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Management of knee osteoarthritis

Management of knee osteoarthritis
Authors:
Leticia Alle Deveza, MD, PhD
Kim Bennell, PhD
Section Editor:
David Hunter, MD, PhD
Deputy Editor:
Philip Seo, MD, MHS
Literature review current through: Dec 2022. | This topic last updated: Apr 05, 2022.

INTRODUCTION — Evidence-based approaches to the treatment of knee osteoarthritis (OA) include nonpharmacologic, pharmacologic, and surgical modalities targeted at relieving pain, improving joint function, and modifying risk factors for disease progression. Treatments to modify the course of the disease have not reached a threshold of efficacy to gain regulatory approval, although some investigational therapies appear to slow structural progression.

There are multiple mechanisms that can contribute to the pain experience, and a holistic assessment of the patient is a paramount component of knee OA treatment. In addition, clinical decision-making is often influenced by specific patient and disease characteristics. This topic will provide an overview of the management of knee OA, with a focus on the management of mild knee OA. Separate topic reviews on OA as well as knee pain include the following:

(See "Pathogenesis of osteoarthritis".)

(See "Investigational approaches to the management of osteoarthritis".)

(See "Epidemiology and risk factors for osteoarthritis".)

(See "Clinical manifestations and diagnosis of osteoarthritis".)

(See "Overview of the management of osteoarthritis".)

(See "Management of moderate to severe knee osteoarthritis".)

(See "Comorbidities that impact management of osteoarthritis".)

(See "Approach to the adult with unspecified knee pain".)

(See "Approach to the adult with knee pain likely of musculoskeletal origin".)

(Related Pathway(s): Knee osteoarthritis: Management in adults.)

DEFINITIONS — These definitions are based on the severity of the impact of the disease on the person rather than on radiographic severity in line with a person-centered approach to management and the fact that symptoms and radiographic findings are not necessarily well correlated and that imaging is not usually required for diagnosis [1]. (See "Overview of the management of osteoarthritis", section on 'Mechanisms of pain'.)

Mild knee osteoarthritis – Patients with mild knee osteoarthritis (OA) have low levels of or intermittent knee pain with relatively well-preserved joint function and quality of life.

Moderate/severe knee osteoarthritis – Patients with moderate to severe OA have persistent pain which significantly impairs functionality, activity participation, and quality of life. (See "Management of moderate to severe knee osteoarthritis".)

GENERAL PRINCIPLES — All patients with osteoarthritis (OA) should be thoroughly assessed with regard to their knowledge about the disease and treatment alternatives, previous experiences with treatment, and expectations of current treatment. The presence of misconceptions, such as that exercise will worsen OA or that OA will inevitably get worse, may attenuate the results of treatment if not properly identified and countered. Patient education about OA and its treatment options can occur during the clinical encounter and can be complemented by provision of written materials and referral to national or rheumatology association websites. Creating realistic and positive expectations for treatment efficacy may enhance adherence, especially to therapies that require lifestyle changes, and has been shown to positively influence treatment outcomes [2,3]. The management principles for OA, including education, self-management, and goal-setting, are discussed in detail separately. (See "Overview of the management of osteoarthritis", section on 'General principles'.)

The management of patients with knee OA should include a holistic assessment. Monitoring of the patient's response to therapy should also be done on a regular basis. A detailed discussion on monitoring and assessment of OA patients can be found elsewhere. (See "Overview of the management of osteoarthritis", section on 'Monitoring and assessment'.)

APPROACH BASED ON CLINICAL PRESENTATION — Patients with knee osteoarthritis (OA) may fall into different categories that must be considered when making treatment decisions.

Our management approach is generally consistent with guidelines developed by professional organizations [4-10].

Mild knee osteoarthritis — Nonpharmacologic therapies alone, focusing on education, exercise, and weight management, or in combination with topical therapies or analgesics on an as-needed basis are likely to provide adequate control of symptoms in this group of patients (algorithm 1).

Moderate/severe knee osteoarthritis — Nonpharmacologic interventions are the first-line therapy for this group of patients, and aquatic exercises are usually better tolerated than land-based exercises in patients with severe pain (algorithm 2). Special consideration should be given to extraarticular factors potentially contributing to pain, such as mood disturbances, pain catastrophizing, sleep problems, and chronic widespread pain (see "Overview of the management of osteoarthritis", section on 'Factors affecting response to therapy'). Other treatment alternatives may be required, including oral nonsteroidal antiinflammatory drugs (NSAIDs), intraarticular glucocorticoids, duloxetine, and surgery.

