Management of osteoarthritis of the knee

What is osteoarthritis and how common is it?

Osteoarthritis is a painful chronic joint disease characterised by structural changes to the whole joint, including loss of articular cartilage, development of osteophytes, synovial inflammation, subchondral bone changes, meniscal damage, muscle weakness, and ligamentous laxity. It results from a complex interplay of genetic, metabolic, biomechanical, and biochemical factors. At the knee, osteoarthritis most commonly affects the medial tibiofemoral and patellofemoral joint compartments.

The reported incidence and prevalence of osteoarthritis of the knee varies, depending on population characteristics and disease definition. There are few population based incidence studies. The longest and most recent reported a relatively low annual cumulative radiographic incidence of 2.3% in middle aged women over a 15 year period.^w1 In a systematic review, prevalence rates of radiographic disease ranged from 4.3% to 78.6%, whereas rates were lower for symptomatic disease (3.2-13.5%).^w2

Who gets osteoarthritis?

Osteoarthritis of the knee is more common in women and older people.^w3 Racial and ethnic differences also exist, with higher rates in black and Chinese people than in white people.^w3Systemic and local risk factors have been identified (fig 1⇓), with obesity and joint injury (particularly anterior cruciate ligament and meniscal injuries in sports people) being important modifiable factors. This last risk factor means that a proportion of those affected will be young active people in their 30s and 40s. Public health strategies targeted towards weight reduction and prevention of knee injuries could prevent large numbers of people developing the condition. Strong longitudinal evidence shows that knee malalignment (varus for medial knee osteoarthritis and valgus for lateral knee osteoarthritis) and obesity increase the risk of structural disease progression in those with established disease.^w3 In contrast, few studies have examined risk factors for functional decline and disability.

Fig 1 Risk factors for osteoarthritis of the knee and related disability. Modified from Suri and colleagues,^w3 with permission from Elsevier and the American Academy of Physical Medicine and Rehabilitation

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How is osteoarthritis diagnosed?

Clinically, osteoarthritis is diagnosed on the basis of a history and physical examination. Radiography is used to confirm clinical suspicion and exclude other conditions. When radiography is used along with physical examination, sensitivity and specificity are 91% and 86%, respectively.^w4 The osteoarthritis task force of the European League against Rheumatism suggests six criteria for a confident clinical diagnosis of osteoarthritis of the knee (box 1).1

Magnetic resonance imaging does not help in decisions about current interventions for osteoarthritis of the knee and should not be performed unless it will change management. This test may be useful when considering rare differential diagnoses such as osteochondritis dissecans, pigmented villonodular synovitis, or avascular necrosis (box 2). Inappropriate use of magnetic resonance imaging can lead to increased detection of incidental meniscal tears, which are common in older people,^w5 and result in unnecessary arthroscopic knee surgery.

What are the principles of prevention and management?

Management of osteoarthritis of the knee has traditionally focused on treating pain and disability. However, a broader approach that includes prevention (reduction of risk factors—especially overweight or obesity, joint injury, and potentially smoking and vitamin D deficiency—to reduce disease incidence) and interventions that slow down disease progression is now recommended. Optimal management requires a combination of conservative non-drug and drug treatments, with surgery reserved for severe clinical disease with structural changes.2 Because the condition is chronic, education, self help, and patient driven treatments are important.

Holistic assessment of the patient’s medical, social, and psychological needs can enable a tailored approach to treatment formulated in partnership with the patient (table⇓).3 4 The risks and benefits of treatment options should be communicated to patients in ways that can be understood. Periodic monitoring (every three months) for effects of treatment on pain, function, psychological status, and quality of life—as well as metrics of intervention, including body weight and muscle strength—can maximise treatment adherence and enable management to be tailored to the patient’s changing needs.4

What are the conservative treatment options?

To ensure safe and effective delivery of the many conservative non-drug treatments suitable for osteoarthritis of the knee, a multidisciplinary approach is needed, with judicious referral to allied health practitioners according to the patient’s needs and the healthcare setting (table). Core conservative treatments for all patients include education and exercise, with weight loss for those who are overweight or obese.

Education about the disease process, pain mechanisms, and treatment options can be delivered in various ways, including informal discussion with the healthcare provider, provision of written materials, support groups, national association websites, and referral to self management programmes. However, meta-analyses show that in isolation these programmes have negligible effect sizes.5

Exercise is essential for all patients, irrespective of disease severity, age, comorbidity, pain severity, or disability. Meta-analyses show small to moderate effect sizes with exercise for pain and function,6 similar to those achieved with analgesics and non-steroidal anti-inflammatory drugs (NSAIDs).5 A Cochrane review found that, compared with fewer than 12 supervised exercise sessions, 12 or more directly supervised exercise sessions with a health professional significantly improved pain (effect size 0.46) and function (0.45) (pain 0.28, function 0.23).6 Local muscle strengthening and general aerobic exercise are recommended,2 4 7 whereas aquatic exercise may be better for people with serious mobility and functional limitations or those who cannot exercise on land.^w6 Tai chi is gaining popularity, and a systematic review of randomised controlled trials (RCTs) found encouraging but limited and not necessarily high quality evidence of benefit.^w7 Although exercise is beneficial, sports that involve twisting and high impact activities such as running should be avoided. Instead, advise younger active people who develop osteoarthritis after a knee injury to modify their activity and participate in low impact sports such as cycling, rowing, swimming, and deep water running. Finally, adherence to exercise and physical activity is vital for long term benefits (box 3).8

