Shari M. Ling
Joan M. Bathon
Osteoarthritis (OA) is the most common form of arthritis in the United States (1,2). It is projected that OA will affect some 60 million Americans by the year 2020. This estimate reflects the increasing lifespan of Americans but does not account for the astounding rise in obesity that will further boost the prevalence of OA, particularly of weight-bearing joints. OA contributes significantly to limitations in the ability of individuals to ambulate and carry out tasks of daily living (3,4). Treatment of OA remains limited and is focused primarily on modification of behaviors that reduce risk of progression, reduction of pain through medicinal and nonmedicinal approaches, and, in some cases, surgical intervention. The search for clinically relevant biologic markers for early detection of disease has intensified over recent years. Although disease-modifying therapies are being sought, few, if any, interventions have proved to slow the progress of OA. The increasing impact of OA on public health has prompted the National Institutes of Health (NIH) to initiate two collaborative OA research networks: the OA Biomarkers Network and the Osteoarthritis Initiative. These networks will use state-of-the-art immunologic, biochemical, and imaging methods to identify risk factors and biomarkers for the development and progression of OA, with the long-term goal of identifying disease modifying or curative therapies for OA. This chapter highlights the current understanding of the pathophysiology, clinical and diagnostic features, and treatment of OA.
Epidemiology, Causes, and Predisposing Factors
OA is the most common form of arthritis in the United States and Europe (1). Given the prolonged life expectancy
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in the United States and the aging of the “baby boomer” cohort, the prevalence of OA is expected to increase further. Although the precise cause of OA is unknown, multiple causes and many factors likely influence disease expression. Epidemiologic and observational studies provide important clues to the mechanisms by which OA develops and progresses and thus identify risk factors that might comprise targets for future interventions (5). Table 75.1 lists these risk factors.
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TABLE 75.1 Factors Contributing to Development of Osteoarthritis |
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The prevalence of OA increases with age and peaks in the 70s. However, OA may begin as early as age 30 years in individuals with multiple risk factors. OA usually is defined in one of two ways in the literature. The diagnosis may be based solely on typical radiographic features (“radiographic OA”) or on a combination of pain/stiffness and radiographic findings (“symptomatic OA”). Thus, prevalence estimates vary by the definition used, as well as by the joint that is targeted. Estimates that originate from population-based epidemiologic studies are most commonly based upon radiographic definition.
Age: Advanced age is the strongest risk factor for the development of OA across all anatomic sites (1). Prevalence rates for both radiographic OA and, to a lesser extent, symptomatic OA (moderate or severe) increase with age, with a steep rise after age 50 years in men and age 40 years in women. In the peripheral joints, radiographic OA of the hand is the most prevalent form, followed by the knee and then the hip. Radiographic knee OA has been reported in as many as 44% of individuals aged 80 years or older, although the prevalence of associated painful symptoms was significantly lower (11% in women and 7% in men). This higher rate of radiographic, compared to symptomatic, disease is typical of most studies of OA (5,6). Thus, it is not unusual to find incidental radiographic OA in an otherwise asymptomatic older patient. OA (whether defined radiographically or symptomatically) is uncommon in individuals younger than 35 years. Symptomatic OA of the knee and of the hip are the most prevalent in both sexes, with symptomatic involvement of the hands increasing in women beginning at menopause (1,7). New onset of radiographic and symptomatic OA of the knee continues to develop in older adults at a rate of 1% to 2% per year, again moreso in women than in men (2).
Gender: Until recently, the risk of OA in young adult years had been higher for men than women. This was attributed to the greater risk of sports-related and occupational injuries endured by men (7). However, the recently observed increase in sports-related injuries of the anterior cruciate ligament (ACL) in women (8) may influence the epidemiologic trends in coming years to match the female predominance observed in middle and later life. It has been postulated that the increased prevalence of OA in women may be due to changes in the hormonal milieu (9,10). A reduced risk of incident hip OA has been observed in longitudinal studies of women receiving hormonal therapy, particularly for bilateral radiographic OA and more severe OA (9). However, estrogen/progestin replacement has not been proven to reduce the odds of knee pain or disability in women with knee symptoms (10). Whether estrogen or hormonal therapy is beneficial to patients with OA remains controversial and further emphasizes that symptoms and pathogenesis of OA likely develop by different mechanisms.
Joint Trauma and Nontraumatic Biomechanical Factors: Joint trauma has been shown to increase the risk of OA (11,12). Meniscectomy is associated with a sixfold increase in risk for development of radiographic OA (13, 14, 15), even if limited rather than total meniscal resection is used (14,15). Obesity, female sex, and pre-existing early-stage OA further increase the risk of symptomatic OA in patients years after a meniscectomy (13), as does the presence of radiographic hand OA (16). Occupation and sports-related repetitive injury and physical trauma contribute to the development of OA of specific joints (e.g., knees in soccer players, elbows of baseball pitchers, and upper limbs of air hammer operators) (8,17,18) and account for occurrence at sites not usually affected by OA. Although the prevalence of knee
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OA is greater in adults who have engaged in occupations that require repetitive bending and strenuous activities, an association with intense exercise or recreational physical activity, such as jogging, has not been proven (19,20).