Knee osteoarthritis with one or more joints involved — OA can be localized in the knee only or occur concomitantly with OA in multiple joints. The best approach for managing patients with multijoint, symptomatic OA is to prioritize therapies that address the pain at the individual level and not at the joint level. Local interventions such as intraarticular steroid injections, topical NSAIDs or capsaicin, and knee braces may help with knee pain but are likely to be insufficient to provide adequate improvement in the patient's OA symptoms as a whole.

Patients with comorbidities — Knee OA is often comorbid with other conditions such as cardiovascular disease, diabetes, hypertension, obesity, depression, and peptic ulcer disease. In addition, knee OA is highly prevalent in the older adult population, although it is important to note that its diagnosis usually occurs earlier in life (median age 55 years) and around two-thirds of the patients are younger than 65 years [11,12]. Therapies should be chosen to minimize the potential for adverse events while optimizing function and quality of life. (See "Comorbidities that impact management of osteoarthritis".)

MILD KNEE OSTEOARTHRITIS — Nonpharmacologic interventions are the backbone of knee osteoarthritis (OA) management, irrespective of OA severity, and can be used in combination with pharmacologic therapy (algorithm 1). The duration of therapy depends upon the individual patient's needs; however, lifelong treatment with nonpharmacologic therapies is generally recommended in order to relieve symptoms and prevent further joint damage. (Related Pathway(s): Knee osteoarthritis: Management in adults.)

Initial nonpharmacologic measures — Nonpharmacologic interventions in the management of patients with mild OA includes exercise and, when pertinent, weight loss.

Exercise — In all patients with knee OA, we recommend ongoing exercise for pain relief and joint protection. Exercise, alongside weight loss when indicated, is a core component of knee OA management [2-4,13,14]. All patients with knee OA should be counseled on exercise irrespective of age, radiographic disease severity, pain intensity, functional levels, and comorbidities. A Cochrane review of 54 trials, among which 19 were considered as "low risk of bias," concluded that there is moderate- to high-quality evidence suggesting that land-based exercise improves knee pain and function with moderate effect size immediately after treatment [13]. This magnitude of effect is comparable to that reported for oral nonsteroidal antiinflammatory drugs (NSAIDs) [4]. However, the benefits of exercise were not sustained in the long term, which is largely related to the decreasing adherence rates to the exercise program over time [14]. Strategies to improve adherence should be adopted, such as patient education about OA and the benefits of exercise and long-term monitoring. (See "Overview of the management of osteoarthritis", section on 'General principles' and "Overview of the management of osteoarthritis", section on 'Monitoring and assessment'.)

At present, there is no strong evidence on the best prescription of exercise modalities and dosage (ie, intensity, duration, and frequency) [15,16]. In clinical practice, exercise prescription is frequently personalized according to individual findings. We refer our patients for physical therapy to optimize the effectiveness of the exercise program [17]. We prefer a combination of low-impact aerobic fitness training (eg, walking, cycling, rowing, and deep-water running) and lower-limb strengthening exercises, which addresses the full spectrum of impairments in most patients with knee OA. Nevertheless, exercise choice should be also based on patient's mobility, specific impairments (eg, strength, range of motion, aerobic fitness, and balance), and preferences [15]. Exercises involving high impact on the joints such as running or jumping are usually discouraged in order to avoid further joint damage, especially in cases of more advanced OA, although research evidence demonstrating an association between running and progression of knee OA is scarce [18]. For those patients who already run or jog for exercise and develop mild symptoms of OA but wish to continue running, we advocate a load management approach with attention paid to factors such as rest days, running surface, distance and speed, and footwear, as well as building up muscle strength. Stretching or flexibility exercises, particularly of the hamstrings to avoid or minimize flexion contracture of the knee, can also be part of the exercise program to increase knee range of motion [15,17].

Aquatic exercise also has clinically relevant effects on knee pain, function, and stiffness, but the effects are small when compared with non-treatment controls [19]. This exercise modality is particularly useful for patients with severe pain and/or poor physical function due to its better tolerance and lower potential to cause adverse events.

We also consider Tai Chi as a treatment option for the rehabilitation of patients with knee OA, according to patients' preferences. Despite the limited number of large trials investigating the long-term effects of Tai Chi, it has been shown to be as effective as a standard exercise program after 12 weeks in terms of knee pain, physical function, and reduction in analgesic use, in addition to having greater improvement in depression [20,21]. Moreover, Tai Chi improves balance and is associated with a reduced falls risk in older patients with knee OA [22].

The use of digital technologies to improve access and adherence to exercise may be of benefit for some patients [23-25].

