Which are the most beneficial therapies for osteoarthritis of the knee? Dr Kelsey Jordan (left) and Dr Nigel Arden examine the evidence

Osteoarthritis (OA) is the most common type of joint disorder in the western world and is associated with significant disability and impaired quality of life. It predominantly affects the hands, knees, hips and the facet joints of the lumbar spine.

The World Health Organization ranks OA the fourth most serious health problem in women, measured by disability-adjusted life years, and the eighth most serious in men.1 It is therefore not surprising that OA has an impact on both primary and secondary care. Consequently, a shared-care approach to treatment is needed.

Knee OA can be demonstrated radiographically in 30% of individuals over 65 years of age, and is more common in women than in men.2 Around one-third of radiographic changes are symptomatic, and approximately 30,000 knee arthroplasties are performed in the UK each year to treat knee OA.3

Knee OA accounts for approximately 5000-6000 consultations per year in the average PCG and direct costs to the NHS are about £320 million per year.

The main risk factors for knee OA are obesity, a genetic predisposition, occupational or sporting activities and previous injury, including arthroscopy.

Treatment strategies can be categorised as nonpharmacological, pharmacological or intra-articular therapies. Figure 1 (below) is an algorithm for the management of patients with knee OA.

Figure 1: Algorithm for the management of osteoarthritis of the knee
management algorithm

Nonpharmacological treatments

Education

Education should form an integral part of the management of patients with knee OA. A meta-analysis of 10 trials has shown that education (understanding what OA is and the importance of exercise and weight reduction) in the form of targeted education (computer-assisted learning or self-care programmes) can improve joint pain, although it has little effect on disability.4

Physiotherapy

Physiotherapy is the cornerstone of treatment in knee OA. Physiotherapists use two main techniques: specific joint strengthening and range of motion exercises, and general aerobic conditioning. Ideally, all patients newly diagnosed with knee OA should see a physiotherapist to be shown quadriceps strengthening exercises to do at home. Several randomised controlled trials (RCTs) have shown benefit in reduction in pain and disability. In 191 men and women with knee pain, a simple quadriceps strengthening programme demonstrated improvement.5

In a further RCT, 439 patients with confirmed knee OA were assigned to undergo aerobic or resistance exercise or receive health education. Both forms of exercise improved measures of self-reported disability, pain and physical performance compared with health education.6

Exercise has an additive effect when used with analgesics.

A recent Cochrane systematic review also reports on the benefits of transcutaneous electrical nerve stimulation (TENS) in pain control in knee osteoarthritis.7 Physiotherapists commonly use this mode of therapy for additional pain control.

Occupational therapy

The use of walking aids, joint braces and taping of the joint have long been adjuncts to treatment. Although there are few trials concerned with these approaches, anecdotal evidence suggests positive effects and uses in terms of both pain and disability.

Pharmacological treatments

Simple analgesics

Many patients with knee OA use paracetamol bought over the counter or on prescription; it has few serious interactions and is a safe and effective medicine, particularly in the elderly.

Paracetamol is safe in long-term use and may also be as effective as ibuprofen in the short term. Guidelines published by the European League Against Rheumatism (EULAR) and also joint guidelines produced by the British Society for Rheumatology and the RCP have recommended its use as the first line oral analgesic.8,9

NSAIDs

It is accepted that there is a substantial mortality risk associated with the use of NSAIDs. It has been calculated that in a PCG caring for 100,000 patients, 24 will experience an NSAID-related gastrointestinal bleed each year, and the risk of a bleed rises with age, up to 1 in 110 in the very elderly.

Many community studies of OA have shown that a large proportion of patients are taking NSAIDs, often without coprescription of simple analgesics.

Many studies have shown a variety of NSAIDs to be more beneficial than placebo for pain control. However, a recent Cochrane systematic review found that there is often no difference in efficacy between different NSAIDs taken in high doses.10

The review also noted that low-dose naproxen and ibuprofen were less effective than other NSAIDs, and that in several comparison studies indomethacin was found to be more toxic than other NSAIDs.

More recently, there has been speculation about the benefit of the cyclo-oxygenase 2 (Cox-II) inhibitors over conventional NSAIDs. Large trials comparing the Cox-II inhibitors celecoxib and rofecoxib with conventional NSAIDs demonstrated a 50% reduction in perforations, ulcers and bleeds,11,12 and a reduction in pain equal to that of the comparator NSAIDs.13,14 However, the reduction in perforations, ulcers and bleeds is lost if cardioprotective aspirin is used. NICE has recently published guidance for the use of the Cox-II selective inhibitors.15

NSAIDs should be used only for patients in whom a trial of simple analgesics and physiotherapy has failed.

