediatric dermatologists from several departments.

Dr. Fitzpatrick and Dr. Prok have expanded her role since she started to fill another void—research in pediatric dermatopathology.

She is involved in multiple research projects dealing with Spitz nevi, the role of Polyomavirus in Langerhans cell histiocytosis, and varicella zoster virus, to name a few.

Pediatric dermatopathology is a niche whose time has come, but so far it has been discovered by only a few physicians, said Dr. Fitzpatrick. If you search the Internet for pediatric dermatopathologists, you'll find a grand total of two, one of whom is Dr. Prok, he noted.

SAN FRANCISCO — As director of the University of Colorado Hospital's dermatopathology services, Dr. James Fitzpatrick manages the handling of 70,000 skin specimens each year, with about 3,000 of those being pediatric specimens.

Those numbers posed a problem for Dr. Fitzpatrick, whose staff (including him) at the Aurora, Colo., hospital numbered only four dermatopathologists, the equivalent of 2.6 full-time employees, none of whom were trained specifically to handle pediatric cases. They got little quality support from the general pathologists, he said.

"General pathologists as a rule are not very good at dermatopathology, particularly in pediatric dermatopathology," he said at a meeting of the Society for Pediatric Dermatology. "There are a lot of glaring omissions" in their reports.

What he needed, he decided, was a pediatric dermatopathologist who also could help with the adult dermatopathology workload.

Dr. Fiztpatrick made his case to the chair of the university's dermatology department and to the Children's Hospital in Aurora, and managed to get funding from the Children's Hospital for a pediatric dermatology fellow to learn dermatopathology from him and his staff.

Some physicians criticized the plan, claiming that anyone could do pediatric dermatopathology.

Dr. Fitzpatrick disagreed: "There are a lot of issues that are unique to pediatric dermatopathology."

For example, there was one skin specimen from a 2-year-old that looked exactly like Sweet's syndrome on histology. Clinically, however, the child had osteomyelitis and anemia, two of the clinical features of genetic Majeed syndrome. Further confusing the diagnosis was the fact that Majeed syndrome, like Sweet's syndrome, can cause fever.

"What's the likelihood of your general pathologist or adult dermatopathologist, like me, getting it right? You really need someone with the proper background" to put the clinical and histologic picture together to make the right diagnosis, he said.

The ideal background for pediatric dermatopathology probably should include knowledge of pediatrics and of genetic syndromes, Dr. Fitzpatrick suggested. Training a dermatology resident or pediatric dermatology fellow to become a dermatopathologist probably makes more sense than trying to teach pediatrics to a dermatopathologist or a pathologist, who lacks clinical expertise.

The department chair wanted to know how the position would pay for itself.

"It's actually an easy sell, because you make more money in dermatopathology than you do seeing a bunch of kids" in clinic as a dermatology fellow, he noted.

The plan has worked out beautifully, Dr. Fitzpatrick said.

Dr. Lori Prok, who is the new pediatric dermatopathologist, works in an office right next to his. "When a clinician calls up and says, 'I have a 3-year-old,' I say, 'Hold on a second.'" He can then transfer the call to Dr. Prok for better care.

Those who were resistant at first to the idea of a pediatric dermatopathologist have since come around. "Now, if Lori's gone for 2 days, they hold everything until she gets back," Dr. Fitzpatrick said. Every other week, a case conference brings Dr. Prok together with pathologists, dermatopathologists, and pediatric dermatologists from several departments.

Dr. Fitzpatrick and Dr. Prok have expanded her role since she started to fill another void—research in pediatric dermatopathology.

She is involved in multiple research projects dealing with Spitz nevi, the role of Polyomavirus in Langerhans cell histiocytosis, and varicella zoster virus, to name a few.

Pediatric dermatopathology is a niche whose time has come, but so far it has been discovered by only a few physicians, said Dr. Fitzpatrick. If you search the Internet for pediatric dermatopathologists, you'll find a grand total of two, one of whom is Dr. Prok, he noted.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

SAN FRANCISCO — Follow-up on 219 patients with Spitz nevi found that 7 (3%) developed malignant melanoma, and in each case the original biopsy showed an atypical or desmoplastic Spitz nevus.

The patients who developed melanoma also were older (aged 34-66 years) at the time the Spitz nevi were diagnosed, compared with patients who did not develop melanoma (whose Spitz nevi appeared predominantly between ages 6 and 30 years), Dr. Lori Prok said at a meeting of the Society for Pediatric Dermatology.

Follow-up of the patients from three clinical sites in Colorado ranged from 1 month to more than 11 years. Many of the Spitz nevi were located on the extremities, especially the lower extremities, "which was a little bit surprising to me," said Dr. Prok, a pediatric dermatopathologist who also handles adult dermatopathology cases at the University of Colorado Hospital, Denver.

Six of the malignant melanomas appeared at different anatomic sites than the Spitz nevus location. One melanoma was re-excised and found to be malignant melanoma in situ. Two patients underwent sentinel node biopsy, with negative results. One patient died of causes unrelated to the tumors.

Dr. Prok and her associates have been studying Spitz nevi to try to better understand the lesion, which histologically shows features of malignant melanoma but is clinically associated with a favorable prognosis. They now are reviewing the charts of the 219 patients to see if the original diagnoses were correct or if melanomas were mistaken for atypical or desmoplastic Spitz nevi. They also will be following these patients for longer-term outcomes.