Weight loss — Because of the substantial load placed on the knees during weightbearing activities, maintaining an ideal body weight is critical to preserve joint structures and improve symptoms. In addition to the mechanical consequences of obesity and overweight to the joint, adipokines released by the adipose tissue such as leptin and adiponectin are directly involved in the inflammatory component of OA and cartilage damage [26,27]. (See "Pathogenesis of osteoarthritis" and "Comorbidities that impact management of osteoarthritis", section on 'Obesity'.)

We encourage health care professionals to consult available local community programs or refer patients to a dietitian to ensure that patients with obesity or who are overweight are offered optimal support to lose weight [28]. (See "Obesity in adults: Overview of management".)

Our approach of a combination of a calorie-restricted diet and physical activity to achieve weight loss is supported by several studies [29]. As an example, the IDEA trial randomized 454 adults with obesity and knee OA into one of three groups: diet plus exercise, diet alone, or exercise alone [30]. Participants in the diet plus exercise group had the highest percentage of weight lost (11.4 percent of body weight) and improvement in pain after 18 months, achieving a decrease in pain scores of approximately 50 percent, with 38 percent of patients reporting no or little pain at the end of the trial. There is also evidence to suggest that interventions involving very low calorie diets with meal replacements are more effective for weight loss and improving physical function than lifestyle interventions in people with OA [31].

Moreover, a dose-response relationship between the extent of percentage change in body weight and improvement in joint symptoms has been demonstrated, with more robust effects achieved when at least a 10 percent reduction in body weight is attained [32,33]. A reasonable initial target is a 5 to 10 percent weight reduction within a six-month period [34], and initial goals should be reassessed periodically and individually for each patient.

Caloric restriction, particularly in order adults, may contribute to loss of lean mass and lead to muscle weakness and should, therefore, be combined with strengthening exercises to prevent these adverse effects. Other interventions such as anti-obesity drugs (eg, orlistat) and surgical approaches (eg, gastric bypass) are less well studied in the context of OA. (See "Obesity in adults: Overview of management".)

Inadequate response to nonpharmacologic measures — Pharmacologic therapy can be started in combination with or after a trial of nonpharmacologic interventions, if satisfactory pain relief is not achieved with these measures alone. Topical therapies (table 1) for the treatment of mild knee OA are particularly appealing due to the frequent presence of comorbid conditions in this patient population and the relatively common side effects of other systemic treatment options. Despite the chronic nature of OA, research evidence on the long-term efficacy (≥1 year) of pharmacologic therapies is limited [35]. Nonetheless, in our experience, topical NSAIDs, used either as needed or on a daily basis, may provide long-term benefits when combined with nonpharmacologic measures. Topical capsaicin, however, is less tolerated by patients due to the relatively high frequency of local side effects, including a local burning sensation. We do not use topical salicylates in our patients with OA.

Topical NSAIDs — We suggest topical nonsteroidal antiinflammatory drugs (NSAIDs) rather than oral NSAIDs for patients with mild OA localized to the knee or with concomitant hand involvement, given the superficial location of the joints in these cases. A Cochrane review found that about 60 percent of patients achieved at least 50 percent improvement in pain with topical NSAIDs, which was comparable to the effect obtained with oral formulations and slightly better than that observed with topical placebo [36]. The risk of gastrointestinal, renal, and cardiovascular toxicity is much lower with topical NSAIDs as compared with its oral formulation due to the reduced systemic absorption (5- to 17-fold lower for topical diclofenac compared with oral) [37,38]. The tolerability profile is also better with topical NSAIDs, with mild skin rashes being the most commonly reported side effect. The drugs studied with the most frequency were diclofenac gel or solution and ketoprofen, applied over the affected knee two to four times daily, for the duration necessary to control symptoms. We most commonly use diclofenac gel, but the choice of topical agent may vary according to local availability and cost.

Topical capsaicin — For patients with mild OA localized to the knee or a few other joints in whom other treatments are ineffective or contraindicated, we suggest topical capsaicin. Capsaicin is a substance derived from hot chili peppers with the potential to alleviate pain through the down-regulation of the TRPV1 receptor activity on nociceptive sensory neurons and the depletion of substance P. Continued use of capsaicin results in desensitization of nociceptive fibers and inhibition of pain stimulus transmission. However, the causative role of substance P depletion on pain reduction associated with capsaicin use has come into question [39].