Malalignment and Laxity: Joint malalignment and laxity are potential causes as well as consequences of OA (21, 22, 23). For example, altered alignment, as in the case of acetabular dysplasia, may increase the risk of hip OA (24). Data indicate that cartilage loss in osteoarthritic knees that are malaligned (varus or valgus deformity) progresses at a more rapid rate (as measured radiographically) than cartilage loss in normally aligned knees (25, 26, 27, 28). Although laxity and malalignment may coexist, laxity independently increases the risk of OA, as well as attenuating the relationship between strength and physical function (22).
Obesity: Cohort studies have demonstrated a clear association of obesity with the development of radiographic knee OA in older women (11) and a weaker association with hip OA (11). It is estimated that persons in the highest quintile of body weight have up to ten times the risk of knee OA than persons in the lowest quintile. Obesity influences painful symptoms in the knees (11), as indicated by the mild to moderate relief in pain afforded by weight reduction. Malalignment appears to explain some of the risk of knee OA progression attributable to obesity (27, 28, 29). Although mechanical factors are assumed to explain the increased risk of knee and hip OA associated with excess weight and obesity (11,29,30), there also is an association of hand OA with weight, which raises the possibility of alternative mechanisms.
Muscle Strength: Weakness of the knee extensor muscles appears to be both a consequence and a risk factor for the development of knee OA (31,32). However, muscle strengthening has not been proven to protect individuals from disease progression (33). In fact, evidence suggests that muscle strengthening may accelerate progression of OA of the knee in individuals whose knees are malaligned (21). Higher hand grip strength is associated with increased risk of proximal interphalangeal and carpometacarpal joint OA in men and of metacarpophalangeal joint OA in men and women (34). However, patients with hand OA often exhibit lower grip and pincer strength (35) than do unaffected individuals.
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FIGURE 75.1. Predisposing and causative factors implicated in osteoarthritis development. These include cellular, structural, and biomechanical factors associated with aging, biomechanical factors that increase detrimental forces across the joint, and traumatic or repetitive injury. |
Genetics: Twin studies have shown that the influence of genetic factors is between 39% and 65% in radiographic OA of the hand and knee in women, approximately 60% in OA of the hip, and approximately 70% in OA of the spine and suggest a heritability of OA of ≥50% (36). Genetic studies of OA to date have focused on identifying polymorphisms of structural components of cartilage. A rare syndrome, inherited as a mendelian dominant, is related to a single base mutation in the type II procollagen gene (COL2A1) and results in mild chondrodysplasia and premature OA, often in the fourth decade (37,38). Type II collagen is a major protein component of articular cartilage that contributes structural integrity during mechanical stress. Whether heterogeneity or polymorphisms of alleles of the COL2A1 gene (37,38) or other molecules such as aggrecan (39) and interleukin (IL)-1 (40,41) play a role in the common forms of OA remains to be determined. One study implicated a defect in the gene for type IX collagen, another collagen important in cartilage structure, as a risk factor for lumbar disk disease and female hip OA (42,43). Other studies have demonstrated an association between early and severe OA with abnormalities in the vitamin D receptor (44, 45, 46, 47).
Pathophysiology of Osteoarthritis
The pathogenesis of OA is multifactorial (Fig. 75.1); however, the final common pathway is believed to be progressive depletion of the collagen and proteoglycan matrix and proliferation of underlying bone with osteophyte formation (48,49). Under normal conditions, chondrocytes
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regulate the amount of extracellular matrix by balancing the synthesis and degradation of its structural components (50,51). In OA, a state of disequilibrium develops in which degradative pathways far outstrip repair processes in a complex milieu of interaction among inflammatory cytokine mediators (51,52), growth factors, degradative enzymes, and chondrocyte apoptosis (53,54). Susceptibility to cartilage damage increases with age and may be the result of abnormal biomechanics that lead to excessive stress or defective matrix components and alteration of the normal structure (55,56). Impact loading and torsional, shear, and repetitive stress are more important than frictional wear (57,58). Changes are most severe in, or may be confined entirely to, areas of maximal stress on the articular cartilage, most striking in weight-bearing areas of the large joints. Synovitis usually is minimal in the early stages but may contribute to joint damage in advanced disease. Changes in the hardness of bone and the cartilage's loss of ability to absorb stress as a primary mechanism in OA also have been proposed. The role of bone pathology in disease progression also has been suggested by observations that higher bone density is positively associated (59), and lower bone density (osteoporosis) negatively associated (60), with OA. The identification of bone marrow lesions in knee OA has contributed significantly to our understanding of the pathogenesis of pain and of the role of bone abnormalities in disease progression (61,62). Finally, deposits of calcium pyrophosphate, hydroxyapatite, or basic calcium salts may play a role in the synovial inflammatory response, pain, or destructive arthropathy in certain patients (63,64).
