Osteoarthritis

PARK CITY, UTAH — Patients with immunobullous disease who are on systemic glucocorticoids require monitoring for bone loss and supportive interventions to prevent drug-induced osteoporosis, Dr. Kim B. Yancey told physicians at a clinical dermatology seminar sponsored by Medicis.

Glucocorticoid-induced osteoporosis primarily affects trabecular bone, he said, labeling the problem as “especially prominent” in children, adolescents, and postmenopausal women. Other adverse effects include osteonecrosis, primarily in the hip, and impairment in bone growth. He described the underlying mechanism as biologic.

The standard glucocorticoid therapy for patients with autoimmune blistering diseases starts at 1 mg/kg per day of oral prednisone. For patients requiring more aggressive treatment, Dr. Yancy, chairman of dermatology and codirector of the cutaneous immunopathology laboratory at the Medical College of Wisconsin in Milwaukee, recommended higher doses of oral prednisone plus 1 g/day of pulse methylprednisolone for 3–5 days.

Pemphigus and pemphigoid patients starting on long-term steroids should also be instructed to take 1,200–1,500 mg of elemental calcium daily and 400 IU of vitamin D twice a day. He recommended a low-sodium diet as well.

Later, after patients have started to benefit from the regimen, he advocated prescribing bisphosphonates and encouraging patients to do simple weight-bearing exercises.

“The main thing is to try to get patients to walk,” which is easier when they are not in severe pain, he said.

Dr. Yancey noted that taking medications associated with low bone mass or bone loss is an indication for bone mineral absorptiometry. He recommended ordering this test of bone density at baseline and 1 year.

For patients who have a notable history of renal stones or otherwise need to have urinary calcium levels monitored, he advocated calling in a consultant. He also suggested requesting a consultation in decisions regarding sex hormone replacement therapy (HRT) for men or women, thiazide diuretics, and calcitonin in patients who do not tolerate bisphosphonates or who have pain from compression fractures. When prescribing corticosteroids, physicians should also consider drug interactions. Some agents, such as azole antifungals and macrolide antibiotics, increase corticosteroid levels and toxicity.

PARK CITY, UTAH — Patients with immunobullous disease who are on systemic glucocorticoids require monitoring for bone loss and supportive interventions to prevent drug-induced osteoporosis, Dr. Kim B. Yancey told physicians at a clinical dermatology seminar sponsored by Medicis.

Glucocorticoid-induced osteoporosis primarily affects trabecular bone, he said, labeling the problem as “especially prominent” in children, adolescents, and postmenopausal women. Other adverse effects include osteonecrosis, primarily in the hip, and impairment in bone growth. He described the underlying mechanism as biologic.

The standard glucocorticoid therapy for patients with autoimmune blistering diseases starts at 1 mg/kg per day of oral prednisone. For patients requiring more aggressive treatment, Dr. Yancy, chairman of dermatology and codirector of the cutaneous immunopathology laboratory at the Medical College of Wisconsin in Milwaukee, recommended higher doses of oral prednisone plus 1 g/day of pulse methylprednisolone for 3–5 days.

Pemphigus and pemphigoid patients starting on long-term steroids should also be instructed to take 1,200–1,500 mg of elemental calcium daily and 400 IU of vitamin D twice a day. He recommended a low-sodium diet as well.

Later, after patients have started to benefit from the regimen, he advocated prescribing bisphosphonates and encouraging patients to do simple weight-bearing exercises.

“The main thing is to try to get patients to walk,” which is easier when they are not in severe pain, he said.

Dr. Yancey noted that taking medications associated with low bone mass or bone loss is an indication for bone mineral absorptiometry. He recommended ordering this test of bone density at baseline and 1 year.

For patients who have a notable history of renal stones or otherwise need to have urinary calcium levels monitored, he advocated calling in a consultant. He also suggested requesting a consultation in decisions regarding sex hormone replacement therapy (HRT) for men or women, thiazide diuretics, and calcitonin in patients who do not tolerate bisphosphonates or who have pain from compression fractures. When prescribing corticosteroids, physicians should also consider drug interactions. Some agents, such as azole antifungals and macrolide antibiotics, increase corticosteroid levels and toxicity.

PARK CITY, UTAH — Patients with immunobullous disease who are on systemic glucocorticoids require monitoring for bone loss and supportive interventions to prevent drug-induced osteoporosis, Dr. Kim B. Yancey told physicians at a clinical dermatology seminar sponsored by Medicis.

Glucocorticoid-induced osteoporosis primarily affects trabecular bone, he said, labeling the problem as “especially prominent” in children, adolescents, and postmenopausal women. Other adverse effects include osteonecrosis, primarily in the hip, and impairment in bone growth. He described the underlying mechanism as biologic.

The standard glucocorticoid therapy for patients with autoimmune blistering diseases starts at 1 mg/kg per day of oral prednisone. For patients requiring more aggressive treatment, Dr. Yancy, chairman of dermatology and codirector of the cutaneous immunopathology laboratory at the Medical College of Wisconsin in Milwaukee, recommended higher doses of oral prednisone plus 1 g/day of pulse methylprednisolone for 3–5 days.

Pemphigus and pemphigoid patients starting on long-term steroids should also be instructed to take 1,200–1,500 mg of elemental calcium daily and 400 IU of vitamin D twice a day. He recommended a low-sodium diet as well.

Later, after patients have started to benefit from the regimen, he advocated prescribing bisphosphonates and encouraging patients to do simple weight-bearing exercises.

“The main thing is to try to get patients to walk,” which is easier when they are not in severe pain, he said.

Dr. Yancey noted that taking medications associated with low bone mass or bone loss is an indication for bone mineral absorptiometry. He recommended ordering this test of bone density at baseline and 1 year.

For patients who have a notable history of renal stones or otherwise need to have urinary calcium levels monitored, he advocated calling in a consultant. He also suggested requesting a consultation in decisions regarding sex hormone replacement therapy (HRT) for men or women, thiazide diuretics, and calcitonin in patients who do not tolerate bisphosphonates or who have pain from compression fractures. When prescribing corticosteroids, physicians should also consider drug interactions. Some agents, such as azole antifungals and macrolide antibiotics, increase corticosteroid levels and toxicity.

LOS ANGELES — Physicians and patients are likely to reject bisphosphonate therapy when treatment efficacy is expressed in terms of absolute risk reduction, as health literacy experts recommend, rather than relative risk reduction, Dr. Christine A. Sinsky reported at the annual meeting of the Society of General Internal Medicine.

A patient's decision to reject lifelong treatment for osteoporosis may have a negative impact on a practice's income if pay for performance is linked to compliance with clinical practice guidelines.

Those guidelines recommend the use of bisphosphonates to treat postmenopausal osteoporosis. Clinicians may deviate from these guidelines; some payers, however, link provider reimbursement for osteoporosis care to guideline adherence.

Practice guidelines, clinical trial reports, and direct to consumer advertising that recommend drug treatment for osteoporosis tend to cite relative risk reduction (RRR) when describing the benefits of therapy. Experts in health literacy, however, prefer to describe treatment benefits as absolute risk reduction (ARR), because RRR tends to overestimate risks when there is a low baseline frequency of a condition, such as hip fracture in osteoporosis. Data from the U.S. Preventive Services Task Force (USPSTF) suggest that after 5 years of treatment with bisphosphonates, the RRR for hip fracture is 35%, whereas the absolute risk of fracture in the at-risk population decreases from 3% to 2%, yield a 1% ARR (Ann. Int. Med. 2002;137:526–8).

“First, you have to get the doctors to understand the difference between RRR and ARR,” stated Dr. Sinsky, an internist in private practice in Dubuque, Iowa. She illustrated these concepts for the physician audience with a 10 by 10 grid of 100 happy faces, with three (those destined for hip fracture regardless of treatment) colored red. If treatment prevents one hip fracture out of three (roughly what the USPSTF found), one red face turned blue. If the reference class includes only the three patients who would have gotten a fracture, regardless of treatment, then the RRR is 33.3%. If the reference class includes all 100 women at risk of fracture, the ARR is 1%.

The investigators hypothesized that both patient and provider willingness to try bisphosphonate therapy for osteoporosis would be significantly lower if the efficacy were presented as ARR rather than as RRR.

The investigators administered a 10-item questionnaire to 641 consecutive female patients (aged 50 years or older) and all general medicine physicians at one university-based practice and one community practice. To assess baseline compliance with clinical practice guidelines, physicians asked patients: “You have a bone density test that indicates osteoporosis. You have full drug coverage. Are you interested in treatment?” Providers were asked: “Your 65-year-old patient has a [dual-energy x-ray absorptiometry] scan that indicates osteoporosis. The patient has full drug coverage. Would you recommend treatment?” Other scenarios presented out-of-pocket costs to the patient ranging from 0% to 90%. Subsequent questions presented similar scenarios but with efficacy of treatment presented as either RRR or ARR.

When treatment benefit was presented as RRR, 86% of patients expressed interest, compared with 57% when benefit was expressed as ARR (P < .005). Similarly, physicians were significantly more likely to recommend osteoporosis treatment for their patients when treatment benefits were presented as RRR (97%) as opposed to ARR (53%) (P < .005).