Glucosamine sulphate

A recent Cochrane review supported the use of glucosamine sulphate in knee OA.16 In pooled data from 16 RCTs, which studied a total of 2029 adults, a clinically significant reduction in pain and improvement in function were noted in those taking glucosamine.

Only four RCTs compared an NSAID (three of low-dose ibuprofen 1200 mg and one of piroxicam 20 mg) with glucosamine. Of these RCTs, two showed equivalent results and two superior results with glucosamine.

In 12 RCTs glucosamine produced superior results to placebo. Side-effects were minimal and they abated when the drug was discontinued.

The mechanism of action of glucosamine sulphate is unknown but it is an essential part of the articular cartilage and is thought to have chondroprotective and perhaps also anti-inflammatory effects.

Evidence from a 3-year prospective double-blind RCT of 212 patients suggests that glucosamine sulphate can protect the cartilage from further damage and act as a disease-modifying agent.17

Topical treatments

Topical treatments can be used as an adjunct to oral analgesics or as first-line analgesia in patients unable to tolerate conventional drug treatments. The two most commonly used are topical NSAIDs and capsaicin.

A meta-analysis of 76 placebo-controlled trials concluded that 65-71% of patients treated with topical NSAIDs had a good response compared with only 30-39% of patients receiving placebo.18 These drugs were also deemed to be safe.

The EULAR guidelines suggest using these drugs in patients in whom simple analgesics have failed.8

Capsaicin, a compound derived from chilli peppers, reversibly depletes stores of substance P from sensory nerve endings and thereby modulates the pain response from the peripheral nerves to higher centres. A review found that capsaicin was more effective than placebo in controlling pain in osteoarthritis.19

Intra-articular therapies

Corticosteroids

Several trials have looked at the use of intra-articular corticosteroids in knee OA. They suggest that injection gives a good short-term benefit, up to 4 weeks, but that this is not sustained over long periods.20, 21

It has always been thought that patients with effusion would have a better outcome following intra-articular corticosteroid injection, but there is little evidence to support this. Therefore, a therapeutic trial of an intra-articular corticosteroid is worthwhile in patients who have significant pain without evidence of infection.

Corticosteroid injections should not be the sole form of therapy, and should ideally be limited to fewer than three injections per year because of their potential to damage the cartilage.

Hyaluronic acid

Hyaluronic acid is found in synovial fluid and is thought to act as a shock absorber and lubricant. In knee OA, there is a reduced concentration of hyaluronic acid, reducing the viscosity of synovial fluid and thereby increasing cartilage loading. Hyaluronic acid is used as a form of visco-supplementation in those patients in whom most conventional medical treatments have failed.

A recent review article reported that intra-articular hyaluronic acid offers a significant advantage over aspiration and placebo injections for up to 6 months.22 It also noted that clinical trials have shown it to be comparable to NSAIDs.

There is some evidence to suggest that hyaluronic acid polymer preparations with higher molecular weights are more effective than those with low molecular weights.

Tidal irrigation

Tidal irrigation is a medical form of washout of the knee. The procedure is performed using a wide gauge needle under local anaesthetic. As there is no need for general anaesthesia more patients are able to undergo the procedure.

Studies suggest an improvement when compared with conservative management,23 a similar outcome to formal arthroscopic lavage24 and a longer duration of pain relief, up to 24 weeks, than an intra-articular corticosteroid.20

In a prospective randomised trial, 77 patients were randomly assigned to conservative medical management or tidal irrigation.

A total of 57 patients completed the study and those undergoing tidal irrigation demonstrated a statistically significant improvement in pain, function and stiffness.23 This improvement was maintained for the duration of the 14-week follow-up period.

In a trial of 32 patients with non-end-stage knee OA, patients were randomly assigned to arthroscopic surgery or tidal irrigation.

At the 3-month follow-up there were no differences between the groups in terms of pain and functional status, and at 1 year, 58% of those who had undergone tidal irrigation reported continued benefit, compared with 44% who had undergone arthroscopy.24

Conclusion

OA of the knee is a major cause of pain and disability, particularly in the elderly.

In December 2000, EULAR published recommendations for the management of knee OA.8 They highlighted the number of therapeutic options currently available for medical management, but stated that more research is needed to help target these interventions to appropriate patients.

The most important message was that the management of patients should be multidisciplinary and involve non-pharmacological and pharmacological treatments in a stepwise manner, geared to the individual patient and his or her needs.