Dermatopathologists are easily confused by Spitz nevi, as illustrated in a study of 10 dermatopathologists who reviewed 30 melanocytic lesions (including 17 Spitzoid lesions) and were blinded to clinical data and patient outcomes. They were asked to choose a label for each lesion from five categories: Spitz nevus, atypical Spitz nevus, malignant melanoma, neoplasm of uncertain behavior, or other.

Only one case engendered agreement by six or more dermatopathologists. At least seven pathologists scored 13 normal lesions as melanomas, and some fatal lesions were categorized by most of the pathologists as Spitz nevi or atypical Spitz nevi (Hum. Pathol. 1999;30:513-20).

"The take-home message is that the pathologists were just not very good," Dr. Prok said. "It's not that pathologists are stupid, it's that it's really difficult" to categorize Spitzoid lesions.

Physicians also are confused by Spitz nevi because they raise unanswered questions in management. If Spitz nevi really are benign, why did a meta-analysis of 716 Spitz nevi conclude that all Spitz nevi should be completely excised, with re-excision of positive margins (J. Am. Acad. Dermatol. 1993;29:667-8)? How wide should those margins be? One paper suggests 1-cm margins, Dr. Prok noted.

Separate, unpublished data analyzed by two of her associates—a dermatopathologist and a cutaneous oncologist at the university—found that 100% of patients who were treated for Spitzoid melanomas or melanomas with Spitzoid features or atypical melanoma tumors were disease-free 7 years later. In comparison, around 75% of patients who were treated for classical, unequivocal melanoma were disease-free 7 years later.

Sentinel lymph node biopsies in 57 patients with atypical Spitz tumors were positive in 27 (47%), a separate study found. The patients with positive nodes were younger (an average 18 years old versus 29 years old in node-negative patients) and had good outcomes at a median follow-up of 44 months. All 27 node-positive patients were alive and disease-free at follow-up (Cancer 2009;115:631-41).

The authors concluded that atypical Spitz tumors do not behave like conventional melanoma, and they questioned the role of sentinel lymph node biopsy in managing atypical Spitz nevi.

SAN FRANCISCO — Hair loss is not just for adults.

Two simple tools can help diagnose early-onset androgenetic alopecia, which affects 15% of adolescents beginning at age 7-17 years.

The hallmark of androgenetic alopecia is miniaturized hairs, meaning the hair follicles get finer and don't grow as long as normal hairs. The number of hair follicles remains the same, but they're short, fine hairs, Dr. Vera H. Price said at a meeting of the Society for Pediatric Dermatology.

She recommended doing a hair-pull test, which will be negative in androgenetic alopecia: Grab a small cluster of scalp hairs (about 0.5 cm in area) between your thumb and forefinger, and pull very slowly to the end of the hairs. If six or more hairs come out during the pull, that's a positive finding indicating a problem other than androgenetic alopecia. If only two to four hairs come out, the pull test is negative.

Next, examine the hairs using a hair card. A hair card is white on one side (to contrast with dark hairs) and black on the other side (to contrast with lighter-colored hairs). Part the hair, place the card next to the scalp, and look at the follicles next to the card.

This can be especially helpful for spotting miniaturized hairs in adolescents, who tend to have less obvious hair thinning than do adults with androgenetic alopecia.

The hair miniaturization also can be seen via a dermatoscope, but “if you can teach yourselves to use a piece of white paper, it will do very much what a dermatoscope does” to diagnose androgenetic alopecia, noted Dr. Price, who is director of the hair research center and professor of clinical dermatology at the University of California in San Francisco.

Clinically, the adolescents are hormonally normal, and they may or may not have a family history of androgenetic alopecia. They (or their parents) may complain that the teen's hair is not growing the way it used to, that it seldom needs cutting, and that the ends are wispy.

Boys may have mildly decreased hair density in the frontal and vertex regions, and subtle accentuation of bitemporal recession, the normal end shape of the hairline near the temples.

Girls may show a widened central part and increased spacing among hairs. If a girl complains that her ponytail is smaller, shorter, and skimpier than it used to be, that's a very helpful diagnostic sign, and suggests that androgenetic alopecia has been present for some time, Dr. Price said.

Clinical signs of puberty usually are present and are reassuring that normal androgen development is taking place. Ask about the patient's diet to check for adequate protein intake, and get a list of medications, if any are being taken.

Lab tests aren't necessary unless there's a clinical reason for them, Dr. Price suggested. If a thyroid problem is suspected, order a TSH test and complete blood count. If you do suspect an androgen problem, order tests for total testosterone, dehydroepiandrosterone sulfate, and prolactin, although usually these aren't needed.

For menstruating girls, you might want to check ferritin and total iron-binding capacity to make sure iron levels are sufficient.

Among the differential diagnoses, alopecia areata would have a positive hair-pull test and patches of missing hair, neither of which are suggestive of androgenetic alopecia. Trichotillomania also presents with patches of missing hair, and a hair card will show broken ends on the follicles.

If there's some reason for hair shedding (such as fever) in the patient's history, the problem may be telogen effluvium. The history would point to anagen arrest as a cause of hair loss if the patient had been on chemotherapy.

Dr. Price treats adolescent androgenetic alopecia with daily applications of minoxidil (Rogaine) if the teenager is willing to make a long-term commitment that is needed since the effects are evaluated after 1 year and will disappear if the drug is stopped.

“I tell them it's not forever that they'll be using this; it's until the next good product” comes along, she said.

She does not use finasteride (Propecia) in adolescents because there have been no studies of its use in boys who were younger than age 18 years, and it is contraindicated for girls of childbearing age. Spironolactone does not enlarge hair follicles, so she doesn't use that agent in these patients, either.

