NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
National Clinical Guideline Centre (UK). Osteoarthritis: Care and Management in Adults. London: National Institute for Health and Care Excellence (UK); 2014 Feb. (NICE Clinical Guidelines, No. 177.)
Update information: December 2020: in the recommendation on adding opioid analgesics NICE added links to other NICE guidelines and resources that support discussion with patients about opioid prescribing and safe withdrawal management. For the current recommendations, see www.nice.org.uk/guidance/CG177/chapter/recommendations.
8.1. Exercise and manual therapy
8.1.1. Clinical introduction
Exercise is widely used by health professionals and patients to reduce pain152,313 and improve function. Exercise and physical activity can be targeted at the affected joint(s) and also at improving general mobility, function, well-being and self efficacy. More intensive exercise can strengthen muscles around the affected joint. However people often receive confused messages about when to exercise if they experience pain on physical activity or find that resting eases the pain. Often people believe that activity ‘wears out’ joints. Patients who have followed an exercise programme sometimes report they have experienced an exacerbation of their symptoms and are reluctant to continue. Whilst some people may experience an exacerbation of symptoms the vast majority of people, including those severely affected, will not have any adverse reaction to controlled exercise.208 For example patients with significant osteoarthritis can ride a bicycle, go swimming or exercise at a gym with often no or minimal discomfort.
The goals of prescribed exercise must be agreed between the patient and the health professional. Changing health behaviour with education and advice are positive ways of enabling patients to exercise regularly. Pacing, where patients learn to incorporate specific exercise sessions with periods of rest interspersed with activities intermittently throughout the day, can be a useful strategy. Analgesia may be needed so that people can undertake the advised or prescribed exercise.
The majority of the evidence is related to osteoarthritis of the knee, few studies have considered the hip and even fewer hand osteoarthritis. This section looks at the research evidence for different types of exercise for the joints usually affected by osteoarthritis.
Manual therapies are passive or active assisted movement techniques that use manual force to improve the mobility of restricted joints, connective tissue or skeletal muscles. Manual therapies are directed at influencing joint function and pain. Techniques include mobilisation, manipulation, soft tissue massage, stretching and passive movements to the joints and soft tissue. Manipulation is defined as high velocity thrusts, and mobilisation as techniques excluding high velocity thrusts, graded as appropriate to the patient’s signs and symptoms. Manual therapy may work best in combination with other treatment approaches, such as exercise.
8.1.2. Methodological introduction: exercise
We looked firstly at studies on investigating the effects of exercise therapy in relation to:
- sham exercise or no treatment control groups, and
- other osteoarthritis therapies.
Secondly we searched for studies that compared the risks and benefits of different exercise therapies with no treatment. Due to the high number of studies in this area only randomised controlled trials were inclused as evidence. Knee osteoarthritis RCTs with N=30 or fewer study completers were also excluded due to the high number of studies relevant to the osteoarthritis population.
Land-based exercise
For the first question, we found one meta-analysis of 13 randomised controlled trials (RCTs) dealing specifically with aerobic and strengthening land-based exercise therapies in the knee osteoarthritis population 385, and an additional 25 RCTs 41,62,139,148,196,198,205,235,249,258,304,306,307,335,350–352,379,437,448,468,182,46,153,208 of land-based exercise.
Five of these RCTs 62,139,196,205,249 were excluded due to multiple methodological limitations, while the remaining 16 were included as evidence.
For the second question, we found 10 RCTs that compared different land-based exercise programs to a no-exercise control group 140,198,263,277,291,306,307,351,352,464. Nine studies were included as evidence, with one study 464 excluded due to multiple methodological limitations.
Hydrotherapy and manual therapy
Nine RCTs28,80,116,127,149,153,184,192,193,482 were identified on hydrotherapy versus no treatment control or other land-based exercise programs. Four of these 171,314,482,503 were excluded due to multiple methodological limitations. One study 80 did not report between-group outcome comparisons adjusted for baseline values, but was otherwise well-conducted, and so was included as evidence along with the remaining two studies 28,149.
A further five RCTs 115,115,116,127,193 on manual therapy compared to land-based exercise or a control group were found. All studies were methodologically sound.
Study quality
Many of the included RCTs on land-based, hydrotherapy and manual therapy categories had the following methodological characteristics:
- Single-blinded or un-blinded
- Randomisation and blinding were flawed or inadequately described
- Did not include power calculations, had small sample sizes or had no ITT analysis. details
8.1.3. Methodological introduction: manual therapy
We looked for studies that investigated the efficacy and safety of manual therapies versus no treatment or other interventions with respect to symptoms, function, quality of life in patients with osteoarthritis. 5 RCTs29,115,193,353,463, one cohort study79 and one non-analytic study271 were found on manual therapy (joint manipulation, mobilisation, stretching, with or without exercise).
The 5 RCTs were all randomized, parallel group studies (apart from 1 study which was cross-over353) and were methodologically sound. Studies differed with respect to:
- Osteoarthritis site (4 RCTs knee, 1 RCT hip).
- Blinding, sample size, trial duration and follow up.
The two non-RCTs were methodologically sound. The cohort study79 compared the effects of one session of manual therapy (oscillatory mobilisations of the hip) on symptoms and function versus pre-treatment values in N=39 patients with knee osteoarthritis. The case-series’ compared the effects of 2–5 weeks of manual therapy (mobilisation and manipulation) on symptoms and function versus pre-treatment values in N=7 patients with hip osteoarthritis.
