#94954: Osteoarthritis

The prevalence of all types of arthritis increases with age. According to a CDC analysis of data from the 2016–2018 NHIS, the prevalence was 7.1% for individuals 18 to 44 years of age, 30.5% for individuals 45 to 64 years of age, and 50.4% for individuals 65 years of age and older [50].

The prevalence of osteoarthritis, specifically, also increases according to age, with the highest prevalence among those 65 years of age and older [50]. (The lower rate of hospitalization for osteoarthritis among individuals 85 years of age and older is more a reflection of lower rates of arthroplasty than of actual frequency of osteoarthritis.) The increases in osteoarthritis over time follow the same age-related pattern. Between 1997 and 2009, the prevalence of osteoarthritis increased 151% among individuals 45 to 64 years of age and 58% among individuals 65 to 84 years of age [8]. Between 2009 and 2013, the prevalence of osteoarthritis increased 42% among individuals 45 to 64 years of age and 25% among individuals 65 to 84 years of age [8,54].

The increased prevalence of radiographic and symptomatic osteoarthritis among older individuals is found across all joints. In the Nurses' Health Study, the risk of hip replacement for women 70 years of age or older was nine times greater than for women younger than 55 years of age [54]. Similarly, in the NHANES III, the prevalence of radiographic knee osteoarthritis increased with age, from a low of 17.7% for the 60 to 64-year age-group to 26.0% for the 80 years and older age-group [55]. The prevalence of hand osteoarthritis also increases significantly with age, and a review of the literature (1950–2009) demonstrated that the prevalence can reach 80% in the older population [56,57].

Data on the age at the time of diagnosis of osteoarthritis at other joints are limited. However, studies have indicated a younger age at the time of clinical presentation of elbow osteoarthritis (approximately 50 years) and ankle osteoarthritis (43 to 58 years) [32,58].

The overall prevalence of arthritis (all types) has consistently been higher among women than men [50]. According to a CDC analysis of NHIS data from 2016–2018, the prevalence of arthritis was approximately 24.2% for women compared with 18.5% for men [50]. With respect to osteoarthritis specifically, women accounted for approximately 59% of hospitalizations for osteoarthritis in 2013, a proportion that has been essentially the same since 1997 [59,60]. One exception to this female predominance relates to age; within the population of individuals younger than 50 years of age, osteoarthritis is more common in men, a difference that has been attributed to a higher rate of osteoarthritis secondary to joint injury [61]. Because osteoarthritis is overall more prevalent in women and women use healthcare resources to a greater degree than men, the economic burden of osteoarthritis is disproportionately high among women. The total expenditures related to osteoarthritis among women account for nearly two-thirds of the increased cost, or $118 billion [17].

Studies have also provided information regarding gender differences in the prevalence of osteoarthritis according to the affected joint. These studies have shown that symptomatic knee, hip, and hand osteoarthritis are more prevalent among women than among men, with the greatest difference related to knee osteoarthritis (Table 2) [45,46,56,62]. Again, there is one exception to female predominance: osteoarthritis of the elbow, which has a male-to-female ratio of approximately 4:1 [58]. This gender difference is likely due to the predominance of elbow osteoarthritis among individuals who have an occupation involving strenuous manual labor [58]. Information on gender differences in osteoarthritis at other joint sites is lacking.

Knee

Osteoarthritis of the knee is estimated to account for 83% of the total number of osteoarthritis cases [2]. Using data from NHANES III, Dillon et al. found that symptomatic radiographic knee osteoarthritis did not differ by gender but that the prevalence of asymptomatic radiographic osteoarthritis was greater among women (42% vs. 31%) [62]. In addition, there were significantly more moderate-to-severe osteoarthritic changes among women (13% vs. 17%) [62]. In the Johnston County Osteoarthritis Project, symptoms, radiographic knee osteoarthritis (mild and moderate-to-severe), and symptomatic knee osteoarthritis were all more prevalent among women than men [45]. Data from the Global Burden of Disease Study 2010 found that the prevalence of knee osteoarthritis in women is nearly twice that of men worldwide [63]. Results of a 2020 study indicate that the worldwide prevalence of knee osteoarthritis in women is more than two-thirds higher than that of men [64].

Hip

In the Johnston County Osteoarthritis study, hip symptoms, mild radiographic osteoarthritis, and symptomatic osteoarthritis were more prevalent among women than men. However, the prevalence of moderate-to-severe radiographic osteoarthritis was similar (2.6% for men vs. 2.5% for women) [46].

Hand

The data on gender differences for osteoarthritis of the hand have been conflicting. Of 1,041 men and women (71 to 100 years of age), the prevalence of symptomatic hand osteoarthritis was twice as high among women in the Framingham Osteoarthritis Study (26% vs. 13%), but NHANES III data showed that the prevalence of symptomatic hand osteoarthritis was similar among men and women [44,56]. The difference may be due to the older age of individuals in the Framingham study, as the prevalence of hand osteoarthritis increases significantly with age [56]. A review of the literature (1950–2009) supports a gender difference in the prevalence of osteoarthritis of the hand [57].

Data from 2016–2018 NHIS showed a higher prevalence of arthritis (all types) in the non-Hispanic White population (23.2%) compared with the non-Hispanic Black (21.8%), Hispanic (16.4%), and Asian/Pacific Islander populations (12.2%) [50]. In contrast, the prevalence was higher for the American Indian/Alaska Native population (26.8%) [50].

Knee

Studies have consistently shown that osteoarthritis of the knee is more prevalent in the Black population than the White population. Multivariable analysis of data from NHANES III showed significantly higher odds of radiographic knee osteoarthritis (Kellgren-Lawrence grade 2 or higher) among non-Hispanic Black participants (52%) compared with White (36%) or Mexican American (38%) participants [62,65]. Although the findings of the Johnston County Osteoarthritis Project also demonstrated that knee-related symptoms, radiographic knee osteoarthritis (mild), and symptomatic knee osteoarthritis were all more prevalent among Black individuals than White individuals, the difference was slight. However, the prevalence of moderate-to-severe radiographic osteoarthritis was significantly greater for both men and women in the Black population (11% vs. 5% for Black vs. White men and 16% vs. 8% for Black vs. White women) [45]. A study of more than 1,000 premenopausal and perimenopausal women demonstrated that early osteoarthritis changes were more prevalent in Black women than White women (23% vs. 9%) [66]. The prevalence of knee osteoarthritis has also been found to be higher in the Chinese population than in the White population [67].

Hip

In the Johnston County Osteoarthritis Project, the greatest racial/ethnic difference was found for mild radiographic hip osteoarthritis among men (23.8% vs. 33.2% for White vs. Black men) [46]. There were also racial differences among men and women for symptomatic hip osteoarthritis (7.6% vs. 11.7% for White vs. Black men, and 10.8% vs. 12.2% for White vs. Black women) [46]. Among women, the prevalence of moderate-to-severe radiographic hip osteoarthritis was higher for the Black population (2.3% vs. 3.5%) [46]. A subsequent study indicated that the radiographic features and patterns of hip osteoarthritis differed according to race and gender, which suggests that anatomic and/or development variations in the joint may contribute to differences [68]. Hip osteoarthritis has been found to be less prevalent among Chinese individuals than among White individuals [67].

Hand

In a study of more than 1,000 younger women (premenopausal and perimenopausal), the prevalence of hand osteoarthritis was higher among Black women (26%) than among White women (19%), and the specific hand joints affected differed between the two groups [66]. However, NHANES III data indicated that symptomatic hand osteoarthritis occurred less frequently among non-Hispanic Black individuals than White individuals [56]. Research has also indicated that hand osteoarthritis is less common in the Chinese population than in the White population [67,68].

Normal adult articular cartilage is made up of extracellular matrix (approximately 98% to 99%) and chondrocytes (1% to 2%) [75]. The chondrocytes secrete enzymes and cytokines that help regulate the normal cycle of degradation and repair of articular cartilage by inhibiting the production of proteoglycans and collagen, the two major components of the extracellular matrix [75]. Damage to the extracellular matrix interferes with its ability to bind or exclude water, resulting in edema and subsequent softening of the cartilage and expansion of the matrix, which makes the matrix vulnerable to further injury and breakdown of its components [9,76,77,78].

