Marian A. Minor

Osteoarthritis: New Insights. Part 2: Treatment Approaches

There is no known cure for osteoarthritis, and the goal of contemporary management of the patient with osteoarthritis remains control of pain and improvement in function and health-related quality of life with avoidance, if possible, of therapeutic toxicity. Recent studies have demonstrated the potential of treatments ranging from newly approved oral medications to nutriceuticals, patient education interventions, and surgery. Increasingly, appropriate treatment of osteoarthritis combines one or more oral agents with exercise and other biomechanical techniques. This article is part 2 of a two-part summary of a National Institutes of Health (NIH) conference, Stepping Away from OA: Prevention of Onset, Progression, and Disability of Osteoarthritis. The conference brought together experts from diverse backgrounds and provided a multidisciplinary and comprehensive summary of recent advances in the prevention of osteoarthritis onset, progression, and disability. For research questions and opportunities identified at the conference, see www.nih.gov/niams/reports/oa/oareport.htm(accessed on 25 May 2000). Systemic and Topical Treatments Dr. Marc C. Hochberg (University of Maryland School of Medicine, Baltimore, Maryland), Dr. Timothy McAlindon (Boston University School of Medicine, Boston, Massachusetts), and Dr. David T. Felson (Boston University School of Medicine): Drug therapy for pain management is most effective when combined with nonpharmacologic strategies (1, 2). In 1995, the American College of Rheumatology issued guidelines for the medical management of osteoarthritis of the hip and knee (2, 3). Since then, several systematic reviews of drug therapy for osteoarthritis have been published (4-6). The following recommendations for systemic and topical treatments (except for glucosamine and chondroitin, which were not evaluated) are derived from updated recommendations of the American College of Rheumatology for the treatment of osteoarthritis. Systemic Treatments Nonopioid Analgesics For many patients with osteoarthritis, the relief of mild to moderate joint pain afforded by the simple analgesic acetaminophen is comparable to that achieved with a nonsteroidal anti-inflammatory drug (NSAID) (7, 8). Accordingly, although acetaminophen fails to adequately relieve pain in many patients, it merits a trial as initial therapy on the basis of its overall cost, efficacy, and toxicity profile (9, 10). The daily dose of acetaminophen should not exceed 4 g. Although it is one of the safest analgesics, acetaminophen can be associated with clinically important adverse events, such as prolongation of the half-life of warfarin (11). At therapeutic doses acetaminophen rarely causes hepatic toxicity, but it should be used cautiously in patients with existing liver disease and avoided in patients with chronic alcohol abuse because of known increased risk in these patients (12-14). Even though acetaminophen was reported to be weakly associated with end-stage renal disease, the Scientific Advisory Committee of the National Kidney Foundation recommended it as the drug of choice for analgesia in patients with impaired renal function (15). Tramadol, a centrally acting oral analgesic, is a synthetic opioid agonist that inhibits reuptake of norepinephrine and serotonin. It has been approved by the U.S. Food and Drug Administration for treatment of moderate to severe pain and can be considered for use in patients in whom acetaminophen therapy has failed and who have contraindications to NSAIDs, including the cyclooxygenase-2 (COX-2)specific inhibitors. Although numerous studies have examined use of tramadol to treat general pain, few controlled studies have examined its use in osteoarthritis. The efficacy of tramadol has been found to be comparable to that of ibuprofen in patients with hip and knee osteoarthritis (16), and it is useful as adjunctive therapy in patients with osteoarthritis whose symptoms were inadequately controlled with NSAIDs (17). Daily doses of tramadol have generally been in the range of 200 to 300 mg given in four divided doses. Side effects are common and include nausea, constipation, and drowsiness. Despite the opioid pharmacology of tramadol, a comprehensive surveillance program has failed to demonstrate significant abuse, and tramadol remains an unscheduled agent. Seizures have been reported as a rare side effect, either at doses above the recommended range or at doses within the recommended range in patients with a history of epilepsy and those taking concomitant medications that lower the seizure threshold. NSAIDs For patients who do not obtain adequate symptom relief with nonopioid analgesics, use of NSAIDs should be considered. The choice between a nonselective NSAID and a COX-2specific inhibitor should be made after evaluation of risk factors, particularly for upper gastrointestinal and renal toxicity. Data from epidemiologic studies show that among persons 65 years