Osteoarthritis (OA) is best described as a chronic pain syndrome affecting one, or more frequently, multiple joints. It most commonly affects the knees, hips, hands, neck and lower back, although any joint can be affected. Defining OA by pathological changes is no longer considered best practice, as the correlation between pathology and symptoms is frequently discordant, i.e. patients with severe structural changes may present with minimum symptoms and vice versa. For this reason, patients should be assessed using a biopsychosocial model, which takes into consideration impact on social and psychological well- being, alongside pathological changes. OA can create substantial mobility problems and is the most common cause of disability in elderly people in the developed world. Prevalence rises with age such that approximately one- third of people in the UK over 45 have sought treatment for OA compared with 40– 50% of people over the age of 75. In the pathological conditions of OA, there are specific hallmarks of damage that affect load- bearing articular cartilage, the formation of new bone at the joint margins (osteophytosis), subchondral bone changes (sclerosis), thickening of the joint capsule, loss of cartilage, and joint space narrowing (Figure 7.1B). In general, structural changes seen on X- ray or CT do not correlate with the pain of OA, but an association does occur between the presence of synovitis, subchondral bone oedema and osteophytes. In OA the vasculature of the osteochondral junction also expresses higher levels of nerve growth factors (NGF) so pain sensitization associated with inflammation is likely to occur. OA is considered by some to be the result of physiological processes originally targeted at joint repair that, over time, cause tissue damage resulting in symptomatic OA. In many cases, severe trauma or pathological repair processes may be contributory factors. Other risk factors for OA include genetic and patient factors, such as age and obesity (see Box 7.1). Anti- NGF drugs may be of benefit, primarily via pain modulation, but OA is not considered to be a disease of inflammation and the mainstay of treatment relies on effective analgesia. The presence of synovitis in late disease is controversial and the presence of joint crystals may confound inflammation in OA. It is clear that wear, tear, and damage is associated with the breakdown of collagen and increased presence of proteolytic enzymes called matrix metalloproteinases (MMPs).
Inhibition of Nrf2/HO-1 signaling leads to increased activation of the NLRP3 inflammasome in osteoarthritis
