Bisphosphonates for osteoarthritis

Osteoarthritis (OA) is increasingly prevalent as the population ages, and current treatments focus on the relatively short-term relief of symptoms. Clinical trials of disease modification are expensive, requiring prolonged follow-up of large numbers of participants. In the current global financial climate, there is renewed interest in the OA-modifying potential of existing treatments that have been developed for other indications. Bisphosphonates represent one such class of agent, and the paper by Moreau and colleagues [1] in a recent issue of Arthritis Research & Therapy provided useful insights into the potential of this class for OA.Moreau and colleagues reported reduced pain responses when subcutaneous tiludronate was administered to dogs after surgical induction of OA. Furthermore, tiludronate reduced synovitis (effusion, synovial fluid prostaglandin E2 concentration, and lining cell score) and increased subchondral bone thickness. By contrast, an earlier clinical trial of risedronate in patients with OA revealed a disappointing lack of symptom relief compared with placebo [2]. However, lack of efficacy may be explained by the limited potency of risedronate or, in this heterogenous disease that varies with time, inadequate targeting to those most likely to benefit. Collectively, these reports raise some important questions about the use of bisphosphonates and general issues for the development of new treatments in OA. How clinically relevant are animal models? Which key pathogenic mechanisms are amenable to intervention? How can treatments be targeted to those mechanisms in the right people at the right time?Surgical models build on the well-recognized association between OA and preceding internal derangement [3]. Their predictable onset and rapid development by comparison with spontaneous models facilitate the testing of pharmacological interventions. Most researchers use small-rodent models of OA, although it has been argued that these may inadequately repres