US Pharm. 2006;1:20-24.

Osteoarthritis (OA) is the most common joint disorder in the United States, affecting approximately 20 million Americans and accounting for significant disability and health care expenditures in the U.S.1-5 Known as degenerative joint disease, OA has been the second most common diagnosis, after chronic heart disease, leading to Social Security disability payments due to long-term absence from work.6 Principally affecting the elderly, OA is the leading cause of disability in individuals older than 65 years and affects 70% to 90% of those older than 75 years.7-9 

The most common form of arthritis, OA is a debilitating, degenerative disease of the articular cartilage and synovial fluid.8 OA primarily affects the spine and joints of the hand and lower extremities, resulting in pain, stiffness, deformity, and loss of function.7,9,10 In elderly patients, some of the most common chronic pain management cases involve OA, as well as low back pain and neuropathy.5 While prevalence of the disease is equal among both men and women, older women are twice as likely as men to have OA of the knees and hands.11 The prevalence and severity of the disease increases with age.11 Other risk factors for OA include mechanical stress, joint injury, and obesity. Diagnosis is based on a physical exam, comprehensive history, and radiographic findings.

While 85% of persons exhibit evidence of OA after age 70, more than 50% of the population will have radiographic evidence of the disease in at least one joint by age 65.5 Not all patients with radiographic evidence of OA have pain or functional limitations.12 The best established predictor of disability in patients with OA is muscle weakness, especially in patients with OA of the knee.12 In fact, reduced quadriceps strength is an early finding in subjects with knee OA; however, it is not clear whether reduced quadriceps strength is a cause or a consequence of knee OA.13

Goals of Therapy
Goals of therapy include controlling pain, improving and/or preserving joint function and mobility, and improving health-related quality of life.1 While not curable, established and experimental therapies seek to modify and/or even reverse the course of OA.8 In order to improve functionality and quality of life as a goal of pain management, a multidisciplinary application of both nonpharmacologic and pharmacologic approaches tailored to the individual is often required to provide the most effective therapeutic outcomes.11,14-16 Communication between patients, clinicians, and pharmacists is an important factor in the pain management process; the best therapeutic outcomes may be obtained through an alliance among these individuals.17

Nonpharmacologic Treatment
Nonpharmacologic therapy, the foundation of the pharmaceutical care plan for OA, should be utilized in all patients and started prior to or simultaneously with the initiation of simple analgesics such as acetaminophen (up to 4 g/day) (table 1 ).7,11




Exercise: Regular exercise (e.g., strengthening, range of motion, isometric, isotonic, isokinetic, postural) maintains healthy cartilage, encourages motility, and helps develop muscles and tendons to absorb stress and prevent further damage from OA.10,18,19 While stretching exercises are of particular importance, inactivity or immobilization for even relatively short periods of time may worsen or accelerate the clinical course of OA.19 Balancing exercise with adequate daytime rest (every four to six hours) allows cartilage to rehydrate and is key. 19

A combination of aerobic exercise (e.g., walking), resistance training (e.g., weight training), and stretching (e.g., yoga) may be helpful for patients with OA. The warmth and buoyancy of exercising in warm water (83°F to 88°F) may also assist with discomfort and stiffness during movement.10 In some cases, a well-planned exercise regimen has the ability to arrest OA of the hip and knee. 19

Physical Therapy: For patients with physical disabilities due to OA, a standardized physical therapy program can provide mobility benefits.5 Physical therapy may even be beneficial in older nursing home residents up to age 89, as behavior modification has been shown to reduce the need for pain medication, the incidence of pain-associated behaviors (e.g., avoiding activities or exercise, complaining of pain), and subjective reports of pain.5,20 Studies continue to confirm that the application of manual physical therapy and supervised exercise produce greater symptomatic relief and functional benefits in patients with OA of the knee.21,22 

Surgery: When conservative nonpharmacologic and pharmacologic therapy fails to relieve pain or improve joint function, total joint replacement (total arthroplasty) is highly effective for treating OA of the hip and knee.19 While types of artificial joints and surgical techniques vary depending upon the joints affected, replacing a joint almost always improves a patient's range of motion and function and dramatically decreases pain.10 The needs and capabilities of a potential surgical candidate should be clearly defined, while considering the treatment goals of improved physical function and pain relief.

Pharmacologic Intervention
Some experts believe that drug therapy is the least important aspect of optimal disease management, perhaps 15% of a total program.19 Whether drug therapy or a nonpharmacologic approach is used, careful consideration of geriatric pharmacokinetics and pharmacodynamics is necessary.5 Understanding and comparing available therapies for OA can help individualize treatment, which may include combination therapy.