There are relatively few randomized controlled trials investigating topical capsaicin treatment for knee OA pain, most with a short follow-up (up to 12 weeks) and overall good methodological quality [40]. In most studies, topical capsaicin was superior to placebo, with an overall 33 percent pain reduction after four weeks in one study, which was significantly greater than placebo [41]. In a 12-week randomized, multicenter trial, 113 patients received either capsaicin 0.025% cream four times daily or placebo [42]. Capsaicin provided greater pain relief after 4 to 12 weeks and a greater number of patients on capsaicin (81 percent) compared with placebo (54 percent) were improved based on physician's global evaluation.

Local burning sensation is the most common side effect of topical capsaicin and may occur in over half of patients. However, it is usually mild to moderate and improves with continued application. In addition, topical capsaicin should not come in contact with mucous membranes, abraded skin, eyes, or genital areas. Systemic adverse effects of capsaicin are not significantly higher compared with placebo. We prefer topical NSAIDs over capsaicin in our practice due to better tolerability and stronger evidence for efficacy. However, if there is insufficient response with one agent (eg, topical NSAIDs) after a few weeks of use, a trial of the other treatment (eg, capsaicin) can be offered as some people may benefit more from one treatment than the other [43].

MODERATE/SEVERE KNEE OSTEOARTHRITIS — The management of moderate to severe knee osteoarthritis (OA) is discussed in detail separately. (See "Management of moderate to severe knee osteoarthritis".) (Related Pathway(s): Knee osteoarthritis: Management in adults.)

THERAPIES LACKING EFFICACY OR OF UNCERTAIN BENEFIT — There are several approaches that have been used to treat patients with knee osteoarthritis (OA) that we generally do not routinely use or recommend due to lack of sufficient evidence base for widespread dissemination such as nerve blocks, nerve ablation, stem cell injections, and joint distraction. In addition, there are other therapies in which the benefit remains uncertain. It would be reasonable, however, to try some of the therapies discussed below as adjunctive measures for patients who do not respond to the approach described above after consideration of potential harm, cost, and patient preference.

Insoles and other specialized footwear — There has been an interest in the use of insoles and other specialized footwear in an effort to reduce stress on osteoarthritic knee compartments and potentially slow disease progression. However, the data in support of these devices suggest limited clinical benefit overall.

Lateral wedge insoles – Due to the evidence indicating against the use of lateral wedge insoles in medial compartment knee OA, we do not routinely suggest their use. However, medially wedged insoles for patients with lateral tibiofemoral OA and valgus deformity may be reasonably tried based on limited evidence from one study of significant improvements in pain for these patients [44]. Nevertheless, there are few studies investigating medial compared with lateral wedge insoles [45].

Lateral wedge insoles have been shown to modestly reduce the external knee adduction moment and thereby reduce medial knee joint loading. However, compared with control inserts (neutral soles), lateral wedge insoles provided no clinically significant improvement in pain in patients with medial knee OA, as examined in meta-analyses including trials with both neutral and no insole control [45,46]. Moreover, a randomized trial including 200 participants with mild to moderate medial knee OA found no differences between full-length lateral wedged insole and flat insole in medial tibial and femoral cartilage volume loss and change in size of bone marrow lesions on magnetic resonance imaging (MRI) over 12 months [47]. Another randomized trial that involved prescreening to select those patients more likely to respond to insoles (ie, those who showed a ≥2 percent reduction in the knee adduction moment with insoles and without patellofemoral OA) found that lateral wedge insoles reduced pain more than control insoles [48]. However, the effect of treatment was small and likely to be of clinical significance in only a minority of patients.

Biomechanical footwear – OA guidelines had traditionally recommended stable supportive shoes solely on the basis of expert opinion. However, a number of footwear styles have been developed and/or marketed for knee OA including unloading shoes with variable-density midsoles and a lateral wedge insole; minimalist shoes that are flexible, flat, and non-heeled; and rocker-sole shoes with a thicker–than-normal sole and a convex curvature in the sagittal plane. There is limited evidence from clinical trials that these shoes offer no additional benefit on pain or clinically relevant effects on function, compared with conventional walking shoes [49-53]. A randomized trial supports guidelines recommending stable supportive shoes. It included 164 patients with moderate to severe symptomatic radiographic medial knee OA, and compared flat flexible shoes with stable supportive shoes [53]. At six months, stable supportive shoes resulted in greater improvements in knee pain on walking compared with flat flexible shoes. Although the study did not compare either intervention with usual shoes, this study suggests that stable supportive shoes may be beneficial.

Another biomechanical approach that used individualized biomechanical footwear based on gait analysis found a potential benefit for the use of convex pods to improve gait. A randomized trial including 220 patients with knee OA found that at 24 weeks of follow-up, patients who received this approach experienced a greater improvement in the mean standardized Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscore (range from 0 to 10) compared with the control footwear group (between-group difference in pain scores was -1.3 [95% CI, -1.8 to -0.9]) [54]. However, the clinical relevance of this difference remains uncertain, and the cost of this approach is considerable.

