Patient Education and Lifestyle Modification

The authors suggest patients with symptomatic OA of the knee be encouraged to participate in self-management educational programs such as those conducted by the Arthritis Foundation, and incorporate activity modifications (e.g., walking instead of running; alternative activities) into their lifestyle. (Grade B, Level II)

Regular contact to promote self-care is an option for patients with symptomatic OA of the knee. (Grade C, Level IV)

The authors recommend patients with symptomatic OA of the knee, who are overweight (as defined by a BMI>25), should be encouraged to lose weight (a minimum of five percent [5%] of body weight) and maintain their weight at a lower level with an appropriate program of dietary modification and exercise. (Grade A, Level I)

Rehabilitation

The authors recommend patients with symptomatic OA of the knee be encouraged to participate in low-impact aerobic fitness exercises. (Grade A, Level I)

Range of motion/flexibility exercises are an option for patients with symptomatic OA of the knee. (Grade C, Level V)

The authors suggest quadriceps strengthening for patients with symptomatic OA of the knee. (Grade B, Level II)

Non-Pharmacological Management

Exercise

A - Regular knee strengthening and aerobic exercises should be encouraged and taught to patients with OA of the knees, as these improve functional ability, aerobic and endurance capacity and reduce knee pain. (Grade A, Level 1+)

Weight Reduction

A - Weight loss can result in significant changes in knee joint biomechanics with improved knee function for stair climbing and other daily activities. It is most effectively achieved by a combination of exercise and dietary control. (Grade A, Level 1+)

Hydrotherapy

A - Regular water-based exercise or exercises in the pool are recommended as these exercises reduce pain and improve physical function in patients with OA of the knees. (Grade A, Level 1++)

Manual Therapy

A - Manual therapy applied to the knee together with an exercise programme may be used to improve knee function and pain relief for patients with OA of the knee. (Grade A, Level 1+)

Mechanical Interventions

The authors suggest patients with symptomatic OA of the knee use patellar taping for short term relief of pain and improvement in function. (Grade B, Level II)

The authors suggest lateral heel wedges not be prescribed for patients with symptomatic medial compartmental OA of the knee. (Grade B, Level II)

The authors are unable to recommend for or against the use of a brace with a valgus directing force for patients with medial uni-compartmental OA of the knee. (Inconclusive, Level II)

The authors are unable to recommend for or against the use of a brace with a varus directing force for patients with lateral uni-compartmental OA of the knee. (Inconclusive, Level V)

Taping

A - Taping may be used to shift the patella medially and provide effective relief of pain in OA of the knee. (Grade A, Level 1++)

Braces and Wedges

B - Lateral wedge insoles (tilt angle of 8.5 to 11 degrees) should be used to provide pain relief for OA of the knee with medial OA symptoms. (Grade B, Level 1+)

B - Valgus knee brace and knee sleeves may be used to provide significant improvement in functional tasks and unloading of varus deformity. (Grade B, Level 1+)

Lateral wedge insoles provide significant pain relief for OA of the knee with varus deformity, while protective knee sleeve and Valgus knee braces can provide significant improvement during functional tasks (stair climbing, 6-minute walk test) by providing improved stability, proprioception and mechanical re-alignment of knee mechanics.

Complementary and Alternative Therapy

The authors are unable to recommend for or against the use of acupuncture as an adjunctive therapy for pain relief in patients with symptomatic OA of the knee. (Inconclusive, Level I)

Needle Lavage

The authors suggest that needle lavage not be used for patients with symptomatic OA of the knee. (Grade B, Level II)

TENS

B - TENS, in the form of strong burst mode with high frequency, should be used to provide short-term relief of OA of the knee pain, reduce stiffness and improve knee range of motion, with effects lasting for 4 weeks. (Grade B, Level 1+)

Interferential Current Therapy

B - Interferential current may be used to reduce pain and increase in knee range of motion for OA of the knee patients. (Grade B, Level 1+)

Other Treatment Modalities

• Thermal therapy, especially heat, has a long traditional and anecdotal history for the relief of pain, muscle soreness, and tightness, and it encourages muscle relaxation. Diathermy or deep heating of tissues and joints is commonly used to reduce pain in osteoarthritis of the knees; however there is only one study that reported significantly reduced pain after 30 sessions of Shortwave diathermy. Superficial heating with infra-red and red laser, twice daily over 10 days, was found to result in reduction of 39% on pain scale with pain relief lasting for 4 months.
• Similarly, ice therapy is also found to be statistically beneficial to reduce pain hence improve quadricep strength in patients with osteoarthritis of the knee.

