This Practice Point commentary discusses the findings and limitations of the first randomized, placebo-controlled trial of twice-yearly denosumab to be performed in postmenopausal women with low BMD but no previous fracture. Bone et al. found that treatment with denosumab significantly increased BMD at all sites measured and reduced the levels of bone turnover markers when compared with placebo. Despite these beneficial effects, denosumab was associated with increased rates of sore throat, rash and infections requiring hospitalization. Furthermore, the study was limited by lack of information on antifracture efficacy, although such information will presumably be forthcoming in the near future. Here, I highlight how denosumab therapy differs from other antiresorptive agents with respect to mechanism of action and effects on BMD. The findings of Bone et al. suggest that denosumab might represent a novel anti-osteoporosis agent. Nonetheless, further investigations of efficacy and long-term safety are needed before denosumab can be adopted into routine clinical practice.