Patients were told that the cost of bisphosphonate therapy is about &dollar;1,000 per year. When the scenario stated that insurance would cover the entire cost of treatment, 81% of patients wanted therapy. In contrast, if insurance would cover only 10% of the cost, 15% of patients wanted therapy (P = .04). Under scenarios in which patients had full coverage, 100% recommended therapy; in contrast, 61% recommended therapy when insurance covered only 10% (P = .02). The data support the investigators' original hypothesis.

The data suggest that better informed patients may choose to reject lifelong drug treatment for osteoporosis.

LOS ANGELES — Physicians and patients are likely to reject bisphosphonate therapy when treatment efficacy is expressed in terms of absolute risk reduction, as health literacy experts recommend, rather than relative risk reduction, Dr. Christine A. Sinsky reported at the annual meeting of the Society of General Internal Medicine.

A patient's decision to reject lifelong treatment for osteoporosis may have a negative impact on a practice's income if pay for performance is linked to compliance with clinical practice guidelines.

Those guidelines recommend the use of bisphosphonates to treat postmenopausal osteoporosis. Clinicians may deviate from these guidelines; some payers, however, link provider reimbursement for osteoporosis care to guideline adherence.

Practice guidelines, clinical trial reports, and direct to consumer advertising that recommend drug treatment for osteoporosis tend to cite relative risk reduction (RRR) when describing the benefits of therapy. Experts in health literacy, however, prefer to describe treatment benefits as absolute risk reduction (ARR), because RRR tends to overestimate risks when there is a low baseline frequency of a condition, such as hip fracture in osteoporosis. Data from the U.S. Preventive Services Task Force (USPSTF) suggest that after 5 years of treatment with bisphosphonates, the RRR for hip fracture is 35%, whereas the absolute risk of fracture in the at-risk population decreases from 3% to 2%, yield a 1% ARR (Ann. Int. Med. 2002;137:526–8).

“First, you have to get the doctors to understand the difference between RRR and ARR,” stated Dr. Sinsky, an internist in private practice in Dubuque, Iowa. She illustrated these concepts for the physician audience with a 10 by 10 grid of 100 happy faces, with three (those destined for hip fracture regardless of treatment) colored red. If treatment prevents one hip fracture out of three (roughly what the USPSTF found), one red face turned blue. If the reference class includes only the three patients who would have gotten a fracture, regardless of treatment, then the RRR is 33.3%. If the reference class includes all 100 women at risk of fracture, the ARR is 1%.

The investigators hypothesized that both patient and provider willingness to try bisphosphonate therapy for osteoporosis would be significantly lower if the efficacy were presented as ARR rather than as RRR.

The investigators administered a 10-item questionnaire to 641 consecutive female patients (aged 50 years or older) and all general medicine physicians at one university-based practice and one community practice. To assess baseline compliance with clinical practice guidelines, physicians asked patients: “You have a bone density test that indicates osteoporosis. You have full drug coverage. Are you interested in treatment?” Providers were asked: “Your 65-year-old patient has a [dual-energy x-ray absorptiometry] scan that indicates osteoporosis. The patient has full drug coverage. Would you recommend treatment?” Other scenarios presented out-of-pocket costs to the patient ranging from 0% to 90%. Subsequent questions presented similar scenarios but with efficacy of treatment presented as either RRR or ARR.

When treatment benefit was presented as RRR, 86% of patients expressed interest, compared with 57% when benefit was expressed as ARR (P < .005). Similarly, physicians were significantly more likely to recommend osteoporosis treatment for their patients when treatment benefits were presented as RRR (97%) as opposed to ARR (53%) (P < .005).

Patients were told that the cost of bisphosphonate therapy is about &dollar;1,000 per year. When the scenario stated that insurance would cover the entire cost of treatment, 81% of patients wanted therapy. In contrast, if insurance would cover only 10% of the cost, 15% of patients wanted therapy (P = .04). Under scenarios in which patients had full coverage, 100% recommended therapy; in contrast, 61% recommended therapy when insurance covered only 10% (P = .02). The data support the investigators' original hypothesis.

The data suggest that better informed patients may choose to reject lifelong drug treatment for osteoporosis.

LOS ANGELES — Physicians and patients are likely to reject bisphosphonate therapy when treatment efficacy is expressed in terms of absolute risk reduction, as health literacy experts recommend, rather than relative risk reduction, Dr. Christine A. Sinsky reported at the annual meeting of the Society of General Internal Medicine.

A patient's decision to reject lifelong treatment for osteoporosis may have a negative impact on a practice's income if pay for performance is linked to compliance with clinical practice guidelines.

Those guidelines recommend the use of bisphosphonates to treat postmenopausal osteoporosis. Clinicians may deviate from these guidelines; some payers, however, link provider reimbursement for osteoporosis care to guideline adherence.

Practice guidelines, clinical trial reports, and direct to consumer advertising that recommend drug treatment for osteoporosis tend to cite relative risk reduction (RRR) when describing the benefits of therapy. Experts in health literacy, however, prefer to describe treatment benefits as absolute risk reduction (ARR), because RRR tends to overestimate risks when there is a low baseline frequency of a condition, such as hip fracture in osteoporosis. Data from the U.S. Preventive Services Task Force (USPSTF) suggest that after 5 years of treatment with bisphosphonates, the RRR for hip fracture is 35%, whereas the absolute risk of fracture in the at-risk population decreases from 3% to 2%, yield a 1% ARR (Ann. Int. Med. 2002;137:526–8).

“First, you have to get the doctors to understand the difference between RRR and ARR,” stated Dr. Sinsky, an internist in private practice in Dubuque, Iowa. She illustrated these concepts for the physician audience with a 10 by 10 grid of 100 happy faces, with three (those destined for hip fracture regardless of treatment) colored red. If treatment prevents one hip fracture out of three (roughly what the USPSTF found), one red face turned blue. If the reference class includes only the three patients who would have gotten a fracture, regardless of treatment, then the RRR is 33.3%. If the reference class includes all 100 women at risk of fracture, the ARR is 1%.

The investigators hypothesized that both patient and provider willingness to try bisphosphonate therapy for osteoporosis would be significantly lower if the efficacy were presented as ARR rather than as RRR.

The investigators administered a 10-item questionnaire to 641 consecutive female patients (aged 50 years or older) and all general medicine physicians at one university-based practice and one community practice. To assess baseline compliance with clinical practice guidelines, physicians asked patients: “You have a bone density test that indicates osteoporosis. You have full drug coverage. Are you interested in treatment?” Providers were asked: “Your 65-year-old patient has a [dual-energy x-ray absorptiometry] scan that indicates osteoporosis. The patient has full drug coverage. Would you recommend treatment?” Other scenarios presented out-of-pocket costs to the patient ranging from 0% to 90%. Subsequent questions presented similar scenarios but with efficacy of treatment presented as either RRR or ARR.

When treatment benefit was presented as RRR, 86% of patients expressed interest, compared with 57% when benefit was expressed as ARR (P < .005). Similarly, physicians were significantly more likely to recommend osteoporosis treatment for their patients when treatment benefits were presented as RRR (97%) as opposed to ARR (53%) (P < .005).

Patients were told that the cost of bisphosphonate therapy is about &dollar;1,000 per year. When the scenario stated that insurance would cover the entire cost of treatment, 81% of patients wanted therapy. In contrast, if insurance would cover only 10% of the cost, 15% of patients wanted therapy (P = .04). Under scenarios in which patients had full coverage, 100% recommended therapy; in contrast, 61% recommended therapy when insurance covered only 10% (P = .02). The data support the investigators' original hypothesis.

The data suggest that better informed patients may choose to reject lifelong drug treatment for osteoporosis.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

FORT LAUDERDALE, FLA. — Bisphosphonate therapy has dramatically improved the lives of patients with Paget's disease, but it's important to keep in mind the caveats when prescribing them, Dr. Kenneth W. Lyles said at a meeting sponsored by the Paget Foundation for Paget's Disease of Bone and Related Disorders.

Clinical trials have demonstrated that all bisphosphonates are capable of improving bone remodeling and reducing pain. Efficacy at normalizing serum alkaline phosphatase levels varies from 15% with etidronate to 53% with pamidronate to 73% with risedronate to 89% with zoledronic acid.

“We are developing drugs that really help control this disease and improve pain. … They're very good drugs, but they come with a set of considerations,” said Dr. Lyles, professor of medicine at Duke University, Durham, N.C.

Potential adverse events are uncommon but have been reported with one or more of the various bisphosphonates:

▸ Osteomalacia. There have been some recent reports of patients developing osteomalacia after receiving etidronate at doses of 5 mg/kg for longer than 6 months, which exceeds the label recommendations.

▸ Iritis. Rarely, iritis occurs with aminobisphosphonate therapy. If further treatment is necessary, patients can be switched to a nonaminobisphosphonate such as etidronate or tiludronate.