of age or older, 20% to 30% of all hospitalizations and deaths due to peptic ulcer disease were attributable to therapy with NSAIDs (18-20). Furthermore, the risk for a catastrophic gastrointestinal event in elderly patients taking NSAIDs is dose dependent (18). Risk factors for upper gastrointestinal bleeding in patients treated with NSAIDs include age 65 years or older, history of peptic ulcer disease or previous upper gastrointestinal bleeding, concomitant use of oral corticosteroids or anticoagulants, and possibly smoking and alcohol consumption (21-23). Risk factors for reversible renal failure in patients with intrinsic renal disease who are treated with NSAIDs include age 65 years or older, hypertension or congestive heart failure, and concomitant use of diuretics and angiotensin-converting enzyme inhibitors (24). Additional considerations involved in a practitioners decision to treat an individual patient with osteoarthritis include existing comorbid conditions and concomitant therapy, as well as the side effects and costs of specific treatments. The options for medical management of the patient with osteoarthritis who is at increased risk for a serious adverse upper gastrointestinal event, such as bleeding, perforation, or obstruction, are use of a COX-2specific inhibitor or a nonselective NSAID with gastroprotective therapy. Two COX-2specific inhibitors, celecoxib and rofecoxib, have been approved by the U.S. Food and Drug Administration for use in patients with osteoarthritis (25, 26). Celecoxib has been found to be more effective than placebo and as effective as naproxen for symptoms in patients with hip or knee osteoarthritis (27-29). Rofecoxib has also been found to be more effective than placebo and is comparable in efficacy to both ibuprofen and diclofenac in patients with hip or knee osteoarthritis (30, 31). Endoscopic studies have shown that celecoxib and rofecoxib are associated with an incidence of gastroduodenal ulcers lower than that of comparator NSAIDs and similar to that of placebo (25). These data suggest an advantageous safety profile compared with nonselective NSAIDs, especially for treatment of high-risk patients (21-23). However, no large long-term studies have been published that were designed to demonstrate differences between COX-2specific inhibitors and nonselective NSAIDs with respect to major gastrointestinal clinical outcomes; such studies are in progress. A further advantage of COX-2specific inhibitors with respect to upper gastrointestinal bleeding is that celecoxib and rofecoxib do not have a clinically significant effect on platelet aggregation or bleeding time. In addition, at doses recommended for treatment of osteoarthritis, these drugs appear to be better tolerated than comparator nonselective NSAIDs, with a lower incidence of dyspepsia and other gastrointestinal side effects. As with nonselective NSAIDs, however, COX-2specific inhibitors can cause renal toxicity. Caution must be exercised, therefore, if these drugs are used in patients with mild to moderate renal insufficiency, and they should not be used in patients with severe renal insufficiency. In addition, celecoxib is contraindicated in patients with a history of allergic reaction to a sulfonamide. The alternative to use of a COX-2specific inhibitor is use of a nonselective NSAID with a gastroprotective agent, an approach endorsed by the American College of Gastroenterology (23). As noted earlier, serious adverse upper gastrointestinal events attributed to NSAIDs in the elderly are dose dependent. Therefore, if nonselective NSAIDs are used, therapy should be begun at low, analgesic doses and increased to full anti-inflammatory doses only if lower doses do not provide adequate relief of symptoms. In a study of 8843 patients with rheumatoid arthritis, misoprostol at a dosage of 200 g four times daily reduced the incidence of serious ulcer complications, including perforation, bleeding, and obstruction, by 51% (32). In a 12-week randomized, double-blind, placebo-controlled endoscopy study, misoprostol at a dosage of 200 g three times per day had comparable efficacy in prevention of both gastric and duodenal ulcers; however, 200 g twice daily conferred significantly less protection against gastric ulcers (33). Side effects, particularly diarrhea and flatulence, may occur with this agent in a dose-dependent manner (33). Alternative approaches to prophylaxis with misoprostol include use of omeprazole or high-dose famotidine, both of which have been shown in carefully conducted endoscopy studies to be effective in treating and preventing NSAID-induced gastropathy (34-37). Histamine-2 blockers in usual doses, however, have not been found to be as effective as misoprostol (36), whereas omeprazole (20 mg/d or 40 mg/d) was as effective as misoprostol (200 g twice daily) in treatment of existing ulcers and was better tolerated and associated with a lower rate of relapse (37). Of note, proton-pump inhibitors have not been approved by the U.S. Food and Dr