Dr. Price has been a consultant for Pfizer Inc., which markets minoxidil and spironolactone, and she has received research funds from Pfizer and from Merck & Co., which markets finasteride.

Minoxidil may cause unwanted facial hair in 5% of patients within 4 weeks of starting therapy, but such hair goes away quickly if treatment is stopped.

Cosmetic options—such as using creative hair styling or hair extensions—also can help the patient and family members cope with adolescent alopecia. “There's a lot of counseling of the patient and family” with this condition, she said.

When prescribing minoxidil, 'I tell them it's not forever … it's until the next good product' comes along. DR. PRICE

Part the hair, place the card next to the scalp, and look at the follicles next to the card. Courtesy Dr. Vera H. Price

SAN FRANCISCO — Hair loss is not just for adults.

Two simple tools can help diagnose early-onset androgenetic alopecia, which affects 15% of adolescents beginning at age 7-17 years.

The hallmark of androgenetic alopecia is miniaturized hairs, meaning the hair follicles get finer and don't grow as long as normal hairs. The number of hair follicles remains the same, but they're short, fine hairs, Dr. Vera H. Price said at a meeting of the Society for Pediatric Dermatology.

She recommended doing a hair-pull test, which will be negative in androgenetic alopecia: Grab a small cluster of scalp hairs (about 0.5 cm in area) between your thumb and forefinger, and pull very slowly to the end of the hairs. If six or more hairs come out during the pull, that's a positive finding indicating a problem other than androgenetic alopecia. If only two to four hairs come out, the pull test is negative.

Next, examine the hairs using a hair card. A hair card is white on one side (to contrast with dark hairs) and black on the other side (to contrast with lighter-colored hairs). Part the hair, place the card next to the scalp, and look at the follicles next to the card.

This can be especially helpful for spotting miniaturized hairs in adolescents, who tend to have less obvious hair thinning than do adults with androgenetic alopecia.

The hair miniaturization also can be seen via a dermatoscope, but “if you can teach yourselves to use a piece of white paper, it will do very much what a dermatoscope does” to diagnose androgenetic alopecia, noted Dr. Price, who is director of the hair research center and professor of clinical dermatology at the University of California in San Francisco.

Clinically, the adolescents are hormonally normal, and they may or may not have a family history of androgenetic alopecia. They (or their parents) may complain that the teen's hair is not growing the way it used to, that it seldom needs cutting, and that the ends are wispy.

Boys may have mildly decreased hair density in the frontal and vertex regions, and subtle accentuation of bitemporal recession, the normal end shape of the hairline near the temples.

Girls may show a widened central part and increased spacing among hairs. If a girl complains that her ponytail is smaller, shorter, and skimpier than it used to be, that's a very helpful diagnostic sign, and suggests that androgenetic alopecia has been present for some time, Dr. Price said.

Clinical signs of puberty usually are present and are reassuring that normal androgen development is taking place. Ask about the patient's diet to check for adequate protein intake, and get a list of medications, if any are being taken.

Lab tests aren't necessary unless there's a clinical reason for them, Dr. Price suggested. If a thyroid problem is suspected, order a TSH test and complete blood count. If you do suspect an androgen problem, order tests for total testosterone, dehydroepiandrosterone sulfate, and prolactin, although usually these aren't needed.

For menstruating girls, you might want to check ferritin and total iron-binding capacity to make sure iron levels are sufficient.

Among the differential diagnoses, alopecia areata would have a positive hair-pull test and patches of missing hair, neither of which are suggestive of androgenetic alopecia. Trichotillomania also presents with patches of missing hair, and a hair card will show broken ends on the follicles.

If there's some reason for hair shedding (such as fever) in the patient's history, the problem may be telogen effluvium. The history would point to anagen arrest as a cause of hair loss if the patient had been on chemotherapy.

Dr. Price treats adolescent androgenetic alopecia with daily applications of minoxidil (Rogaine) if the teenager is willing to make a long-term commitment that is needed since the effects are evaluated after 1 year and will disappear if the drug is stopped.

“I tell them it's not forever that they'll be using this; it's until the next good product” comes along, she said.

She does not use finasteride (Propecia) in adolescents because there have been no studies of its use in boys who were younger than age 18 years, and it is contraindicated for girls of childbearing age. Spironolactone does not enlarge hair follicles, so she doesn't use that agent in these patients, either.

Dr. Price has been a consultant for Pfizer Inc., which markets minoxidil and spironolactone, and she has received research funds from Pfizer and from Merck & Co., which markets finasteride.

Minoxidil may cause unwanted facial hair in 5% of patients within 4 weeks of starting therapy, but such hair goes away quickly if treatment is stopped.

Cosmetic options—such as using creative hair styling or hair extensions—also can help the patient and family members cope with adolescent alopecia. “There's a lot of counseling of the patient and family” with this condition, she said.

When prescribing minoxidil, 'I tell them it's not forever … it's until the next good product' comes along. DR. PRICE

Part the hair, place the card next to the scalp, and look at the follicles next to the card. Courtesy Dr. Vera H. Price

SAN FRANCISCO — Hair loss is not just for adults.

Two simple tools can help diagnose early-onset androgenetic alopecia, which affects 15% of adolescents beginning at age 7-17 years.

The hallmark of androgenetic alopecia is miniaturized hairs, meaning the hair follicles get finer and don't grow as long as normal hairs. The number of hair follicles remains the same, but they're short, fine hairs, Dr. Vera H. Price said at a meeting of the Society for Pediatric Dermatology.

