The Safety of Common Treatments for Osteoporosis

Abstract: Treatments for osteoporosis are generally well-tolerated and safe. Bisphosphonate therapy carries a very low risk of osteonecrosis of the jaw (ONJ) that is higher after invasive oral surgeries and with high doses of zoledronate for cancer. Bisphosphonates entail very low risk of atypical femoral fractures (AFF) that increases with years of treatment and declines soon after discontinuation. The first treatment with IV zoledronate causes flu-like symptoms in about 25-30% and less commonly ( ~10%) after subsequent doses. Pre-treatment treatment with acetaminophen reduces symptoms. In the largest clinical trial, denosumab had no adverse effects except, rarely, eczema and cellulitis. Stopping denosumab after 3 years increases the risk of vertebral fractures. Teriparatide and abaloparatide uncommonly cause mild postural hypotension (light headedness, palpitation) and rarely arthralgias and myalgias. The largest placebo-controlled trial of Romosozumab found no adverse effects. There were with rare cases of ONJ and AFF. Romosozumab had no increased risk of CVD. Another trial of alendronate vs. romosozumab reported a difference in CVD events that can be attributed to chance.

Learning Objectives:
1). Recognize potential adverse effects of antiresorptive treatments for osteoporosis—alendronate, zoledronate, and denosumab.
2). Recognize the potential adverse effects of teriparatide and abaloparatide.
3). Critically appraise the concern about cardiovascular effects of romosozumab.