Prevention of incident fractures in patients with prevalent fragility fractures: Current and future approaches.

Fragility fractures are a significant, independent risk factor for new fractures, but treatment uptake in subjects with prevalent fractures is disappointing. We addressed the question of the efficacy of pharmacological interventions in reducing the risk of incident fractures in patients with prevalent fragility fractures. For this, we reviewed randomised controlled trials (RCTs), pre-planned and post-hoc analyses of RCTs of approved agents for the treatment of osteoporosis. Results showed that a number of agents decrease the risk of incident vertebral and nonvertebral fractures in subjects with prevalent vertebral fractures, justifying the recommendation of treating such patients independently of the level of bone mineral density (BMD). By contrast, the evidence of antifracture efficacy of these agents in patients with prevalent nonvertebral fractures is limited. Advances in our understanding of the regulation of bone metabolism at the molecular level have identified targets for the development of new therapeutics for osteoporosis, some of which are currently in phase 3 clinical development.