She recommended doing a hair-pull test, which will be negative in androgenetic alopecia: Grab a small cluster of scalp hairs (about 0.5 cm in area) between your thumb and forefinger, and pull very slowly to the end of the hairs. If six or more hairs come out during the pull, that's a positive finding indicating a problem other than androgenetic alopecia. If only two to four hairs come out, the pull test is negative.

Next, examine the hairs using a hair card. A hair card is white on one side (to contrast with dark hairs) and black on the other side (to contrast with lighter-colored hairs). Part the hair, place the card next to the scalp, and look at the follicles next to the card.

This can be especially helpful for spotting miniaturized hairs in adolescents, who tend to have less obvious hair thinning than do adults with androgenetic alopecia.

The hair miniaturization also can be seen via a dermatoscope, but “if you can teach yourselves to use a piece of white paper, it will do very much what a dermatoscope does” to diagnose androgenetic alopecia, noted Dr. Price, who is director of the hair research center and professor of clinical dermatology at the University of California in San Francisco.

Clinically, the adolescents are hormonally normal, and they may or may not have a family history of androgenetic alopecia. They (or their parents) may complain that the teen's hair is not growing the way it used to, that it seldom needs cutting, and that the ends are wispy.

Boys may have mildly decreased hair density in the frontal and vertex regions, and subtle accentuation of bitemporal recession, the normal end shape of the hairline near the temples.

Girls may show a widened central part and increased spacing among hairs. If a girl complains that her ponytail is smaller, shorter, and skimpier than it used to be, that's a very helpful diagnostic sign, and suggests that androgenetic alopecia has been present for some time, Dr. Price said.

Clinical signs of puberty usually are present and are reassuring that normal androgen development is taking place. Ask about the patient's diet to check for adequate protein intake, and get a list of medications, if any are being taken.

Lab tests aren't necessary unless there's a clinical reason for them, Dr. Price suggested. If a thyroid problem is suspected, order a TSH test and complete blood count. If you do suspect an androgen problem, order tests for total testosterone, dehydroepiandrosterone sulfate, and prolactin, although usually these aren't needed.

For menstruating girls, you might want to check ferritin and total iron-binding capacity to make sure iron levels are sufficient.

Among the differential diagnoses, alopecia areata would have a positive hair-pull test and patches of missing hair, neither of which are suggestive of androgenetic alopecia. Trichotillomania also presents with patches of missing hair, and a hair card will show broken ends on the follicles.

If there's some reason for hair shedding (such as fever) in the patient's history, the problem may be telogen effluvium. The history would point to anagen arrest as a cause of hair loss if the patient had been on chemotherapy.

Dr. Price treats adolescent androgenetic alopecia with daily applications of minoxidil (Rogaine) if the teenager is willing to make a long-term commitment that is needed since the effects are evaluated after 1 year and will disappear if the drug is stopped.

“I tell them it's not forever that they'll be using this; it's until the next good product” comes along, she said.

She does not use finasteride (Propecia) in adolescents because there have been no studies of its use in boys who were younger than age 18 years, and it is contraindicated for girls of childbearing age. Spironolactone does not enlarge hair follicles, so she doesn't use that agent in these patients, either.

Dr. Price has been a consultant for Pfizer Inc., which markets minoxidil and spironolactone, and she has received research funds from Pfizer and from Merck & Co., which markets finasteride.

Minoxidil may cause unwanted facial hair in 5% of patients within 4 weeks of starting therapy, but such hair goes away quickly if treatment is stopped.

Cosmetic options—such as using creative hair styling or hair extensions—also can help the patient and family members cope with adolescent alopecia. “There's a lot of counseling of the patient and family” with this condition, she said.

When prescribing minoxidil, 'I tell them it's not forever … it's until the next good product' comes along. DR. PRICE

Part the hair, place the card next to the scalp, and look at the follicles next to the card. Courtesy Dr. Vera H. Price

SAN FRANCISCO — New guidelines for managing patients with asymptomatic primary hyperparathyroidism eliminate urine calcium as an indication for surgery and call for monitoring serum calcium annually instead of every 6 months in patients who do not have surgery.

The guidelines, the product of a 2008 international workshop and consensus panel, recommend parathyroidectomy for patients aged under 50 years with primary hyperparathyroidism and symptoms of hypercalcemia. Surgery also is recommended in asymptomatic patients with serum total calcium 1 mg/dL above the upper limit of normal, or estimated glomerular filtration rate less than 60 mL/min, or bone mineral density T scores of −2.5 or lower at the lumbar spine, hip, or distal third of the radius on dual x-ray absorptiometry (J. Clin. Endocrinol. Metab. 2009;94:335-9).

The guidelines note that medical surveillance of patients who undergo surgery for primary hyperparathyroidism is neither possible nor desirable, Dr. Dolores M. Shoback said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For patients who don't go to surgery, the only change in monitoring recommendations compared with the last version of the guidelines in 2002 is the switch from semiannual to annual monitoring of serum calcium levels, said Dr. Shoback, professor of medicine at the university.

Serum creatinine and bone mineral density should be measured at three sites—lumbar spine, hip, and distal third of the radius—yearly. Tests that were included in 1990 guidelines but are no longer recommended include 24-hour urinary calcium, creatinine clearance, and abdominal x-ray.