Integrative Review of Physical Activity Intervention Research with Aging Adults

This paper reviews randomized, controlled trials (RCTs) that have attempted to increase physical activity behavior by aging adults. A systematic review was necessary because numerous studies target older adults, and previous reviews have addressed a limited range of primary studies. Computerized database, ancestry, and extensive search strategies by authors of research reported in English between 1960 and 2000 located diverse intervention trials. RCTs reporting endurance physical activity or exercise behavioral outcomes for at least five subjects were included. Integrative review methods were used to summarize extant research. Forty‐two studies were retrieved. Seventeen RCTs with 6,391 subjects were reviewed. A wide variety of intervention strategies were reported. The most common interventions were self‐monitoring, general health education, goal setting, supervised center‐based exercise, problem solving, feedback, reinforcement, and relapse prevention education. Few studies individually adapted motivational interventions, used mediated intervention delivery, or integrated multiple theoretical frameworks into the intervention. Links between individual intervention components and effectiveness were not clear. Common methodological weaknesses included small samples, untested outcome measures, and time‐limited longitudinal designs. Significant numbers of aging adults increased their physical activity in response to experimental interventions. The amount of increased activity rarely equaled accepted behavior standards to achieve positive health outcomes. Further work is essential to identify successful strategies to increase activity by larger numbers of elders and to accelerate the increase in activity by those who change activity behaviors. Sex and ethnic differences need further investigation. There is a vital need for rigorously designed studies to contribute to this science.

EXERCISE IN THE TREATMENT OF OSTEOARTHRITIS

Exercise, both therapeutic and recreational, is an effective therapy in successful management of osteoarthritis. Exercise is integral in reducing impairment, improving function, and preventing disability. Benefits of flexibility, muscular conditioning, and cardiovascular exercise and the role of regular physical activity in maintaining general health are discussed. Exercise recommendations and safety considerations are provided.

RECREATIONAL EXERCISE IN ARTHRITIS

For the person with arthritis, the consequences of prolonged inactivity add measurably, and unnecessarily, to disease-related impairments, functional limitation, and disability. Inadequate levels of regular physical activity also increase the risk of cardiovascular disease, hypertension, diabetes, and obesity. This article reviews the benefits of regular physical activity for general health as well as the literature on conditioning exercise in rheumatoid arthritis and osteoarthritis. Recommendations and guidelines are given for including conditioning exercise in comprehensive management.

THE ROLE OF PHYSICAL THERAPY AND PHYSICAL MODALITIES IN PAIN MANAGEMENT

This article provides an overview to arthritis care of the common physical modalities (heat, cold, transcutaneous electrical nerve stimulation, low-energy laser, topical applications, and external devices). The rationale for use and effectiveness of the various physical modalities are discussed. Exercise is presented in terms of mode and effect of range of motion, muscle conditioning, and aerobic exercise.

Randomized trial of 2 interventions to increase older women's exercise.

OBJECTIVE To test 2 interventions to increase older womens physical activity. METHODS A randomized 2-way factorial experimental design compared the effects of 2 limited-contact interventions, motivational sessions and periodic prompts, among 190 women. Experimental participants received a 3-encounter motivational intervention. Those randomized to prompts received weekly telephone or mail-delivered cues. RESULTS The prompting intervention consistently increased exercise and physical activity scores. The motivational intervention did not affect outcome scores. CONCLUSIONS Prompting is a low-cost strategy for increasing exercise and physical activity among older women. Future research should examine alternative modes for prompt delivery.

Measurement of varus/valgus alignment in obese individuals with knee osteoarthritis.

Frontal plane knee malalignment may increase progression of knee osteoarthritis (OA) and hasten functional decline. An accurate nonradiographic measure of knee alignment is necessary because the gold standard measure, the long‐leg radiograph, is costly and often unavailable. Moreover, nonradiographic measures of knee alignment have not been validated in an obese population, where knee OA is common. The purpose of this study was to develop and assess the concurrent validity and reliability of a nonradiographic measure of frontal plane knee alignment and demonstrate the accuracy of the measure in an obese population.