Because there are no nerve fibers in articular cartilage, early changes in cartilage associated with OA are generally asymptomatic. However, as the disease progresses, pain is thought to evolve from involvement of noncartilaginous structures. Periosteal irritation as a result of proliferating bone, denuded bone, compression of soft tissues by osteophytes in confined spaces, microfractures of subchondral bone, stress on ligaments as a result of loss of cartilage and joint incongruity, low-grade synovitis, effusion, and spasm of surrounding muscles are all potential sources of pain in OA.
General Clinical Features and Diagnosis
Table 75.2 lists the distribution of joints usually affected by OA. The clinical presentation differs somewhat depending on the particular joint(s) involved, but many of the signs and symptoms are consistent from joint to joint. The American College of Rheumatology (ACR) has developed a set of criteria for the diagnosis of OA. The ACR criteria combine symptoms, physical signs, and x-ray films of the affected joints (65) and are summarized in Table 75.3.
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TABLE 75.2 Distribution of Joint Involvement in Primary Osteoarthritis |
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History
Stiffness of the joint after sleep or prolonged inactivity (gel phenomenon) is the most common first symptom. It usually is short in duration (5**30 minutes) and quickly abates with joint movement. This should be distinguished from
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the morning stiffness associated with inflammatory joint diseases that persists beyond 30 minutes.
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TABLE 75.3 Criteria for Diagnosis of Osteoarthritis of the Hand, Knee, and Hip |
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As the disease progresses, joint pain or aching is the hallmark symptom of OA. The pain is elicited by maneuvers that stress the joint. For example, in patients with patellofemoral OA, knee pain is elicited by squatting and descending stairs. Patients with hip OA often report groin or thigh pain upon weight-bearing pain or with activities that require flexion of the hip, such as the donning of pants. Pain usually begins insidiously but worsens over time in a significant proportion of patients. As the disease advances, pain and aching may persist even when the joint is at rest, often leading to significant sleep interruption. A sensation of “locking” or “giving way” may signal internal derangement of the joint. The patient should be asked about a prior or recent history of joint injury, which may warrant further orthopedic evaluation.
Physical Findings
Physical examination of a joint with early radiographic OA frequently is normal. As the disease becomes more severe and/or symptomatic, however, abnormalities noted on examination are more common. Generally, tenderness can be elicited at the joint margins, and pain may be reproduced by passive range of motion. The examiner can detect crepitus by feeling the joint as it moves through its range of motion. Bony enlargement of the distal interphalangeal joints (Heberden nodes), and less commonly of the proximal interphalangeal joints (Bouchard nodes), becomes evident as osteophytes and chondrophytes progress. Although less inflammatory than rheumatoid arthritis, mild warmth and/or effusion of the joint may be present, indicating some degree of synovial inflammation. Pain elicited by manual compression of the patella during quadriceps activation usually signals patellofemoral OA. Hip pain is reproduced on passive internal rotation of the hip. Patients with advanced knee OA frequently have varus (or less commonly valgus) malalignment and/or limited extension (flexion contracture). During ambulation, patients with knee or hip OA may exhibit an antalgic gait that limits weight-bearing on the symptomatic side. In addition, patients with advanced hip OA and hip girdle weakness sway toward the affected side during ambulation in the so-calledTrendelenburg lurch.
Functional Limitations
Numerous cross-sectional and longitudinal studies have clearly established that OA, particularly of the knee and hip, is a major cause of disability in the United States (66, 67, 68). Evidence indicates that disability may begin early in the course of the disease (31). Disability is manifested early in the course of hip and knee OA by a slowed and painful gait, often accompanied by a limp (antalgic gait). As the pain worsens, affected individuals curtail their physical activity and avoid difficult or pain-inducing tasks. Muscle weakness accompanies OA in all anatomic locations and may result in difficulty with mobility as well as with self-care tasks. Finally, musculoskeletal pain and OA both predispose older adults to risk of falls, enhancing the possibility of further functional impairment (69,70).
Laboratory Findings
Routine laboratory tests are normal in OA unless the patient has a concomitant disease process(es). Although acute phase reactants, including the erythrocyte sedimentation rate and the C-reactive protein (CRP), are normal in patients with OA compared to patients with more inflammatory arthritides (e.g., rheumatoid arthritis or acute gout), several studies suggest that modestly elevated CRP levels predict the development and/or progression of OA (71, 72, 73). However, obesity is common in OA, and obesity itself is associated with elevated levels of inflammatory markers, leading some to call into question the direct association of inflammation with development and progression of OA. Nonetheless, others have demonstrated elevated levels of other inflammatory molecules in OA, including IL-6 and soluble receptors for tumor necrosis factor (74).
