Sequential therapy: The way to go to prevent fragility fractures

Recently there has been a growing interest in the establishing of sequential therapeutic schemes, especially in patients with severe osteoporosis at high risk of fracture. The objective of this review is to update evidence regarding the use of osteoporosis drugs in sequence to increase bone mineral density. On the basis of the available data the following conclusions can be drawn: in patients with severe osteoporosis first line anabolic therapy followed by an antiresorptive drug should be recommended; switching from teriparatide (or other anabolics) to either denosumab or bisphosphonates is associated with an increase in BMD; switching from bisphosphonates to teriparatide results in a transient loss of cortical BMD, however, the effect of teriparatide on bone microstructure and strength seems to be irrespective of prior bisphosphonate use; switching from denosumab to teriparatide, at present, is not recommended because does not seem able to halt the loss of cortical bone following the interruption of denosumab; in patients non responders to bisphosphonates and at high fracture risk switching to denosumab could be considered. Further studies aimed to define the effectiveness of sequential schemes in reducing osteoporotic fractures are warranted.