Nutritional supplements — A variety of nutritional supplements have been evaluated in the management of knee OA.

Curcumin and Boswellia serrata – Interest in the use of curcumin, commonly known as turmeric, and Boswellia serrata is largely based on limited data suggesting that these agents have antiinflammatory and analgesic properties, among others [55]. This is largely based on low-quality evidence of benefit and no evidence of increased risk of side effects compared with placebo [56,57]. Curcumin is poorly absorbed by the gastrointestinal tract; curcumin supplements formulated to enhance absorption and bioavailability are usually preferred (eg, combinations of curcumin with piperine or bioperine, a constituent of black pepper).

Data supporting the use of curcumin come from randomized trials and meta-analyses [56,57]. As an example, a trial including 70 adults with painful knee OA with ultrasound-confirmed effusion synovitis randomly assigned patients to receive Curcuma longa capsules (1000 mg daily) or placebo [57]. After 12 weeks, patients who received Curcuma longa had a greater reduction in pain as measured by both a visual analog scale (VAS; -9.1 mm [95% CI, -17.8 to -0.4 mm]) and WOMAC knee pain scale (-47.2 mm [CI, -81.2 to -13.2 mm]). Although the reduction in pain measures were statistically significant, the clinical importance is uncertain as the degree of change was of a magnitude smaller than the estimated minimum clinically important difference. Measures of effusion-synovitis volume on MRI were similar between the two groups, as were adverse events. Larger trials are needed to determine the clinical relevance of these findings.

Findings from a meta-analysis of seven randomized trials comparing Boswellia serrata extract with placebo in patients with OA suggested that Boswellia serrata extract may help relieve pain, stiffness, and function [58]. However, the quality of the trials included in the analysis was low, with unclear risk of bias in several studies.

Glucosamine and chondroitin – In our clinical practice, we recommend against glucosamine and/or chondroitin; however, we do not discourage their use for patients who are keen to take them, especially if symptomatic benefit is achieved with their use.

In general, there have been conflicting results from randomized trials evaluating the efficacy of glucosamine and chondroitin in knee OA [59]. Results from reviews with larger, methodologically sound studies found negligible effects of glucosamine hydrochloride on knee pain, while higher doses or higher-grade formulations of glucosamine sulfate (1500 mg/day) or chondroitin (800 mg/day) showed more favorable results and may have a statistically significant but small effect on symptoms compared with placebo [60-63]. As an example, in an industry-sponsored randomized trial including 604 patients with symptomatic knee OA who were followed for six months, pharmaceutical-grade chondroitin sulfate was found to be statistically superior to placebo and similar to celecoxib in reducing pain and improving function [63]. Either chondroitin (800 mg), celecoxib (200 mg), or placebo was given once daily in the evening. One important limitation of the study is the uncertain clinical relevance of the statistical significance for the primary outcomes, which were based on a degree of change from baseline on a VAS for pain (0 to 100 mm) and the Lequesne index (a composite score of pain and function). Also, the number of patients who achieved the minimal clinically important improvement of 20 mm on the VAS for pain was not different among the three groups. Other meta-analyses also suggested that glucosamine sulfate (1500 mg/day) and chondroitin (800 mg/day) may have small effects in delaying structural progression of OA with long-term use (two to three years) [64,65].

A strong placebo effect has been demonstrated in the studies involving these dietary supplements. This is well illustrated by the landmark Glucosamine/Chondroitin Intervention Trial (GAIT), in which around 60 percent of participants experienced at least 20 percent pain reduction irrespective of whether they received placebo, glucosamine hydrochloride, chondroitin, or the combination of both [66] (see "Overview of the management of osteoarthritis", section on 'Factors affecting response to therapy' and "Overview of the management of osteoarthritis", section on 'Role of placebo effect'). In another multicenter randomized trial, 164 patients with moderate to severe knee OA were treated with either chondroitin sulfate plus glucosamine or placebo [67]. At six months' follow-up, the mean reduction in the global pain score was greater in the placebo group (33 percent) compared with the chondroitin sulfate plus glucosamine group (19 percent). Limitations of the study include the small size and potentially inadequate dosing of chondroitin and glucosamine. Whether some patient subgroups may benefit more from glucosamine than others has also been investigated, but no difference from placebo was found in any of the prespecified subgroups according to baseline pain severity, body mass index (BMI), sex, presence of inflammatory signs, or radiographic severity [68]. However, it is of note that the risk of any adverse event with these supplements is low and comparable to placebo. Due to these contradictory and still uncertain data, glucosamine and chondroitin are not endorsed by OA guidelines developed by professional organizations [10,69-71].