Among the enzymes stimulated by chondrocytes are matrix metalloproteinases (e.g., collagenase, stromelysin, and gelatinase) and other proteinases (e.g., cathepsin and tissue plasminogen activator). Interleukin-1 (IL-1) is the cytokine that has been identified as playing an important role in promoting the synthesis of degradative enzymes, and tumor necrosis factor-alpha and IL-6 have been found to work synergistically with IL-1. Inhibitors of these enzymes and cytokines, such as tissue inhibitor of metalloproteinase (TIMP) and plasminogen activator inhibitor-7 (PAI-7), help stimulate a repair process by keeping degradation in check. In addition, polypeptides, such as insulin-like growth factor-1 (IGF-1) and transforming growth factor-beta (TGF-beta), stimulate chondrocytes to synthesize proteoglycans. When chondrocyte function is lost, the balance between degradation and repair is lost, resulting in damage to the articular cartilage [79].

There are some indications that the early structural changes of osteoarthritis (such as bone marrow lesions and cartilage defects) may be reversible, especially among younger individuals [72,74]. However, it is difficult to detect early changes, given the high percentage of individuals who are asymptomatic during the early development of osteoarthritis [70]. Still, the potential reversibility sets up early changes as a target for disease-modifying interventions, and research is being directed in this area.

As damage occurs to the articular cartilage, fragments of cartilage may break off and enter into the joint capsule, where they can damage the synovial lining of the joint and interfere with proper joint function. Continued erosion of cartilage results in narrowing of the joint space, with the potential for bone-to-bone contact. Eburnation, or the formation of a new articulating surface from subchondral bone, may occur. Bone remodeling may also occur in the subchondral bone, which may cause overgrowth of bone at the edges of the joint. These osteophytes usually develop in the nonweight-bearing area of a joint. In osteoarthritis of the distal interphalangeal joints, these osteophytes are dorsolateral swellings referred to as Heberden's nodes [36].

The lack of clarity about the etiology of osteoarthritis is further complicated by the terminology used to refer to the disease. The term "osteoarthritis" implies an inflammatory process, but inflammation is not a hallmark characteristic of the disease; if inflammation is involved, it is usually mild and affects only the synovium and periarticular tissues [79]. Alternative terms that have been suggested include "osteoarthrosis" and "degenerative joint disease," but neither term is completely satisfactory. The former is vague, and although the latter term is more accurate, it implies a process that naturally occurs with aging, and many differences between the osteoarthritic joint and the aging joint have been identified (Table 3) [9,72].

The definition and natural history of osteoarthritis continues to evolve as research provides new information. Some researchers have now posited that an inflammatory process is present during the early development of osteoarthritis, with a suggestion that osteoarthritis has a biochemical and inflammatory profile similar to that of metabolic syndrome [74,80]. Another study providing evidence of a different natural history of osteoarthritis indicated that structural changes precede articular damage. In that study, the results of magnetic resonance imaging (MRI) of healthy knees and knees with early osteoarthritis suggested that such changes as subchondral bone expansion, bone marrow lesions, and meniscal tears and extrusion lead to defects in the articular cartilage, which may or may not subsequently result in loss of articular cartilage and radiographic evidence of osteoarthritis [74].

The cause of osteoarthritis-related pain is not well understood. Because articular cartilage is aneural and avascular, degradation of cartilage, a primary characteristic of osteoarthritis, is not likely to be the direct source of pain, stiffness, or other typical symptoms [70]. The probable sources of pain, therefore, are other tissues in the joint structure that are richly innervated, such as the subchondral bone, periosteum, periarticular ligaments, periarticular muscle, synovium, and joint capsule [9,70]. Pain is most likely generated by several factors, and the predominant source of pain has been unclear, as the severity of osteoarthritis on radiographs does not correspond to the degree of pain [70]. However, the improved imaging of the joint provided by MRI has allowed researchers to explore the source of osteoarthritis-related pain, and studies have shown that bone marrow lesions, synovitis/effusion, subarticular bone attrition, osteophytes in the patellofemoral compartment, and meniscal tears are strongly associated with severity of pain in knee osteoarthritis [9,41,81,82,83]. The evidence has been strongest for bone marrow lesions and synovitis, and the association is greater for pain on weight-bearing (compared with nonweight-bearing) joints [83]. Psychologic and social factors also play an important role in osteoarthritis-related pain [9,70].

There is substantial heterogeneity in osteoarthritis across anatomic sites with regard to risk factors, clinical features, and outcomes, which has drawn some researchers to conclude that osteoarthritis of different joints are distinct clinical entities [84,85]. Some examples to support the concept of distinct disease entities include [31,32,36,86]:

Osteoarthritis of more than one joint may be a distinct disease in which a genetic predisposition plays a more important role than biomechanical factors [84].

Poor bone alignment resulting from developmental abnormalities or injury changes the load distribution on a joint [84]. The resultant increase in compressive loading in an area of the joint can increase the risk of osteoarthritis [84]. For example, genu varum (bow-leggedness) and genu valgum ("knock-kneed") have been shown to increase the risk of osteoarthritis at the medial and lateral compartment of the knee, respectively [135,136]. However, study results have varied.

One evaluation of 110 knees with tibiofemoral osteoarthritis and 356 random control knees demonstrated that knee alignment was not associated with either radiographic tibial osteoarthritis or medial tibiofemoral osteoarthritis, and the authors suggested that malalignment was a marker of disease severity rather than a risk factor [137]. An observational, longitudinal study of the Multicenter Osteoarthritis Study cohort found that varus but not valgus alignment increased the risk of incident tibiofemoral osteoarthritis, and that both varus and valgus alignment increased the risk of disease progression in arthritic knees [138]. A third study of malalignment included 881 subjects from the Multicenter Osteoarthritis Study and 1,358 subjects from the Osteoarthritis Initiative study. The researchers found that all strata of malalignment increased the risk of progression of radiographic knee osteoarthritis and incidence as well as the risk of lateral cartilage damage [139]. Forefoot varus malalignment has been found to be related to a higher rate of hip osteoarthritis and hindfoot malalignment with a higher rate of ankle osteoarthritis [32,140].

Bone density is related to osteoarthritis, with a high bone mineral density found in association with an increased prevalence of knee, hip, and hand osteoarthritis [35,36,84,141,142,143,144]. Higher bone mineral density has also been reported in association with osteoarthritis of the spine [145,146]. The reason for the relationship is not clear, and some inconsistencies and areas of controversy remain [142]. Shared genetic factors and lifetime exposure to estrogen (exogenous and endogenous) have been suggested [35,142,147,148].

Deficiency of vitamin C or D has been targeted as a potential contributor to osteoarthritis because of its role in antioxidation or bone metabolism, respectively [84]. The literature on the role of vitamin deficiency in osteoarthritis is limited, but the findings of some early studies have indicated that low levels of vitamin C and D may be associated with early osteoarthritic changes [35,74]. For example, in the Framingham Osteoarthritis Study, the risk of radiographic osteoarthritis of the knee and knee pain were substantially lower among individuals in the highest tertile of vitamin C intake [149]. A study of the effect of dietary antioxidants, including vitamin C, found a significant positive association between dietary vitamin C intake and radiographic knee osteoarthritis [150]. Ascorbic acid has also been found to provide protection for human chondrocytes against oxidative stress that can lead to osteoarthritis and cartilage aging [151]. Vitamin D deficiency appears to be related to progression of osteoarthritis rather than initial development; this may be because the lack of vitamin D impairs the bone response to osteoarthritic changes [84]. Low levels of vitamin D were not related to the prevalence of osteoarthritis in the Framingham Osteoarthritis Study, but the risk for progression was three times higher for individuals in the lowest tertile of vitamin D level than for individuals in the highest tertile [152]. However, later studies found that vitamin D supplementation does not reduce knee pain or progression of osteoarthritis of the knee, though there may be an association between a low level of vitamin D and an increased risk of both new-onset hip osteoarthritis and its progression [153,154,155,156,157]. One study suggests that vitamin D deficiency exacerbates pain and dysfunction and results in a poorer quality of life in patients with knee osteoarthritis [158]. However, a subsequent study found no association between serum vitamin D concentration and knee pain in patients with osteoarthritis [159].

There is increasing evidence that estrogens fulfill an important role in maintaining the homeostasis of articular tissues and of the joint itself and that they may also have a protective role against the development of osteoarthritis [160]. The dramatic rise in the prevalence of osteoarthritis among postmenopausal women, which is associated with the presence of estrogen receptors in joint tissues, suggests a link between osteoarthritis and loss of ovarian function [161,162,163,164,165]. Numerous clinical studies have shown that osteoarthritis is related to estrogen levels, with a greater prevalence in women than men and a clear increase in women at menopause [161,162,166,167,168]. Additional research will help shed light on the role that estrogen deficiency plays in the mechanisms of menopause-induced osteoarthritis [160].

