Goal-directed osteoporosis treatment: are bone mineral density targets valid?

Over the last decade, goal-directed management of osteoporosis has been developed as a concept. In 2024, a working group of the American Society for Bone and Mineral Research (ASBMR) determined that this concept should include specific bone mineral density (BMD) targets during treatment, to ensure optimal fracture risk reduction. Two observations were key to this recommendation: that higher on-treatment BMDs are associated with lower fracture risks in several studies, and that, in a meta-regression of individual clinical trials, agents producing larger increases in BMD also produced greater reduction in fracture risk. However, the inferences drawn from these studies might be unsound. First, on-treatment BMD is the sum of baseline BMD and its change on therapy. In trials in which these variables have both been considered, it was found that the influence of on-treatment BMD is substantially a reflection of the effect of baseline BMD on fracture risk rather than an effect of on-treatment BMD change. Second, the meta-regression findings are heavily dependent on the inclusion of less effective treatments in the analysis. Among more effective antiresorptives, no such relationship is seen. For example, although denosumab has greater effects on BMD than zoledronate, these agents have similar anti-fracture efficacy in trials. Therefore, a key conclusion of the treat-to-BMD-target framework-that denosumab is needed for many patients to reach their BMD targets-has no clinical trial support, suggesting the framework is flawed. Thus, use of BMD treatment targets in osteoporosis management is not supported by available evidence, so the frequent BMD measurements required by the treat-to-target framework will increase costs without demonstrable benefit.