Targets to tackle--the pathophysiology of the disease

Osteoarthritis, the degeneration of the joints, is the leading source of physical disability with severely impaired quality of life due to pain and loss of joint functioning in industrialized nations. Clinically, degeneration affects mostly the large weight bearing joints of the legs like the hip or the knees, but in principle it can affect any joint of the body. Osteoarthritis represents a disease group with disease subsets that have different underlying pathophysiological mechanisms. Therefore primary osteoarthritis has to be distinguished from secondary forms of the disease, which are due to traumatic events, endocrine or metabolic disorders etc. The enormous frequency of this disease makes osteoarthritis one of the most expensive conditions in the Western world, both in terms of direct as well as indirect costs. So far, despite intensive efforts over several decades, the success of disease-modifying approaches have been rather limited and mostly restricted to analgesis and non-pharmacologic therapy (e.g. nonsteroidal anti-inflammatory agents, exercise, and physiotherapy). Joint replacement is still the unsurpassed therapy for the symptomatic relief of advanced and incapacitating OA. It is evident that there is a great need for the development of disease modifying agents in order to improve quality of life as well as to relieve the community of the enormous socio-economic burden of the disease.