▸ Acute phase response. This transient flu-like syndrome consisting of fever, myalgia, and leukopenia has been reported 24–96 hours after first treatment with a bisphosphonate in 5%–40% of patients. It is seen more often with the intravenously agents than the oral ones. Its mechanism isn't completely understood, although it appears to be associated with an excessive release of tumor necrosis factor and interleukin-6 in treatment-naive patients. Patients should be warned of the possibility, and treated with aspirin, ibuprofen, or acetaminophen if it occurs, he advised.

▸ Osteonecrosis of the jaw. A series of papers since 2003 have reported this complication with alendronate, pamidronate, and zoledronate therapy. Most cases have occurred in patients who undergo tooth extraction or other dental procedures while on bisphosphonates, although malignancy and renal impairment have also been identified as risk factors. In patients who must undergo dental procedures, it may be best to give higher doses of bisphosphonate and shorten the course.

▸ Hypocalcemia. Because aminobisphosphonates rapidly block bone resorption, they can lead to hypocalcemia followed by a secondary hyperparathyroid response to restore normocalcemia. Although hypocalcemia has been reported in less than 1% overall among treated patients, severe cases have occurred in patients with malignancy, hypoparathyroidism, and unrecognized vitamin D deficiency. Patients should always be screened for vitamin D and parathyroid hormone prior to initiation of bisphosphonate therapy, and should be on calcium supplementation afterward. “If you miss this, you can have substantial problems,” Dr. Lyles noted.

▸ Vitamin D deficiency. Vitamin D insufficiency and frank deficiency are being observed increasingly among the elderly in general, and among patients with Paget's disease in particular. Indeed, one study of 104 subjects over age 98 years revealed that 95% had undetectable levels of serum 25-hydroxyvitamin D, and that 38 of them had sustained a total of 55 fractures (J. Clin. Endocrinol. Metab. 2003;88:5109–15). Vitamin D supplementation is advised for patients with Paget's disease of bone before, during, and after bisphosphonate treatment, he advised.

Dr. Lyles has financial ties to Procter & Gamble, Aventis, Amgen, Roche/GlaxoSmithKline, Merck & Co., and Novartis Pharmaceuticals.

He holds a patent for the use of zoledronate in patients who have sustained hip fractures.

The human monoclonal antibody denosumab has been found to increase bone mineral density in postmenopausal women, results of a recent randomized phase II study suggest.

Evaluation of the primary end point—the percentage change in lumbar spine bone mineral density from baseline to 12 months—indicated that denosumab was active and significantly superior to placebo (N. Engl. J. Med. 2006;354:821–31).

Dr. Michael R. McClung, of the Providence Portland (Ore.) Medical Center, and his fellow researchers evaluated 12 months of denosumab, compared with open-label oral alendronate (70 mg once weekly) or placebo in postmenopausal women with low bone mineral density, as defined by a “T score of −1.8 to −4.0 at the lumbar spine or −1.8 to −3.5 at either the femoral neck or total hip,” the researchers reported.

Subjects randomized to the experimental arm received denosumab every 3 or 6 months.

Of the 412 study participants, 319 women were randomized to the seven denosumab groups, 47 to the alendronate group, and 46 to the placebo group; 369 women completed the 12-month treatment study.

At study end, women receiving denosumab had increases in bone mineral density at the lumbar spine of 3.0%–6.7%, compared with a 0.8% decrease with placebo, or a mean increase of 4.6% with alendronate. Bone mineral density was also found to be superior with denosumab, compared with placebo at the total hip (mean change, 1.9%–3.6% vs. −0.6%, respectively), the distal third of the radius (0.4%–1.3% vs. −2.0%), and the total body (0.6%–2.8% vs. −0.2%), the researchers reported.

They noted that “in exploratory comparisons, the observed mean changes in bone mineral density were at least as great with denosumab as with alendronate.”

Denosumab targets the receptor activator of nuclear factor-β ligand (RANKL). By specifically binding to RANKL with a high affinity, denosumab inhibits RANKL activity.

In an accompanying editorial, Dr. Michael P. Whyte expressed concern that inhibiting RANKL, a member of the “tumor necrosis factor superfamily,” might have unintended effects on the immune system (N. Engl. J. Med. 2006; 354:860–3). “Accordingly, larger and longer clinical trials of denosumab for the prevention of osteoporotic fracture must search for these potential complications,” Dr. Whyte suggested.

During the study, an investigation into bone turnover indicated a significant decrease in serum C-telopeptide with denosumab that had a dose-dependent duration; a similar pattern was noted for the urinary N-telopeptide to creatinine ratio. These markers of bone turnover were at least equivalent with denosumab, compared with alendronate.

Adverse events were calculated in 406 study participants who received at least one dose of denosumab, alendronate, or placebo. Dyspepsia, however, was found to be greater in the alendronate group.

In the denosumab-treated group, 5.7% of study participants reported a serious adverse event, compared with 4.3% in the placebo group, and 2.2% in the alendronate group. In both the denosumab and placebo arms, 2.2% of the women withdrew from the study due to adverse events, and 3.8% of the denosumab group reported clinical fractures, compared with 2.2% in both the placebo and alendronate groups.

Dr. McClung and his investigators noted that their study was not designed to test equivalency, and denosumab should be further investigated for the treatment and prevention of bone-loss diseases.

The study was developed and supported by Amgen Inc., the manufacturer of denosumab. Dr. McClung disclosed having served as a consultant for, and having received grant support from, Amgen.

The human monoclonal antibody denosumab has been found to increase bone mineral density in postmenopausal women, results of a recent randomized phase II study suggest.

Evaluation of the primary end point—the percentage change in lumbar spine bone mineral density from baseline to 12 months—indicated that denosumab was active and significantly superior to placebo (N. Engl. J. Med. 2006;354:821–31).

Dr. Michael R. McClung, of the Providence Portland (Ore.) Medical Center, and his fellow researchers evaluated 12 months of denosumab, compared with open-label oral alendronate (70 mg once weekly) or placebo in postmenopausal women with low bone mineral density, as defined by a “T score of −1.8 to −4.0 at the lumbar spine or −1.8 to −3.5 at either the femoral neck or total hip,” the researchers reported.

Subjects randomized to the experimental arm received denosumab every 3 or 6 months.

Of the 412 study participants, 319 women were randomized to the seven denosumab groups, 47 to the alendronate group, and 46 to the placebo group; 369 women completed the 12-month treatment study.

At study end, women receiving denosumab had increases in bone mineral density at the lumbar spine of 3.0%–6.7%, compared with a 0.8% decrease with placebo, or a mean increase of 4.6% with alendronate. Bone mineral density was also found to be superior with denosumab, compared with placebo at the total hip (mean change, 1.9%–3.6% vs. −0.6%, respectively), the distal third of the radius (0.4%–1.3% vs. −2.0%), and the total body (0.6%–2.8% vs. −0.2%), the researchers reported.

They noted that “in exploratory comparisons, the observed mean changes in bone mineral density were at least as great with denosumab as with alendronate.”

Denosumab targets the receptor activator of nuclear factor-β ligand (RANKL). By specifically binding to RANKL with a high affinity, denosumab inhibits RANKL activity.

In an accompanying editorial, Dr. Michael P. Whyte expressed concern that inhibiting RANKL, a member of the “tumor necrosis factor superfamily,” might have unintended effects on the immune system (N. Engl. J. Med. 2006; 354:860–3). “Accordingly, larger and longer clinical trials of denosumab for the prevention of osteoporotic fracture must search for these potential complications,” Dr. Whyte suggested.

During the study, an investigation into bone turnover indicated a significant decrease in serum C-telopeptide with denosumab that had a dose-dependent duration; a similar pattern was noted for the urinary N-telopeptide to creatinine ratio. These markers of bone turnover were at least equivalent with denosumab, compared with alendronate.

Adverse events were calculated in 406 study participants who received at least one dose of denosumab, alendronate, or placebo. Dyspepsia, however, was found to be greater in the alendronate group.

In the denosumab-treated group, 5.7% of study participants reported a serious adverse event, compared with 4.3% in the placebo group, and 2.2% in the alendronate group. In both the denosumab and placebo arms, 2.2% of the women withdrew from the study due to adverse events, and 3.8% of the denosumab group reported clinical fractures, compared with 2.2% in both the placebo and alendronate groups.

Dr. McClung and his investigators noted that their study was not designed to test equivalency, and denosumab should be further investigated for the treatment and prevention of bone-loss diseases.

The study was developed and supported by Amgen Inc., the manufacturer of denosumab. Dr. McClung disclosed having served as a consultant for, and having received grant support from, Amgen.

The human monoclonal antibody denosumab has been found to increase bone mineral density in postmenopausal women, results of a recent randomized phase II study suggest.

Evaluation of the primary end point—the percentage change in lumbar spine bone mineral density from baseline to 12 months—indicated that denosumab was active and significantly superior to placebo (N. Engl. J. Med. 2006;354:821–31).

Dr. Michael R. McClung, of the Providence Portland (Ore.) Medical Center, and his fellow researchers evaluated 12 months of denosumab, compared with open-label oral alendronate (70 mg once weekly) or placebo in postmenopausal women with low bone mineral density, as defined by a “T score of −1.8 to −4.0 at the lumbar spine or −1.8 to −3.5 at either the femoral neck or total hip,” the researchers reported.

