OSTEOARTHRITIS: UNDERSTANDING THE PATHOPHYSIOLOGY, GENETICS, AND TREATMENTS: COMPLICATIONS

16 Feb
2010

The general complications of OA include loss of range of motion, extremity deformity due to asymmetric loss of joint space, subluxation, ankylosis or complete bony fusion of a joint, and intraarticular loose bodies related to subchondral fractures.

TREATMENT

OA remains an irreversible disease of unknown etiology. The goal of the treatment is to reduce pain, improve or maintain mobility, and minimize disability. The initial step is to reduce joint loading by discontinuing the offending activity (i.e. pitching, working with the jackhammer, etc.), improving posture, losing weight if obese, wearing splints and/or braces, using wedged insoles to correct abnormal biomechanics due to varus deformity of the knee, and using cane, crutch, or walker. Physical therapy should be aimed at increasing the range of motion and improving strength in periar-tricular muscles. Ettinger and colleagues showed that quadriceps strengthening and aerobic exercises for patients with knee OA resulted in approximately 10% improvement in functional outcomes, even though there was no radiographic evidence of recovery Angst et al. also measured outcomes in patients with hip and knee OA undergoing a three-month structured exercise program. They showed greatest responsiveness to exercise in women and in knee OA and less in men and hip OA.
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There are numerous studies showing benefits of weight loss. For example, Felson and colleagues showed that decrease in weight by 5.1 pounds over 10 years resulted in 50% decrease in risk of developing OA. Another study showed that weight loss combined with exercise resulted in improvements in both functional and pain outcomes, as well as health-related quality of life status.

From the beginning, the patients should be educated on the disease, treatment options, and prognosis and encouraged to participate in a self-management program such as the Arthritis Foundation Self-Management Program. Occupational therapy can also be useful, if needed, to assist patients with activities of daily living.

The most recent American College of Rheumatology recommendations came out in 2000. The pharmacologic therapy for now is limited to pain relief and should always be preceded by or combined with nonpharmacologic strategies listed above. The first line agent for relief of mild-to-moderate joint pain may be acetaminophen, since it is comparable with the pain relief provided by the previous first line agents—NSAIDs. Even though a number of patients do not respond to acetaminophen, it should be attempted first because of its efficacy, low cost, and low toxicity profile. It should be noted that daily dose should not exceed 3 gm to avoid liver toxicity. If acetaminophen fails to bring pain relief, the next agent should be a cyclooxygenase 2 (COX-2) specific inhibitor. This class of drugs has a similar mechanism of action as NSAIDs, lower GI toxicity, and convenience of once-daily dosing. canadian pharmacy viagra

The next class of agents to be tried is nonsteroidal anti-inflammatory drugs (NSAIDs), since they have proven efficacy in treating joint pain. These drugs are especially useful if there is an inflammatory component, such as joint effusion. However, before starting on NSAIDs, patients must be evaluated for risk factors for serious upper gastrointestinal and renal toxicity (such as active peptic ulcers or renal failure). Those with an increased risk of GI side effects may take such Gl-protective agents as misoprostol or proton pump inhibitors. It should be noted that some patients may achieve pain relief with some NSAIDs, while others may not. Therefore, at least six NSAIDs are usually tried before declaring a patient unresponsive to this class of drugs. A new alternative to the classic oral NSAIDs is the topical formulation. Existing data shows that topical NSAIDs are just as effective for treatment of joint pain and carry lower risk of serious side effects than their oral counterparts, as would be expected, considering their low systemic circulation.

Other oral agents to treat joint pain in OA include paracetamol, an acetaminophen-like analgesic. Pure analgesics such as tramadol and opioids also are recommended in cases refractive to other oral therapies. Finally, other topical analgesic agents for OA include capsaicin and methyl-salicylate.

The new category of drugs for OA are called symptomatic slow acting drugs for osteoarthritis or SYSADOA and include glucosamine sulfate, chondroitin sulfate, diacerein, and hyaluronic acid. These agents are new and the evidence of their efficacy is incomplete. Intraartricular injections of hyaluronan have been shown to delay progression of knee OA, decrease pain, and increase functionality. Oral chondroitin sulfate and glucosamine sulfate has been shown to decrease OA pain and improve function. These agents might be useful in patients who cannot take or have already failed therapy with acetaminophen, NSAIDs or COX-2 inhibitors.

For short-term management of acute exacerbation of pain with or without effusion, an intraartricular injection of long-acting steroid may be beneficial. The effect lasts only several weeks. However, care should be taken to avoid excessive injections (more than twice a year) as they could lead to steroid arthropathy and tendon rupture.

Current advances in research on pathophysiology and biochemical derangements in OA, reviewed above, have resulted in numerous new pharmacological targets, offering a possibility to not only improve the symptoms by also modify the disease. Neutralization of inflammatory agents, such as IL-1 and TNF-alpha, is one of the possibilities. Soluble IL-1 receptor antagonists have been shown to decrease metalloprotease transcription in a rabbit model. Another potential strategy is to stimulate chondrocyte compensatory biosynthesis pathways with such agents as TGF-beta or insulin-like growth factor-1. There are also antiinflammatory cytokines, such as IL-4, IL-10, and IL-13. IL-4 has been shown to be just as effective as low-dose dexamethasone in suppressing IL-1 and TNF-alpha synthesis. Futher animal, and eventually human trials are necessary to confirm efficacy of these agents. Future research in OA pathophysiology is necessary as it is likely to produce even more drug targets for an eventual medical cure for OA.

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