Denosumab reduces fracture risk better than placebo

Clinical question Is denosumab safe and effective for the prevention of fractures in women with osteoporosis?

Bottom line Like bisphosphonates, denosumab modestly decreases the risk of clinical fracture in postmenopausal women with significant osteoporosis (T score = –2.5 to –4). Denosumab was not compared with bisphosphonates because it is unlikely that this new drug is more effective. We should therefore only prescribe it for women who cannot tolerate bisphosphonates, as the cost of denosumab is approximately $1,000 per year, which is much higher than generic bisphosphonates. (Level of evidence = 1b)

Synopsis These authors included women between the ages of 60 years and 90 years with a bone mineral density T score between ≥2.5 and ≥4.0 at the lumbar spine or hip. Women were excluded as being inappropriately high risk for a placebo-controlled study if they had one severe vertebral fracture (or at least two of any severity). The 7,808 included women were randomized to receive denosumab (an injected human monoclonal antibody that inhibits osteoclast-mediated bone resorption) or placebo. The drug is given at a dosage of 60 mg subcutaneously every 6 months. Women underwent radiography once a year to look for vertebral fractures, and were followed up for a total of 3 years. The mean age of women was 72 years, most were from Europe, and 24% had a prevalent radiologic vertebral fracture on enrollment. Analysis was by intention to treat, but procedures for concealment of allocation to groups were not described. After 3 years, the patients receiving denosumab had a reduced risk of new clinical vertebral fracture (0.8% vs 2.6%; P < .001; number needed to treat [NNT] = 56 for 3 years) and a slightly reduced risk of hip fracture (0.7% vs 1.2%; P = .04; NNT = 200 for 3 years). Eczema and cellulitis were more common in patients receiving the active drug, but, oddly, falling and concussion were less common in those women.

Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361(8):756-765.