Subjects randomized to the experimental arm received denosumab every 3 or 6 months.

Of the 412 study participants, 319 women were randomized to the seven denosumab groups, 47 to the alendronate group, and 46 to the placebo group; 369 women completed the 12-month treatment study.

At study end, women receiving denosumab had increases in bone mineral density at the lumbar spine of 3.0%–6.7%, compared with a 0.8% decrease with placebo, or a mean increase of 4.6% with alendronate. Bone mineral density was also found to be superior with denosumab, compared with placebo at the total hip (mean change, 1.9%–3.6% vs. −0.6%, respectively), the distal third of the radius (0.4%–1.3% vs. −2.0%), and the total body (0.6%–2.8% vs. −0.2%), the researchers reported.

They noted that “in exploratory comparisons, the observed mean changes in bone mineral density were at least as great with denosumab as with alendronate.”

Denosumab targets the receptor activator of nuclear factor-β ligand (RANKL). By specifically binding to RANKL with a high affinity, denosumab inhibits RANKL activity.

In an accompanying editorial, Dr. Michael P. Whyte expressed concern that inhibiting RANKL, a member of the “tumor necrosis factor superfamily,” might have unintended effects on the immune system (N. Engl. J. Med. 2006; 354:860–3). “Accordingly, larger and longer clinical trials of denosumab for the prevention of osteoporotic fracture must search for these potential complications,” Dr. Whyte suggested.

During the study, an investigation into bone turnover indicated a significant decrease in serum C-telopeptide with denosumab that had a dose-dependent duration; a similar pattern was noted for the urinary N-telopeptide to creatinine ratio. These markers of bone turnover were at least equivalent with denosumab, compared with alendronate.

Adverse events were calculated in 406 study participants who received at least one dose of denosumab, alendronate, or placebo. Dyspepsia, however, was found to be greater in the alendronate group.

In the denosumab-treated group, 5.7% of study participants reported a serious adverse event, compared with 4.3% in the placebo group, and 2.2% in the alendronate group. In both the denosumab and placebo arms, 2.2% of the women withdrew from the study due to adverse events, and 3.8% of the denosumab group reported clinical fractures, compared with 2.2% in both the placebo and alendronate groups.

Dr. McClung and his investigators noted that their study was not designed to test equivalency, and denosumab should be further investigated for the treatment and prevention of bone-loss diseases.

The study was developed and supported by Amgen Inc., the manufacturer of denosumab. Dr. McClung disclosed having served as a consultant for, and having received grant support from, Amgen.

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”

TORONTO — Women with pelvic organ prolapse may be at increased risk for fracture, according to a new analysis of data from the Women's Health Initiative trial.

“As a clinician, if I see a woman who is early postmenopausal with moderate to severe prolapse, it would behoove me to get her bone density assessed to quantify her risk for fracture, because now I believe this woman is more likely to have some form of fragility phenomenon happening,” said principal investigator Dr. Lubna Pal of Albert Einstein College of Medicine, New York.

The study, which she presented as a poster at the annual meeting of the Society for Gynecologic Investigation, was based on the hypothesis that collagen deficiencies may be a unifying explanation for both pelvic organ prolapse (POP) and enhanced fracture risk in postmenopausal women, said Dr. Pal.

There is a high incidence of both prolapse and fractures in collagen-deficiency disorders such as Marfan syndrome and Ehlers-Danlos syndrome, she said. And the connection is biologically plausible, given that 90% of bone is collagen (thus making deficiency a risk factor for fracture) and that qualitative or quantitative deficiencies of tissue collagen may be more common in women with POP, than in women without.

The cross-sectional analysis included 11,096 postmenopausal women aged 60 years or older who were part of the entire WHI cohort. It found moderate to severe POP in 9% of the subjects and fragility fracture (fracture after age 55 years) in 19%.

After adjusting for confounders including age, body mass index, age at menopause, history of osteoporosis, late menarche, hormone replacement and oral contraceptive use, family history of fractures, smoking, nulliparity, and white race, the researchers found a statistically significant association between POP and fracture risk.

Women reporting moderate to severe POP were significantly more likely to have reported ever breaking a bone, compared with women with absent or mild POP (45% vs. 41%), and were also more likely to have reported a fragility fracture (21% vs. 19%), although this association was not statistically significant.

When bone mineral density (BMD) was analyzed in this context, women with moderate to severe prolapse had significantly lower total body and total hip BMD, compared with women who had absent or mild POP. They also had lower lumbar spine BMD—although this difference did not reach significance.

“Maybe as clinicians we should be recognizing this association and focusing on bone health in women who demonstrate genital prolapse,” said Dr. Pal. “We would first of all tell them they are at risk for fracture; [second,] identify any bone problems [that] are treatable; and [third,] try to optimize their bone collagen or protein content with calcium, vitamin D, weight-bearing exercise, and protein intake.”

The osteoporosis drug raloxifene is as effective as tamoxifen in preventing invasive breast cancer in postmenopausal women, according to initial results of the Study of Tamoxifen and Raloxifene (STAR) trial. The large, randomized, double-blind trial also determined that women taking raloxifene experienced fewer side effects than did those taking tamoxifen.

Raloxifene is approved for treating and preventing osteoporosis in postmenopausal women. At present, tamoxifen is the only drug approved for reducing breast cancer risk in pre- and postmenopausal women.

“This is good news for women,” said Dr. Leslie Ford, associate director for clinical research in the National Cancer Institute's Division of Cancer Prevention. “We think that this gives women a real choice for addressing two of the leading causes of morbidity and mortality as they age: breast cancer and fractures. … We can't advocate for the off-label use of drugs, but we anticipate that the company that makes raloxifene will be requesting an approval from the [Food and Drug Administration] for breast-cancer risk reduction.”

In the STAR trial, 167 of the 9,745 women in the raloxifene group and 163 of the 9,726 women in the tamoxifen group developed invasive breast cancers. There were no significant differences between the two groups in the risk of developing invasive breast cancer, which was the primary outcome of the trial.

For every 1,000 women similar to the high-risk women enrolled in the STAR trial, about 40 would be expected to develop breast cancer within 5 years if they did not take either drug. The risk would be decreased to about 20 cases of breast cancer for every 1,000 women within 5 years if they took either tamoxifen or raloxifene.

Women taking raloxifene had 36% fewer uterine cancers and 29% fewer blood clots than the women who took tamoxifen.

Dr. D. Lawrence Wickerham, associate chair of the National Surgical Adjuvant Breast and Bowel Project, characterized the results in unusually blunt terms. “We think raloxifene is the winner of this trial,” he said at a joint press briefing held by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project. The results have not yet been published. Additional data will be presented at the 42nd annual meeting of the American Society for Clinical Oncology (ASCO) to be held in Atlanta, Ga., in June.

The 19,471 women for whom complete information was available took tamoxifen or raloxifene daily for an average of 47 months. The average age of the women in the study was 58. There were no statistically significant differences in the number of fractures of the hip, wrist, and spine, with 100 for in the tamoxifen group and 96 in the raloxifene group.

Raloxifene proved inferior to tamoxifen in only one important measure. Tamoxifen has previously been shown to reduce by about half the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). Of the women taking tamoxifen, 57 developed LCIS or DCIS, compared with 81 of the women taking raloxifene.

The STAR study has been supported to date by &dollar;88 million from the National Cancer Institute and &dollar;30 million from Eli Lilly & Co., the maker of raloxifene. Both Eli Lilly and AstraZeneca Pharmaceuticals, the maker of tamoxifen, provided their drugs and matching placebos free of charge.

The osteoporosis drug raloxifene is as effective as tamoxifen in preventing invasive breast cancer in postmenopausal women, according to initial results of the Study of Tamoxifen and Raloxifene (STAR) trial. The large, randomized, double-blind trial also determined that women taking raloxifene experienced fewer side effects than did those taking tamoxifen.

Raloxifene is approved for treating and preventing osteoporosis in postmenopausal women. At present, tamoxifen is the only drug approved for reducing breast cancer risk in pre- and postmenopausal women.

“This is good news for women,” said Dr. Leslie Ford, associate director for clinical research in the National Cancer Institute's Division of Cancer Prevention. “We think that this gives women a real choice for addressing two of the leading causes of morbidity and mortality as they age: breast cancer and fractures. … We can't advocate for the off-label use of drugs, but we anticipate that the company that makes raloxifene will be requesting an approval from the [Food and Drug Administration] for breast-cancer risk reduction.”

In the STAR trial, 167 of the 9,745 women in the raloxifene group and 163 of the 9,726 women in the tamoxifen group developed invasive breast cancers. There were no significant differences between the two groups in the risk of developing invasive breast cancer, which was the primary outcome of the trial.

For every 1,000 women similar to the high-risk women enrolled in the STAR trial, about 40 would be expected to develop breast cancer within 5 years if they did not take either drug. The risk would be decreased to about 20 cases of breast cancer for every 1,000 women within 5 years if they took either tamoxifen or raloxifene.

