Update on pharmacologic management of osteoarthritis

Abstract

Purpose: Provide an overview of new approaches to the management of osteoarthritis (OA). Methods: Review of the recent literature. Results: A number of studies have recently concluded that have addressed both symptom and disease modification in OA. These studies are expanding our understanding of the mechanisms associated with pain generation and perception in OA as well as providing insight into the importance of pathways of cartilage metabolic homeostasis, respectively. Reduction of peripheral nerve input, attained by means of monoclonal inhibition of nerve growth factor (NGF), a neurotrophin capable of sensitizing peripheral nociceptors, has been demonstrated in phase 3 clinical trials to result in significant pain relief in OA, with the magnitude of the pain relief being greater than what is observed with NSAIDs in the same studies. Importantly, this approach has also been shown to be effective in low back pain and is being investigated in neuropathic pain models. Currently, the further development of this class of drugs is on hold pending a more complete understanding of their safety profile. Centrally acting compounds, specifically serotonin-norepinephrine reuptake inhibitors (SNRIs) have also been shown to provide pain modification in musculoskeletal pain conditions (OA, low back pain), adding to the armamentarium available for the management of these conditions. Novel topical agents as well as different formulations of existing opioids are also being investigated at this time. In terms of disease modification, recent trials have examined the effects of oral calcitonin on progression of structural disease as well as evaluating inhibition of the inducible nitric oxide synthase pathway, believed to be responsible for inflammatory and catabolic pathways in cartilage leading to OA. Conclusions: Inhibition of both peripheral and central pain pathways has been shown to be effective at reducing pain and improving function in people with OA. Further studies are needed to define the safety profile of therapy directed at inhibition of NGF. Disease modification remains a challenging goal, but a better understanding of the mechanism of cartilage damage has allowed new agents to be considered for study in this condition.