Bisphosphonates in orthopedic applications

Bisphosphonates (BPs) exert potent effects on the skeleton. As such, there are important questions relating to how treatment with BPs for metabolic disorders might affect outcomes of orthopedic problems. A further question is what role, if any, might BPs play as adjunctive therapeutics for orthopedic problems. This article outlines the research thus far in the application of BPs to the management of osteonecrosis, bone repair, and joint arthroplasty. Many animal studies show a benefit to decreasing bone resorption in models of osteonecrosis. These include studies in both small and large animals, backed up by limited human data. Further clinical trials are underway for this indication. In bone repair, again, multiple studies exist. There are concerns that BPs could interfere with the normal processes of healing. Some of the controversy about benefits or adverse effects of BPs in this context can be distilled down to effects of dosing and administration. With some exceptions, longer intervals between dosing seem to be more beneficial while not producing adverse healing effects in animal studies. In joint arthroplasty, animal studies suggest a role for topical or systemic BPs for enhancing bone on-growth to implant surfaces and strength of mechanical fixation, although these are yet to be confirmed in clinical studies. Clinical studies show that BPs inhibit periprosthetic bone loss due to strain-adaptive remodeling and after impaction bone grafting, although an efficacy in inhibiting inflammatory bone loss due to wear particle-induced osteolysis has not been confirmed. Lastly, as anabolic drugs have become available, there is increasing interest in their combined use with BPs. From experimental data, manipulation of both the anabolic and catabolic responses is a powerful approach in models of bone repair.