Women taking raloxifene had 36% fewer uterine cancers and 29% fewer blood clots than the women who took tamoxifen.

Dr. D. Lawrence Wickerham, associate chair of the National Surgical Adjuvant Breast and Bowel Project, characterized the results in unusually blunt terms. “We think raloxifene is the winner of this trial,” he said at a joint press briefing held by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project. The results have not yet been published. Additional data will be presented at the 42nd annual meeting of the American Society for Clinical Oncology (ASCO) to be held in Atlanta, Ga., in June.

The 19,471 women for whom complete information was available took tamoxifen or raloxifene daily for an average of 47 months. The average age of the women in the study was 58. There were no statistically significant differences in the number of fractures of the hip, wrist, and spine, with 100 for in the tamoxifen group and 96 in the raloxifene group.

Raloxifene proved inferior to tamoxifen in only one important measure. Tamoxifen has previously been shown to reduce by about half the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). Of the women taking tamoxifen, 57 developed LCIS or DCIS, compared with 81 of the women taking raloxifene.

The STAR study has been supported to date by &dollar;88 million from the National Cancer Institute and &dollar;30 million from Eli Lilly & Co., the maker of raloxifene. Both Eli Lilly and AstraZeneca Pharmaceuticals, the maker of tamoxifen, provided their drugs and matching placebos free of charge.

The osteoporosis drug raloxifene is as effective as tamoxifen in preventing invasive breast cancer in postmenopausal women, according to initial results of the Study of Tamoxifen and Raloxifene (STAR) trial. The large, randomized, double-blind trial also determined that women taking raloxifene experienced fewer side effects than did those taking tamoxifen.

Raloxifene is approved for treating and preventing osteoporosis in postmenopausal women. At present, tamoxifen is the only drug approved for reducing breast cancer risk in pre- and postmenopausal women.

“This is good news for women,” said Dr. Leslie Ford, associate director for clinical research in the National Cancer Institute's Division of Cancer Prevention. “We think that this gives women a real choice for addressing two of the leading causes of morbidity and mortality as they age: breast cancer and fractures. … We can't advocate for the off-label use of drugs, but we anticipate that the company that makes raloxifene will be requesting an approval from the [Food and Drug Administration] for breast-cancer risk reduction.”

In the STAR trial, 167 of the 9,745 women in the raloxifene group and 163 of the 9,726 women in the tamoxifen group developed invasive breast cancers. There were no significant differences between the two groups in the risk of developing invasive breast cancer, which was the primary outcome of the trial.

For every 1,000 women similar to the high-risk women enrolled in the STAR trial, about 40 would be expected to develop breast cancer within 5 years if they did not take either drug. The risk would be decreased to about 20 cases of breast cancer for every 1,000 women within 5 years if they took either tamoxifen or raloxifene.

Women taking raloxifene had 36% fewer uterine cancers and 29% fewer blood clots than the women who took tamoxifen.

Dr. D. Lawrence Wickerham, associate chair of the National Surgical Adjuvant Breast and Bowel Project, characterized the results in unusually blunt terms. “We think raloxifene is the winner of this trial,” he said at a joint press briefing held by the National Cancer Institute and the National Surgical Adjuvant Breast and Bowel Project. The results have not yet been published. Additional data will be presented at the 42nd annual meeting of the American Society for Clinical Oncology (ASCO) to be held in Atlanta, Ga., in June.

The 19,471 women for whom complete information was available took tamoxifen or raloxifene daily for an average of 47 months. The average age of the women in the study was 58. There were no statistically significant differences in the number of fractures of the hip, wrist, and spine, with 100 for in the tamoxifen group and 96 in the raloxifene group.

Raloxifene proved inferior to tamoxifen in only one important measure. Tamoxifen has previously been shown to reduce by about half the incidence of lobular carcinoma in situ (LCIS) and ductal carcinoma in situ (DCIS). Of the women taking tamoxifen, 57 developed LCIS or DCIS, compared with 81 of the women taking raloxifene.

The STAR study has been supported to date by &dollar;88 million from the National Cancer Institute and &dollar;30 million from Eli Lilly & Co., the maker of raloxifene. Both Eli Lilly and AstraZeneca Pharmaceuticals, the maker of tamoxifen, provided their drugs and matching placebos free of charge.

SAN FRANCISCO — The burning issue of how best to make sure that patients get enough vitamin D comes down to this conclusion: Recommending intentional exposure to the sun is inappropriate, Dr. Henry W. Lim said.

For patients at risk of vitamin D deficiency, it is better to recommend a vitamin D-fortified diet and daily supplements of 800 IU of vitamin D (ideally vitamin D₃) plus calcium, he said at the annual meeting of the American Academy of Dermatology.

Dr. Lim, chairman of the dermatology residency program at Henry Ford Hospital, Detroit, organized a 2005 consensus conference for the academy called Sunlight, Tanning Booths, and Vitamin D. At the annual meeting he discussed more recent data on vitamin D and presented his preferred approach to vitamin D management.

Intentional sun exposure is a problem because the harmful side effects of UVB can't be separated from the beneficial vitamin D photosynthesis that sunlight provides. UV light acutely damages skin DNA and can cause erythema, sunburn, and photoimmunosuppression. In the long term, UV irradiation leads to photoaging and possible photocarcinogenesis. Half of all cancers in humans are skin cancers.

In addition, vitamin D synthesis appears to occur at different rates in people of different skin types. That, plus significant daily and seasonal variability in weather patterns and availability of sunlight make it difficult to craft public health policies based on intentional sun exposure, Dr. Lim said.

Studies have identified certain populations that may not be getting adequate vitamin D, including the elderly, people with darkly pigmented skin, and those living in wintry climates. Other studies, however, show that most people achieve adequate vitamin D serum levels in the course of normal daily life, even when using sunscreen, presumably through incidental sun exposure, dietary intake, and supplementation, he added.

Recent data suggest that levels in U.S. whites averaged 80 nmol/L, “which is considered nowadays by most studies to be an adequate level of serum vitamin D,” Dr. Lim noted. In Hispanic Americans, however, serum levels averaged 60 nmol/L, and in U.S. blacks, serum vitamin D averaged 50 nmol/L.

Very modest sun exposure produces maximal vitamin D photosynthesis in fair-skinned people. This makes prolonged sun exposure unnecessary and potentially dangerous for these people, he said.

Separate data on individuals older than 60 years—who presumably are less active and spend more time indoors—suggest that 67% of whites and 88% of blacks have serum vitamin D levels below 80 nmol/L.

The 2005 consensus conference concluded that it may be time to increase recommended dietary levels of vitamin D for both the frail elderly and dark-skinned people who get little sun exposure.

Natural dietary sources of vitamin D are few: saltwater fish, cod liver oil, and egg yolks. U.S. guidelines have led to vitamin D fortification of foods, most commonly milk, orange juice, cereal, butter, margarine, and chocolate mixes.

Current U.S. recommendations for daily vitamin D intake call for 200 IU for children and adults up to age 50 years, 400 IU for those aged 51–70 years, and 600–800 IU for those older than 70 years.

“In the past few years there is increasing evidence that these recommendations probably are too low,” Dr. Lim said. One recent study suggested that maintaining sufficient vitamin D levels requires 800–1,000 IU per day of vitamin D₃ or 50,000 IU once per month, a dose that's available by prescription only (Photochem. Photobiol. 2005;81:1246–51). Keep in mind that vitamin D intoxication doesn't occur until daily doses exceed 10,000 IU, Dr. Lim said. “Therefore, even at 800–1,000 IU, there is still a significant margin of safety.”

Dr. Lim recommended three sets of articles as helpful references in the ongoing debate about vitamin D:

▸ Results of the 2005 consensus conference: J. Am. Acad. Dermatol. 2005;52:868–76.

▸ A series of seven articles on UV radiation, beginning with one entitled, UV radiation, vitamin D, and human health: an unfolding controversy: Photochem. Photobiol. 2005;81:1243–5.

▸ An overview of the proceedings from the experimental biology 2004 symposium on vitamin D insufficiency: J. Nutr. 2005;135:301–37.

SAN FRANCISCO — The burning issue of how best to make sure that patients get enough vitamin D comes down to this conclusion: Recommending intentional exposure to the sun is inappropriate, Dr. Henry W. Lim said.

For patients at risk of vitamin D deficiency, it is better to recommend a vitamin D-fortified diet and daily supplements of 800 IU of vitamin D (ideally vitamin D₃) plus calcium, he said at the annual meeting of the American Academy of Dermatology.

Dr. Lim, chairman of the dermatology residency program at Henry Ford Hospital, Detroit, organized a 2005 consensus conference for the academy called Sunlight, Tanning Booths, and Vitamin D. At the annual meeting he discussed more recent data on vitamin D and presented his preferred approach to vitamin D management.

Intentional sun exposure is a problem because the harmful side effects of UVB can't be separated from the beneficial vitamin D photosynthesis that sunlight provides. UV light acutely damages skin DNA and can cause erythema, sunburn, and photoimmunosuppression. In the long term, UV irradiation leads to photoaging and possible photocarcinogenesis. Half of all cancers in humans are skin cancers.