The primary symptom of osteoarthritis of the knee is pain, especially with weight-bearing exercise or activity, that improves with rest. Stiffness in the joint occurs in the morning, lasting 30 minutes or less, and may occur after periods of inactivity [185].

Individuals with osteoarthritis of the knee usually have tenderness on joint palpation, osseous enlargement, crepitus on motion, and/or limitation of joint motion [185]. Inflammation is not typically present; when present, it is mild and usually localized to the joint [185].

Radiographs of the knee are not routinely needed for a diagnosis of knee osteoarthritis. The characteristic findings of osteoarthritis on radiographs include osteophytes and joint space narrowing. Changes in the structure of the knee joint have been found more frequently on MRI than on plain radiographs, and the use of MRI in diagnosis may become more common [74]. MRI may also be helpful in ruling out other causes of knee pain with radiographic findings similar to those of osteoarthritis, such as osteochondritis dissecans and avascular necrosis [19].

The ACR developed the classification criteria for osteoarthritis of the knee with three "trees" designed to enable diagnosis based on only the clinical findings (history and physical examination), a combination of clinical and radiographic findings, or a combination of clinical and laboratory findings (Table 7) [174,177]. The criteria for clinical and radiographic findings has the best reported sensitivity/specificity (91%/86%), compared with that for clinical and laboratory findings (92%/75%) and clinical findings only (95%/69%) [174].

According to the EULAR guidelines on the diagnosis of knee osteoarthritis, a diagnosis can be made with 99% confidence when three symptoms and three signs are present [173]:

The clinical presentation of hip osteoarthritis is similar to that of knee osteoarthritis, with pain being the most common symptom driving individuals to seek medical care [177,186]. Pain related to hip osteoarthritis is an ache—most often diffuse—that is usually felt during use of the joint and relieved by rest. Pain is typically gradual, variable, or intermittent; the joint may feel stiff after a period of inactivity [177,186]. The loss of function or mobility is usually related to the degree of pain.

The strongest sign of hip osteoarthritis on physical examination is pain that is exacerbated by internal or external rotation of the hip with the knee in full extension [38,177]. Other signs include crepitus and gait abnormalities (resulting from alterations in walking to avoid pain) [186]. Deformity and instability are late signs of severe osteoarthritis, but they are uncommon [186]. Both hips should be examined if osteoarthritis is suspected, as the disease occurs bilaterally in approximately 20% of individuals [38].

The ACR criteria for classification enable diagnosis of osteoarthritis of the hip on the basis of the clinical presentation and either laboratory or radiographic findings. According to this set of criteria, which has a reported sensitivity/specificity of 89%/91%, diagnosis requires patient-reported pain in the hip and at least two of the following three signs [175,177]:

Osteoarthritis of the hand is characterized by pain with use, which affects one or a few joints at any one time, and mild stiffness in the morning and/or after a period of inactivity [178]. The severity of osteoarthritis-related pain varies, and the pain may be intermittent. The joints most often affected are the distal and proximal interphalangeal joints and the base of the thumb [176,177,178]. Individuals who have evidence of osteoarthritis at several joints in the hand are at increased risk for generalized osteoarthritis, and clinicians should evaluate such patients as appropriate [178].

Osteoarthritis of the hand may be associated with substantial limitations in function, and the clinician should ask the patient whether he or she has difficulty with such tasks as dressing, eating, writing, handling or fingering small objects, and carrying or lifting 10 pounds [44,56]. Several validated questionnaires are available to assess function of the hand, and the choice of questionnaire depends primarily on the clinical question [171]. Individuals with symptomatic osteoarthritis of the hand also may have reduced maximal grip strength [44,56].

The ACR criteria for classification of osteoarthritis of the hand enable diagnosis on the basis of only clinical findings [176,177]. They consist of pain, aching, or stiffness in the hand and at least three of the following features:

The 10 selected joints are the second and third distal interphalangeal, the second and third proximal interphalangeal, and the first carpometacarpal joints of both hands [177]. This set of criteria yields a sensitivity/specificity of 94%/87% [176]. The evidence-based recommendations for the diagnosis of hand osteoarthritis developed by EULAR support the ACR's criteria of only clinical findings, stating that a confident clinical diagnosis can be made in adults older than 40 years of age on the basis of the described clinical findings [171].

Hard tissue enlargements on the distal interphalangeal joints (Heberden and Bouchard nodes) are the clinical finding that is most characteristic of osteoarthritis of the hand [56,176,177]. Although radiographic findings are not an established diagnostic criterion, evidence of osteophytes is the only unique radiographic criterion for a diagnosis [176]. Other classic radiographic findings include joint space narrowing, subchondral bone sclerosis, or subchondral cysts [171,176]. The diagnosis of hand osteoarthritis does not require blood tests, but such tests may be helpful in excluding coexisting disease or in identifying an inflammatory arthritis [171].

Pain related to osteoarthritis of the shoulder is typically progressive, related to activity, deep in the joint, and often localized posteriorly [30]. Pain is usually present at rest and interferes with sleep, with nocturnal pain becoming more common as the disease progresses. More advanced disease is also associated with stiffness that limits function.

Younger patients with shoulder pain should be asked about previous trauma, dislocation, or surgery for shoulder instability, as all have been related to the development of osteoarthritis [30]. In the early stages of disease, the findings of the physical examination may be unremarkable. Some signs indicative of osteoarthritis are painful crepitus, enlargement of the joint, tenderness at the joint line, and joint effusion. The range of motion is usually decreased, especially in external rotation and abduction. In advanced stages of disease, grinding may be audible or palpable when mechanical stress is placed on the shoulder. Signs that are not indicative of shoulder osteoarthritis are lack of pain on palpation or passive range of motion (e.g., bursitis, rotator cuff disease, or biceps tenderness) and loss of passive or active range of motion (e.g., calcific tendinitis or idiopathic adhesive capsulitis) [187].

Unlike the case with osteoarthritis at other sites, imaging studies are essential for the diagnosis of osteoarthritis of the shoulder [30]. Signs of early disease include slight narrowing of the joint space, small osteophytes, subchondral sclerosis, cysts, and eburnation or advanced loss of articular cartilage. Narrowing of the joint space can be best detected with either an axillary view or an anteroposterior view, with the arm held in 45 degrees of abduction [188]. MRI can demonstrate wearing of articular cartilage, and computed tomography arthrograms can be used to localize articular defects [30].

A blood panel can help identify infection. An erythrocyte sedimentation rate greater than 45 mm/hour may indicate rheumatoid arthritis, an underlying malignancy, or chronic infection. These blood tests are sensitive but not specific in determining causes of shoulder pain [189].

Individuals with osteoarthritis of the elbow typically have pain, stiffness, and weakness in the joint [31]. Later stage disease is associated with pain when carrying a heavy object at the side of the body with the elbow in extension. The history is important when evaluating symptoms related to the elbow because of the strong relationship between trauma or occupation with osteoarthritis, especially in individuals who are younger than 40 years of age [58]. Primary osteoarthritis of the elbow is often associated with osteoarthritis at another joint site, especially the second and third metacarpophalangeal joints, the knee, and the hip, and those joints should be evaluated as appropriate [190].

Range of motion should be examined in flexion-extension and pronation-supination. Most patients will have pain at the endpoints of range of motion rather than at other points throughout the arc of motion. Crepitus can usually be heard during range of motion.

As with osteoarthritis of the shoulder, osteoarthritis of the elbow can be diagnosed with standard radiographs, and anteroposterior and lateral projections are best [31,58]. A distinction of primary elbow osteoarthritis is preservation of the joint space, even when disease is at an advanced stage [31,58]. Other radiographic characteristics of primary osteoarthritis are an anterior and medial osteophyte (involving the coronoid process) and a posteromedial osteophyte (olecranon process). The location and size of osteophytes can be determined by computed tomography (CT) with three-dimensional reconstructions [58]. It may be difficult to detect loose bodies on plain radiographs [58].

A history of ankle fracture or ligamentous injury is a hallmark feature of osteoarthritis of the ankle [32]. Diagnostic evaluation includes radiographs of the ankles made with the patient standing. MRI is also recommended, as it can provide evidence of osteonecrosis as well as indicate the amount of involvement, the extent of bone loss, and the size of subchondral cysts [32].

