Therapeutic Approaches to Secondary Fracture Prevention in High Risk Populations: Current Recommendations and Advances

Abstract

Background: Osteoporotic fragility fracture is a burgeoning health epidemic that is associated with high rates of disability, morbidity, and mortality. Based on NHANES data, approximately 10 million Americans are affected by this disease. Areas of Uncertainty: Successful secondary fracture prevention measures are often limited by the under-diagnosis of osteoporosis after fragility fractures because of lack of patient and physician awareness of the disease, lack of follow-up, and medical nonadherence. Therapeutic Advances: Current guidelines recommend the use of Bisphosphonate as the first-line therapy for secondary fracture prevention. Compared with placebo, randomized controlled trials have demonstrated a significant reduction in vertebral and nonvertebral fractures using Alendronate, Risedronate, Ibandronate, and Zoledronic acid. All but Ibandronate showed a significant reduction in hip fractures as well (all trials with P < 0.05). Denosumab is an option in patients with impaired renal function or who are unresponsive to other therapies. It significantly decreases the risk of new vertebral fracture [hazard ratio (HR) = 0.32, 95% confidence interval (CI), 0.26–0.41], hip fracture (HR = 0.60, 95% CI, 0.37–0.97) and nonvertebral fracture (HR = 0.80; 95% CI, 0.67–0.95) without an increased in adverse events. Hormonal therapy has been shown to be effective but should be used in the lowest effective dose to minimize the risk of coronary heart disease, stroke, and venous thromboembolism. Selective estrogen replacement modulators, calcitonin, and parathyroid hormone analog are other alternatives described in this article. In addition to current therapies, emerging therapies under investigation such as Abaloparatide, a parathyroid receptor ligand, and Romosozumab, a monoclonal anti-sclerotin antibody both showed a reduction in new morphometric vertebral fractures compared with placebo (0.58% vs. 4.22%, relative risk = 0.14, 95% CI, 0.05–0.39 and 0.5 vs. 1.8%, relative risk = 0.27, 95% CI, 0.16–0.47, respectively). In this article, we summarize advances in current therapeutic agents used for secondary fracture prevention and provide insight into potential therapies that hold promise in the future of osteoporosis. Conclusion: Secondary prevention of fragility fractures through care coordination and initiation of various pharmacologic agents is crucial in the elderly population. Careful risk assessment and stratification should be performed before the initiation of pharmacologic treatment to optimize disease management.