In addition, vitamin D synthesis appears to occur at different rates in people of different skin types. That, plus significant daily and seasonal variability in weather patterns and availability of sunlight make it difficult to craft public health policies based on intentional sun exposure, Dr. Lim said.

Studies have identified certain populations that may not be getting adequate vitamin D, including the elderly, people with darkly pigmented skin, and those living in wintry climates. Other studies, however, show that most people achieve adequate vitamin D serum levels in the course of normal daily life, even when using sunscreen, presumably through incidental sun exposure, dietary intake, and supplementation, he added.

Recent data suggest that levels in U.S. whites averaged 80 nmol/L, “which is considered nowadays by most studies to be an adequate level of serum vitamin D,” Dr. Lim noted. In Hispanic Americans, however, serum levels averaged 60 nmol/L, and in U.S. blacks, serum vitamin D averaged 50 nmol/L.

Very modest sun exposure produces maximal vitamin D photosynthesis in fair-skinned people. This makes prolonged sun exposure unnecessary and potentially dangerous for these people, he said.

Separate data on individuals older than 60 years—who presumably are less active and spend more time indoors—suggest that 67% of whites and 88% of blacks have serum vitamin D levels below 80 nmol/L.

The 2005 consensus conference concluded that it may be time to increase recommended dietary levels of vitamin D for both the frail elderly and dark-skinned people who get little sun exposure.

Natural dietary sources of vitamin D are few: saltwater fish, cod liver oil, and egg yolks. U.S. guidelines have led to vitamin D fortification of foods, most commonly milk, orange juice, cereal, butter, margarine, and chocolate mixes.

Current U.S. recommendations for daily vitamin D intake call for 200 IU for children and adults up to age 50 years, 400 IU for those aged 51–70 years, and 600–800 IU for those older than 70 years.

“In the past few years there is increasing evidence that these recommendations probably are too low,” Dr. Lim said. One recent study suggested that maintaining sufficient vitamin D levels requires 800–1,000 IU per day of vitamin D₃ or 50,000 IU once per month, a dose that's available by prescription only (Photochem. Photobiol. 2005;81:1246–51). Keep in mind that vitamin D intoxication doesn't occur until daily doses exceed 10,000 IU, Dr. Lim said. “Therefore, even at 800–1,000 IU, there is still a significant margin of safety.”

Dr. Lim recommended three sets of articles as helpful references in the ongoing debate about vitamin D:

▸ Results of the 2005 consensus conference: J. Am. Acad. Dermatol. 2005;52:868–76.

▸ A series of seven articles on UV radiation, beginning with one entitled, UV radiation, vitamin D, and human health: an unfolding controversy: Photochem. Photobiol. 2005;81:1243–5.

▸ An overview of the proceedings from the experimental biology 2004 symposium on vitamin D insufficiency: J. Nutr. 2005;135:301–37.

SAN FRANCISCO — The burning issue of how best to make sure that patients get enough vitamin D comes down to this conclusion: Recommending intentional exposure to the sun is inappropriate, Dr. Henry W. Lim said.

For patients at risk of vitamin D deficiency, it is better to recommend a vitamin D-fortified diet and daily supplements of 800 IU of vitamin D (ideally vitamin D₃) plus calcium, he said at the annual meeting of the American Academy of Dermatology.

Dr. Lim, chairman of the dermatology residency program at Henry Ford Hospital, Detroit, organized a 2005 consensus conference for the academy called Sunlight, Tanning Booths, and Vitamin D. At the annual meeting he discussed more recent data on vitamin D and presented his preferred approach to vitamin D management.

Intentional sun exposure is a problem because the harmful side effects of UVB can't be separated from the beneficial vitamin D photosynthesis that sunlight provides. UV light acutely damages skin DNA and can cause erythema, sunburn, and photoimmunosuppression. In the long term, UV irradiation leads to photoaging and possible photocarcinogenesis. Half of all cancers in humans are skin cancers.

In addition, vitamin D synthesis appears to occur at different rates in people of different skin types. That, plus significant daily and seasonal variability in weather patterns and availability of sunlight make it difficult to craft public health policies based on intentional sun exposure, Dr. Lim said.

Studies have identified certain populations that may not be getting adequate vitamin D, including the elderly, people with darkly pigmented skin, and those living in wintry climates. Other studies, however, show that most people achieve adequate vitamin D serum levels in the course of normal daily life, even when using sunscreen, presumably through incidental sun exposure, dietary intake, and supplementation, he added.

Recent data suggest that levels in U.S. whites averaged 80 nmol/L, “which is considered nowadays by most studies to be an adequate level of serum vitamin D,” Dr. Lim noted. In Hispanic Americans, however, serum levels averaged 60 nmol/L, and in U.S. blacks, serum vitamin D averaged 50 nmol/L.

Very modest sun exposure produces maximal vitamin D photosynthesis in fair-skinned people. This makes prolonged sun exposure unnecessary and potentially dangerous for these people, he said.

Separate data on individuals older than 60 years—who presumably are less active and spend more time indoors—suggest that 67% of whites and 88% of blacks have serum vitamin D levels below 80 nmol/L.

The 2005 consensus conference concluded that it may be time to increase recommended dietary levels of vitamin D for both the frail elderly and dark-skinned people who get little sun exposure.

Natural dietary sources of vitamin D are few: saltwater fish, cod liver oil, and egg yolks. U.S. guidelines have led to vitamin D fortification of foods, most commonly milk, orange juice, cereal, butter, margarine, and chocolate mixes.

Current U.S. recommendations for daily vitamin D intake call for 200 IU for children and adults up to age 50 years, 400 IU for those aged 51–70 years, and 600–800 IU for those older than 70 years.

“In the past few years there is increasing evidence that these recommendations probably are too low,” Dr. Lim said. One recent study suggested that maintaining sufficient vitamin D levels requires 800–1,000 IU per day of vitamin D₃ or 50,000 IU once per month, a dose that's available by prescription only (Photochem. Photobiol. 2005;81:1246–51). Keep in mind that vitamin D intoxication doesn't occur until daily doses exceed 10,000 IU, Dr. Lim said. “Therefore, even at 800–1,000 IU, there is still a significant margin of safety.”

Dr. Lim recommended three sets of articles as helpful references in the ongoing debate about vitamin D:

▸ Results of the 2005 consensus conference: J. Am. Acad. Dermatol. 2005;52:868–76.

▸ A series of seven articles on UV radiation, beginning with one entitled, UV radiation, vitamin D, and human health: an unfolding controversy: Photochem. Photobiol. 2005;81:1243–5.

▸ An overview of the proceedings from the experimental biology 2004 symposium on vitamin D insufficiency: J. Nutr. 2005;135:301–37.

BETHESDA, MD. — The current recommended dietary allowance for calcium of 1,200 mg/day for people older than 50 was supported by the results of the Women's Health Initiative's calcium and vitamin D trial.

Although the trial's results failed to prove the study's primary hypothesis, that a daily supplement of calcium and vitamin D would significantly cut the incidence of hip fractures in postmenopausal women aged 50–79, the trial produced enough positive results to support the existing recommended dietary allowance, Dr. Rebecca D. Jackson said at a conference on the Women's Health Initiative, sponsored by the Department of Health and Human Services.

A practical guide for physicians is that each glass of milk or dairy serving provides about 300 mg of calcium. So if a postmenopausal woman eats three to four dairy servings a day, she is probably getting enough calcium. If not, a calcium supplement is a good idea, said Dr. Johnson, a professor of medicine at Ohio State University, Columbus, and a principal investigator of the WHI.

After the WHI's calcium and vitamin D study was designed, it was piggybacked onto the two other studies that had already begun, the hormone therapy and diet modification trials. More than 36,000 women who were already enrolled in one or both of these ongoing WHI studies were randomized to get a daily supplement of 500 mg elemental calcium and 200 IU vitamin D or placebo, and they were followed for an average of 7 years.

The enrollment criteria did not contain exclusions based on calcium and vitamin D intake, and it specifically allowed women to take additional supplements of up to 1,000 mg calcium and 600 IU vitamin D per day. At baseline, before the study began, a third of the enrolled women had a total daily calcium intake of at least 1,200 mg calcium, and another 45% had a daily intake of at least 1,000 mg, which meant that 78% of the participants already had a sufficient supply and were “probably not the best candidates for a calcium supplement trial,” said Joan A. McGowan, Ph.D., director of the musculoskeletal diseases branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

The study's primary end point was the incidence of hip fractures, with a secondary end point of incidence of all fractures.

The incidence of hip fractures was 0.14% in the supplement group and 0.16% in the placebo group, a relative reduction of 12% that was not statistically significant (N. Engl. J. Med. 2006;354:669–83). The incidence of all fractures was 1.64% and 1.70% in the intervention and placebo groups, respectively, also a nonsignificant difference.

These analyses were done on an intention-to-treat basis. During the first 3 years of the study, 60%–63% of women were adherent to the regimen, taking at least 80% of their assigned supplements. By the end of the study, 59% were still taking at least 80%.

