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Possible New Option for Treating Osteoporosis

Both men who were receiving androgen-deprivation therapy and postmenopausal women gained bone density with denosumab.

Denosumab is a monoclonal antibody that attenuates bone resorption by inhibiting a cytokine essential for osteoclast function. This drug, which is under FDA review but is not yet approved, is the focus of two industry-sponsored randomized trials.

In one trial, nearly 8000 postmenopausal women with osteoporosis received subcutaneous injections of denosumab or placebo every 6 months for 3 years. Denosumab — compared with placebo — was associated with lower incidences of new radiographic vertebral fractures (2.3% vs. 7.2%), clinical vertebral fractures (0.8% vs. 2.6%), nonvertebral fractures (6.5% vs. 8.0%), and hip fractures (0.7% vs. 1.2%). Incidences of side effects were similar in the two groups.

Androgen-deprivation therapy causes bone loss and raises fracture risk. In another study, 1468 men using androgen-deprivation therapy for prostate cancer received denosumab or placebo. During 3 years, new radiographic vertebral fractures occurred significantly less often with denosumab than with placebo (1.5% vs. 3.9%). A small difference in any-site fractures did not reach significance (5.2% vs. 7.2%; P=0.10).

In both studies, denosumab groups — compared with placebo groups — gained significantly more bone-mineral density. Adverse events appeared to be comparable in the denosumab and placebo groups.

Comment: If the FDA approves denosumab, primary care physicians will need guidance about its place in osteoporosis treatment algorithms. An editorialist, who remains noncommittal about its role, notes that we should gather more long-term safety data and that cost likely will influence how denosumab is used. Readers should also note that clinically silent radiographic vertebral fractures constituted a substantial portion of the prevented fractures in these trials.

— Allan S. Brett, MD

Published in Journal Watch General Medicine August 20, 2009

Citation(s):

Cummings SR et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009 Aug 20; 361:756.

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• Medline abstract (Free)

Smith MR et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009 Aug 20; 361:745.

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• Medline abstract (Free)

Khosla S. Increasing options for the treatment of osteoporosis. N Engl J Med 2009 Aug 20; 361:818.

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• Medline abstract (Free)