Education and self-management, through lifestyle modifications are universally recognized as the core of treatment in clinical guidelines [193]. This recommendation is based on research showing that education helps patients become more involved in their care, leading to improved outcomes [207]. The AHRQ notes that an effective partnership is the key to the effective management of osteoarthritis; the healthcare professional's role in this partnership is to [207]:

Clinicians should emphasize to patients that adhering to the management program will alleviate their symptoms, improve their function, and enhance their quality of life. Education should be tailored to address individual needs. For example, patients who participate in sports should be advised to avoid sports with direct contact and high impact and to wear protective equipment to prevent injury [84]. Similarly, for patients in occupations with high risk for osteoarthritis, clinicians should discuss the importance of avoiding high-risk tasks. Education and training in ergonomic principles, pacing of activity, and use of assistive devices should be offered to patients with hand osteoarthritis [171]. It is also essential to encourage patients with osteoarthritis of the glenohumeral joint or the elbow to modify activities that led to the development of the disease [31,58]. Periodic contact during follow-up can help promote self-management [193].

Self-management programs are recommended by the American Academy of Orthopaedic Surgeons to improve pain and function for patients with knee osteoarthritis.

(https://www.aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-knee/oak3cpg.pdf Last Accessed: September 22, 2022)

Strength of Recommendation: Strong (Evidence from two or more high-quality studies with consistent findings for recommending for or against the intervention)

Clinicians should also encourage patients to participate in formal self-management programs in the community or online and to use reliable educational resources, such as the Arthritis Foundation (https://www.arthritis.org) [172].

When educating a patient about osteoarthritis and its management, it is essential to ensure that he or she understands the treatment plan and his or her role in self-management. However, according to the National Assessment of Health Literacy, 14% of individuals in the United States have "below basic" health literacy, which means they lack the ability to understand health information and make informed health decisions [183,209]. Data from 2017 indicate that this figure is 19% [210]. Understanding the problem of health literacy is especially important for clinicians managing osteoarthritis, as low health literacy is more common among older individuals, the population most affected by the disease [211]. Health literacy also varies widely according to race/ethnicity, and level of education, and clinicians are often unaware of the literacy level of their patients [210,211,212]. Predictors of limited health literacy are poor self-rated reading ability, low level of education, male gender, and non-White race [212,213]. Ensuring that patients understand health information is essential, as limited health literacy has been associated with poor health outcomes [214].

Several instruments are available to test patients' literacy level, and they vary in the amount of time needed to administer and reliability in identifying low literacy. A review of several instruments demonstrated that the two most accurate tools for identifying literacy are the Rapid Estimate of Adult Literacy in Medicine (REALM) and the shortened version of the Test of Functional Health Literacy in Adults (S-TOFHLA) [211]. REALM takes 3 minutes to administer, whereas S-TOFHLA takes 7 to 12 minutes to administer [211]. More rapid testing is available in the form of the Newest Vital Sign (NVS), an instrument named to promote the assessment of health literacy as part of the overall routine patient evaluation [183,215]. The NVS takes fewer than three minutes to administer, has correlated well with more extensive literacy tests, and has performed moderately well at identifying limited literacy [211,212]. Two questions have also been found to perform moderately well in identifying patients with inadequate or marginal literacy: "How confident are you in filling out medical forms by yourself?" and "How often do you have someone help you read health information?" [211].

Compounding health literacy are language and cultural barriers, which have the potential for far-reaching effect, given the growing percentages of racial/ethnic populations. According to the U.S. Census Bureau, more than 66 million Americans speak a language other than English in the home, with approximately 25.3 million of them (8.2% of the population) speaking English less than "very well" [216]. It has been suggested that when patients are first evaluated, they should be asked what language is spoken at home and if they speak English "very well" [217]. In addition, patients should also be asked what language they prefer for their medical care information, as some patients prefer their native language even though they have said they can understand and discuss symptoms in English [217]. Many studies have demonstrated that the lack of an interpreter for patients with limited English proficiency compromises the quality of care and that the use of professional interpreters improves communication (errors and comprehension), utilization, clinical outcomes, and patient satisfaction with care.

"Ad hoc" interpreters (e.g., family members, friends, and bilingual staff members) are often used instead of professional interpreters for a variety of reasons, including convenience and cost. However, clinicians should check with their state's health officials about the use of ad hoc interpreters, as several states have laws about who can interpret medical information for a patient [218]. Even when allowed by law, the use of a patient's family member or friend as an interpreter should be avoided, as the patient may not be as forthcoming with information and the family member or friend may not remain objective [218]. Children should especially be avoided as interpreters, as their understanding of medical language is limited and they may filter information to protect their parents or other adult family members [218]. Individuals with limited English language skills have actually indicated a preference for professional interpreters rather than family members [219].

Most important, perhaps, is the fact that clinical consequences are more likely with ad hoc interpreters than with professional interpreters [220]. A systematic review of the literature showed that the use of professional interpreters facilitates a broader understanding and leads to better clinical care than the use of ad hoc interpreters, and many studies have demonstrated that the lack of an interpreter for patients with limited English proficiency compromises the quality of care and that the use of professional interpreters improves communication (errors and comprehension), utilization, clinical outcomes, and patient satisfaction with care [221,222].

Clinicians should adapt their discussions and educational resources to a patient's identified health literacy level and degree of language proficiency. The use of plain language (free of medical jargon), asking patients to repeat pertinent information, regularly assessing recall and comprehension, and using translated educational materials can all help ensure that patients better understand their disease and its management, ultimately leading to higher quality care.

Given the strong correlation between overweight/obesity (defined as a BMI greater than 25) and osteoarthritis of the knee and hip, weight reduction and maintenance of a healthy weight are central to guidelines on the management of osteoarthritis at these sites [185,198,206,223,224]. A systematic review showed that a moderate weight-loss program (0.25% of body weight per week) can reduce pain and physical disability for individuals with osteoarthritis of the knee [225]. In its 2021 guideline for the treatment of osteoarthritis of the knee, the AAOS recommends weight reduction, specifically, achieving and/or maintaining a BMI ≤25 [198].

The recommended approach to weight loss is through dietary modifications and an exercise program [224]. The Arthritis, Diet, and Activity Promotion Trial (ADAPT), which involved 316 overweight or obese adults with knee osteoarthritis, demonstrated that an 18-month program of modest weight loss and modest exercise provided the most benefit (compared with a diet-only or exercise-only program) [226]. Individuals in the diet-plus-exercise group had significant improvements in self-reported physical function, six-minute walk distance, stair-climb time, and knee pain. The 2019 ACR guideline specifies weight reduction counseling [185].

Regular, moderate exercise can help maintain overall health, muscle strength, and range of motion of the joint. In addition, several physical therapy strategies can help improve function and relieve pain.

Regular Exercise

Some patients may fear that regular exercise will exacerbate pain, but a review of the literature has shown that moderate exercise does not increase the risk for progression of osteoarthritis, provided that care is taken to avoid injury [110,227]. The goal of an exercise program is to control pain, increase flexibility, and improve muscle strength and endurance [228]. The exercise program should be individualized to the patient, with consideration given to the patient's age, comorbidities, and mobility [229]. Guidelines suggest that exercise should be prescribed for all patients with osteoarthritis, regardless of age, severity of pain and disability, and comorbidity [199]. The American Geriatric Society notes that absolute contraindications to an exercise program include uncontrolled arrhythmias, third-degree heart block, changes on recent electrocardiography, unstable angina, acute myocardial infarction, and acute congestive heart failure [228]. Relative contraindications include cardiomyopathy, valvular heart disease, poorly controlled blood pressure, and uncontrolled metabolic disease [228].

Promoting exercise as part of an overall positive lifestyle change can increase the effectiveness of the program [229]. Supervised group exercise and home-based programs have been shown to be equally effective, allowing patients to select the type of program they prefer [229]. The Ottawa Panel recommends that significant weight-loss occur before starting weight-bearing exercise (particularly for obese patients) in order to maintain joint integrity and to avoid joint disease and dysfunction [224].

Low-impact aerobic exercise, such as walking, bicycling, swimming, or water aerobics, has shown to offer substantial benefit in terms of improved physical function, reduction of pain and disability, and enhanced perceived quality of life in individuals with knee osteoarthritis, especially overweight/obese individuals [198,227,230,231]. Although there is little evidence that exercise is of benefit to individuals with hip osteoarthritis, one systematic review found that land-based (as opposed to water-based) therapeutic exercise programs can reduce pain and improve physical function [229,231]. Adherence is the primary predictor of long-term outcome from exercise for the management of knee or hip osteoarthritis; because of this, clinicians should encourage patients to engage in exercises they enjoy, as this can enhance the likelihood of long-term adherence. Long-term monitoring, frequent contact during follow-up, and/or involving family members in the program may also enhance adherence [193,229,232].