Others – There is limited evidence supporting the use of other nutritional supplements for knee OA. We do not routinely recommend nutritional supplements such as vitamin D, diacerein, avocado soybean unsaponifiables (ASU), and fish oil due to lack of clear evidence demonstrating a clinically important benefit from these supplements.

A systematic review and meta-analysis of nutritional supplements for OA of the knee, hand, or hip including 69 studies (20 different supplements) reported clinically meaningful improvements in short-term pain reduction (≤3 months) for 7 supplements (L-carnitine supplementation, Pycnogenol, curcumin, Boswellia serrata extract, Curcuma longa extract, passion fruit peel extract, and collagen hydrolysate) compared with placebo [56]. Most of these supplements were investigated in only a limited number of small trials, and the quality of evidence for this finding was variable (very low to moderate). Six other supplements (undenatured type II collagen, ASU, methylsulfonylmethane, diacerein, glucosamine, and chondroitin) were statistically better than placebo, but it was unclear if the effects were clinically important. Among the trials reporting long-term outcomes (>6 months, n = 17), no supplement was found to have clinically important effects on pain. The meta-analysis found no increased risk of side effects of supplements compared with placebo, except for diacerein, although safety profile was investigated in only a limited number of trials. It is also important to note that most trials (64 percent) were industry funded and were considered at high or unclear risk of bias (46 and 44 percent, respectively).

In another study, vitamin D supplementation had no benefit over placebo on pain and change in tibial cartilage volume over two years in a large clinical trial [72]. A study assessing the efficacy of low- versus high-dose fish oil (0.45 and 4.5 g omega 3 fatty acids, respectively) on clinical outcomes found greater improvements in pain and function in the group receiving low-dose fish oil at two years [73]. Adverse events were common in both groups, particularly gastrointestinal events (around 60 percent in each group) such as gastrointestinal upset and reflux. Fish oil has also been studied in rheumatoid arthritis with positive results, probably through the antiinflammatory effects of the eicosapentaenoic and docosahexaenoic acids. However, its clinical benefit in OA is still unclear.

Limited evidence has also suggested that phytoflavonoids, a class of natural compounds with antiinflammatory properties, may have beneficial effects on knee OA symptoms [74-76]. Flavocoxid, a specific type of phytoflavonoid, has been associated with reports of serious adverse events related to liver injury and hypersensitivity pneumonitis, and its use is not recommended. (See "Hepatotoxicity due to herbal medications and dietary supplements", section on 'Flavocoxid'.)

Opioids — Due to the relatively high incidence of side effects such as drowsiness, dizziness, and nausea, and the potential to cause harm with long-term use, we avoid using opioids whenever possible, especially in the older adult population. In our clinical practice, we use opioids only in patients with severe pain awaiting joint replacement (ie, short-term use). We use it in the lowest dose and duration necessary to control symptoms and monitor common side effects. (See "Use of opioids in the management of chronic non-cancer pain".)

Several studies of patients with knee OA have found the efficacy of opioids with respect to pain reduction to be similar to that of NSAIDs. A meta-analysis revealed an overall small effect size (standardized mean difference [SMD] -0.28, 95% CI -0.35 to -0.20) of non-tramadol opioids on pain reduction, which corresponds to a difference of 0.7 cm on VAS (0 to 10 cm) between opioids and placebo [77]. Improvement in knee function was also small, and there was no influence of daily morphine equivalence dose on the benefits on function. Patients receiving opioids were more likely to drop out due to adverse events and more likely to experience side effects (6.5 versus 1.7 percent and 22 versus 15 percent, respectively) [77]. A network meta-analysis also did not demonstrate a difference in efficacy between potent opioids (hydromorphone and oxycodone), a less-potent opioid (tramadol), and NSAIDs in trials of at least eight weeks' duration [78]. In addition, a randomized trial including 240 patients with chronic back pain or hip or knee OA pain did not demonstrate a difference in pain-related function after 12 months of treatment with non-opioid versus opioid medications [79].

In addition to the known potential risks and harms of opioid use, there are some data to suggest an association between tramadol use and increased mortality among patients with OA. In a propensity score-matched study using data from 88,902 patients with OA, patients prescribed tramadol had a higher rate of mortality over the one-year follow-up period compared with commonly prescribed NSAIDs such as naproxen (hazard ratio 1.71 [95% CI 1.41-2.07]) [80]. These findings, however, may be susceptible to confounding by indication as the tramadol users had a higher comorbidity burden than patients receiving NSAIDs prior to propensity score matching.

