Osteoarthritis Quo Vadis

In osteoarthritis, inflammation appears to begin early, progressing in parallel with disease worsening. (See Figure 2, p. 15.) Synovitis of involved joints is almost universally seen in patients coming to total joint replacement. The cause of the inflammation is multifold, involving release of inflammatory cytokine mediators, such as IL-1 and TNF-α, and prostaglandins; activation of inflammatory proteases targeted toward destruction of both collagen and proteoglycans; NF-κB activation; and nitric oxide formation.²

Initiation of inflammatory mediator activation and release occurs early with an interplay of responses between synovium and cartilage. It has been hypothesized that suppression of inflammation has the potential to be disease modifying, slowing down disease progression. Perhaps daily intake of nonsteroidal anti-inflammatory agents, if tolerated safely over a prolonged period of time, could be structure modifying as well as pain relieving. Such a hypothesis has yet to be tested.

FIGURE 1: Standing X-ray of OA of the knee. Joint-space narrowing and osteophytes are hallmark pathologic changes.

OA Risk Factor

Major risk factors for OA include age, gender, obesity, heredity, trauma (related to sports or occupation), joint overuse (such as repetitive knee bending), and joint instability or malalignment.³ Does the increased incidence with age result from OA’s asymptomatic early development at age 30 or 40, becoming clinically evident only after 10 or 20 years, or does the aging process itself play a role? There is a suggestion that aging per se may play a role in the form of advanced glycation end products that lead to formation of cross-links between sugars and proteins, making the cartilage more susceptible to injury from other risk factor inputs (obesity, chronic trauma, etc.). Osteoarthritis is more common in women after menopause, possibly relating to estrogen deficiency or (in the case of hand osteoarthritis) genetic predisposition.⁴

Obesity has a strong relationship to incident osteoarthritis but is even more likely to play a pathogenic role in the presence of joint instability or malalignment. A relationship of osteoarthritis to genetic mutations has been demonstrated, particularly as related to collagen abnormalities.⁵ Studies suggest that run-of-the-mill osteoarthritis has a hereditary component, with a number of genes under suspicion. Since the only risk factors you can really control at this time are body weight and over- or under-exercise, disease prevention is not easy. Perhaps we ought to be studying not who gets the disease, but who doesn’t get the disease.

Symptomatic Treatment Approaches

There is an umbrella-like nonpharmacologic approach to management that all patients should receive. Pain in OA has both an inflammatory and non-inflammatory origin. (See Table 1, left.) Therapeutic approaches include weight reduction, appropriate exercise (both joint targeted and nontargeted), avoidance of joint overuse, and use of various orthotics. Unfortunately, most patients require additional analgesic or anti-inflammatory therapy. Guidelines, formulated by the ACR in 2000 (see Figure 3, below right),⁶ are being reformulated by several groups including the Osteoarthritis Research Society International (OARSI), the European League Against Rheumatism (EULAR), and the ACR. The OARSI recommendations were recently published.⁷