Denosumab in postmenopausal women with low bone mineral density

Despite the availability of drugs that lower the risk of bone fracture in osteoporotic patients, few patients comply fully with current treatments. The investigators evaluated denosumab-previously known as AMG 162-a fully human monoclonal antibody (immunoglobulin G 2 ) that binds strongly and specifically to RANKL or receptor activator of nuclear factor-KB ligand. RANKL is a protein expressed by osteoblastic stromal cells and is the major mediator of osteoclast differentiation, activation, and survival. RANKL underlies osteoclast-mediated bone resorption. Denosumab acts by blocking the interaction of RANKL with RANK and mimics the effects of osteoprotegerin. This randomized, placebo-controlled study examined the effects of subcutaneously administered denosumab over 12 months in 412 postmenopausal women aged up to 80 years with low bone mineral density (BMD) defined as a T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur. Participants were assigned to receive denosumab either every 3 months in a dose of 6, 14, or 30 mg or every 6 months in a dose of 14, 60, 100, or 120 mg; alendronate orally in a dose of 70 mg once a week (on an open-label basis); or placebo. The primary end point was the percentage change in BMD at the lumbar spine after 12 months. A total of 369 women, 90% of the original sample, completed 12 months of treatment. BMD at the lumbar spine increased from 3.0% to 6.7% at 12 months in women given denosumab compared with a decrease of 0.8% in placebo recipients (P <.001). Total hip BMD increased by a mean of 1.9% to 3.6% with denosumab treatment and fell 0.6% in placebo patients (P <.001). BMD also increased in the distal radius in women given denosumab. Alendronate increased BMD compared with placebo at 12 months. Serum levels of C-telopeptide, a marker of bone turnover, decreased in women given denosumab compared with placebo patients. Alendronate also lowered markers of bone turnover. A small reduction in the albumin-adjusted serum calcium level was noted in the denosumab group, and concentrations of intact parathyroid hormone increased. Side effects were similar in all groups except for dyspepsia, which was significantly more frequent in women given alendronate. Denosumab deserves further study as a possible treatment for osteoporosis in postmenopausal women.