References

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  2. Cooper C. Epidemiology of osteoarthritis. In: Klippel JH, Dieppe PA, Eds. Rheumatology (2nd ed). London: Mosby, 1998, pp. 1-20.
  3. Dieppe P, Basler HD, Chard J et al. Knee replacement surgery for osteoarthritis: effectiveness, practice variations, indications and possible determinants of utilisation. Rheumatology 1999; 38: 73-83.
  4. Superio-Cabuslay E, Ward MM, Lorig KR. Patient education interventions in osteoarthritis and rheumatoid arthritis: a meta-analytic comparison with non-steroidal anti-inflammatory drug treatment. Arthritis Care Research 1996; 9: 292-301.
  5. O'Reilly SC, Muir KR, Doherty M. Effectiveness of home exercise on pain and disability from osteoarthritis of the knee: a randomised controlled trial. Ann Rheumatic Dis 1999; 58: 15-19.
  6. Ettinger WH Jr, Burns R, Messier SP et al. A randomised controlled trial comparing aerobic exercise and resistance exercise with a health education programme in older adults with knee osteoarthritis. The Fitness Arthritis Seniors Trial (FAST). JAMA 1997; 277: 25-31.
  7. Osiri M, Welch V, Brosseau L et al. Transcutaneous electrical nerve stimulation for knee osteoarthritis (Cochrane Review). In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software.
  8. Pendleton A, Arden N, Dougados M et al. EULAR recommendations for the management of knee osteoarthritis: report of a task force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCISIT). Annals Rheum Dis 2000; 59(12): 936-44.
  9. Scott DL. Guidelines for the diagnosis, investigation and management of osteoarthritis of the hip and knee. Report of a Joint Working Group of the British Society for Rheumatology and the Research Unit of the Royal College of Physicians. J R Coll Physicians Lond 1993; 27: 391-6.
  10. Towheed T, Shea B, Wells G, Hochberg M. Analgesia and non-aspirin, non-steroidal anti-inflammatory drugs for osteoarthritis of the hip (Cochrane Review). In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software.
  11. Silverstein FE, Faich G, Goldstein JL et al. Gastrointestinal toxicity with celecoxib vs. nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomised controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284(10): 1247-55.
  12. Langman MJ, Jensen DM, Watson DJ et al. Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs. JAMA 1999; 282(20): 1929-33.
  13. Bensen WG, Zhao SZ, Burke TA et al. Upper gastrointestinal tolerability of celecoxib, a COX-2 specific inhibitor, compared to naproxen and placebo. J Rheumatol 2000; 27(8): 1876-83.
  14. Cannon GW, Caldwell JR, Holt P et al. Rofecoxib, a specific inhibitor of cyclo-oxygenase 2, with clinical efficacy comparable with that of diclofenac sodium: results of a one-year, randomised, clinical trial in patients with osteoarthritis of the knee and hip. Arthritis Rheum 2000; 43(5): 978-87.
  15. Guidance on the use of cyclo-oxygenase (Cox) II selective inhibitors, celecoxib, rofecoxib, meloxicam, and etodolac for osteoarthritis and rheumatoid arthritis. Technology Appraisal Guidance – No 27. NICE, July 2001.
  16. Towheed TE, Anastassiades TP, Shea B et al. Glucosamine therapy for treating osteoarthritis (Cochrane review). In: The Cochrane Library, Issue 4, 2001. Oxford: Update Software
  17. Reginster JY. Deroisy R. Rovati LC et al. Long- term effects of glucosamine sulphate on osteoarthritis progression: a randomised, placebo-controlled clinical trial. Lancet 2001; 357(9252): 251-6.
  18. Moore RA, Tramer MR, Carroll D et al. Review: Topical non-steroidal anti-inflammatory drugs are effective and safe for pain. Br Med J 1998; 316: 333-8.
  19. Rosenstein ED. Topical agents in the treatment of rheumatic disorders. Rheum Dis Clin North Am 1999; 25(4): 899-918, viii.
  20. Ravaud P, Moulinier L, Giraudeau B et al. Effects of joint lavage and steroid injection in patients with osteoarthritis of the knee: results of a multicenter, randomised, controlled trial. Arthritis Rheum 1999; 42(3): 475-82.
  21. Dieppe PA, Sathapatayavongs B, Jones HE et al. Intra-articular steroids in osteoarthritis. Rheumatol Rehabil 1980; 19: 212-17.
  22. Hochberg MC. Role of intra-articular hyaluronic acid preparations in medical management of osteoarthritis of the knee. Semin Arthritis Rheum 2000; 30(2 Suppl 1): 2-10
  23. Ike RW, Arnold WJ, Rothschild EW, Shaw HL. Tidal irrigation versus conservative medical management in patients with osteoarthritis of the knee: a prospective randomised study. Tidal Irrigation Cooperating Group. J Rheumatol 1992; 19(5): 772-9.
  24. Chang RW, Falconer J, Stulberg SD et al. A randomised, controlled trial of arthroscopic surgery versus closed needle joint lavage for patients with osteoarthritis of the knee. Arthritis Rheum 1993; 36: 289-96.

Guidelines in Practice, February 2002, Volume 5(2)
© 2002 MGP Ltd
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