No medications are approved to treat primary hyperparathyroidism. Studies of alendronate therapy show that it does not reverse or control the biochemical abnormalities of hyperparathyroidism, but it does seem to stabilize or even enhance bone mineral density in these patients, Dr. Shoback said.

The calcium mimetic cinacalcet also has been studied, with some promising results. Physicians might consider using this drug in patients with primary hyperparathyroidism to control hypercalcemia if the patients are too sick for surgery or declined or failed surgery, she said.

Dr. Shoback has been a consultant for Amgen, which markets cinacalcet, and was a researcher on a study examining the use of cinacalcet in parathyroid carcinoma patients.

The natural history of the disease was highlighted in what might be the largest and longest follow-up study that will be seen for a very long time, she said.

Among 116 patients with primary hyperparathyroidism (17 of whom were symptomatic), 51% went straight to surgery, which normalized biochemistries and improved bone mineral density in all patients during 15 years of follow-up (J. Clin. Endocrinol. Metab. 2008;93:3462-70).

The 57 patients who did not have surgery initially for a variety of reasons (although it was recommended to some) tended to remain biochemically stable for the first decade but then developed significant increases in serum calcium levels. Bone density was stable in the lumbar spine but declined significantly after year 9 or 10 in the femoral neck and radius—by 10% and 35%, respectively. In comparison, bone density at these sites increased by 10% or more in patients who initially went to surgery.

Of eight patients who had kidney stones at baseline yet refused recommended surgery, six had recurrent stones during follow-up. Patients with kidney stones who agreed to initial parathyroidectomy had no recurrent stones, Dr. Shoback said.

Medical surveillance of patients who undergo surgery is neither possible nor desirable. DR. SHOBACK

SAN FRANCISCO — New guidelines for managing patients with asymptomatic primary hyperparathyroidism eliminate urine calcium as an indication for surgery and call for monitoring serum calcium annually instead of every 6 months in patients who do not have surgery.

The guidelines, the product of a 2008 international workshop and consensus panel, recommend parathyroidectomy for patients aged under 50 years with primary hyperparathyroidism and symptoms of hypercalcemia. Surgery also is recommended in asymptomatic patients with serum total calcium 1 mg/dL above the upper limit of normal, or estimated glomerular filtration rate less than 60 mL/min, or bone mineral density T scores of −2.5 or lower at the lumbar spine, hip, or distal third of the radius on dual x-ray absorptiometry (J. Clin. Endocrinol. Metab. 2009;94:335-9).

The guidelines note that medical surveillance of patients who undergo surgery for primary hyperparathyroidism is neither possible nor desirable, Dr. Dolores M. Shoback said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For patients who don't go to surgery, the only change in monitoring recommendations compared with the last version of the guidelines in 2002 is the switch from semiannual to annual monitoring of serum calcium levels, said Dr. Shoback, professor of medicine at the university.

Serum creatinine and bone mineral density should be measured at three sites—lumbar spine, hip, and distal third of the radius—yearly. Tests that were included in 1990 guidelines but are no longer recommended include 24-hour urinary calcium, creatinine clearance, and abdominal x-ray.

No medications are approved to treat primary hyperparathyroidism. Studies of alendronate therapy show that it does not reverse or control the biochemical abnormalities of hyperparathyroidism, but it does seem to stabilize or even enhance bone mineral density in these patients, Dr. Shoback said.

The calcium mimetic cinacalcet also has been studied, with some promising results. Physicians might consider using this drug in patients with primary hyperparathyroidism to control hypercalcemia if the patients are too sick for surgery or declined or failed surgery, she said.

Dr. Shoback has been a consultant for Amgen, which markets cinacalcet, and was a researcher on a study examining the use of cinacalcet in parathyroid carcinoma patients.

The natural history of the disease was highlighted in what might be the largest and longest follow-up study that will be seen for a very long time, she said.

Among 116 patients with primary hyperparathyroidism (17 of whom were symptomatic), 51% went straight to surgery, which normalized biochemistries and improved bone mineral density in all patients during 15 years of follow-up (J. Clin. Endocrinol. Metab. 2008;93:3462-70).

The 57 patients who did not have surgery initially for a variety of reasons (although it was recommended to some) tended to remain biochemically stable for the first decade but then developed significant increases in serum calcium levels. Bone density was stable in the lumbar spine but declined significantly after year 9 or 10 in the femoral neck and radius—by 10% and 35%, respectively. In comparison, bone density at these sites increased by 10% or more in patients who initially went to surgery.

Of eight patients who had kidney stones at baseline yet refused recommended surgery, six had recurrent stones during follow-up. Patients with kidney stones who agreed to initial parathyroidectomy had no recurrent stones, Dr. Shoback said.

Medical surveillance of patients who undergo surgery is neither possible nor desirable. DR. SHOBACK

SAN FRANCISCO — New guidelines for managing patients with asymptomatic primary hyperparathyroidism eliminate urine calcium as an indication for surgery and call for monitoring serum calcium annually instead of every 6 months in patients who do not have surgery.

The guidelines, the product of a 2008 international workshop and consensus panel, recommend parathyroidectomy for patients aged under 50 years with primary hyperparathyroidism and symptoms of hypercalcemia. Surgery also is recommended in asymptomatic patients with serum total calcium 1 mg/dL above the upper limit of normal, or estimated glomerular filtration rate less than 60 mL/min, or bone mineral density T scores of −2.5 or lower at the lumbar spine, hip, or distal third of the radius on dual x-ray absorptiometry (J. Clin. Endocrinol. Metab. 2009;94:335-9).

