Combination and Sequential Osteoanabolic/Antiresorptive Therapy in Osteoporosis Treatment

Abstract

Osteoporosis medications can be classified as either antiresorptive or osteoanabolic based on their mechanism of action. As discussed in prior chapters, the most commonly used antiresorptive agents include the nitrogen-containing bisphosphonates and the receptor activator of NFκB (RANK)-ligand inhibitor, denosumab, whereas the currently available osteoanabolic drugs, teriparatide and abaloparatide, both act through activation of the receptor to parathyroid hormone and parathyroid hormone-related protein. While the standard of care for osteoporosis treatment is monotherapy, combined osteoanabolic/antiresorptive therapy has been evaluated in numerous clinical trials as a means to improve efficacy. These combination studies have generally demonstrated limited utility with the exception of the combination of denosumab and teriparatide which appears uniquely capable of additively increasing bone mineral density and improving bone microarchitecture and strength compared to any individual drug. Additionally, as osteoporosis therapy options have expanded, and clinical guidelines have begun to include the concept of limiting treatment courses to several years, defining the optimal use of multiple agents in sequence has become an area of increasing interest. The results of the initial studies in this area appear to support the concept of the initial use of an osteoanabolic drug followed by an antiresorptive agent, especially in patients with severe osteoporosis in whom long-term therapy will likely be necessary.