Advances in Osteoporosis Therapy: Focus on Osteoanabolic Agents, Secondary Fracture Prevention, and Perioperative Bone Health

Abstract

Purpose of review: This review summarizes recently published data and other developments around osteoanabolic osteoporosis therapies in patients with very high fracture risk, including those undergoing bone-related surgery.

Recent findings: Two osteoanabolic agents, abaloparatide and romosozumab, were recently approved for treatment of patients with osteoporosis at high fracture risk. These agents, along with teriparatide, are valuable for primary and secondary fracture prevention. Orthopedic surgeons are well positioned to facilitate secondary fracture prevention via referrals to fracture liaison services or other bone health specialist colleagues. This review aims to help surgeons understand how to identify patients with sufficiently high fracture risk to warrant consideration of osteoanabolic therapy. Recent evidence around the perioperative use and potential benefits of osteoanabolic agents in fracture healing and other orthopedic settings (e.g., spinal fusion and arthroplasty) in individuals with osteoporosis is also discussed. Osteoanabolic agents should be considered for patients with osteoporosis at very high fracture risk, including those with prior osteoporotic fractures and those with poor bone health who are undergoing bone-related surgery.

Keywords: Abaloparatide; Orthopedic surgery; Romosozumab; Spine surgery; Teriparatide.

Fig. 1

Evidence for early fracture risk reduction with osteoanabolic agents versus bisphosphonates. Left panel shows early separation of Kaplan–Meier curves for clinical fractures (Fx) in postmenopausal women with severe osteoporosis treated with teriparatide or risedronate during the first 12 months of the VERO trial (adapted from [7]). VERO showed that 24 months of teriparatide significantly reduced the risk of clinical, vertebral, and multiple vertebral fractures versus risedronate. Middle panel shows clinical fracture Kaplan–Meier curves for women with PMO treated with abaloparatide or open-label teriparatide over the first 12 months of the ACTIVE trial (adapted from [8]). In light of the VERO trial results (left panel), these data indirectly imply an early benefit of abaloparatide versus risedronate. ACTIVE showed that 18 months of abaloparatide significantly reduced the risk of major osteoporotic fractures versus teriparatide. Right panel shows hazard ratios and 95% confidence intervals for clinical, vertebral, and major non-vertebral fractures in women with PMO treated for 12 months with romosozumab versus alendronate in the ARCH trial, with P values of 0.027, 0.003, and 0.019, respectively (adapted from [10])

Fig. 2

Potential approach for treating patients with osteoporosis at very high fracture risk (adapted from [51]). Many of these risk factors are listed in Table 1. Clinical practice guidelines recommend 1–2 years of osteoanabolic therapy (e.g., 12 months of romosozumab or 18–24 months of teriparatide or abaloparatide) to rapidly increase bone mass and reduce fracture risk. The resulting BMD gains should be consolidated (i.e., preserved or further increased) by follow-on therapy with potent antiresorptives such as amino-bisphosphonates (BPs, e.g., alendronate or zoledronic acid) or denosumab (DMAb). Fracture risk should be re-evaluated thereafter to determine the need for continued therapy; if fracture risk remains high, consider additional treatment with potent antiresorptives or re-treat with osteoanabolics. If fracture risk is sufficiently reduced, bisphosphonate therapy may be stopped or temporarily suspended, though discontinuation of denosumab without another follow-on therapy (e.g., bisphosphonate or romosozumab) leads to rapid bone loss and an increased risk of vertebral fractures