Other Alternative Therapies

A - Needle electro-acupuncture may be used as an adjunct for symptomatic relief of pain and improvement of knee function. (Grade A, Level 1++)

Pain Relievers

The authors suggest patients with symptomatic OA of the knee receive one of the following analgesics for pain unless there are contraindications to this treatment:

• Acetaminophen [not to exceed 4 grams per day]
• NSAIDs

(Grade B, Level II)

The authors suggest patients with symptomatic OA of the knee and increased GI risk (Age > 60 years, comorbid medical conditions, history of peptic ulcer disease, history of GI bleeding, concurrent corticosteroids and/or concomitant use of anticoagulants) receive one of the following analgesics for pain:

• Acetaminophen [not to exceed 4 grams per day]
• Topical NSAIDs
• Nonselective oral NSAIDs plus gastro-protective agent
• COX-2 inhibitors

(Grade B, Level II)

Analgesics in OA of the Knees

Oral Paracetamol

A - Paracetamol (acetaminophen) should be considered as the first line of treatment for relieving pain and improving physical functioning in OA (Towheed et al., 2003; Jordan et al., 2003; Altman et al., 2000). (Grade A, Level 1+)

NSAIDs

A - Non-selective NSAIDs should be used for the acute relief of pain and improvement in function for as short a period as possible. The benefits of using NSAIDs should be weighed against the potential adverse reactions, especially with long-term use, in individuals at risk (Watson et al., 2000). (Grade A, Level 1+)

GPP - The selection of a NSAID for prescription for OA knee should be based upon relative safety, patient acceptability and cost effectiveness. (GPP)

GPP - Patients who develop hypersensitivity reactions to NSAIDs are usually able to tolerate COX-2 selective inhibitors. These should preferably be prescribed following demonstration of tolerance through supervised drug provocation tests. (GPP)

A - Patients with moderately high risk for gastroduodenal bleeds should receive concomitant GPA when using nonselective NSAIDs (Gabriel, Jaakkimainen, & Bombadier, 1991).

Risk factors for gastrointestinal complications include (Gabriel, Jaakkimainen, & Bombadier, 1991):

• Age greater than 60 years
• Previous history of gastrointestinal events (e.g., peptic ulcer disease)
• Concomitant corticosteroid use

(Grade A, Level 1+)

A - Recommended prophylactic GPA against gastroduodenal ulcers include (Rostom et al., 2002):

• Standard dose of proton-pump inhibitors (omeprazole 20 mg once daily)
• Misoprostol 400-800 mcg/day
• Double dose of H2-receptor antagonists (famotidine 40 mg bd, ranitidine 300 mg bd)

(Grade A, Level 1+)

COX-2 Selective Inhibitors

A - COX-2 selective inhibitors may be used acutely in the reduction of pain from OA of the knees (Bombardier et al., 2000; Silverstein et al., 2000; Schnitzer et al., 2004). Although these drugs have relatively lower risk of gastroduodenal adverse effects, long-term use has been associated with myocardial and cerebral infarction (Bresalier et al., 2005; Solomon et al., 2005; Nussmeier et al., 2005). (Grade A, Level 1+)

GPP - When NSAIDs (including both COX-2 selective and non-selective NSAIDs) are needed for the management of an individual patient, they should be prescribed at the lowest effective dose. The duration of treatment should be periodically reviewed and kept as short as possible. (GPP)

GPP - All NSAIDs should not be prescribed in patients who have recently undergone CABG surgery and revascularization procedures. (GPP)

GPP - The benefits and risks of celecoxib and etoricoxib should be carefully assessed before they are prescribed to any individual patient, taking into consideration other available therapeutic options. (GPP)

GPP - Celecoxib or etoricoxib should not be prescribed for patients with established ischaemic heart disease, stroke or congestive heart failure. (GPP)