In 2000, the ACR guidelines for the management of knee and hip osteoarthritis included a recommendation for aerobic exercise [71]. A year later, the AGS published evidence-based recommendations for exercise as part of managing osteoarthritis in older individuals. (These recommendations were not joint-specific.) In 2005, a European multidisciplinary expert panel developed evidence-based recommendations for exercise to manage osteoarthritis of the knee or hip [229]. The AAOS incorporated these previous recommendations into its 2008 guideline for the treatment of knee osteoarthritis, noting that patients should be encouraged to participate in low-impact aerobic fitness exercises (level of evidence: I, A) and quadriceps strengthening (level of evidence: II, B) [232]. Subsequent reviews of the literature have supported that exercise reduces pain and improves physical function [227,233]. The 2021 AAOS guideline on the treatment of knee osteoarthritis strongly recommends the implementation of a variety of physical therapy and exercise modalities, including low-impact aerobic exercise, aquatic exercise, strength training, self-management programs, and neuromuscular education [198]. Exercise recommendations should be consistent with national guidelines. The 2019 ACR Technical Expert Panel recommends land- or water-based aerobic exercise for all patients (depending on patient preference) except those who are extremely overweight or aerobically deconditioned; for these patients, water-based exercise is recommended until conditioning (i.e., improved aerobic capacity) is achieved [185].

Physical Therapy Strategies

Substantial improvement in symptoms related to osteoarthritis of the knee has been achieved through several physical therapy strategies, including range-of-motion (flexibility) exercises, muscle stretching, and soft tissue mobilization [172]. A combination of physical therapy (to the knee as well as to the lumbar spine, hip, and ankle, as required) and a standardized exercise program provided more benefit than placebo (subtherapeutic ultrasound to the knee) in a small randomized study (83 patients) of the management of knee osteoarthritis [234]. Patients treated with the combination therapy had clinically and statistically significant improvements in WOMAC score and six-minute walk distance, whereas no improvements were found in the placebo group. The benefits were sustained at one year, and fewer patients in the treatment group had undergone knee arthroplasty (5% vs. 20%) at that time. Another small randomized study compared home-based physical therapy with clinically based physical therapy [235]. The 134 participants with knee osteoarthritis were randomly assigned to a clinic treatment group or a home exercise group. The clinic treatment group received supervised exercise and individualized manual therapy; they also completed a four-week home exercise program. The home exercise group completed the four-week home exercise program, with reinforcement at a clinic visit two weeks later. Both groups showed clinically and statistically significant improvements in six-minute walk distances and WOMAC scores at four weeks and eight weeks. By four weeks, WOMAC scores had improved by 52% in the clinic treatment group and by 26% in the home exercise group. Average six-minute walk distances had improved about 10% in both groups. At one year, both groups were substantially and about equally improved over baseline measurements. Subjects in the clinic treatment group were less likely to be taking medications for their arthritis and were more satisfied with the overall outcome of their rehabilitative treatment compared with subjects in the home exercise group [235].

The AGS guidelines recommend flexibility exercises, strengthening exercises, and endurance exercises, along with heat modalities, for older patients with all types of osteoarthritis. Range-of-motion (flexibility) exercises can help decrease stiffness, increase joint mobility, and prevent soft-tissue contractures [228]. Static stretching can improve range of motion. Exercises that combine flexibility and resistance training (e.g., yoga, tai chi) have significant therapeutic benefit for knee osteoarthritis [185,198]. The goal of strengthening exercises is to increase the strength of the muscles that support the affected joint [228]. Exercises to strengthen the quadriceps muscles have led to improvements in pain and function for individuals with knee osteoarthritis [172]. In addition, studies suggest that strengthening the quadriceps muscles may help delay progression of knee and hip osteoarthritis [229]. In general, patients should begin a strengthening exercise regimen with isometric exercises and advance to isotonic resistance exercises as tolerated [228]. Isometric, isotonic, and isokinetic training have similar long-term benefits [198]. In general, it appears that exercise is beneficial, but the mode of exercise may not matter as much as engaging in any exercise program [198].

The findings of a systematic review suggest that therapeutic ultrasound may help reduce pain and increase function for patients with osteoarthritis of the knee [236]. However, the quality of the evidence is low, which left the authors of this and another review uncertain about the magnitude of the effects of the treatment modality [236,237]. The AAOS guideline on the treatment of knee osteoarthritis refrains from making a recommendation for or against therapeutic ultrasound; however, the authors of the guideline reviewed several studies showing evidence of its benefit, particularly when combined with various forms of exercise [198].

With regard to other joints, EULAR guidelines recommend an exercise regimen that involves range-of-motion and strengthening exercises for all individuals with osteoarthritis of the hand [178]. The guidelines also recommend local application of heat, especially before exercise; heat can be applied with a hot pack or paraffin wax [178]. Thermal agents/modalities in combination with exercise are also endorsed by the ACR [185].

The AAOS found inconclusive evidence for physical therapy as an effective treatment option for osteoarthritis of the glenohumeral joint and is unable to recommend for or against physical therapy as part of initial treatment of the condition [197]. Similarly, a supervised physical therapy program is not routinely a treatment approach for osteoarthritis of the ankle [32]. Physical therapy should begin in the early stages of osteoarthritis of the elbow (mild pain and loss of less than 15 degrees of motion) [31]. Strategies may include gentle range-of-motion exercises to maintain mobility and strength [31].

Braces

Although valgus or varus bracing can theoretically relieve pain and improve function by shifting joint load away from the medial or lateral compartment of the knee, respectively, the AAOS found inconclusive evidence of the efficacy of these types of braces in terms of relieving pain or improving function or quality of life [198]. Braces can provide significant pain relief and improved function to patients who have unicompartmental knee osteoarthritis. Braces also can provide a subjective feeling of more normal tibiofemoral kinematics. There is a theoretical benefit of increased confidence in the knee during activities by providing a sense of security to the knee. Apart from some skin irritation or discomfort, there are almost no harms in trialing a brace [198].

With regard to other joints, a thumb splint may be helpful for people with osteoarthritis of the thumb base, and a brace has been suggested as part of conservative management of osteoarthritis of the ankle. However, these recommendations are based on expert opinion only [32,178].

Orthotics

It has been proposed that lateral and medial wedges may help relieve the symptoms of medial and lateral compartment osteoarthritis of the knee, respectively, by reducing joint load. However, studies have not provided evidence that wedges alone improve osteoarthritis-related symptoms [172,198,238]. The ACR guidelines suggest that patients may benefit from the use of wedged insoles to correct abnormal biomechanics related to varus deformity of the knee, but the AAOS recommends that lateral heel wedges not be prescribed for patients with symptomatic medial compartmental osteoarthritis of the knee [185,198].

Walking Aids

The ACR recommends use of a cane on the contralateral side to help decrease pain and improve function for patients who have persistent pain related to knee or hip osteoarthritis [172,185].

Footwear

Clinicians should also advise patients with hip or knee osteoarthritis about appropriate footwear; the optimum shoe may be one that is flat or has a low heel and that is flexible (rather than stabilizing) [238]. Foot orthoses to correct varus malalignment of the forefoot may help reduce pain in the hip among individuals with osteoarthritis of that joint [140]. Modifications to footwear may be helpful for people with osteoarthritis of the ankle [32].

Other

The ACR recommends patellar taping for the short-term relief of pain and improvement of function among individuals with symptomatic osteoarthritis of the knee [185]. Although the AAOS has previously endorsed taping, the 2021 update does not address this approach [198,232].

Transcutaneous electrical nerve stimulation (TENS) has been used as part of management of knee osteoarthritis, but the data on its effectiveness are conflicting. One review of the literature (systematic reviews published between 2000 and 2007) demonstrated evidence of moderate quality that TENS reduces pain [233]. The authors of a subsequent review (up to 2008) reported that they could not confirm the benefit of TENS for the relief of pain, noting that the review was inconclusive because of the inclusion of small trials of questionable quality [239]. The ACR recommends the use of electrical stimulation only for patients with severe pain who are candidates for total knee arthroplasty but who are unwilling or unable to undergo the procedure (i.e., contraindication due to comorbidities/medication) [185]. The AAOS is unable to recommend for or against any form of electrotherapy [198].

According to the American Academy of Orthopaedic Surgeons, acupuncture may improve pain and function in patients with knee osteoarthritis.