Synovial fluid in OA usually is of the noninflammatory type (i.e., white blood cells <2,000/mm3, protein content <4 g/dL, and glucose concentration approximately equal to a simultaneous serum glucose concentration; see Chapter 74). A more inflammatory fluid with elevated white cell count may occur when crystals of calcium pyrophosphate or hydroxyapatite are present (see Chapter 76).
Efforts to develop biologic markers for diagnosis, disease activity, or progression of OA have not yet reached a degree of specificity or sensitivity to be clinically useful (49,75, 76, 77, 78, 79, 80, 81, 82, 83). Both synthetic and degradative constituents of cartilage and bone can be detected in individuals with OA, illustrating the complexity and delicate balance in degradation and repair processes of cartilage and bone in determining a healthy versus a diseased joint (75, 76, 77, 78, 79, 80, 81). Identification of a biomarker(s) is greatly needed because it would facilitate early diagnosis and/or identification of individuals at risk for rapid disease progression (82). It is possible that combinations or clusters of markers may improve the predictive power of identifying OA, rather than relying upon a single marker (83).
Imaging Osteoarthritis
Bony osteophytes at the joint margins, subchondral sclerosis, and joint space narrowing compose the radiographic hallmarks of OA (Fig. 75.2). Conventional radiography remains the definitive procedure in routine clinical care for (a) confirmation of a diagnosis of OA, (b) classification and estimation of disease severity, (c) assessment of disease
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progression, and (d) exclusion of alternative causes of painful symptoms. It should be emphasized that the presence and severity of radiographic findings of OA do not correlate well with the presence or severity of joint pain. The ACR criteria for OA take this discrepancy into account by incorporating historical, physical, and radiographic components as diagnostic criteria.
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FIGURE 75.2. A: Hands of a patient with degenerative joint disease. Note soft-tissue enlargement on the right over the second distal interphalangeal (DIP) joint (Heberden node); loss of joint space and bony proliferation of all DIP joints, especially 2 and 3 in the right hand and 3 in the left hand; involvement of the carpometacarpal joint of both thumbs with narrowing and increased density of subchondral bone; and normal metacarpophalangeal joints and wrist joints. B: X-ray film of the knee showing degenerative joint disease with loss of joint space (cartilage), especially in the medial compartment, sclerotic subchondral bone, subchondral cysts, and early marginal spurs especially on lateral side. C: Pelvic film of a patient with advanced degenerative joint disease in the right hip. Note joint space narrowing and proliferation of subchondral bone. The left hip shows minimal change of marginal sclerosis. D: Lateral x-ray film of the same knee shown in B illustrating involvement of the patellofemoral joint with narrowing and spur formation superiorly. E: X-ray film of the hip showing early degenerative joint disease. Note the narrowed joint space and spur formation of the femoral head at the upper margin of the acetabulum. F: X-ray film of the lateral cervical spine showing degenerative joint disease. Note narrowing of C5–6 and especially C–7 interspace with anterior lipping and spur formation. G: Oblique x-ray view of cervical spine of the same patient shown in F demonstrating osteophytes encroaching on neural foramina C5–6 and C6–7. |
Conventional radiography is most commonly used in patients under evaluation for OA as a confirmatory diagnostic tool. However, relatively normal radiographs in patients with early disease should be expected given the limited sensitivity of conventional radiographs. Conversely, radiographic OA is a frequent incidental finding in older patients who have no joint pain. Conventional radiographs also are useful in excluding alternative etiologies of pain (e.g., fracture, avascular necrosis, or bone infarction). Although conventional radiography is used to determine whether or not and to what extent a patient's disease has progressed, it has become apparent that minor alterations in joint positioning can influence the assessment of joint space significantly. As such, fluoroscopically guided, semiflexed views of the knees and nonfluoroscopically guided variable flexion views are used in clinical trials to provide a more standardized method for obtaining and grading joint space width and hence radiographic severity. Published grading systems provide standardized measures for assessing the presence and radiographic severity of OA for clinical and epidemiologic studies (84).
To confirm a diagnosis of OA of the hands, a single anteroposterior (AP) view of both hands is sufficient in most cases. However, additional views usually are necessary to exclude other diagnoses such as rheumatoid arthritis. Similarly, a single AP pelvis radiograph is sufficient to confirm OA of the hips, but additional views may be required to better visualize the hip joint if other abnormalities are suspected. Non–weight-bearing AP radiographs are not adequate for evaluating the knee. Weight-bearing AP and lateral radiographs should be obtained with an additional skyline view if patellofemoral arthritis is suspected. In evaluating the cervical spine, lateral and oblique views are warranted to visualize the neural foramina and to localize nerve root compression by bony spurs. Although lateral and AP views are capable of demonstrating OA of the lumbar spine, flexion and extension stress is required to elucidate malalignment or instability.