GPP - Caution should be exercised when prescribing celecoxib or etoricoxib to patients who have the following risk factors: hypertension, hyperlipidaemia, diabetes and smoking, as well as patients with peripheral arterial disease. (GPP)

GPP - Etoricoxib should not be prescribed for patients with hypertension whose blood pressure has not been adequately controlled. (GPP)

NSAIDs with Preferential COX-2 Inhibition

A - Meloxicam and nimesulide are two NSAIDs with preferential COX-2 inhibition which may be used in the short term relief of pain from OA of the knees (Bianchi & Broggini, 2003; Herrera & Gonzalez, 2003; Chang et al., 2001; Hawkey et al., 1998). (Grade A, Level 1+)

Tramadol

A- Tramadol may be used as an alternative to NSAIDs for pain relief and improvement in physical functioning, especially where the risks of adverse effects from NSAIDs outweigh the benefits (Cepeda et al., 2006; Babul et al., 2004). (Grade A, Level 1+)

Oral Corticosteroids

GPP - Oral corticosteroids are not indicated for management of knee OA. (GPP)

Cost-Effectiveness Issues

GPP - Pain medications are important in managing OA symptoms and should be used concurrently with nutritional, physical, and educational interventions. Doctors should consider efficacy, adverse side effects, dosing frequency, and cost to the patient when recommending OA treatments. (GPP)

C - For mild to moderate OA pain, paracetamol is the drug of choice as it is cost-effective and has minimal side-effects. In treating moderate to severe OA pain, the use of NSAIDs and COX-2 specific inhibitors (for a patient who is at high risk of adverse upper gastrointestinal events) should be considered only if the patient is not responding to paracetamol (Kamath et al., 2003). (Grade C, Level 2+)

Pain Relievers

The authors suggest patients with symptomatic OA of the knee and increased GI risk (Age > 60 years, comorbid medical conditions, history of peptic ulcer disease, history of GI bleeding, concurrent corticosteroids and/or concomitant use of anticoagulants) receive one of the following analgesics for pain:

• Acetaminophen [not to exceed 4 grams per day]
• Topical NSAIDs
• Nonselective oral NSAIDs plus gastro-protective agent
• Cyclooxygenase-2 inhibitors

(Grade B, Level II)

Topical NSAIDs and Medications

A - Topical NSAIDs can be considered for the short-term symptomatic relief of pain in OA. Side effects of topical NSAIDs are usually minor. (Grade A, Level 1+)

A - Topical capsaicin may also be considered in relieving pain due to OA. Transient local burning sensation may occur at the site of application. (Grade A, Level 1+)

Complementary and Alternative Therapy

The authors recommend glucosamine and/or chondroitin sulfate or hydrochloride not be prescribed for patients with symptomatic OA of the knee. (Grade A, Level I)

Glucosamine/Chondroitin in the Treatment of OA

Efficacy

Neither glucosamine hydrochloride nor chondroitin sulfate alone has been shown to be more efficacious than placebo for the treatment of knee pain.

B - Patients who have failed to respond to analgesics and nonpharmacologic measures and want to try glucosamine may be given glucosamine sulphate 1500 mg once daily as pharmacologic studies suggest that maximal benefit is better achieved at this dose (Persiani et al., 2005). (Grade B, Level 2++)

B - Patients who are already taking glucosamine and report improvement in symptoms may discontinue after a period of 6 months as evidence suggests that regular use for more than 6 months is no more effective than placebo in the relief of joint pain (Cibere et al., 2004). (Grade B, Level 1+)

GPP - Patients allergic to shellfish should be warned about possible allergic reactions to glucosamine. (GPP)

Intra-Articular Injections

The authors suggest intra-articular corticosteroids for short-term pain relief for patients with symptomatic OA of the knee. (Grade B, Level II)

The authors cannot recommend for or against the use of intra-articular hyaluronic acid for patients with mild to moderate symptomatic OA of the knee. (Inconclusive, Level I and II)

Intra-articular Injections

Viscosupplementation

B - Viscosupplementation can be used for treatment of OA of the knee, where general measures or systemic therapies have failed or are contraindicated. It is effective with beneficial effects on pain, function and patient global assessment; and at different post injection periods but especially at the 5 to 13 week post injection period when compared with placebo (Bellamy et al., 2006). (Grade B, Level 1+)

GPP - In Singapore, data on effectiveness are too limited to allow any conclusions to be drawn regarding cost-effectiveness of viscosupplementation. However, in view of the relative high cost of viscosupplementation and its comparable efficacy with other forms of systemic intervention, it should be considered only if general measures and systemic therapies have failed or are contraindicated. (GPP)

Hyaluronic acid products had more prolonged effects than intra-articular corticosteroids.