A secondary analysis that focused only on the adherent participants showed that the incidence of hip fracture was 29% lower in the women taking calcium and vitamin D, compared with the placebo group, a statistically significant difference.

Another secondary analysis focused only on women aged 60 or older, the group at highest risk of fracture. In this subgroup, the risk of hip fracture was 21% lower in the women in the active treatment arm, also a significant difference.

The main adverse effect of calcium supplementation was a 17% increased risk of having kidney stones, a significant difference. “Although there was an increased risk of kidney stones, the possible benefits of calcium with vitamin D supplementation for the risk of fracture cannot be totally ignored,” Dr. Joel S. Finkelstein, an endocrinologist at Massachusetts General Hospital, Boston, wrote in an editorial that accompanied the published findings (N. Engl. J. Med. 2006;354:750–2).

BETHESDA, MD. — The current recommended dietary allowance for calcium of 1,200 mg/day for people older than 50 was supported by the results of the Women's Health Initiative's calcium and vitamin D trial.

Although the trial's results failed to prove the study's primary hypothesis, that a daily supplement of calcium and vitamin D would significantly cut the incidence of hip fractures in postmenopausal women aged 50–79, the trial produced enough positive results to support the existing recommended dietary allowance, Dr. Rebecca D. Jackson said at a conference on the Women's Health Initiative, sponsored by the Department of Health and Human Services.

A practical guide for physicians is that each glass of milk or dairy serving provides about 300 mg of calcium. So if a postmenopausal woman eats three to four dairy servings a day, she is probably getting enough calcium. If not, a calcium supplement is a good idea, said Dr. Johnson, a professor of medicine at Ohio State University, Columbus, and a principal investigator of the WHI.

After the WHI's calcium and vitamin D study was designed, it was piggybacked onto the two other studies that had already begun, the hormone therapy and diet modification trials. More than 36,000 women who were already enrolled in one or both of these ongoing WHI studies were randomized to get a daily supplement of 500 mg elemental calcium and 200 IU vitamin D or placebo, and they were followed for an average of 7 years.

The enrollment criteria did not contain exclusions based on calcium and vitamin D intake, and it specifically allowed women to take additional supplements of up to 1,000 mg calcium and 600 IU vitamin D per day. At baseline, before the study began, a third of the enrolled women had a total daily calcium intake of at least 1,200 mg calcium, and another 45% had a daily intake of at least 1,000 mg, which meant that 78% of the participants already had a sufficient supply and were “probably not the best candidates for a calcium supplement trial,” said Joan A. McGowan, Ph.D., director of the musculoskeletal diseases branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

The study's primary end point was the incidence of hip fractures, with a secondary end point of incidence of all fractures.

The incidence of hip fractures was 0.14% in the supplement group and 0.16% in the placebo group, a relative reduction of 12% that was not statistically significant (N. Engl. J. Med. 2006;354:669–83). The incidence of all fractures was 1.64% and 1.70% in the intervention and placebo groups, respectively, also a nonsignificant difference.

These analyses were done on an intention-to-treat basis. During the first 3 years of the study, 60%–63% of women were adherent to the regimen, taking at least 80% of their assigned supplements. By the end of the study, 59% were still taking at least 80%.

A secondary analysis that focused only on the adherent participants showed that the incidence of hip fracture was 29% lower in the women taking calcium and vitamin D, compared with the placebo group, a statistically significant difference.

Another secondary analysis focused only on women aged 60 or older, the group at highest risk of fracture. In this subgroup, the risk of hip fracture was 21% lower in the women in the active treatment arm, also a significant difference.

The main adverse effect of calcium supplementation was a 17% increased risk of having kidney stones, a significant difference. “Although there was an increased risk of kidney stones, the possible benefits of calcium with vitamin D supplementation for the risk of fracture cannot be totally ignored,” Dr. Joel S. Finkelstein, an endocrinologist at Massachusetts General Hospital, Boston, wrote in an editorial that accompanied the published findings (N. Engl. J. Med. 2006;354:750–2).

BETHESDA, MD. — The current recommended dietary allowance for calcium of 1,200 mg/day for people older than 50 was supported by the results of the Women's Health Initiative's calcium and vitamin D trial.

Although the trial's results failed to prove the study's primary hypothesis, that a daily supplement of calcium and vitamin D would significantly cut the incidence of hip fractures in postmenopausal women aged 50–79, the trial produced enough positive results to support the existing recommended dietary allowance, Dr. Rebecca D. Jackson said at a conference on the Women's Health Initiative, sponsored by the Department of Health and Human Services.

A practical guide for physicians is that each glass of milk or dairy serving provides about 300 mg of calcium. So if a postmenopausal woman eats three to four dairy servings a day, she is probably getting enough calcium. If not, a calcium supplement is a good idea, said Dr. Johnson, a professor of medicine at Ohio State University, Columbus, and a principal investigator of the WHI.

After the WHI's calcium and vitamin D study was designed, it was piggybacked onto the two other studies that had already begun, the hormone therapy and diet modification trials. More than 36,000 women who were already enrolled in one or both of these ongoing WHI studies were randomized to get a daily supplement of 500 mg elemental calcium and 200 IU vitamin D or placebo, and they were followed for an average of 7 years.

The enrollment criteria did not contain exclusions based on calcium and vitamin D intake, and it specifically allowed women to take additional supplements of up to 1,000 mg calcium and 600 IU vitamin D per day. At baseline, before the study began, a third of the enrolled women had a total daily calcium intake of at least 1,200 mg calcium, and another 45% had a daily intake of at least 1,000 mg, which meant that 78% of the participants already had a sufficient supply and were “probably not the best candidates for a calcium supplement trial,” said Joan A. McGowan, Ph.D., director of the musculoskeletal diseases branch of the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

The study's primary end point was the incidence of hip fractures, with a secondary end point of incidence of all fractures.

The incidence of hip fractures was 0.14% in the supplement group and 0.16% in the placebo group, a relative reduction of 12% that was not statistically significant (N. Engl. J. Med. 2006;354:669–83). The incidence of all fractures was 1.64% and 1.70% in the intervention and placebo groups, respectively, also a nonsignificant difference.

These analyses were done on an intention-to-treat basis. During the first 3 years of the study, 60%–63% of women were adherent to the regimen, taking at least 80% of their assigned supplements. By the end of the study, 59% were still taking at least 80%.

A secondary analysis that focused only on the adherent participants showed that the incidence of hip fracture was 29% lower in the women taking calcium and vitamin D, compared with the placebo group, a statistically significant difference.

Another secondary analysis focused only on women aged 60 or older, the group at highest risk of fracture. In this subgroup, the risk of hip fracture was 21% lower in the women in the active treatment arm, also a significant difference.

The main adverse effect of calcium supplementation was a 17% increased risk of having kidney stones, a significant difference. “Although there was an increased risk of kidney stones, the possible benefits of calcium with vitamin D supplementation for the risk of fracture cannot be totally ignored,” Dr. Joel S. Finkelstein, an endocrinologist at Massachusetts General Hospital, Boston, wrote in an editorial that accompanied the published findings (N. Engl. J. Med. 2006;354:750–2).

SAN DIEGO — Heel ultrasound is a promising way to initially identify low bone mass in developmentally disabled patients, Dr. Kelly D. Krohn said during a poster session at the annual meeting of the International Society for Clinical Densitometry.

The finding is important because low bone density “is a common, complicated problem in people who have physical disabilities,” Dr. Krohn, director of clinical research, department of medicine, at Mercy Hospital in Pittsburgh, Pa., said in an interview. “A big part of it is that they're not able to bear weight. They're sitting in a wheelchair for 25–30 years and they have really fragile bones. But they're also challenging to bring to the office and do standard DXA [dual-energy x-ray absorptiometry] bone density testing on.”

He and his associates used a portable heel ultrasound densitometer to screen 135 mentally and physically challenged men and women who were living in intermediate care facilities in Allegheny County, Pa. Screenings took place either in their residence or at the hospital's on-site medical clinic.

The researchers, who were led by Dr. Vinee Varma, also of Mercy Hospital, collected data on age, gender, race, and weight-bearing status.

They defined low bone mass as having a T score of −1.0 or lower.

If heel scans were positive, the researchers forwarded the results to the physician.

When indicated, patients were referred for a central DXA of the hip and spine.

The average age of the 135 patients was 50; about half (68) were men; and most (90%) were white.

Of the patients, 55% had full weight-bearing capabilities, 42% were unable to bear weight, and 3% were able to partially bear weight.

Dr. Krohn and his associates found that 80% of the women and 72% of the men had evidence of low bone density on heel ultrasound. In addition, 91% of patients who were unable to bear weight had low bone mass, compared with 70% of patients who had full weight-bearing capabilities.

Subsequent central DXA scans performed in 91 patients confirmed the overall results of the positive heel ultrasounds. When the researchers used a heel ultrasound T score of −1.0 or lower, 70% had low bone mineral density (BMD) on central DXA. When they used a heel ultrasound score of −2.0 or lower, 81% had low BMD on central DXA.

In another component of the study, five patients with a normal heel ultrasound had central DXA performed. Low BMD was found in two of the five.