Magnetic resonance imaging (MRI) is a tool increasingly used in orthopedic and rheumatologic clinical practice to relate articular complaints to disruption of joint integrity (85). Small localized defects in cartilage can be identified early by MRI, and quantitative techniques for measuring regional cartilage thickness and total cartilage volume have been developed (86, 87, 88). Semiquantitative methods for assessing the integrity of all articular and periarticular structures have been developed for the knee and currently are being used in large-scale studies of the natural history of knee OA (85,89,90). Future clinical trials likely will prove these quantitative and semiquantitative methods to be superior to conventional radiography for assessing the ability of novel therapies to slow progression of OA. In addition to its sensitivity for assessing loss of cartilage, MRI provides direct visualization of cartilage, menisci, ligaments, synovium, synovial fluid, and subchondral bone. MRI is the best imaging method for visualizing the axial skeleton in patients with persistent back pain, particularly if there are neurologic impairments (91), and to confirm a diagnosis of spinal stenosis (92) (see Chapter 71).
Differential Diagnosis of Osteoarthritis
Arthritis is one of many causes of musculoskeletal pain. Pain that is not associated with use of the joint or cannot be reproduced by palpation of the joint line and/or by passive motion of the joint should suggest an alternate periarticular source (e.g., bursitis, tendonitis, periostitis). Likewise, pain in the metacarpophalangeal joints, wrists, elbows, or ankles, joints that are not commonly affected by primary OA, should prompt an alternative diagnosis. Inflammatory or systemic symptoms, such as prolonged morning stiffness (>1 hour), unintentional weight loss, and fatigue, should raise suspicion of an inflammatory arthritis such as rheumatoid arthritis or polymyalgia rheumatica. Intense inflammation on examination suggests an infectious or microcrystalline process such as gout or pseudogout. Furthermore, OA can be the secondary result of other disease states, such as inflammatory arthritis; metabolic diseases, such as ochronosis; and diseases predisposing to chondrocalcinosis, such as hemochromatosis, hyperparathyroidism, and acromegaly. These conditions should be identified and treated to minimize joint and other organ damage. Finally, conditions such as fibromyalgia (see Chapter 74) and vitamin D deficiency (see Chapter 84) may be superimposed upon OA and would not respond to conventional analgesic or anti-inflammatory therapies (93, 94, 95).
Management
Although there is no cure for the disease, much can be done to relieve symptoms, minimize disability, and perhaps delay progression of the disease. The focus in managing patients with OA should not only be centered on the improvement of pain but also improvement of function. Hence medicinal and nonmedicinal treatment should be used in combination to alleviate symptoms (Fig. 75.3) (96, 97, 98). Furthermore, treatments to improve, or at least preserve, function should be used along with strategies for joint protection (99). Advances in understanding the mechanisms involved in disease pathogenesis suggest that
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new methods of treatment directed toward slowing cartilage degeneration may soon be within reach.
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FIGURE 75.3. Management options for osteoarthritis. The various treatments for improving osteoarthritis symptoms are illustrated under the categories of medicinal, nonmedicinal, and surgical. Medicinal interventions should be used in conjunction with nonmedicinal interventions and should be exhausted prior to consideration of surgical intervention. |
Health Behavior Modification
Patient Education
Altering health behaviors is one of the most important and most challenging approaches to the management of OA. The essential elements of patient education include information about OA, symptom-directed management options, joint-protective strategies, reassurance, and enhanced patient compliance. A team approach that provides nursing care and rehabilitative services in addition to primary care can contribute critical aspects to OA management. Patient-directed educational resources are available through the Arthritis Foundation, the ACR, the Association of Rheumatology Health Professionals, and the “Age Page” published by the National Institute on Aging (http://www.niapublications.org/agepages/arthritis.asp).
Weight Management
Weight reduction in obese and overweight patients can alleviate painful symptoms of weight-bearing joints. A 10% reduction in weight is a reasonable objective and should be achieved at a rate not to exceed 1 to 2 lb per week (see Chapter 83). In many cases, a structured weight management program with counseling may be necessary to achieve weight loss. Combined diet and exercise (see below) may be the most effective means of reducing weight in sedentary, obese adults (100, 101, 102, 103). Although the benefits of weight loss on joint protection are intuitive, the extent to which weight reduction attenuates progression of OA in weight-bearing joints is not known.
