Osteoarthritis (OA) is the commonest form of arthritis in the Western population and is the single most important cause of disability in older adults; knee OA results in disabling knee symptoms in an estimated 10–15% of the UK population over the age of 55 years. The pain reported by a patient with OA may not correlate well with radiographic changes. Several clinical guidelines have been published in recent years, including those from NICE. All highlight the need for non-pharmacological measures including patient education and advice regarding weight control and exercise, physiotherapy including use of transcutaneous electrical nerve stimulation (TENS) and heat/cold applications.

Paracetamol remains the first drug of choice, with opioid medication and anti-inflammatory drugs (including COX-2 specific drugs) reserved until necessary and only after careful consideration of risks and benefits. Anti-inflammatory agents should be co-prescribed with a proton pump inhibitor (PPI). There remains a role for topical agents including topical non-steroidal anti-inflammatory agents (NSAIDs) and capsaicin. If a single joint is affected, and the patient experiences an inflammatory flare, an intra-articular steroid injection may be appropriate; for severe and resistant cases, joint replacement may be considered. Measures not supported in recent NICE guidance included acupuncture, hyalgan injections, glucosamine and chondroitin. 

Introduction

The prevalence of OA rises steeply with age at all joint sites.2 Hand and knee OA is more common in women than men but there is little sex difference in the incidence of hip OA. Radiographic improvement with time is uncommon, and several longitudinal studies of the incidence and progression of OA have now been performed.3 Determinants of progression include obesity, joint injury and physical activity. In recent years there have been a flurry of guidelines to aid healthcare professionals in managing this condition, including the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR), and most recently supplemented by a NICE clinical guideline published in 2008. This review will highlight the recommendations from these papers.4-6 The reader is also referred to the OARSI evidence based expert consensus guidelines for management of the hip and knee, published in 2008.7

Current guidance: the state of play

All available guidance highlights one factor; safety is obviously of great importance, particularly given the chronic nature of OA. Hence there is a general consensus that paracetamol should be the first line analgesic, in view of its favourable side effect and efficacy profile. Non-steroidal agents have traditionally been associated with gastrointestinal side effects, and more recently with cardiovascular risks as well; the cyclo-oxygenase -2 agents (COX-2 inhibitors) were developed in the hope that they might offer effective analgesia without these complications, but unfortunately recent data has linked these agents to serious cardiovascular and cardio-renal side effects. To highlight the potential dangers, a recent meta-analysis linked NSAID use for at least two months with a 21% absolute risk of an endoscopically diagnosed ulcer and 2.2% incidence of bleeding or perforation.8

Given the risk associated with any drug, non-pharmacological therapy should obviously be utilised in all patients. Patient education is important in explaining the cause of pain, strategies to help cope with it, and risk factors that the patient may be able to address, weight loss, physiotherapy exercises and application of ice or heat to the affected area being important examples. Quadriceps strengthening exercises and those designed to maintain knee mobility are felt to be beneficial. Manipulation and stretching may be appropriate, particularly for OA hip. While the NICE clinical guideline was supportive of a trial of TENS, it did not advocate acupuncture, due to lack of evidence.

If a single joint is affected, an intra-articular injection might be considered. Results from intra-articular corticosteroid injections are generally more disappointing than those performed for generalised inflammatory conditions, and typically are most effective in patients with an inflammatory aspect to their arthritis, with an effusion.

Hyalgan injections were not supported in the recent NICE clinical guideline. The NICE guideline states that "Referral for arthroscopic lavage and debridement should not be offered as part of treatment for osteoarthritis, unless the person has knee osteoarthritis with a clear history of mechanical locking (not gelling, ‘giving way’ or X-ray evidence of loose bodies)". Some clinicians use injection therapy in the event of a flare in pain, particularly if there is an effusion. If radiographs suggest severe joint damage, and pain is intractable and waking the patient at night, then joint replacement might be appropriate, particularly if the patient is otherwise in good health and the osteoarthritic joint is limiting their daily activities.