Sample-size restrictions preclude any definitive comment on the safety of the hyaluronic acid class of products. However, within the constraints of the trial designs employed, no major safety issues were detected.

Intra-Articular Corticosteroid

B - In patients with knee OA who are symptomatic despite general measures and systemic therapies, evidence supports short term (up to two weeks) improvement of symptoms from intra-articular corticosteroid injection (Arroll & Goodyear-Smith, 2004). (Grade B, Level 1)

GPP - Regular use of intra-articular steroids is not recommended for OA of the knees in the general practice setting. (GPP)

Note: This guideline covers treatment of OA of the knee in adults up to, but not including, knee replacement.

Surgical Intervention

The authors recommend against performing arthroscopy with debridement or lavage in patients with a primary diagnosis of symptomatic OA of the knee. (Grade A, Level I and II)

Arthroscopic partial meniscectomy or loose body removal is an option in patients with symptomatic OA of the knee who also have primary signs and symptoms of a torn meniscus and/or a loose body. (Grade C, Level V)

The authors cannot recommend for or against an osteotomy of the tibial tubercle for patients with isolated symptomatic patello-femoral OA. (Inconclusive, Level V)

Realignment osteotomy is an option in active patients with symptomatic unicompartmental OA of the knee with malalignment. (Grade C, Level IV and V)

The authors suggest against using a free-floating interpositional device for patients with symptomatic unicompartmental OA of the knee. (Grade B, Level IV)

Surgery

GPP - A referral to the orthopaedic surgeon should be made when conservative management mentioned previously has failed. (GPP)

Cost-Effectiveness Issues

C - For patients who have failed medical therapy and who are suitable for surgical interventions, both unicompartmental and total knee arthroplasty are cost effective in terms of quality of life gain (Soohoo et al., 2006; Slover et al., 2006; Lavernia, Guzman, & Gachupin-Garcia, 1997). (Grade C, Level 2+)

Note: Refer to the original guideline document for diagnosis-specific surgical options.

Levels of Evidence for Primary Research Question¹

1. A complete assessment of quality of individual studies requires critical appraisal of all aspects of the study design.
2. A combination of results from two or more prior studies.
3. Studies provided consistent results.
4. Study was started before the first patient enrolled.
5. Patients treated one way (e.g., cemented hip arthroplasty) compared with a group of patients treated in another way (e.g., uncemented hip arthroplasty) at the same institution.
6. The study was started after the first patient enrolled.
7. Patients identified for the study based on their outcome, called "cases" (e.g., failed total hip arthroplasty) are compared to those who did not have outcome, called "controls" (e.g., successful total hip arthroplasty).
8. Patients treated one way with no comparison group of patients treated in another way.

Grading the Recommendations

A: Good evidence (Level I Studies with consistent finding) for or against recommending intervention.

B: Fair evidence (Level II or III Studies with consistent findings) for or against recommending intervention.

C: Poor quality evidence (Level IV or V) for or against recommending intervention.

I: There is insufficient or conflicting evidence not allowing a recommendation for or against intervention.

Levels of Evidence

Grades of Recommendation

Both groups performed searches of electronic databases to collect the evidence; AAOS also performed hand-searches of published literature (both primary and secondary sources). AAOS provides a description of methods used to collect and select the evidence, which includes the names of the electronic databases searched (Cochrane and PubMed), the date up to which evidence was searched for (February 22^nd, 2008), inclusion/exclusion criteria applied, the number of source documents, and search strategies used.