Exercise
Several large intervention studies proved aerobic exercise to be safe and beneficial for patients with OA of the knee (100,104,105); therefore, aerobic exercise is recommended for all patients with OA of the lower extremities (106). Water aerobic classes or deep-water walking may be a tolerable alternative to land-based exercise for patients with weight-bearing symptoms. The Surgeon General currently recommends that people of all ages strive to accumulate 30 minutes of moderate intensity lifestyle activity throughout the day on most days of the week. This approach to exercise, often termed “lifestyle activity,” can include all leisure, occupational, or household activities that are at least moderate to vigorous in intensity. Examples include brisk walking, raking leaves, and gardening. Fortunately, exercise need not be conducted in a single prolonged high-intensity session but can be accrued in a series of short moderate-intensity bouts throughout the day. For example, three 10-minute vigorous walks per day can achieve health benefits equivalent to one 30-minute walk per day. Use of a pedometer may provide additional incentive to increase physical activity (107).
Resistive-type strengthening exercises of the lower extremities also have proved safe and beneficial in many patients with OA of the knee. However, data suggest that patients with knee OA who have malaligned knees and higher quadriceps strength experience more rapid progression of disease than patients with malaligned knees but lower quadriceps strength (108). Whether an active intervention program of quadriceps strengthening is harmful in OA patients with a malaligned knee(s) has yet to be determined. Direct electrical muscle stimulation is capable of achieving improved quadriceps strength and physical
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performance as an alternative to exercise for patients who are unable to engage in the lifestyle activities described (109,110).
Therapy Services
Physical and occupational therapy services provide important modalities for alleviating painful symptoms and improve joint motion and muscle strength and function (111,112). These services include manual techniques as well as ultrasound, heat, and ice. However, the response of an individual patient to these modalities is difficult to predict (113). Therapists also provide assessments and recommendations for environmental modifications and devices to maximize safe living and reduce risk of injury and falls.
Physical Therapy and Mobility Devices
Physical therapy is a useful adjunctive strategy for managing arthritis symptoms and maximizing function. The physical therapist focuses on lower-extremity function and evaluates the patient's need for devices to overcome mobility limitations, such as a raised toilet seat, shower and bathtub bars, and walking devices such as canes. Proper use of a cane, crutch, or walker can provide much needed stability to disabled patients with advanced OA while providing additional proprioceptive cues. In addition, a properly fitted cane can redistribute weight-bearing away from the problematic side and alleviate painful knee and hip symptoms. To achieve this, the top of the cane should be on the same level as the greater trochanter of the hip. Patients with advanced hip OA have difficulty flexing at the hip and frequently benefit from devices that aid in donning and doffing socks and grabbing items from the floor.
Occupational Therapy
Occupational therapists provide recommendations for assistive devices and exercises that improve upper-extremity and self-care function, as well as local treatment modalities (heat, paraffin or contrast baths). Anecdotal evidence suggests beneficial effects of thermal therapy administered as moist heat packs or paraffin wax or water baths. With all modalities of heat therapy, prolonged exposure to high temperatures (>43°C) should be avoided to prevent skin damage.
Complementary and Alternative Approaches
Many patients with rheumatic diseases use complementary and alternative treatments that include acupuncture, magnets, mind–body exercises, and nutritional supplements (114,115). Except for nutritional supplements (i.e., glucosamine and chondroitin sulfate, seeMedicinal Treatments) and acupuncture, the efficacy of most of these treatments in the management of OA is unstudied or unproven and therefore are not standard recommendations for the management of OA. A single-blinded, randomized trial tested conventional acupuncture compared to sham acupuncture or education in >500 patients with knee OA (116). True acupuncture was associated with statistically significant, albeit modest, improvements in knee pain and function compared to the sham acupuncture and education groups (116). Acupuncture can be considered a safe and modestly effective method for alleviating pain in patients with knee OA.
Symptom-Directed Medicinal Treatments
Medicinal interventions usually are required to alleviate painful symptoms and should be implemented in conjunction with nonmedicinal interventions. When medications are needed, the least toxic and least expensive drugs should be used first.
Acetaminophen: Although originally reported to be as effective as NSAIDs for relief of pain in OA (117), more recent studies have suggested acetaminophen to be less effective (118,119). Nonetheless, because of its more favorable toxicity profile, acetaminophen (up to 4 g/day) is the recommended first-line agent in management of OA with mild to moderate pain (120,121). The major serious side-effect, hepatotoxicity, is not seen at the recommended dosages, except perhaps in patients with liver disease. It is a safer drug than are NSAIDs in patients with renal impairment (122).
Nonsteroidal Anti-Inflammatory Drugs
For patients with more severe symptoms unrelieved by acetaminophen and non-medicinal interventions, nonsteroidal anti-inflammatory drugs (NSAIDs) are the next recommended treatment. Chapter 77 provides an extensive discussion of conventional and cyclooxygenase-2–specific NSAIDs.
Analgesics
Tramadol (200 mg/day), a non-narcotic analgesic, can be used in patients who have an inadequate response to acetaminophen or NSAIDs (123,124). Tramadol can be taken in conjunction with acetaminophen (125), providing additive analgesic effects and allowing dose reduction of concurrently used NSAIDs (126). A long-acting preparation is now available (124,127). The potential for addiction to tramadol appears to be low (128).