“Any screening test has failures,” Dr. Krohn noted.

“You miss some and you overcall some. For us, heel ultrasound has been a nice way to get a good handle on [the BMD in] several hundred disabled residents. A large number of them have a real risk for fractures. This is an easy way to identify them,” he said.

'Heel ultrasound has been a nice way to get a good handle on [BMD in] several hundred disabled residents.' DR. KROHN

SAN DIEGO — Heel ultrasound is a promising way to initially identify low bone mass in developmentally disabled patients, Dr. Kelly D. Krohn said during a poster session at the annual meeting of the International Society for Clinical Densitometry.

The finding is important because low bone density “is a common, complicated problem in people who have physical disabilities,” Dr. Krohn, director of clinical research, department of medicine, at Mercy Hospital in Pittsburgh, Pa., said in an interview. “A big part of it is that they're not able to bear weight. They're sitting in a wheelchair for 25–30 years and they have really fragile bones. But they're also challenging to bring to the office and do standard DXA [dual-energy x-ray absorptiometry] bone density testing on.”

He and his associates used a portable heel ultrasound densitometer to screen 135 mentally and physically challenged men and women who were living in intermediate care facilities in Allegheny County, Pa. Screenings took place either in their residence or at the hospital's on-site medical clinic.

The researchers, who were led by Dr. Vinee Varma, also of Mercy Hospital, collected data on age, gender, race, and weight-bearing status.

They defined low bone mass as having a T score of −1.0 or lower.

If heel scans were positive, the researchers forwarded the results to the physician.

When indicated, patients were referred for a central DXA of the hip and spine.

The average age of the 135 patients was 50; about half (68) were men; and most (90%) were white.

Of the patients, 55% had full weight-bearing capabilities, 42% were unable to bear weight, and 3% were able to partially bear weight.

Dr. Krohn and his associates found that 80% of the women and 72% of the men had evidence of low bone density on heel ultrasound. In addition, 91% of patients who were unable to bear weight had low bone mass, compared with 70% of patients who had full weight-bearing capabilities.

Subsequent central DXA scans performed in 91 patients confirmed the overall results of the positive heel ultrasounds. When the researchers used a heel ultrasound T score of −1.0 or lower, 70% had low bone mineral density (BMD) on central DXA. When they used a heel ultrasound score of −2.0 or lower, 81% had low BMD on central DXA.

In another component of the study, five patients with a normal heel ultrasound had central DXA performed. Low BMD was found in two of the five.

“Any screening test has failures,” Dr. Krohn noted.

“You miss some and you overcall some. For us, heel ultrasound has been a nice way to get a good handle on [the BMD in] several hundred disabled residents. A large number of them have a real risk for fractures. This is an easy way to identify them,” he said.

'Heel ultrasound has been a nice way to get a good handle on [BMD in] several hundred disabled residents.' DR. KROHN

SAN DIEGO — Heel ultrasound is a promising way to initially identify low bone mass in developmentally disabled patients, Dr. Kelly D. Krohn said during a poster session at the annual meeting of the International Society for Clinical Densitometry.

The finding is important because low bone density “is a common, complicated problem in people who have physical disabilities,” Dr. Krohn, director of clinical research, department of medicine, at Mercy Hospital in Pittsburgh, Pa., said in an interview. “A big part of it is that they're not able to bear weight. They're sitting in a wheelchair for 25–30 years and they have really fragile bones. But they're also challenging to bring to the office and do standard DXA [dual-energy x-ray absorptiometry] bone density testing on.”

He and his associates used a portable heel ultrasound densitometer to screen 135 mentally and physically challenged men and women who were living in intermediate care facilities in Allegheny County, Pa. Screenings took place either in their residence or at the hospital's on-site medical clinic.

The researchers, who were led by Dr. Vinee Varma, also of Mercy Hospital, collected data on age, gender, race, and weight-bearing status.

They defined low bone mass as having a T score of −1.0 or lower.

If heel scans were positive, the researchers forwarded the results to the physician.

When indicated, patients were referred for a central DXA of the hip and spine.

The average age of the 135 patients was 50; about half (68) were men; and most (90%) were white.

Of the patients, 55% had full weight-bearing capabilities, 42% were unable to bear weight, and 3% were able to partially bear weight.

Dr. Krohn and his associates found that 80% of the women and 72% of the men had evidence of low bone density on heel ultrasound. In addition, 91% of patients who were unable to bear weight had low bone mass, compared with 70% of patients who had full weight-bearing capabilities.

Subsequent central DXA scans performed in 91 patients confirmed the overall results of the positive heel ultrasounds. When the researchers used a heel ultrasound T score of −1.0 or lower, 70% had low bone mineral density (BMD) on central DXA. When they used a heel ultrasound score of −2.0 or lower, 81% had low BMD on central DXA.

In another component of the study, five patients with a normal heel ultrasound had central DXA performed. Low BMD was found in two of the five.

“Any screening test has failures,” Dr. Krohn noted.

“You miss some and you overcall some. For us, heel ultrasound has been a nice way to get a good handle on [the BMD in] several hundred disabled residents. A large number of them have a real risk for fractures. This is an easy way to identify them,” he said.

'Heel ultrasound has been a nice way to get a good handle on [BMD in] several hundred disabled residents.' DR. KROHN

SAN DIEGO — A chief advantage of assessing bone turnover markers such as serum osteocalcin and urine hydroxyproline in osteoporosis patients is that they provide an integrated assessment of skeletal metabolism, Dr. Marc C. Hochberg reported at the annual meeting of the International Society for Clinical Densitometry.

Among other advantages of using these markers:

▸ They show rapid and large changes with therapy.

▸ Automated assays are widely available, and they are less expensive than dual-energy x-ray absorptiometry, although more expensive than ultrasound.

▸ Elevated bone turnover is associated with fracture risk, independent of bone mineral density.

However, “as with everything, there are advantages and limitations” to bone turnover markers, said Dr. Hochberg, head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

For example, some bone markers reflect both bone formation and bone resorption.

Also, “most of the markers are present in tissues other than bone and may be influenced by nonskeletal processes,” he said.

Further, changes in bone turnover markers are not disease specific, and measurement of the markers varies.

Potential uses for bone turnover markers include the ability to predict the rate of future bone loss and the occurrence of osteoporotic fractures, to monitor the efficacy of treatment, to enhance adherence to therapy, to identify patients for treatment, and to allow selection of the optimal agent.

Most 'are present in tissues other than bone and may be influenced by nonskeletal processes.' DR. HOCHBERG

SAN DIEGO — A chief advantage of assessing bone turnover markers such as serum osteocalcin and urine hydroxyproline in osteoporosis patients is that they provide an integrated assessment of skeletal metabolism, Dr. Marc C. Hochberg reported at the annual meeting of the International Society for Clinical Densitometry.

Among other advantages of using these markers:

▸ They show rapid and large changes with therapy.

▸ Automated assays are widely available, and they are less expensive than dual-energy x-ray absorptiometry, although more expensive than ultrasound.

▸ Elevated bone turnover is associated with fracture risk, independent of bone mineral density.

However, “as with everything, there are advantages and limitations” to bone turnover markers, said Dr. Hochberg, head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

For example, some bone markers reflect both bone formation and bone resorption.

Also, “most of the markers are present in tissues other than bone and may be influenced by nonskeletal processes,” he said.

Further, changes in bone turnover markers are not disease specific, and measurement of the markers varies.

Potential uses for bone turnover markers include the ability to predict the rate of future bone loss and the occurrence of osteoporotic fractures, to monitor the efficacy of treatment, to enhance adherence to therapy, to identify patients for treatment, and to allow selection of the optimal agent.

Most 'are present in tissues other than bone and may be influenced by nonskeletal processes.' DR. HOCHBERG

SAN DIEGO — A chief advantage of assessing bone turnover markers such as serum osteocalcin and urine hydroxyproline in osteoporosis patients is that they provide an integrated assessment of skeletal metabolism, Dr. Marc C. Hochberg reported at the annual meeting of the International Society for Clinical Densitometry.

Among other advantages of using these markers:

▸ They show rapid and large changes with therapy.

▸ Automated assays are widely available, and they are less expensive than dual-energy x-ray absorptiometry, although more expensive than ultrasound.

▸ Elevated bone turnover is associated with fracture risk, independent of bone mineral density.

However, “as with everything, there are advantages and limitations” to bone turnover markers, said Dr. Hochberg, head of the division of rheumatology and clinical immunology at the University of Maryland, Baltimore.

For example, some bone markers reflect both bone formation and bone resorption.

Also, “most of the markers are present in tissues other than bone and may be influenced by nonskeletal processes,” he said.

Further, changes in bone turnover markers are not disease specific, and measurement of the markers varies.

Potential uses for bone turnover markers include the ability to predict the rate of future bone loss and the occurrence of osteoporotic fractures, to monitor the efficacy of treatment, to enhance adherence to therapy, to identify patients for treatment, and to allow selection of the optimal agent.

Most 'are present in tissues other than bone and may be influenced by nonskeletal processes.' DR. HOCHBERG