Act Healthy: promoting health behaviors and self-efficacy in the workplace

Chronic health conditions and multiple health risk factors afflict Americans and burden employers, but effective, affordable, workplace-based health promotion interventions have not been widely implemented. This is the first study to adapt the empirically validated Chronic Disease Self-Management Program for a general employee population in a workplace setting with an emphasis on disease prevention and health promotion. A quasi-experimental, wellness standard of care comparison, prospective cohort design was used among employee participants at a large University employer. Ninety-one individuals participated in the program. Participants reported significantly increased health behavior frequency and self-efficacy after the intervention, compared with their pre-intervention scores, and improvements were sustained at 3-month follow-up [self-rated abilities for health practices scale (SRA): F = 30.89, P < 0.001; health promoting lifestyle profile-II (HPLP-II): F = 36.30 P < 0.001]. Individuals in the intervention group reported improved self-efficacy and health behaviors compared with the wellness standard of care comparison group at post intervention (SRA: F = 12.45, P < 0.001; HPLP-II: F = 25.28, P < 0.001). Adapting lay-facilitated self-management for the workplace offers promise as a replicable, scalable, affordable model for culture change in organizations.

A Randomized Controlled Trial to Evaluate Outcomes of a Workplace Self-Management Intervention and an Intensive Monitoring Intervention.

The purpose of this study was to determine and compare outcomes of two voluntary workplace health management methods: an adapted worksite self-management (WSM) approach and an intensive health monitoring (IM) approach. Research participants were randomly assigned to either the WSM group or the IM group by a computer-generated list (n = 180; 92 WSM and 88 IM). Participants completed baseline, 3 and 12-month follow-up surveys. Individuals receiving workplace WSM and IM improved in self-efficacy and nearly all health behaviors and health status variables after the intervention, compared to before the intervention. Individuals in the WSM group improved in depression symptoms at 3 and 12 months (P < 0.0001, P < 0.0001), and individuals in the IM group did not improve at either time period (P < 0.1488, P < 0.0521). Participants in the WSM group reported more improvement in physical activity and energy, health interfering less with personal life and daily activities and fewer depression symptoms at follow up, compared to participants in the IM group. This study provided additional support for worksite-based health promotion programs to promote healthy lifestyles and improve health status, and documented effectiveness of both methods, with superior performance and greater scalability for the WSM program.

An evidence-based recommendation for the inclusion of specific local intrinsic factors in the study of knee osteoarthritis

OBJECTIVE Adequate characterization of the mechanical environment of the knee with osteoarthritis (OA) is important. These local intrinsic factors are difficult to measure and there is little evidence to guide their selection. This study makes an evidence-based recommendation for the inclusion of specific factors in the future study of knee OA. METHOD Forty-six subjects with knee OA were examined. Observed function was measured by the Timed Chair Rise (TCR). Self-reported function was measured by the WOMAC Function Scale and pain was measured by the WOMAC Pain Scale. Local intrinsic factors measured included varus/valgus alignment, anterior/posterior (A/P) laxity, proprioception, isometric knee extension (KE) strength, isometric knee flexion (KF) strength, and knee range of motion (ROM). RESULTS Factors were recommended for inclusion in future research if they were significantly correlated with at least one measure of function or pain and if the factor made a significant unique contribution to a regression model when more than one local intrinsic factor was correlated with the same measure of function or pain. Alignment was correlated with pain (r=0.48, p=0.001) and WOMAC function (r=0.38, p=0.009). A/P laxity was correlated with pain (r=0.30, p=0.04) and WOMAC function (r=0.37, p=0.01). Knee ROM was correlated to WOMAC function (r=-0.35, p=0.02). KE strength was correlated with TCR (r=0.32, p=0.03). Alignment made a significant contribution to prediction of pain (p=0.003). A/P laxity (p=0.004) and ROM (p=0.008) made a significant contribution to WOMAC function. CONCLUSION We recommend future knee OA studies include the variables varus/valgus alignment, A/P laxity, ROM, and KE strength.