A meta-analysis of a limited number of RCTs showed that a reduction in body weight of at least 5% at a rate of 0.24% per week over 20 weeks in overweight and obese people improved pain and disability, although the effect sizes were small (0.20-0.23).9 A high quality RCT also showed that weight loss improved all cause mortality in overweight or obese people with knee osteoarthritis by 10%.^w8 Furthermore, a computer simulation model of knee osteoarthritis and obesity using national US census and obesity data showed that a 0.6 unit reduction in mean body mass index (about 1.7 kg in a 1.7 m tall person) would reduce total knee replacements over the remaining lifespan of this population by 1.9%.^w9 Ottawa Panel guidelines have been developed specifically for overweight or obese people with osteoarthritis. These graded recommendations are based on a systematic review of evidence (RCTs, controlled clinical trials, cohort studies, and head to head studies) that consider the strength of evidence and rigour of experimental design. The review showed that, compared with either intervention alone or control, a combination of physical activity (aerobic exercise plus or minus strength training) and a weight reducing diet produced the most benefit on a range of clinical outcomes, with highest level recommendations for pain relief, functional status, strength, and quality of life.10 The panel recommends weight loss before weight bearing exercise is implemented to maintain joint integrity. A recent longitudinal study found that significant weight loss is accompanied by loss of leg muscle tissue and strength, so strengthening exercise should be undertaken alongside weight loss strategies.^w10

A variety of other interventions may be useful depending on the patient’s presentation and preferences. Despite gait aids being widely recommended, the first RCT of cane use has only just been published.^w11 It found that compared with no cane use, two months of daily cane use reduced pain and improved function (effect size 0.18 and 0.13, respectively). A recent RCT found that, compared with flat insoles, lateral wedge insoles had no effect on symptoms or cartilage loss over 12 months.11 RCTs show that unloading knee braces can improve malalignment and improve symptoms,12 ^w12 but their use in clinical practice has been limited by important patient factors including adherence, comfort, and fitting.^w12 A small number of RCTs have shown that medially directed knee taping by a physiotherapist can reduce pain.7 A systematic review of 12 RCTs found that the addition of passive manual mobilisations to an exercise programme produced superior pain relief (effect size 0.69) to strengthening exercise (0.38) or combination exercise (0.34) alone.13

Because psychological factors can influence the pain experience, interventions such as cognitive behavioural therapy (training in pain coping skills) are recommended for some patients.7 However, the evidence is limited; a meta-analysis identified few clinical trials of cognitive behavioural therapy in knee arthritis and the effect size for pain reduction was small (0.18).14 The number of RCTs of acupuncture in the treatment of osteoarthritis of the knee has increased. These show significant and clinically relevant reductions in pain, although much of this is due to expectation (placebo effects).15 American College of Rheumatology guidelines recommend acupuncture only for patients with moderate to severe pain who are candidates for joint replacement but are unwilling or unable to have the operation.7 Similar recommendations were made for transcutaneous electrical nerve stimulation.7

What drugs are available to control pain in osteoarthritis of the knee?

Analgesics can be useful. Paracetamol (acetaminophen), in doses of up to 4 g/day, is currently recommended for the initial treatment of mild to moderate pain in osteoarthritis of the knee.5 However, because of concerns about the risk of hepatotoxicity, an advisory committee of the US Food and Drug Administration recently recommended that the maximum adult daily dose should be less than 4 g/day and that the content in single doses of over the counter analgesics be limited to 650 mg.^w13 A systematic review of RCTs that provided a head to head comparison between paracetamol and NSAIDs showed better efficacy and patient preference for NSAIDs, although side effects were greater.5 No good evidence supports one NSAID over another with regard to efficacy for symptoms. Cardiovascular safety concerns with highly potent cyclo-oxygenase-2 selective inhibitors have led to some of these drugs being taken off the market and have drawn attention to similar concerns for non-selective NSAIDs as well as gastrointestinal safety risks. Practitioners must therefore be aware of the warnings, precautions, and contraindications associated with the use of these agents. If it is deemed necessary to prescribe an oral NSAID for people with risk factors for gastrointestinal toxicity, consider the use of a cyclo-oxygenase-2 selective inhibitor or combined use of a non-selective NSAID with a gastroprotective agent (proton pump inhibitor). For people over 75 years, the American College of Rheumatology strongly recommends the use of topical rather than oral NSAIDs (box 4).7

Because some people with osteoarthritis of the knee also have depression and neuropathic pain symptoms (shooting or burning pain, pins and needles), the role of centrally active agents, including selective serotonin and noradrenaline reuptake inhibitors, has been of interest. At this stage, duloxetine is the only agent to have been examined in a high quality RCT.16 In this study, 65% of participants in the duloxetine group reported more than a 30% reduction in pain compared with 44% in the placebo group.16 This was the result of a primary analgesic effect and not elevation in mood or changes in anxiety or depression.16 These centrally active agents may be useful in subgroups of people with osteoarthritis of the knee.