(https://www.aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-knee/oak3cpg.pdf Last Accessed: September 22, 2022)

Strength of Recommendation: Limited (Evidence from two or more moderate-quality studies with consistent findings, or evidence from a single high-quality study for recommending for or against the intervention)

The available literature demonstrates that acupuncture provides minimal, short-term relief of pain related to knee osteoarthritis [233,240,241]. Acupuncture was considered to be a therapy "under investigation" at the time of publication of the 2000 ACR guidelines for the management of osteoarthritis of the knee and hip [71]. The 2019 ACR expert panel recommends the use of acupuncture only for patients with severe pain who are candidates for total knee arthroplasty but who are unwilling or unable to undergo the procedure [185]. The AAOS applied a limited strength recommendation for the use of acupuncture as an adjunctive therapy for pain relief in patients with symptomatic osteoarthritis of the knee. This is a downgraded recommendation because of inconsistent evidence and a lack of internal consistency with recommendations of equal supporting evidence [198]. No recommendations have been made regarding the use of acupuncture as part of the treatment of osteoarthritis at other joint sites.

Because of the wide range of pain relievers available, the challenge is to select an agent that will provide optimum relief with minimum adverse events. The oral pain relievers used for osteoarthritis include acetaminophen, nonselective NSAIDs, cyclooxygenase-2 (COX-2) selective NSAIDs, opioids, and tramadol. The 2021 AAOS guideline specifies NSAIDs (oral or topical) as first-line pharmacologic treatments for symptomatic osteoarthritis of the knee. The guideline does not recommend tramadol, citing a significant increase of adverse events and lack of efficacy at improving pain or function for treatment of osteoarthritis of the knee [198]. The 2019 ACR guideline recommends NSAIDs (including COX-2-selective agents) and tramadol as first-line treatment for hand osteoarthritis, and acetaminophen, NSAIDs, and tramadol for knee and hip osteoarthritis [185].

The American Academy of Orthopaedic Surgeons asserts that oral NSAIDs and/or acetaminophen are recommended to improve pain and function in the treatment of knee osteoarthritis, when not contraindicated.

(https://www.aaos.org/globalassets/quality-and-practice-resources/osteoarthritis-of-the-knee/oak3cpg.pdf Last Accessed: September 22, 2022)

Strength of Recommendation: Strong (Evidence from two or more high-quality studies with consistent findings for recommending for or against the intervention)

Some guidelines recommended acetaminophen as the initial analgesic for the management of mild-to-moderate pain related to osteoarthritis, but this recommendation has since been shown to be questionable [193]. A comparative effectiveness study conducted by the AHRQ found good evidence that acetaminophen is modestly inferior in efficacy compared with NSAIDs but has a lower risk of gastrointestinal complications [244]. An update to this study found that no currently available analgesic offered a clear overall advantage compared with the others [200]. Its original findings on acetaminophen remained the same, with the addition that acetaminophen poses a higher risk of liver injury [200]. Other research has shown that NSAIDs are more effective than acetaminophen for relieving osteoarthritis-related pain, especially moderate-to-severe pain [245]. The 2021 AAOS guideline provides a strong recommendation for oral acetaminophen to improve pain and function in the treatment of knee osteoarthritis when not contraindicated [198]. The working group noted that when oral acetaminophen was compared to NSAIDs, the use of oral NSAIDs provided a significant reduction in pain and improved function. As a result, providers may consider using oral NSAIDs instead of acetaminophen when a contraindication to oral NSAIDs does not exist [198]. NSAIDs should be prescribed at the lowest effective dose, and their long-term use should be avoided [193]. A COX-2 selective agent or an NSAID with a prescription for a gastroprotective agent (such as a proton-pump inhibitor) may be used for patients who have an increased risk for gastrointestinal complications [193].

There is good evidence that nonselective NSAIDs and COX-2-selective NSAIDs have comparable efficacy and that COX-2-selective agents are comparable to each other [200,246]. Although COX-2-selective agents have better tolerability in general compared with NSAIDs, there is considerable variability across individual drugs in terms of protection against serious gastrointestinal events [246]. In addition, some COX-2 selective NSAIDs have been associated with an increased risk of myocardial infarction, and these drugs should be used with caution in patients with cardiovascular risk factors [200,246].

Studies have found that opioids were more effective overall than control interventions with respect to pain relief and improved function, but the beneficial effects were small to moderate and were outweighed by a substantial increase in the risk of adverse events [247,248]. The authors of the review concluded that opioids should not be used routinely for individuals with osteoarthritis, even for severe pain. Some guidelines suggest the use of weak narcotics or opioids for pain that has been refractory to other pharmacologic agents; however, the guidelines note that strong opioids should be used sparingly [193]. The 2021 AAOS guideline on the treatment of knee osteoarthritis emphasizes the importance of removal of oral narcotics from the medications prescribed due to the rise of the opioid epidemic in the United States [198]. The ACR guidelines conditionally recommend against using opioid analgesics for osteoarthritis of the hand [185].

In reviewing the literature for its guidelines on the treatment of osteoarthritis of the glenohumeral joint, the AAOS was not able to find sufficient evidence to support several pharmacologic treatments, including acetaminophen, NSAIDs, opioids, or narcotics. As a result, the AAOS states it is unable to recommend for or against the use of any of these options for the initial treatment of patients with osteoarthritis of this joint [197].

Moderate-quality evidence indicates that compared with placebo, tramadol alone or in combination with acetaminophen probably has no important benefit on mean pain or function in people with osteoarthritis, although slightly more people in the tramadol group report an important improvement (defined as 20% or more). Moderate-quality evidence shows that adverse events probably cause substantially more participants to stop taking tramadol. The increase in serious adverse events with tramadol is less certain, due to the small number of events [249].

The American College of Rheumatology and the Arthritis Foundation conditionally recommend against topical capsaicin in patients with hand osteoarthritis.

(https://www.rheumatology.org/Portals/0/Files/Osteoarthritis-Guideline-Early-View-2019.pdf Last Accessed: September 22, 2022)

Strength of Recommendation: Conditional against

There is good evidence that topical NSAIDs have efficacy comparable to oral NSAIDs, although most trials have involved knee osteoarthritis only, and head-to-head trials have not been large enough to evaluate the comparative risk of serious cardiovascular events and gastrointestinal effects [200]. There is also good evidence that topical NSAIDs are safer than oral NSAIDs, but a systematic literature review showed that systemic adverse events have occurred in a substantial proportion of older adults treated with topical NSAIDs [250]. Capsaicin has also been effective in relieving osteoarthritis-related pain, and some guidelines have suggested the use of this topical agent as an alternative treatment or an adjunct to treatment with oral analgesics [193]. The ACR guideline recommends against the use of topical capsaicin for hand osteoarthritis and for topical NSAIDs for hand and knee osteoarthritis [185]. The AHRQ comparative review found that topical capsaicin was superior to placebo but associated with increased local adverse events and withdrawals due to adverse events [200].

As is the case for oral analgesics, the AAOS was not able to find sufficient evidence to support the use of topical analgesics for the treatment of glenohumeral joint osteoarthritis and is unable to recommend for or against the use of these agents for the initial treatment of patients with osteoarthritis of that joint [197].

Most of the evidence regarding the efficacy of intra-articular injection of long-acting corticosteroids comes from the literature on osteoarthritis of the knee, and many experts have called for more research on this treatment approach at the hip and other joints [35,223]. In general, this treatment option is used for moderate-to-severe pain in a joint that has not responded to nonpharmacologic measures or to oral analgesics. Pain relief is thought to be related to the anti-inflammatory effects of the corticosteroid [251,252].

Certain guidelines conditionally recommend intra-articular injection of corticosteroids into the knee or hip, especially after aspiration of fluid in patients who have signs of local inflammation with joint effusion [9,185,206]. For example, the ACR recommends this therapy for knee and hip osteoarthritis if the patient does not have satisfactory response to acetaminophen and topical NSAIDs and if there is a contraindication to oral NSAIDs. The AAOS provides a moderate recommendation for the use of intra-articular corticosteroid therapies. Extended release agents are recommended over immediate release to improve patient outcomes [198].]. Although the approach is otherwise widely recommended, it is acknowledged that intra-articular corticosteroids provide short-term relief only [35,253,254]. A meta-analysis of 28 trials (1,973 patients) of knee osteoarthritis showed a benefit of pain relief for two to four weeks, with no benefit in terms of functional improvement and no benefit in either pain or function beyond four weeks [253]. An update to the meta-analysis, which included 27 trials (1,767 patients), found that the overall quality of the evidence did not clearly support a benefit of intra-articular corticosteroid use after one to six weeks [254]. Despite the short-term benefit found in most studies, clinical experience has shown longer relief in many patients [35]. Because of the potential side effects of intra-articular injections, which include long-term damage to joint cartilage, flare after injection, and infection, most physicians do not recommend more than three to four injections per joint per year [9,35]. Intra-articular injection is more technically difficult in the hip joint than in the knee, and radiographic or ultrasonographic guidance has been suggested, although there are no comparative data to provide evidence that accuracy is increased with such guidance [9,223].

