The next step after anti-osteoporotic drug discontinuation: an up-to-date review of sequential treatment

Several antiresorptive drugs, like bisphosphonates and denosumab, are currently available for the treatment of osteoporosis due to their evidenced efficacy in reducing fracture risk at mid-term. Osteoanabolic therapies, like teriparatide, whose treatment duration is limited to 2 years, have also shown efficacy in the reduction of fracture risk. However, depending on the severity of osteoporosis and the presence of other associated risk factors for fracture, some patients may require long-term treatment to preserve optimal bone strength and minimize bone fracture risk. Given the limited duration of some treatments, the fact that most of the antiresorptive drugs have not been assessed beyond 10 years, and the known long-term safety issues of these drugs, including atypical femoral fractures or osteonecrosis of the jaw, the long-term management of these patients may require an approach based on drug discontinuation and/or switching. In this regard, interest in sequential osteoporosis therapy, wherein drugs are initiated and discontinued over time, has grown in recent years, although the establishment of an optimal and individualized order of therapies remains controversial. This review reports the currently available clinical evidence on the discontinuation effects of different anti-osteoporotic drugs, as well as the clinical outcomes of the different sequential treatment regimens. The objective of this article is to present up-to-date practical knowledge on this area in order to provide guidance to the clinicians involved in the management of patients with osteoporosis.