Are intra-articular injections beneficial in osteoarthritis?

Intra-articular corticosteroids are used widely in the management of osteoarthritis of the knee. A Cochrane review found that the reduction in pain lasts for only one to two weeks.17 Given this short duration of benefit, the cost, and the potential adverse effects, their use may not be merited in a chronic disease such as osteoarthritis. Despite their appeal for use in patients with clinical features of inflammation (such as a large effusion), the evidence to support this is limited. However, they do have a role in patients who also have pseudogout and calcium pryophosphate dihydrate crystals.

Intra-articular injections of viscosupplements (hyaluronic acid) usually given weekly for three to five weeks, have been extensively researched. A recent meta-analysis found that trials are generally of low quality and that viscosupplementation is associated with a small and clinically irrelevant reduction in pain and an increased risk of serious adverse events.18 A recent RCT showed a marked carryover effect for at least one year and that symptoms improved between cycles, compared with placebo, suggesting that repeated injection cycles might be effective.19

New drugs for osteoarthritis of the knee

Newer analgesics, including nerve growth factor inhibitors, are being developed. High quality RCTs have shown that these drugs reduce pain in osteoarthritis of the knee.20 However, this optimism has been clouded by potential safety concerns—a small number of patients treated with tanezumab have developed rapid joint destruction.^w14

Unfortunately, none of the drugs used in osteoarthritis of the knee has convincing structural disease modifying efficacy. New drugs are being developed for osteoarthritis, with trials mainly testing pro-anabolics (growth factors and hormones), with a modest selection of anti-catabolics (interleukin 1, inhibitor of κB kinase (IκK)), and inducible nitric oxide synthase inhibitors) and cell therapy (mainly mesenchymal stem cells from bone marrow or adipose tissue).^w15

What is the evidence for glucosamine and other complementary medicines?

The most commonly used alternative treatment is glucosamine. In RCTs, glucosamine has a similar effect to placebo on pain, with industry independent trials showing smaller effects than commercially funded ones.5 Evidence for a possible structure modifying effect remains controversial. In contrast, a meta-analysis (just three RCTs of two years’ duration) found that chondroitin had a small effect on symptoms and structure (effect size 0.23).21 A Cochrane review of herbal therapy in osteoarthritis found two studies with promising results for avocado soybean unsaponifiables,22 and there is some low level evidence of efficacy for diacerein, rosehip powder, and methylsufonylmethane.5 However, high quality trials are urgently needed before any conclusions can be drawn about the usefulness of such treatments. American College of Rheumatology guidelines conditionally recommend that healthcare providers do not use nutritional supplements (such as glucosamine) or topical capsaicin.7

What is the role of surgery?

The surgical treatment of choice depends mainly on symptoms, disability, radiographic severity, and the patient’s age. The American Academy of Orthopaedic Surgeons recommends that arthroscopic lavage or debridement (or both) and meniscal resection be performed only in patients with mechanical symptoms, such as sudden onset of inability to fully extend the knee or repeated disabling catching or locking.23 This operation has no demonstrable effect on pain in osteoarthritis of the knee, with the latest RCT showing similar benefits to optimised physical and medical treatment.24

Joint arthroplasty is reserved for patients with severe disease defined as persistent moderate to severe pain, functional limitation, and reduced quality of life despite optimal conservative treatment, together with radiological disease. Patients should be referred to an orthopaedic surgeon at the time when joint replacement is needed and preferably before substantive functional decline has occurred because this may not be regained after surgery. Although there are no RCTs, higher quality prospective studies of consecutive unselected patients find that joint arthroplasty is generally successful, with 80% of patients reporting reductions in pain.^w16 Weight loss before surgery is important because obesity increases the risk of surgical complications and is associated with poorer longer term outcomes.^w17 Preoperative exercise for two to three months can optimise the physical status of patients awaiting joint replacement. It is not clear whether this enhances postoperative functional recovery—a recent meta-analysis of 12 quasi-randomised or randomised controlled trials found no benefits.^w18 However, the authors thought that the exercise programmes in these trials had poor therapeutic validity and that this may have masked the potential benefits.

In patients under 60 years, the main concern in performing joint arthroplasty is implant wear because revision arthroplasty is less successful than primary arthroplasty. Although there is no definitive answer as to how young is too young for this surgical procedure, the decision should be based on whether benefits outweigh risks for each individual. Only low impact activities such as cycling, swimming, and walking are recommended after joint arthroplasty because implant wear seems to be partly related to the amount and type of activity. An alternative operation in younger or more active patients with unicompartmental disease is a high tibial osteotomy, which decreases symptoms, slows down the osteoarthritis process, and delays the need for arthroplasty by unloading the osteoarthritic compartment. A recent meta-analysis of cohort studies found that nine to 12 years after a valgus high tibial osteotomy only 16% of patients had needed joint arthroplasty.25