The guidelines note that medical surveillance of patients who undergo surgery for primary hyperparathyroidism is neither possible nor desirable, Dr. Dolores M. Shoback said at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For patients who don't go to surgery, the only change in monitoring recommendations compared with the last version of the guidelines in 2002 is the switch from semiannual to annual monitoring of serum calcium levels, said Dr. Shoback, professor of medicine at the university.

Serum creatinine and bone mineral density should be measured at three sites—lumbar spine, hip, and distal third of the radius—yearly. Tests that were included in 1990 guidelines but are no longer recommended include 24-hour urinary calcium, creatinine clearance, and abdominal x-ray.

No medications are approved to treat primary hyperparathyroidism. Studies of alendronate therapy show that it does not reverse or control the biochemical abnormalities of hyperparathyroidism, but it does seem to stabilize or even enhance bone mineral density in these patients, Dr. Shoback said.

The calcium mimetic cinacalcet also has been studied, with some promising results. Physicians might consider using this drug in patients with primary hyperparathyroidism to control hypercalcemia if the patients are too sick for surgery or declined or failed surgery, she said.

Dr. Shoback has been a consultant for Amgen, which markets cinacalcet, and was a researcher on a study examining the use of cinacalcet in parathyroid carcinoma patients.

The natural history of the disease was highlighted in what might be the largest and longest follow-up study that will be seen for a very long time, she said.

Among 116 patients with primary hyperparathyroidism (17 of whom were symptomatic), 51% went straight to surgery, which normalized biochemistries and improved bone mineral density in all patients during 15 years of follow-up (J. Clin. Endocrinol. Metab. 2008;93:3462-70).

The 57 patients who did not have surgery initially for a variety of reasons (although it was recommended to some) tended to remain biochemically stable for the first decade but then developed significant increases in serum calcium levels. Bone density was stable in the lumbar spine but declined significantly after year 9 or 10 in the femoral neck and radius—by 10% and 35%, respectively. In comparison, bone density at these sites increased by 10% or more in patients who initially went to surgery.

Of eight patients who had kidney stones at baseline yet refused recommended surgery, six had recurrent stones during follow-up. Patients with kidney stones who agreed to initial parathyroidectomy had no recurrent stones, Dr. Shoback said.

Medical surveillance of patients who undergo surgery is neither possible nor desirable. DR. SHOBACK

SAN FRANCISCO — Despite results from five major studies showing the effects of intensive glycemic control in patients with diabetes, the question remains: How low should one go?

Dr. Elizabeth J. Murphy distilled the data into a simple prescription for clinicians at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For most patients with diabetes, aiming for a glycosylated hemoglobin (HbA_1c) level below 7% “is still a very good goal,” said Dr. Murphy, chief of endocrinology at San Francisco General Hospital. Consider striving for lower HbA_1c targets in younger, healthier, newly diagnosed patients “where you haven't seen adverse events. We know that in that population we can do the most to prevent the sequelae” of the disease, she added.

For patients who are expected to live less than 5 years or who have severe hypoglycemia, advanced complications, or other significant comorbid conditions, “higher targets like 8% might be appropriate,” Dr. Murphy said.

A 2009 position statement by the American Diabetes Association, American Heart Association, and American College of Cardiology reached similar conclusions in its interpretation of the recent data (Diabetes Care 2009;32:187-92). The position statement “is a long way of saying that we don't change anything,” Dr. Murphy said.

The new data and the joint position statement by the three groups were not enough to convince the American Association of Clinical Endocrinologists to modify its recommendation to aim for an HbA_1c level below 6.5% in most patients, “but I still feel that less than 7%, given the data we have, is what we should stick with,” said Dr. Murphy, who based her advice on five key trials:

▸ 10-year follow-up of patients in the United Kingdom Prospective Diabetes Study (UKPDS) (N. Engl. J. Med. 2008;359:1577-89).

▸ Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N. Engl. J. Med. 2008;358:2545-59).

▸ Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

▸ Veterans Affairs Diabetes Trial (VADT) (N. Engl. J. Med. 2009;360:129-39).

▸ The Steno-2 trial from the Steno Diabetes Center in Copenhagen (N. Engl. J. Med. 2008;358:580-91).

All of the data, with the possible exception of VADT, suggest that lower HbA_1c levels are better for preventing the microvascular complications of diabetes. To prevent macrovascular complications, the benefits of glycemic control are small in comparison to managing hypertension and dyslipidemia, which play far larger roles in morbidity and mortality.

“I hate to say this as an endocrinologist, but blood pressure control is much more important than glycemic control,” especially in patients with type 2 diabetes, she said, but “in type 1 diabetes that might not be the case.”

Aggressive treatment in the early stages of diabetes has long-lasting microvascular and macrovascular benefits, the data show, but aggressive blood pressure lowering must be continued to maintain the benefits.

Some of these major studies are ongoing, and “we will have to await longer follow-up” for a better picture of the relationship between HbA_1c levels and cardiovascular complications, Dr. Murphy said.

She has been a consultant for Daiichi Sankyo Co., which markets drug therapies for diabetes.

SAN FRANCISCO — Despite results from five major studies showing the effects of intensive glycemic control in patients with diabetes, the question remains: How low should one go?

Dr. Elizabeth J. Murphy distilled the data into a simple prescription for clinicians at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For most patients with diabetes, aiming for a glycosylated hemoglobin (HbA_1c) level below 7% “is still a very good goal,” said Dr. Murphy, chief of endocrinology at San Francisco General Hospital. Consider striving for lower HbA_1c targets in younger, healthier, newly diagnosed patients “where you haven't seen adverse events. We know that in that population we can do the most to prevent the sequelae” of the disease, she added.