The EULAR released guidelines for the treatment of knee osteoarthritis, in addition to highlighting the use of paracetamol at the first line oral therapy (as it was both effective and safe), also recommended that topical administration of NSAIDs or capsaicin be considered. NICE was generally supportive of this, advocating the use of topical NSAIDs above oral NSAIDs and opioid drugs. Another topical agent, capsaisin, is also supported for use in hand and knee osteoarthritis; however, patients should be warned that their symptoms will flare before improving if they try this due to release of nociceptive substances from pain endings.

Most guidelines suggest that NSAIDs/COX-2 agents be added, or substituted if the above approaches with paracetamol and topical agents prove inadequate. However, NICE highlights the need to use these agents at the lowest dose for the shortest possible time because of the risks highlighted above. They suggest that: "When offering treatment with an oral NSAID/COX-2 inhibitor, the first choice should be either a standard NSAID or a COX-2 inhibitor (other than etoricoxib 60mg). In either case, these should be co-prescribed with a PPI, choosing the one with the lowest acquisition cost".

In addition, if a patient is taking aspirin, then other analgesics should be considered before starting an NSAID/COX-2 agent. Opioid medication may also be problematic; drugs may lead to constipation, drowsiness and a propensity of falls, and even dependence.

COX-2

The first COX-2 selective drugs celecoxib and rofecoxib became available in the late 1990s, and were rapidly adopted into clinical guidelines worldwide because of concerns about the safety profile of traditional NSAIDs. The Vioxx Gastrointestinal Outcomes Research (VIGOR) trial was designed to compare the gastrointestinal side effects of the COX-2 selective drug rofecoxib with the nonselective agent naproxen in patients with rheumatoid arthritis.9 While results confirmed that this was the case, the incidence of myocardial infarction was four fold higher in rofecoxib treated patients. When a second study (APPROVe) also found an excess risk of cardiovascular risk in rofecoxib treated patients, the trial was stopped and rofecoxib subsequently withdrawn from the market (amid a flurry of law suits).10 Results from the Ademona Prevention with Celecoxib (APC) trial suggested that cardiovascular adverse events were due to a class effect of COX-2 selective anti-inflammatory drugs, not just rofecoxib,11 and this was supported by an observation of excess cardiovascular risk in a trial of the agent valdecoxib. Recent publications now suggest that this class effect may extend still further to non-selective NSAIDs as well as COX-2 selective drugs, and highlight the need for caution.12

Glucosamine and chondroitin

Glucosamine and chondroitin have been promoted for some years as potentially useful in reducing pain from OA and perhaps even slowing progression of the disease. They have been attractive agents to consider due to their favourable safety profile and lack of interaction with other agents. However, this view has been contested more recently, and the recent NICE guidance did not support their use. In a meta-analysis published this year, large scale randomised controlled trials in more than 200 patients with osteoarthritis of the knee or hip that compared glucosamine, chondroitin, or their combination with placebo or head to head were examined.13 Researchers included 10 trials in 3803 patients. On a 10cm visual analogue scale the overall difference in pain intensity compared with placebo was very modest for both glucosamine and chondroitin, and was statistically insignificant, as were the differences in changes in minimal width of joint space.

Summary

OA is the commonest joint disorder whose prevalence increases with age. It is a multifaceted condition that affects patients in different ways; disability and pain are often poorly correlated with radiographic appearance. Involvement of the patient in the management of their condition is critical; exercise and lifestyle modification play a very important role and require the patient’s cooperation. Non-pharmacological approaches that may be valuable include physiotherapy, application of heat or cold and a trial of TENS. Recent guidance did not routinely support the use of acupuncture. Of the available agents, paracetamol is considered the first line oral therapy of choice because it is generally safe and effective, but topical NSAIDs may be appropriate. If these prove inadequate, NSAIDs/ COX-2 agents or opioid based drugs may be considered, although risks and benefits need to be carefully weighed up.

 

Conflict of interest: none declared


References

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