Hyaluronans — The use of any intraarticular hyaluronic acid (HA) formulation is not widely recommended and not routinely used in our practice due to the lack of robust evidence demonstrating clinically relevant benefits over intraarticular placebo [7,69-71]. There has been a longstanding debate and conflicting data across trials and meta-analyses regarding the benefit of viscosupplementation (ie, intraarticular HA) for the treatment of symptomatic knee OA. The evidence from large, double-blinded, and high-quality trials indicates that intraarticular HA has a small, clinically irrelevant benefit over intraarticular placebo [81-83]. Moreover, intraarticular HA is associated with high costs and potential side effects such as pain flare-ups and joint infection, although the latter is a rare complication.

Platelet-rich plasma — Due to the lack of solid evidence for the benefit of platelet-rich plasma (PRP) injection in patients with knee OA, we do not recommend its use. Although initial evidence supporting the efficacy of PRP for knee OA symptoms has been promising [84,85], a subsequent trial has not demonstrated benefit both in terms of pain and structural changes [86]. A randomized trial including 288 patients with symptomatic mild to moderate radiographic knee OA found that, compared with saline placebo, intraarticular injections of PRP resulted in similar outcomes in terms of both pain scores and medial tibial cartilage volume loss on MRI [86]. Factors that may contribute to variability between studies include differences in the number of injections (generally one to four), interval between injections, preparation of the PRP, and volume injected [85]. Additional information on the use of PRP for OA can be found elsewhere. (See "Investigational approaches to the management of osteoarthritis", section on 'Platelet-rich plasma'.)

Acetaminophen — Due to safety concerns pertaining to acetaminophen (paracetamol) use and an increased awareness of its negligible and non-clinically significant effects on pain [69,87-90], we do not initiate treatment with acetaminophen for knee OA in our clinical practice. Data from a meta-analysis including 10 trials (3541 patients) revealed that there is high-quality evidence that paracetamol has only small, non-clinically meaningful benefits for pain in the short term [89]. This finding was further strengthened by a network meta-analysis comparing different analgesics for the treatment of OA pain, which demonstrated that paracetamol was not superior when compared with placebo irrespective of the dose (4 mm difference on a 0 to 100 mm VAS) [87]. The risk of harm of acetaminophen is usually higher with increasing dose but may also occur at doses within the therapeutic range, including gastrointestinal bleeding, liver toxicity, renal failure, and cardiovascular disease [90]. This is especially concerning due to the risk of unintentional overdose, as paracetamol is frequently combined with other common over-the-counter medications used to treat pain and cold symptoms.

Transcutaneous electrical nerve stimulation — Data on the efficacy of transcutaneous electrical nerve stimulation (TENS) in OA are conflicting [91]. Its mechanism of action is based on the gate-control theory, in which modulation of the nociceptive stimulus to the brain occurs through its presynaptic inhibition in the spinal cord dorsal horn. A Cochrane review found that the evidence regarding the efficacy for TENS was inconclusive based on the poor methodological quality of most studies, small sample sizes, and moderate to high heterogeneity between trials [91]. Another trial including 203 patients found no additional pain or function benefits from TENS, interferential currents, or shortwave diathermy compared with sham interventions in patients participating in an education and exercise training program [92]. In addition, there is evidence indicating a significant placebo component of the effect of TENS [92,93].

Acupuncture — The use of acupuncture in the management of OA is discussed elsewhere. (See "Acupuncture", section on 'Knee osteoarthritis'.)

Local heat and cold — Local application of heat using a heat pack or hot-water bottle as a self-management strategy may have beneficial short-term effects on pain in patients with knee OA [94-96]. In a small cohort study of patients with knee OA, local heat application in addition to routine management was associated with more improvements in pain and disability compared with routine management alone [96]. However, there are no robust clinical trials evaluating its effectiveness. Similarly, while not well studied, some patients may find icing of the joint useful temporarily to deal with a flare in pain or increase in swelling, for example, after an activity that has exacerbated symptoms.

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Basics topics (see "Patient education: Osteoarthritis (The Basics)" and "Patient education: Physical activity for people with arthritis (The Basics)")

Beyond the Basics topics (see "Patient education: Osteoarthritis symptoms and diagnosis (Beyond the Basics)" and "Patient education: Osteoarthritis treatment (Beyond the Basics)" and "Patient education: Arthritis and exercise (Beyond the Basics)")

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Osteoarthritis" and "Society guideline links: Meniscal injury".)

