Osteoarthritis (OA) is affecting large proportions of the population worldwide.So far, no effective disease modifying drug has been developed for this disease, limiting the therapeutic options to pain medications, physiotherapy and 9 10 ultimately surgical approaches, mainly joint implant surgery. In vitro and animal studies have demonstrated that bisphosphonates have the potential to become effective modalities for the treatment of OA. This group of pharmacological agents modulate crucial aspects of OA pathogenesis (subchondral bone turnover and loss, bone marrow edema formation, cartilage degeneration and synovitis, and have shown clear efficacy in animal models of OA. Human studies have, however, so far been disappointing with only one of six clinical studies showing clear short-term efficacy. Possible reasons for these discrepancies will be discussed.
Osteoarthritis Definition, classification and epidemiologyOsteoarthritis (OA) is defined as a joint disorder characterized by cellular stress and extracellular matrix degradation initiated by micro-and macro-injury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. This in turn manifests initially as a molecular derangement, abnormal joint tissue metabolism and subsequently by anatomic and physiologic perturbations [1].These processes can present as cartilage degeneration, increased bone remodeling, and osteophyte formation accompanied by inflammation in joint tissue including synovitis, resulting in pain, and loss of normal joint function [2]. Structure-pain relationships in OA remain difficult to understand, however, because it is often unclear which structures may be contributing to pain in the individual patient. Intraarticular candidates include bone and synovium, though it is worth noting that the amount of pain that pathologies in these tissues explain is small [3] and extra-articular features (e.g. tendinitis and bursitis) may confound associations. Clinically, OA refers to a syndrome of joint pain accompanied by varying degrees of functional limitations and reduced quality of life. At least 242 million people globally have hip/knee OA [4]. In addition, with an ageing population and rising risk factors such as obesity, this prevalence is growing [5]. As a result of the disability caused by OA, the cost to the global economy is significant [6]. Current management of OA involves pharmacological, non-pharmacological and ultimately surgical approaches. Conventional pharmacological treatments have limited efficacy and are associated with a number of side-effects, restricting the number of patients who can use them. New pharmacological therapies for managing