For patients who are expected to live less than 5 years or who have severe hypoglycemia, advanced complications, or other significant comorbid conditions, “higher targets like 8% might be appropriate,” Dr. Murphy said.

A 2009 position statement by the American Diabetes Association, American Heart Association, and American College of Cardiology reached similar conclusions in its interpretation of the recent data (Diabetes Care 2009;32:187-92). The position statement “is a long way of saying that we don't change anything,” Dr. Murphy said.

The new data and the joint position statement by the three groups were not enough to convince the American Association of Clinical Endocrinologists to modify its recommendation to aim for an HbA_1c level below 6.5% in most patients, “but I still feel that less than 7%, given the data we have, is what we should stick with,” said Dr. Murphy, who based her advice on five key trials:

▸ 10-year follow-up of patients in the United Kingdom Prospective Diabetes Study (UKPDS) (N. Engl. J. Med. 2008;359:1577-89).

▸ Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N. Engl. J. Med. 2008;358:2545-59).

▸ Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

▸ Veterans Affairs Diabetes Trial (VADT) (N. Engl. J. Med. 2009;360:129-39).

▸ The Steno-2 trial from the Steno Diabetes Center in Copenhagen (N. Engl. J. Med. 2008;358:580-91).

All of the data, with the possible exception of VADT, suggest that lower HbA_1c levels are better for preventing the microvascular complications of diabetes. To prevent macrovascular complications, the benefits of glycemic control are small in comparison to managing hypertension and dyslipidemia, which play far larger roles in morbidity and mortality.

“I hate to say this as an endocrinologist, but blood pressure control is much more important than glycemic control,” especially in patients with type 2 diabetes, she said, but “in type 1 diabetes that might not be the case.”

Aggressive treatment in the early stages of diabetes has long-lasting microvascular and macrovascular benefits, the data show, but aggressive blood pressure lowering must be continued to maintain the benefits.

Some of these major studies are ongoing, and “we will have to await longer follow-up” for a better picture of the relationship between HbA_1c levels and cardiovascular complications, Dr. Murphy said.

She has been a consultant for Daiichi Sankyo Co., which markets drug therapies for diabetes.

SAN FRANCISCO — Despite results from five major studies showing the effects of intensive glycemic control in patients with diabetes, the question remains: How low should one go?

Dr. Elizabeth J. Murphy distilled the data into a simple prescription for clinicians at a meeting on diabetes and endocrinology sponsored by the University of California, San Francisco.

For most patients with diabetes, aiming for a glycosylated hemoglobin (HbA_1c) level below 7% “is still a very good goal,” said Dr. Murphy, chief of endocrinology at San Francisco General Hospital. Consider striving for lower HbA_1c targets in younger, healthier, newly diagnosed patients “where you haven't seen adverse events. We know that in that population we can do the most to prevent the sequelae” of the disease, she added.

For patients who are expected to live less than 5 years or who have severe hypoglycemia, advanced complications, or other significant comorbid conditions, “higher targets like 8% might be appropriate,” Dr. Murphy said.

A 2009 position statement by the American Diabetes Association, American Heart Association, and American College of Cardiology reached similar conclusions in its interpretation of the recent data (Diabetes Care 2009;32:187-92). The position statement “is a long way of saying that we don't change anything,” Dr. Murphy said.

The new data and the joint position statement by the three groups were not enough to convince the American Association of Clinical Endocrinologists to modify its recommendation to aim for an HbA_1c level below 6.5% in most patients, “but I still feel that less than 7%, given the data we have, is what we should stick with,” said Dr. Murphy, who based her advice on five key trials:

▸ 10-year follow-up of patients in the United Kingdom Prospective Diabetes Study (UKPDS) (N. Engl. J. Med. 2008;359:1577-89).

▸ Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (N. Engl. J. Med. 2008;358:2545-59).

▸ Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial (N. Engl. J. Med. 2008;358:2560-72).

▸ Veterans Affairs Diabetes Trial (VADT) (N. Engl. J. Med. 2009;360:129-39).

▸ The Steno-2 trial from the Steno Diabetes Center in Copenhagen (N. Engl. J. Med. 2008;358:580-91).

All of the data, with the possible exception of VADT, suggest that lower HbA_1c levels are better for preventing the microvascular complications of diabetes. To prevent macrovascular complications, the benefits of glycemic control are small in comparison to managing hypertension and dyslipidemia, which play far larger roles in morbidity and mortality.

“I hate to say this as an endocrinologist, but blood pressure control is much more important than glycemic control,” especially in patients with type 2 diabetes, she said, but “in type 1 diabetes that might not be the case.”

Aggressive treatment in the early stages of diabetes has long-lasting microvascular and macrovascular benefits, the data show, but aggressive blood pressure lowering must be continued to maintain the benefits.

Some of these major studies are ongoing, and “we will have to await longer follow-up” for a better picture of the relationship between HbA_1c levels and cardiovascular complications, Dr. Murphy said.

She has been a consultant for Daiichi Sankyo Co., which markets drug therapies for diabetes.

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to the NIH (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3-T MRI of the radius, tibia, and femur; hr-pQCT of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both hrMRI and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a two- to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

Earlier studies of hrMRI showed that calcitonin-salmon nasal spray helped maintain trabecular microarchitecture vs. placebo (J. Bone Miner. Res. 2005; 20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Dr. Link has received research funding and support from Merck, which markets medication to treat osteoporosis.

