New Frontiers in Osteoporosis Therapy.

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone-related peptide analog abaloparatide. Clinical trial data show significant antifracture benefits with recently approved romosozumab. Studies using abaloparatide build on our longstanding experience with teriparatide and the importance of consolidating the bone mineral density gains achieved from an anabolic agent by following it with an antiresorptive. Combination and sequential treatments using osteoporosis medications with different mechanisms of action have also been tested with promising results. On the horizon is the potential for cell-based therapies (e.g., mesenchymal stem cells) and drugs that target the elimination of senescent cells in the bone microenvironment.