1. Home>
2. Specialties>
3. Women's Health>
4. Summary and Comment

A New Agent for Postmenopausal Osteoporosis?

Biannual subcutaneous denosumab injections prevented vertebral, nonvertebral, and hip fractures.

Osteoporosis results largely from bone resorption by osteoclasts, which depend on a cytokine known as receptor activator of nuclear factor-B ligand (RANKL) to develop, function, and survive. Denosumab, a human monoclonal antibody against RANKL, inhibits osteoclast-mediated bone resorption. In a manufacturer-sponsored trial, 7868 women (mean age, 72; mean spine and total hip BMD T-scores at enrollment, –2.8 and –1.9, respectively) were randomized to receive 60-mg denosumab or placebo subcutaneously every 6 months for 3 years.

Relative risk for new radiographically diagnosed vertebral fractures was 68% lower in the denosumab group than in the placebo group (36-month incidence, 2.3% vs. 7.2%; P<0.001). Risk for hip fractures was 40% lower (0.7% vs. 1.2%; P=0.04) and for nonvertebral fractures was 20% lower (6.5% vs. 8.0%; P=0.01) in the denosumab group. Overall incidence of adverse events, cancer, cardiovascular events, and opportunistic infections was similar between groups. Although cellulitis occurred equally often in both groups, 12 denosumab recipients and 1 placebo recipient were hospitalized for the condition.

Comment: The anabolic agent teriparatide and the bisphosphonate zoledronic acid are considered to be among the osteoporotic drugs that are most effective in preventing fractures. If denosumab receives FDA approval, what role will it play in managing bone loss in postmenopausal women as well as in men who receive androgen-deprivation therapy (JW Oncol Hematol Aug 11 2009)? As an editorialist notes, denosumab seems to be as effective as teriparatide and zoledronic acid (and perhaps more effective than oral bisphosphonates). Uncommon but serious adverse events (e.g., osteonecrosis of the jaw) associated with long-term bisphosphonate use are unlikely to be linked to short-acting agents such as denosumab. Because denosumab is an antibody, its potential to affect the immune system requires scrutiny. Long-term adherence to oral bisphosphonate therapy is often poor, making the relative ease of biannual denosumab injections attractive. Although teriparatide and intravenous bisphosphonates are expensive, weekly oral alendronate is available at low cost as a generic; accordingly, denosumab's cost will likely play a central role in determining how it is used clinically.

— Andrew M. Kaunitz, MD

Dr. Kaunitz participated in a manufacturer-sponsored roundtable discussion on osteoporosis to be published in OBG Management.

Published in Journal Watch Women's Health August 11, 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. (http://dx.doi.org/10.1056/NEJMoa0809493)

• Original article (Subscription may be required)
• Medline abstract (Free)

Khosla S. Increasing options for the treatment of osteoporosis. N Engl J Med 2009 Aug 20; 361:818. (http://dx.doi.org/10.1056/NEJMe0905480)

• Original article (Subscription may be required)
• Medline abstract (Free)