Recommendations for the use of intra-articular corticosteroids at other joints are based primarily on expert opinion, as randomized controlled trials are lacking or have included small numbers of patients. EULAR guidelines for osteoarthritis of the hand note that intra-articular corticosteroids are effective for painful flares of osteoarthritis, especially of the trapeziometacarpal joint [178]. As with data on the hip and knee, intra-articular injections have provided benefit for up to four weeks [9,178].

Although intra-articular corticosteroids are often used in clinical practice to treat shoulder pain of all etiologies, the AAOS concluded that there was insufficient evidence to support the use of this approach for the treatment of osteoarthritis of the glenohumeral joint [197]. Intra-articular corticosteroids are also options for refractory pain in individuals with osteoarthritis of the elbow or ankle, although data are lacking to support the approach [31,32,58].

Endogenous hyaluronan (also known as hyaluronic acid) is a primary component of the extracellular matrix of synovial membrane and tissue and articular cartilage, as well as the synovial fluid [255]. It provides viscoelasticity and lubrication to the joint and helps to maintain tissue hydration. The use of exogenous hyaluronan to treat osteoarthritis—known as viscosupplementation—began in the 1960s; several formulations of viscosupplements are now available, each produced by different manufacturers with different molecular weights. Data on comparison of high-molecular-weight and low-molecular-weight hyaluronic acid have been conflicting, with some studies indicating that high-molecular-weight hyaluronic acid is more effective, whereas other analyses have shown that the efficacy is similar [256,257]. Research reviewed by the AAOS panel suggests that high-molecular-weight hyaluronic acid is more effective than low-molecular-weight [198]. The AAOS guideline does not recommend hyaluronic acid for routine use in the treatment of symptomatic knee osteoarthritis [198]. How hyaluronan and similar products alleviate osteoarthritis-related symptoms is not entirely clear, but its action is thought to be related to its anti-inflammatory, anabolic, and chondroprotective properties [71,258].

It is difficult to determine the efficacy of hyaluronan because research evidence is confounded by different molecular weights of hyaluronan preparations, different dosing schedules, and poor trial design, and the level of evidence across studies has been low [223,255,256,259]. Most of the evidence available is related to osteoarthritis of the knee, with limited data available on use of the treatment for osteoarthritis of the hip, hand, or shoulder.

Since the publication of the 2000 ACR guidelines, certain studies and analyses have supported the efficacy of hyaluronan/hylan derivatives for relieving pain and improving function in patients with symptomatic osteoarthritis of the knee (compared with placebo), with the greatest benefit found in conjunction with less severe pain and disability at 5 to 13 weeks after injection [206,256,260,261]. However, researchers have noted that the effect size is small compared with placebo and that the effect may be overestimated as a result of publication bias [255,256,262]. When compared with NSAIDs, hyaluronan takes longer to relieve knee symptoms; additionally, the dosing schedule necessitates more office visits than intra-articular corticosteroids, creating inconvenience and increasing costs [206,223]. Uncontrolled and small studies of hyaluronic acid for hip osteoarthritis have shown pain reduction after treatment, but intra-articular corticosteroids were more effective in one small study [223,259,263].

In its 2019 recommendations, the ACR conditionally recommends against using intra-articular therapies for hand osteoarthritis [185]. This recommendation is based largely on the absence of evidence from randomized controlled trials to support the benefits as well as the potential for harm from such therapy [185].

In its 2021 guideline on the treatment of osteoarthritis of the knee, the AAOS notes that it cannot recommend the use of intra-articular hyaluronic acid for individuals with symptomatic disease [198]. The rationale for this recommendation is based on a lack of efficacy, not potential harm. Treatment with hyaluronan has been reported to be well tolerated, with a low incidence of adverse events [259,260,264]. Among the potential adverse events are transient pain (mild to moderate) at the injection site and increases in joint pain and/or swelling [71]. The NICE guidelines, revised in 2014, also note that intra-articular injections of hyaluronan cannot be recommended for the treatment of osteoarthritis [199,255].

Evidence of benefit of hyaluronan for osteoarthritis of other joints is limited. A small study (56 patients) showed that a single course of three injections of intra-articular sodium hyaluronate relieved pain and improved joint function in patients with osteoarthritis of the carpometacarpal joint of the thumb. Although the effects were achieved more slowly than treatment with triamcinolone, the duration of benefit was longer (up to six months) [265]. In another small study (16 men), intra-articular sodium hyaluronate (administered once weekly for five weeks) improved scores for pain (primarily at rest) related to osteoarthritis of the trapeziometacarpal joint [178].

The AAOS recommends viscosupplementation as an option for patients with glenohumeral joint osteoarthritis but notes that the level of evidence for the recommendation is weak [197]. A case series of 18 patients with post-traumatic osteoarthritis of the elbow demonstrated short-term pain relief and very limited improvement in function, and the authors concluded that viscosupplementation was not suitable for the condition [266]. Descriptions of suggested treatment options for osteoarthritis of the ankle have not included hyaluronan, although a review of seven studies (275 patients) published between 2006 and 2008 suggested that viscosupplementation may be of benefit for osteoarthritis at that joint [267].

In the United States, glucosamine and chondroitin are heavily marketed as dietary supplements that promote "joint health" and relieve the symptoms of osteoarthritis of the knee and hip. Glucosamine and chondroitin are both made in the body; glucosamine is an amino sugar that is thought to enhance the formation and repair of cartilage, and chondroitin is a carbohydrate found in cartilage that is thought to promote water retention and elasticity and to inhibit the enzymes that degrade cartilage. More than 20 products contain glucosamine alone, chondroitin alone, or a combination of the two, and contamination or mislabeling has been found for some products [268].

Data on the efficacy of glucosamine and chondroitin are available primarily for osteoarthritis of the knee, with limited data on its effectiveness for osteoarthritis of the hip; no studies have been done to evaluate the use of these supplements for osteoarthritis at other joint sites. Several early systematic reviews failed to show a benefit of glucosamine and/or chondroitin in terms of pain, stiffness, and function when compared with placebo [223,269]. These findings were supported by the results of the Glucosamine/Chondroitin Arthritis Intervention Trial (GAIT), a randomized study involving 1,583 patients with symptomatic knee osteoarthritis that has provided the best evidence to date on these supplements [201,270]. The results demonstrated that glucosamine and chondroitin sulfate, alone or in combination, did not reduce pain more effectively than placebo [270]. A multicenter study done as part of GAIT showed that the combination of glucosamine and chondroitin sulfate did not alter progression of knee osteoarthritis, with no clinically important difference in the loss of joint space width compared with placebo [271]. A report on the two-year results from GAIT noted that there were no significant differences in pain among groups treated with glucosamine, chondroitin sulfate, a combination of the two supplements, or a placebo [272].

A systematic review evaluated the benefit and harm of chondroitin compared with placebo or a comparable oral medication (e.g., NSAIDs, analgesics, opioids, glucosamine) [273]. The review included 43 randomized controlled trials, including 4,962 participants treated with chondroitin and 4,148 participants given placebo or another control. The majority of trials were in osteoarthritis of the knee, with few in the hip or hand, and the length of the trials varied from one month to three years. In studies of less than six months in length, participants treated with chondroitin achieved significantly better pain scores than those given placebo (absolute risk difference: 10% lower); the risk difference for pain was 9% lower in studies longer than six months. A 20% reduction in knee pain was achieved by 53 of 100 participants in the chondroitin group versus 47 of 100 in the placebo group. Differences in the composite of pain, function, and disability favored chondroitin compared with placebo in studies of less than six months. Chondroitin was associated with significantly lower odds of serious adverse events compared with placebo. Chondroitin alone or in combination with glucosamine or another supplement is associated with a significant reduction in pain compared with placebo or an active control; no significant differences in the numbers of adverse events were reported. As stated, the authors found that most of the randomized trials included were of low quality; overall, the benefit of chondroitin was small to moderate [273]. Other analyses and results of randomized controlled trials have indicated that glucosamine and/or chondroitin sulfate have no or modest benefit in terms of pain, function, or structural alterations [274,275,276].

