Sequential Treatment of Osteoporosis

Osteoporosis is a chronic disease characterized by the imbalance between bone formation and bone resorption. In the last three decades the armamentarium for the treatment of osteoporosis has progressively increased with the development of novel, and more potent, antiresorptives (i.e., denosumab and zoledronic acid), bone anabolic agents (i.e., teriparatide and abaloparatide), and the recently approved anti-sclerostin antibody (i.e., romosozumab). Nevertheless, osteoporosis therapies can only reduce the risk of fracture without abolishing it. Moreover, the fear of rare adverse events related to prolonged treatment with bisphosphonates and the regulatory 2-year limit on teriparatide have posed an additional challenge with chronic and severe osteoporotic patients. Therefore, sequential treatment is likely to be actuated over a lifetime and the choice of the most appropriate sequential treatment is crucial for a successful risk reduction strategy. In addition, a preplanned sequential treatment should be optimally constructed at the very first pharmacologic prescription. There is growing evidence supporting sequential treatment aimed to build the bone up with an initial course with anabolic agents followed by antiresorptive, regardless of the severity of osteoporosis. In this review we present the evidence supporting and opposing different therapeutic sequential strategies for the treatment of osteoporosis.