Immediate and controlled-release preparations of oxycodone (with or without acetaminophen) are useful in some patients, particularly those who are not candidates for surgery or who are awaiting surgery. There preparations have proved to be superior to placebo for treating OA pain and improving sleep quality (129). The controlled-release preparation may be better tolerated, with less
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nausea and dry mouth. All narcotic preparations can cause constipation and have risk for cross-dependency (130).
Nutritional Supplements
Glucosamine is an amino-monosaccharide component of articular cartilage. Chondroitin sulfate is a proteoglycan component of articular cartilage. The two substances frequently are sold over the counter in combination preparations as dietary supplements. The ACR and European League Against Rheumatism have acknowledged that glucosamine (500 mg three times daily) and chondroitin sulfate (800 mg daily) may be useful for treatment of OA. However, meta-analyses of randomized, placebo-controlled trials have been in conflict about whether or not glucosamine is more effective than placebo (131, 132, 133) and do not support the use of chondroitin sulfate for symptom modification in OA (131,134).
Both glucosamine and chondroitin sulfate have been examined for their potential disease-modifying effects. Glucosamine treatment was associated with a slower rate of joint space narrowing over 2 to 3 years compared to placebo in patients with early knee OA in two randomized, controlled studies (135,136). More recently, treatment for 2 years with chondroitin-4 and chondroitin-6 sulfate was associated with less radiographic progression in patients with knee OA compared to patients who received placebo (134). The radiographic methods used in these three studies have been subject to criticism, however, and an NIH-sponsored trial in the United States currently is underway to reexamine these conclusions. Fortunately, all evidence suggests that both agents are well tolerated and safe (131, 132, 133). Because glucosamine and chondroitin sulfate are sold in the United States as over-the-counter nutraceuticals, manufacture of these supplements is not as tightly regulated as prescription drugs, and cost is not generally reimbursable by third-party prescription plans. The cost of the two agents combined can be prohibitive.
Intra-Articular Therapies
Judicious use of intra-articular therapies is appropriate for OA patients who are not candidates for, or who have inadequate responses to, oral analgesics or anti-inflammatory agents.
Corticosteroids
Intra-articular injection of corticosteroids has been a time-honored option for treatment of moderate to severe OA. Although not always effective, intra-articular steroids often provide pain relief for several months. Presumably effective because of its anti-inflammatory properties, evidence demonstrating an effect on inflammatory mediators in the joint is lacking. Evidence suggests that repeated injections over time can be effective and do not result in accelerated joint damage (137).
Hyaluronic Acid
Injections of hyaluronic acid derivatives (Synvisc, Hyalgan, Orthovisc) have been demonstrated to relieve pain in some patients with OA of the knee and of the hip (138,139). All preparations are administered over a series of three to five weekly injections and are relatively safe with the exception of occasional flares postinjection. Response has been comparable to that obtained with acetaminophen, NSAIDs, and intra-articular glucocorticoids (140). Although effective, the mechanism of action of this therapy has not been delineated. Furthermore, additional studies are needed to evaluate the long-term effects of these agents (141). Because this mode of therapy is invasive, expensive, and likely, at most, only equally effective as NSAID therapy, it probably should be reserved for patients who have not responded to analgesics and a vigorous nonpharmacologic program or for those in whom NSAIDs are contraindicated. Like NSAIDs, hyaluronic acid injections may be marginally beneficial in patients with very severe disease.
Management of Acute Flare
Some degree of synovial inflammation is common in OA (48). Patients with OA may have occasional acute or subacute painful episodes with swelling and exacerbation of the inflammatory process in the affected joint. These patients may have evidence of inflammation, with pain, swelling, warmth, and some erythema on occasion. When the knee is involved, there usually is an effusion. The episodes, which often are precipitated by minor trauma, may be caused by sudden release into the joint of cartilaginous debris or microcrystalline deposits contained therein, although such crystals are also found in a significant proportion of unselected patients with effusions of the knee due to OA (142). Sepsis occasionally complicates an osteoarthritic joint but is a much less common event than occurs in a rheumatoid arthritic joint.
A patient with established OA who develops an acutely swollen painful joint should have the joint aspirated and the fluid analyzed because of the possibility of a complicating microcrystalline-induced or septic arthritis (see Chapter 74).
Modifying the Disease
At present, no medicinal or nonmedicinal treatments have been proven unequivocally to alter the natural course of OA. This can be accomplished only by altering the underlying pathophysiologic processes that lead to the development and progression of OA. Detection of meaningful differences in radiographic outcomes between study groups over successive visits is fraught with methodologic challenges and requires rigorously standardized imaging methods that are capable of detecting small changes over long
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periods of time. These requirements have not been met in OA clinical trials to date, and this has tempered acceptance of the results, for example, of published clinical trials of glycosaminoglycan-peptide complex, glycosaminoglycan polysulfate, diacerein, and glucosamine sulfate (143). MRI, as discussed under Imaging Osteoarthritis, offers the potential for more sensitive and accurate measurements of small changes in cartilage volume over time and for assessing the impact of novel therapies on this rate of change (88).