All three imaging modalities correlate reasonably well with micro-CT as a standard of reference. DR. LINK

High-resolution peripheral quantitative CT (left) and high-resolution 3-T MRI (right) each have characteristic advantages and disadvantages for imaging bone. Photos Courtesy Dr. Thomas M. Link

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to the NIH (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3-T MRI of the radius, tibia, and femur; hr-pQCT of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both hrMRI and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a two- to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

Earlier studies of hrMRI showed that calcitonin-salmon nasal spray helped maintain trabecular microarchitecture vs. placebo (J. Bone Miner. Res. 2005; 20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Dr. Link has received research funding and support from Merck, which markets medication to treat osteoporosis.

All three imaging modalities correlate reasonably well with micro-CT as a standard of reference. DR. LINK

High-resolution peripheral quantitative CT (left) and high-resolution 3-T MRI (right) each have characteristic advantages and disadvantages for imaging bone. Photos Courtesy Dr. Thomas M. Link

SAN FRANCISCO — Advances in imaging techniques are providing new insights into trabecular and cortical bone structure and may help assess bone quality, a key component of bone strength identified by a 2001 National Institutes of Health consensus panel.

Recent studies suggest that high-resolution MRI (hrMRI), multidetector CT, and high-resolution peripheral quantitative CT (hr-pQCT) each may be useful in assessing bone quality. But each brings different advantages and disadvantages, and it's unclear which imaging modality will be best for identifying osteoporotic fractures and monitoring treatment-related changes in bone structure.

The three imaging modalities can produce significantly different absolute numbers compared with each other when assessing trabecular or cortical bone structure, yet all correlate reasonably well with micro-CT as a standard of reference, Dr. Thomas M. Link said at a conference sponsored by the International Society for Magnetic Resonance in Medicine. Because of differences in acquisition and analysis of the images, bone structure data from the three imaging modalities are not directly comparable.

Trabecular and cortical bone structure are key components of bone quality, which was deemed to be an important component of bone strength, according to the NIH (JAMA 2001;285:785–95).

In one randomized, double-blind study, for example, 51 postmenopausal women with osteopenia were treated with alendronate or placebo and followed over a 2-year period by 3-T MRI of the radius, tibia, and femur; hr-pQCT of the radius and tibia; and dual x-ray absorptiometry measures of bone mineral density. Both hrMRI and hr-pQCT results for trabecular bone showed moderate but significant correlation with bone density as a reference, even though there was a two- to fourfold difference between hrMRI and hr-pQCT in parameter values such as trabecular number, thickness, or separation (J. Bone Miner. Res. 2008;23:463–74).

Earlier studies of hrMRI showed that calcitonin-salmon nasal spray helped maintain trabecular microarchitecture vs. placebo (J. Bone Miner. Res. 2005; 20:1548–61) and that testosterone replacement may improve trabecular architecture in hypogonadal men (J. Clin. Endocrinol. Metab. 2003;88:1497–502).

Another study of 106 postmenopausal women found no difference in conventional bone mineral density measurements between the 35 women with a history of fractures and the fracture-free women in the rest of the cohort, but hr-pQCT imaging showed significant differences in trabecular structure (J. Clin. Endocrinol. Metab. 2005;90:6508–15).

Multidetector CT was used in a separate study showing significant increases in trabecular microstructure in 65 postmenopausal women treated for 12 months with teriparatide for osteoporosis (J. Bone Miner. Res. 2007;22:1426–33).

For corticol bone imaging, a newer area of research, two 2008 studies using hr-pQCT showed substantial differences between postmenopausal women with hip or wrist fractures, compared with fracture-free women, said Dr. Link, professor of radiology at the University of California, San Francisco.

Both hrMRI and hr-pQCT are being used experimentally to assess cortical bone porosity, which affects bone stability. One recent study using hr-pQCT found significant differences between normal premenopausal women, normal postmenopausal women, and postmenopausal women with renal osteodystrophy. “This is quite exciting to see these changes in cortical bone porosity. We don't really know what they mean yet, but they're clearly associated with fracture risk,” Dr. Link said.

MRI or hr-pQCT provide high spatial resolution and produce no or relatively little radiation, compared with high-radiation exposure from multidetector CT. Multidector CT has the advantage of allowing imaging of more central skeletal sites such as the spine or proximal femur, he said. The hr-pQCT scanners image only peripheral sites such as small areas of the radius and tibia and possibly the calcaneus, while hrMRI covers larger areas of the radius, tibia, and possibly the femur.

The CT techniques provide measures of bone densitometry. Although hrMRI gives no densitometric data, some studies suggest it may be used to analyze bone marrow composition through spectroscopy in order to assess bone stability. The three techniques appear to have similar rates of reproducibility.

MRI is expensive, and the time needed for imaging results in motion artifacts. In comparison, hr-pQCT requires a dedicated scanner. Although exam time is shorter with hr-pQCT, motion artifacts remain a problem. Multidetector CT is widely available and requires less time for a scan. Postimage processing requires sophisticated techniques with MRI, but also is technically challenging with hr-pQCT.

Dr. Link has received research funding and support from Merck, which markets medication to treat osteoporosis.

All three imaging modalities correlate reasonably well with micro-CT as a standard of reference. DR. LINK

High-resolution peripheral quantitative CT (left) and high-resolution 3-T MRI (right) each have characteristic advantages and disadvantages for imaging bone. Photos Courtesy Dr. Thomas M. Link