In most patients with OA, acetaminophen in increasing doses of up to 1 g four times daily (not to exceed 4 g/day) is the first choice for pain relief because the drug is effective and generally safer than NSAIDs.7,11,19,23 For patients who show signs of inflammation or do not respond to acetaminophen, treatment with an NSAID should be considered. While the adverse effects (e.g., gastrointestinal [GI] toxicity) of older NSAIDs (e.g., piroxicam, oxaprozin, naproxen, ibuprofen) are similar, incidence varies by agent and individual patients. Seniors are at high risk for adverse effects of NSAIDs; as many as 60% of seniors can develop peptic ulceration and/or hemorrhage asymptomatically.23 The lowest effective dose of an NSAID for the shortest possible duration is recommended in this population. Declining renal function should also be considered, especially when the creatinine clearance is 30 mL/min or less.23 Due to a decline in renal blood flow and glomerular filtration rate associated with the progression of age, seniors may be particularly sensitive to nephrotoxicity associated with NSAID therapy, especially if treatment consists of concomitant NSAID and angiotensin II converting enzyme inhibitor (ACEI) therapy.24 Elderly patients may demonstrate adverse effects from NSAIDs at lower doses than younger adults. The long-term use of full-dosage, longer half-life, non-COX-selective NSAIDs (e.g., naproxen, oxaprozin, piroxicam) have the potential to produce GI bleeding, renal failure, high blood pressure, and heart failure and are considered potentially inappropriate medications in this population.23 Adverse effects to the central nervous system include agitation, confusion, and hallucination.23

COX-2 inhibitors are used to control inflammation and decrease pain. In April 2005, the FDA asked manufacturers of all prescription nonselective NSAIDs and COX-2-selective NSAIDs to revise their product labeling to include a boxed warning highlighting the potential for increased cardiovascular events and/or any well-described, serious, potentially life-threatening GI bleeding associated with their use.25 Both older NSAIDs and COX-2 inhibitors can impair renal function and cause sodium and water retention and should be used cautiously in elderly patients, especially those with renal disease, volume depletion, heart failure, or liver disease.7

Opioid analgesics can be used to treat OA if they improve a patient's function and quality of life. However, a patient's need for prolonged use of opioid analgesics should be evaluated to avoid possible physical dependency.7 Tramadol, a synthetic opioid agonist, has a rare side effect of seizures in those taking doses above the recommended range, in patients with known seizure disorders, and in patients receiving concomitant medications that lower the seizure threshold (e.g., antipsychotic agents, antidepressants).12 While corticosteroids should not be used systemically, delivery as an intra-articular depot injection is helpful when effusions (fluid accumulation that may cause swelling) or signs of inflammation are present and should be limited to infrequent and intermittent use. 10,19 They are indicated for the symptomatic relief of pain from large joints unresponsive to usual therapy. 7 

Intra-articular hyaluronic acid injections have been shown to improve symptoms of knee OA; recent data support their potential use as an effective long-term therapeutic option for patients with knee OA.7,26 Topical preparations (e.g., capsaicin) may be especially useful as monotherapy or as an adjunct to analgesic therapy in patients with OA of the knees or hands.7,19 Oral nutraceuticals, such as chondroitin and glucosamine sulfate, have shown promise for patients with knee OA. Results of the NIH Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT) are expected to be released soon. The study is the first multicenter trial in the U.S. to test the ability of chondroitin and glucosamine sulfate, individually and concomitantly, in reducing pain and improving function in patients with knee OA.

Researchers are seeking established and experimental modalities to modify and/or reverse OA, which include colchicine, bisphosphonates, hormones, dietary therapeutics such as green tea and ginger, and experimental treatments such as growth factors, gene therapy, matrix metalloproteinase inhibitors, nitric oxide, and cytokines. 8 Studies are exploring therapies that allow chondrocyte grafting or preserve cartilage.19

Several factors, such as impaired cognitive function, multiple potential causes of pain, unique geriatric pharmacokinetics and pharmacodynamics, and clinician anxiety regarding opioid addiction, may impede the assessment and pharmacologic management of chronic pain in older individuals.5 Pharmacists in various practice settings can have an active role by clarifying the differences between agents, assisting in the assessment of pain (e.g., using pain scales) on an ongoing basis, educating patients about the proper administration of drugs, recommending appropriate agents, alternatives, and adjustments in dosage, and monitoring for side effects and drug interactions to assist with these important treatment issues.

Conclusion
Pharmacotherapy for OA generally consists of analgesics, NSAIDs, COX-2 inhibitors, corticosteroids, viscosupplementation, and symptomatic slow-acting drugs (i.e., nutraceuticals). Improving function and quality of life are the goals of pain management in elderly patients. To achieve these goals, a multidisciplinary application of both nonpharmacologic and pharmacologic approaches is often necessary. Both aerobic and strengthening exercises seem to be equally effective to reduce pain and improve function. Management regimens that can slow, alter, or reverse the degenerative process of OA continue to be sought.

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