The growing recognition that subchondral bone lesions are associated with pain and more rapid progression of OA of the knee (61) has been strengthened by cross-sectional data suggesting that estrogen and bisphosphonate use reduce the number of bone lesions and overall periarticular bone attrition as measured by MRI (144). The efficacy of antiresorptive therapies for OA depends upon whether the increased bone turnover that occurs in OA results in increased subchondral stiffness (145).
Several pharmacologic agents that target mediators of joint destruction are in various stages of development as potential disease-modifying therapies for OA and are reviewed in detail elsewhere (146,147). These include inhibitors of matrix metalloproteinases that exert their effects by inhibiting the synthesis or activation of an enzyme(s) or as chelators. In a randomized, placebo-controlled trial of patients with unilateral knee OA, treatment with doxycycline (100 mg twice daily) attenuated the rate of loss of joint space width in the index knee but did not reduce pain severity or prevent loss of joint space width in the nonaffected knee (148). Modulation of IL-1 activity with an antagonist of the IL-1 receptor or an inhibitor of IL-1 converting enzyme has been undertaken in clinical trials of rheumatoid arthritis (seeChapter 77) and may hold potential promise as treatment for OA.
Surgical Management
Patients in whom function and mobility are compromised by pain despite maximal medical therapy and in whom there is structural instability may be candidates for surgical intervention.
Arthroscopy, Tidal Irrigation, and Débridement
Although some investigators have argued that these procedures are effective for pain management of OA of the knee, these procedures have come under scrutiny. In a randomized, controlled study, arthroscopy with tidal irrigation of the knee was no more effective in relieving pain or improving function than was sham irrigation (149). Thus, arthroscopic irrigation is no longer justified as a general strategy for pain management in OA (149). Arthroscopy with débridement still is useful principally in patients with meniscal injury and loose bodies that result in knee locking and give-way weakness.
Osteotomy
High tibial osteotomy may be undertaken in patients with painful knee OA who have varus (bowlegged) malalignment due to severe cartilage loss in the medial compartment (150). Surgical realignment is achieved by removing a segment of the proximal tibia. Although osteotomy has been tried in combination with other cartilage-preserving or regenerating procedures, clinical trials have not been undertaken to adequately test the efficacy of specific combinations.
Total joint arthroplasty remains the procedure of choice for patients with severe, deforming OA whose symptoms and disability are unresponsive to maximal nonsurgical therapeutic interventions. Use of unicondylar prosthesis and “minimally invasive” arthroplasty have met with good results, including improved early motion, less blood loss, and shorter hospital stays than standard surgical techniques (151). Despite these advances, consideration must be given first to whether or not a given patient is a surgical candidate, that is, will the patient be able to withstand the risks and stresses of surgery, and will joint replacement restore meaningful function? Patients with OA who have substantial other comorbid conditions face greater perioperative risk (152). Full recovery of mobility and function may not be realistically achieved in the presence of significant cognitive impairment or function-limiting cardiopulmonary disease, because these conditions can impede postoperative rehabilitation. Consideration must be given to timing of joint replacement surgery. That surgical outcomes are best in patients who have not yet developed significant disability, appreciable muscle weakness, or generalized or cardiovascular deconditioning suggests that joint replacement surgery should be considered sooner rather than later. Despite this, preoperative exercise interventions have not improved functional recovery following surgery (153). For patients with severe bilateral OA of the knee or hip, simultaneous replacement of both joints might be contemplated. However, the rate of perioperative complications may be slightly higher with simultaneous bilateral arthroplasties than with staged arthroplasty (154, 155, 156). Contraindications to joint arthroplasty include neuromuscular or sensory deficits, severe peripheral vascular disease, and cognitive impairment. Contrary to anecdotal reports, obesity does not appear to independently alter outcomes following total joint arthroplasty (157,158).
Transplantation and Regenerative Interventions
Cartilage is minimally cellular and avascular and thus has limited capacity for self-repair. Numerous attempts have been made to repair cartilage lesions and to re-establish mature cartilage with the biomechanical properties of native tissue. Autologous chondrocyte
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implantation and osteochondral transplantation have been successful in repairing discrete defects in articular cartilage (159), but no prospective clinical trials support their use over conventional surgical interventions (160,161). Furthermore, these procedures are of limited utility for repairing large defects due to issues of graft viability at the transplantation site, concerns for donor site viability, and limited repair following harvest (161). In contrast, clinical experience with allogeneic osteochondral and chondral grafting has been good. However, enthusiasm for the procedure is tempered by the scarcity of fresh donor tissues.
Specific References*
For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.
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