PATIENT PERSPECTIVE TOPIC — Patient perspectives are provided for selected disorders to help clinicians better understand the patient experience and patient concerns. These narratives may offer insights into patient values and preferences not included in other UpToDate topics. (See "Patient perspective: Knee osteoarthritis".)

SUMMARY AND RECOMMENDATIONS

General principles – All patients with knee osteoarthritis (OA) should be thoroughly assessed with regard to their knowledge about the disease and treatment alternatives, previous experiences with treatment, and expectations of current treatment. Patient education about OA and its treatment options can occur during the clinical encounter and can be complemented by provision of written materials. Monitoring of the patient's response to therapy should also be done on a regular basis. (See 'General principles' above.)

Approach based on clinical presentation – Patients with knee OA may fall into different categories, based on patient presentation rather than imaging, that must be considered when making treatment decisions (see 'Approach based on clinical presentation' above):

Mild knee OA – Patients with mild knee OA have low levels of or intermittent knee pain with relatively well-preserved joint function and quality of life. Nonpharmacologic therapies alone or in combination with topical therapies or analgesics on an as-needed basis are likely to provide adequate control of symptoms (algorithm 1). (See 'Mild knee osteoarthritis' above.)

Moderate/severe knee OA – Patients with moderate to severe OA have persistent pain which significantly impairs functionality, activity participation, and quality of life. Nonpharmacologic interventions are also first-line therapy, but other treatment alternatives are usually required, including oral nonsteroidal antiinflammatory drugs (NSAIDs), intraarticular glucocorticoids, duloxetine, and possibly surgery (algorithm 2). (See 'Moderate/severe knee osteoarthritis' above.)

Knee OA with one or more joints involved – The best approach for management of patients with multijoint, symptomatic OA is to prioritize therapies that address the pain at the individual level and not the joint level. (See 'Knee osteoarthritis with one or more joints involved' above.)

Patient with comorbidities – Knee OA is often comorbid with other conditions (eg, cardiovascular disease, diabetes); therapies should be chosen to minimize the potential for adverse events while optimizing function and quality of life. (See 'Patients with comorbidities' above.)

Mild knee OA (algorithm 1)

Initial nonpharmacologic measures

-Exercise – For all patients with knee OA, we recommend ongoing exercise for pain relief and joint protection (Grade 2B). There is no strong evidence on the best prescription of exercise modalities and dosage (ie, intensity, duration, and frequency). We prefer a combination of low-impact aerobic fitness training (eg, walking, cycling, rowing, and deep-water running) and lower-limb strengthening exercises. (See 'Exercise' above.)

-Weight loss – For patients with knee OA who are overweight, we suggest a calorie-restricted diet and exercise program to preserve joint structures and improve symptoms (Grade 2B). We encourage health care professionals to consult the available local community programs or refer patients to a dietitian to ensure that patients with obesity or who are overweight are offered optimal support to lose weight. (See 'Weight loss' above.)

Inadequate response to nonpharmacologic measures

-Topical NSAIDs – For patients with mild OA localized to the knee or with concomitant hand involvement, we suggest initial treatment with a topical NSAID rather than an oral NSAID (Grade 2C). The risk of gastrointestinal, renal, and cardiovascular toxicity is much lower with topical NSAIDs as compared with its oral formulation due to the reduced systemic absorption. (See 'Topical NSAIDs' above.)

-Topical capsaicin – For patients with mild OA localized to the knee or a few other joints in whom other treatments are ineffective or contraindicated, we suggest topical capsaicin (Grade 2C). (See 'Topical capsaicin' above.)

Moderate/severe knee OA – The management of moderate to severe knee OA is discussed in detail separately (algorithm 2). (See "Management of moderate to severe knee osteoarthritis".)

Therapies lacking efficacy or of uncertain benefit – There are several approaches that have been used to treat patients with knee OA that we generally do not routinely use due to lack of data demonstrating efficacy. These include therapies for which the benefit remains uncertain; thus, some may be reasonable to try as adjunctive measures for patients who do not respond to the approach described above. These include:

Insoles and footwear (see 'Insoles and other specialized footwear' above)

Nutritional supplements (see 'Nutritional supplements' above)

Opioids (see 'Opioids' above)

Hyaluronans (see 'Hyaluronans' above)

Platelet-rich plasma (PRP) (see 'Platelet-rich plasma' above)

Acetaminophen (see 'Acetaminophen' above)

Transcutaneous electrical nerve stimulation (TENS) (see 'Transcutaneous electrical nerve stimulation' above)

Acupuncture (see 'Acupuncture' above)

Local heat (see 'Local heat and cold' above)

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Topic 111177 Version 30.0

References