To assess the quality and strength of the evidence, both groups used weighting according to a rating scheme and provide the scheme. AAOS and SMOH performed a review of published meta-analyses to analyze the evidence, as well as a systematic review (AAOS' systematic review incorporated evidence tables). AAOS also performed a meta-analysis of randomized controlled trials, and it provides a description of methods used to analyze the evidence.

With regard to cost-analyses, AAOS did not perform a formal cost analysis and did not review published cost analyses. SMOH, in contrast, reviewed published cost analyses and summarized cost-effectiveness issues in the "Major Recommendations" field as well as in the original guideline document.

Both groups employed expert consensus (AAOS specifies the nominal group technique) to formulate their recommendations. The strength of the recommendations was graded by both groups, and the rating schemes are provided. Peer review was used as a method of guideline validation by both groups; AAOS specifies that it used internal and external peer review. AAOS also provides a description of the peer review process.

This guideline and the systematic review upon which it is based were funded by the AAOS, with additional funding received from the Arthroscopy Association of North American (AANA) and the American Orthopedic Society of Sports Medicine (AOSSM).

Singapore Ministry of Health

Effective treatment of OA of the knee in adults

• Appropriate management of OA of the knees
• Reduction in pain and improved physical functioning

Individuals with OA of the knee often complain of joint pain, stiffness, and functional deficits. The aim of treatment is pain relief and improvement or maintenance of the patient's functional status. Long term results were often not available and adverse events varied by study (frequently they were not reported) in the literature available for this guideline. Most treatments are associated with some known risks, especially invasive and operative treatments. Therefore, discussion of available treatments and procedures applicable to the individual patient rely on mutual communication between the patient and physician, weighing the potential risks and benefits for that patient.

Oral Paracetamol

Gastrointestinal discomfort was more frequent with NSAIDs than with paracetamol.

Non-Selective NSAIDs

• Gastrointestinal (gastroduodenal perforations, ulcers and bleeds, small bowel perforations)
• Renal (hyperkalaemia, hypertension, oedema, acute renal insufficiency)
• Hypersensitivity reactions including periorbital angioedema, urticaria, rhinitis or attacks of asthma

Emerging evidence suggests that there are cardiovascular risks associated with non-selective NSAIDs as well, although this could not be conclusively demonstrated in a recent meta-analysis.

COX-2 Selective Inhibitors

• Supervised drug provocation tests by specialists trained in allergy/immunology are recommended before using COX-2 inhibitors in NSAID-sensitive individuals.
• Although these drugs have relatively lower risk of gastroduodenal adverse effects, long-term use has been associated with myocardial and cerebral infarction.
• The COX-2 selective inhibitors have recently been found to be associated with increased cardiovascular events, leading to the withdrawal of rofecoxib in Singapore in October 2004.
• In addition to the increased cardiovascular risks, reports of severe cutaneous reactions (Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis) among patients taking valdecoxib resulted in the drug being removed from the market in several countries including Singapore in April 2005.
• All NSAIDs should not be prescribed in patients who have recently undergone CABG surgery and revascularization procedures.
• Celecoxib or etoricoxib should not be prescribed for patients with established ischaemic heart disease, stroke or congestive heart failure.
• Caution should be exercised when prescribing celecoxib or etoricoxib to patients who have the following risk factors: hypertension, hyperlipidaemia, diabetes and smoking, as well as patients with peripheral arterial disease.
• Etoricoxib should not be prescribed for patients with hypertension whose blood pressure has not been adequately controlled.

NSAID with Preferential COX-2 Inhibitors

Although it is indicated for the short-term relief of joint pain, there have been reports of elevated liver enzymes and hepatitis.

Tramadol

Nausea/giddiness

Glucosamine/Chondroitin

Patients allergic to shellfish should be warned about possible allergic reactions to glucosamine.

Viscosupplementation

Viscosupplements were comparable in efficacy to systemic forms of active intervention (e.g., NSAIDs), with more local reactions (post injection inflammation) but fewer systemic adverse events.

Topical NSAIDs and Medications

Topical capsaicin may cause local burning sensation, and this may limit its use in some patients.

Contraindications vary widely based on the treatment administered. Therefore, discussion of available treatments and procedures applicable to the individual patient rely on mutual communication between the patient and physician, weighing the potential risks and benefits for that patient.

None provided