Sequential Therapy for the Long-Term Treatment of Postmenopausal Osteoporosis

Abstract Osteoporosis is a chronic condition characterized by decreased bone mass, loss of skeletal integrity, and increased susceptibility to fracture. Drugs used to treat osteoporosis can be classified as those that block bone resorption (antiresorptive), stimulate bone formation (anabolic), or do both. While all currently approved medications reduce the risk of fragility fractures in high-risk populations, they are generally unable to fully restore bone strength in most patients with established disease. Thus, the majority of patients require disease management over many years. Unfortunately, the continuous use of a single drug has limitations, both in terms of efficacy and safety, and so sequential therapy is commonly required. Given the expanding list of pharmacological agents currently available, careful consideration needs to be given as to which drugs to use and in what sequence. This review will evaluate the differential effects of antiresorptive, bone-forming, and dual-acting drugs when used in specific sequences and will explore the current evidence favoring the initial use of bone-forming/dual-acting drugs followed by antiresorptive medications. This review will also examine the notion that long-term treatment with an antiresorptive drug may diminish the efficacy of subsequent treatment with a bone-forming/dual-acting drug. Finally, this review will explore the current evidence pertaining to the specific issue of how to best prevent the clinical ramifications of denosumab cessation.