In its guidelines on the management of osteoarthritis of the hand, knee, and hip, the ACR deems the evidence on glucosamine and chondroitin to be inconclusive and conditionally recommends against their use [185]. The 2021 AAOS guideline on the management of knee osteoarthritis suggests that glucosamine and/or chondroitin may be helpful in reducing pain and improving function for patients with mild-to-moderate knee osteoarthritis; however, the evidence is inconsistent and limited, and additional research clarifying the efficacy of each supplement is needed [198]. With regard to osteoarthritis of the glenohumeral joint, the AAOS is not able to recommend for or against the use of glucosamine and/or chondroitin [197].

In a systematic review undertaken to evaluate the effectiveness of 22 herbal medicinal products, there was some evidence of pain relief with topical capsaicin, avocado-soybean unsaponifiables, and SKI306X (a Chinese herbal mixture). However, none of the 22 products had proof of effectiveness beyond doubt [277]. According to a review of studies involving antioxidant and anti-inflammatory supplements, the following cannot be recommended for the treatment of osteoarthritis: vitamin E (alone); a combination of vitamins A, C, and E; ginger; turmeric; omega-3 fatty acids; or Zyflamend (an extract of 10 different herbs) [278]. Additional clinical trials are needed before alternative supplements can be recommended.

According to the National Collaborating Centre for Chronic Conditions, referral for joint replacement surgery should be considered for people with osteoarthritis who experience joint symptoms (pain, stiffness and reduced function) that have a substantial impact on their quality of life and are refractory to non-surgical treatment. Referral should be made before there is prolonged and established functional limitation and severe pain.

(https://www.nice.org.uk/guidance/cg177 Last Accessed: September 22, 2022)

Level of Evidence: Expert Opinion/Consensus Statement

Total arthroplasty (joint replacement) is considered when all other options have failed. Indications for the procedure are severe symptomatic disease (chronic pain and disability) [19]. The procedure has led to high rates of good-to-excellent results when done at the knee and hip and is cost-effective compared with nonoperative management [19,38].

Knee Arthroplasty

In 2018, an estimated 715,203 total knee arthroplasties were completed in the United States [284]. According to the National Institutes of Health, the success of total knee arthroplasty in most patients is strongly supported by more than 20 years of follow-up data, with significant improvement in pain, joint function, and quality of life in 90% of patients [285]. However, some patients will experience prosthesis failure, and risk factors for failure include male gender, age younger than 55 years at the time of surgery, obesity, and the presence of comorbidities. In terms of factors related to the surgeon, greater procedure volume (both of the surgeon and the facility), prosthesis choice, and surgical technique (e.g., proper alignment of the prosthesis) all contribute to better patient outcomes [285]. It is important to note that both knee and hip arthroplasty are associated with a high risk of deep vein thrombosis (DVT) and pulmonary embolism compared with other surgeries. Without prophylaxis, DVT will develop in most patients [286]. Therefore, prophylactic treatment, usually with either low-molecular-weight heparin or warfarin, is recommended for patients undergoing one of these procedures, unless contraindications are present.

Because there are anatomic differences in joint structure and size between men and women, a gender-specific knee prosthesis was designed specifically for women [287]. Researchers believed that the better fit would lead to improvements in recovery and outcomes for women who had total knee arthroplasty. In one study, 85 women who received a standard joint in one knee and the gender-specific joint in the other knee were followed up for two years after the surgery [287]. Patient satisfaction, range of motion while lying, and WOMAC scores were similar for both prostheses. The researchers did note that the standard prostheses appeared to fit at the distal part of the femur better than the gender-specific type; furthermore, the small size of the gender-specific prosthesis exposed more bone and resulted in more bleeding immediately after surgery. Although the study concluded that there were no benefits to the use of gender-specific prostheses in women undergoing total knee arthroplasty, research evaluating long-term effects is necessary.

Postoperative rehabilitation is a necessary component of recovery after operative treatment of osteoarthritis and requires cooperation of the entire multidisciplinary team. In the case of total knee arthroplasty, patients should be guided on a postoperative exercise and rehabilitation plan that focuses on obtaining an acceptable level of joint function, range of motion, and quality of life (e.g., ability to perform activities of daily living unassisted). In some cases, a continuous passive motion device may be used. This device has been suggested as a means to obtain greater range of motion more quickly after surgery [288]. While this may be the case, no long-term benefits (e.g., ultimate range of motion) have been definitively proven, and evidence on the short-term effects are conflicting [286,288,289]. It is not a recommendation of the AAOS or the ACR at this time.

In general, the institution of a structured exercise plan, guided by the physician and physical therapist, will assist patients in regaining range of motion and return to performing daily activities. A daily physical therapy program after total knee arthroplasty should continue for four to six weeks, at which point the patient's needs will be reassessed. According to one study, the greatest improvements in lower-extremity functional status after total knee arthroplasty were demonstrated in the first 12 weeks, with little improvement noted after 26 weeks [290]. By the end of physical therapy, the patient should be able to perform activities of daily living and progress to ambulating on flat surfaces and stairs. Strengthening and stretching exercises focusing on the hamstrings and quadriceps should be incorporated into the program.

There is some debate regarding the importance of supervised outpatient physical therapy compared with exercise programs carried out in the patient's home. One meta-analysis of 10 randomized controlled trials found that supervised physical therapy provided no benefits for patients who were younger at the time of surgery and had few or no comorbidities [291]. However, the researchers noted that there is a lack of evidence regarding the use of outpatient physical therapy for older patients with comorbidities and those who have undergone more complicated surgeries.

One study that included older patients (60 to 79 years of age) was designed to determine the functional differences between the effects of supervised physiotherapy with a standardized home exercise program following total knee arthroplasty [292]. All patients were evaluated for joint range of motion, pain, functional status, overall quality of life, and depressive symptoms. Postoperative assessment showed a significant clinical improvement in both groups, and the authors found no significant difference between the groups in range of motion and functional status.

Hip Arthroplasty

Total hip arthroplasty is also relatively common, with 599,494 procedures completed in 2018 [293]. This procedure is recommended for the treatment of osteoarthritis in older patients for whom nonsurgical interventions have been ineffective. Some data suggest that the benefit of arthroplasty of the hip is greater when done earlier in the course of disease [38]. According to one study, female gender, the presence of comorbidities, contralateral hip osteoarthritis, back pain, and poor preintervention health or mental health status were predictors of poorer outcomes and lesser improvements in quality-of-life measures after total hip arthroplasty [294].

Although steps are taken to prevent it, leg length can be altered as a result of total hip arthroplasty. It is important for the leg on the operative side to be measured and, if there is a discrepancy, corrected with the use of orthotics.

As with knee arthroplasty, individuals who have undergone total hip arthroplasty require a physical therapy and exercise regimen that will allow them to obtain the optimal level of joint function and flexibility. The goals of therapy are the same as those described for total knee arthroplasty. One consideration is when to initiate physical therapy in order to gain the most improvement, particularly considering that improvements seem to plateau after 12 to 26 weeks. In a study of 593 patients who had total hip arthroplasty (performed by six different surgeons using different surgical techniques), 191 began physical therapy on the day of surgery and the remaining 402 patients began physical therapy on postoperative day 1 [295]. The length of stay was significantly shorter for the patients who had early physical therapy (2.16 days compared with 3.38 days).

Another consideration is the type of postoperative exercise and rehabilitation program recommended. One study compared a conventional rehabilitation program with the use of early maximal strength training in patients who had received a total hip replacement [296]. Individuals in the treatment group performed leg press and abduction with the operated leg five times a week for four weeks in addition to the conventional program (supervised physical therapy three to five times per week for four weeks). The researchers found that those who included maximal strength training in their postsurgical physical therapy had a significantly larger increase in muscular strength and a trend toward a better work efficiency than those in the conventional therapy group.

Other Joints

Other joint replacement procedures are not done as widely and are not associated with the same success as knee and hip arthroplasty. The AAOS guideline on the treatment of osteoarthritis of the glenohumeral joint includes a weak recommendation for total shoulder arthroplasty and hemiarthroplasty as options, with a moderate recommendation for total arthroplasty over hemiarthroplasty [197].

The use of total elbow arthroplasty is limited by the high risk for instability and loosening and is rarely used to treat primary osteoarthritis [31,58]. When performed in younger patients, long-term success of the procedure has been limited because of high functional demands [31]. As a result, total replacement should be reserved for patients older than 65 years of age who are willing to accept low levels of activity [31,58].

The complex anatomic and biomechanical features of the ankle joint have challenged the use of joint replacement [32]. New designs of prostheses have led to good-to-excellent outcomes postoperatively, but complications have included osteomyelitis and osteolysis. In addition, only short-term data are available.