Introduction: Osteoarthritis (OA) is the most prevailing form of joint disease, with symptoms affecting 10 – 12% of the adult population with a projection of a 50% increase in prevalence in the next two decades. The disease characteristics are defined by articular cartilage damage, low-grade synovial inflammation and hypertrophic bone changes, leading to pain and functional deterioration. To date, available pain treatments are limited in their efficacy and have associated toxicities. No structural disease modification agents have been approved by regulatory agencies for this indication.

Areas covered: We reviewed drugs in Phase II – III for OA pain and joint structure modification. Different aspects of structure modification are divided into targets of inflammatory pathway, cartilage catabolism and anabolism, and subchondral bone remodeling.

Expert opinion: Further insight into the pathophysiology of the disease will allow for development of novel target classes focusing on the link between symptomatology and structural changes. Given the complexity of OA, one single therapy is unlikely to be universally and uniformly effective. Promising therapies are under development, but there are obstacles in the translation of treatment from preclinical models and trial designs need to be cognizant of the complex reasons for previous trial failures.