8.1.4. Evidence statements: land-based exercise
Table 36
Pain.
Table 37
Stiffness.
Table 38
Patient Function.
Table 39
Examination findings.
Table 40
Quality of Life.
Table 41
Use of concomitant medication.
8.1.5. Evidence statements: comparing different land-based exercise regimens
Table 42
Pain.
Table 43
Stiffness.
Table 44
Patient function.
Table 45
Examination findings.
Table 46
Quality of life.
8.1.6. Evidence statements: hydrotherapy
Table 47
Pain.
Table 48
stiffness.
Table 49
Patient function.
Table 50
Examination findings.
Table 51
Quality of Life.
8.1.7. Evidence statements: exercise vs manual therapy
Table 52
Pain.
Table 53
Patient function.
Table 54
Examination findings.
Table 55
Quality of life.
Table 56
Use of concomitant medication.
8.1.8. Evidence statements: manual therapy
Table 57
Pain.
Table 58
Stiffness.
Table 59
Function.
Table 60
Global assessment.
Table 61
Quality of life.
Table 62
Adverse Events.
Table 63
Study withdrawals.
8.1.9. Health economic evidence overview
We looked at studies that focused on economically evaluating exercise programmes compared to other exercise interventions, or to no treatment/placebo for the treatment of adults with Osteoarthritis. Thirteen studies were identified through the literature search as possible cost effectiveness analyses in this area. On closer inspection nine of these studies56,80,145,204,207,239,284,291,342,473 were excluded for:
- not directly answering the question;
- not including sufficient cost data to be considered a true economic analyses;
- involving a study population of less than 30 people.
Four papers were found to be methodologically sound and were included as health economics evidence. After the re-run search, 2 more papers were included as health economic evidence.
One recent UK study involved a full pragmatic, single-blind randomized clinical trial accompanied by a full economic evaluation 291. The study duration was 1 year, and the study population included 214 patients meeting the American College of Rheumatology’s classification of knee OA, selected from referrals from the primary and secondary care settings. The interventions considered were:
- Group 1: A home exercise programme aimed at increasing lower-limb strength, and endurance, and improving balance.
- Group 2: The second group was supplemented with 8 weeks of twice-weekly knee classes run by a physiotherapist. Classes represented typical knee class provision in the UK.
Effectiveness data was taken from the accompanying RCT. An NHS perspective was taken meaning that costs included resource use gathered from patient records and questionnaires, the cost of the intervention estimated from resource use data and national payscale figures, capital and overhead costs, and one-off expenses incurred by the patient. Travel costs were considered in sensitivity analysis. QALYs were calculated through converting EQ-5D scores obtained at baseline, 1, 6, and 12 months in to utilities.
One recent UK study 447 conducted a cost effectiveness analysis of exercise, telephone support, and no intervention. The study duration was 2 years and the study population involved adults aged over 45-years reporting current knee pain (exclusion criteria included having had a total knee replacement, lower limb amputation, cardiac pacemaker, unable to give informed consent, or no current knee pain). The intervention groups were:
- Exercise therapy. This included quadriceps strengthening, aerobic exercise taught in a graded program, and resistance exercises using a rubber exercise band. A research nurse taught the program in the participants’ homes. The initial training phase consisted of 4 visits lasting ~30 minutes in the first 2 months, with follow-up visits scheduled every 6 months thereafter. Participants were encouraged to perform the program daily, taking 20–30 minutes.
- Monthly telephone support. This was used to monitor symptoms and to offer simple advice on the management of knee pain. This aimed to control for the psychological impact of the exercise program.
- Combination of exercise and telephone support.
- No intervention. Patients in this group received no contact between the biannual assessment visits.
Effectiveness data was obtained from an accompanying RCT (786 participants). Health provider and patient perspectives are considered regarding costs, however patient specific costs were only considered in terms of time, and a monetary cost was not placed on this. This means that costs reported are those relevant for the health provider perspective (direct treatment costs, medical costs).
A limitation of the study is that it does not distinguish between medical costs incurred due to knee pain and medical costs incurred due to any other type of illness. This may bias results because changes in costs may not reflect changes in costs associated with knee pain.
One US study 414 conducted an economic analysis comparing exercise interventions and an education intervention. The study was 18 months long and focused on people aged 60 or over who have pain on most days of the month in one or both knees; who have difficulty with one of a variety of everyday activities; radiographic evidence of knee OA in the tibial-femoral compartments on the painful knee(s) as judged by a radiologist. The interventions included were:
- Aerobic exercise program = 3-month facility-based program and a 15-month home-based program. At each session exercise lasted 60 minutes including warm-up, stimulus, and cool-down phases. Exercise was prescribed three times per week. During the three-month period training was under the supervision of a trained exercise leader. Between 4 and 6 months participants were instructed to continue exercise at home and were contacted bi-weekly by the program leader who made 4 home visits and 6 telephone follow-up calls to participants. For months 7–9 telephone contact was made every 3 weeks, and during months 10–18 monthly follow-up telephone calls were made.
- Resistance exercise program = 3-month facility based, 15 month home-based. Duration of session, the number, timing, and type of follow-up was consistent with the aerobic exercise. Weights were used.
- Health education = this was used as a control to minimize attention and social interaction bias. During months 1–3 participants received a monthly 1.5 hr educational session, and during months 4–18 participants were regularly contacted by a nurse to discuss the status of their arthritis and any problems with medications. Telephone contacts were bi-weekly during months 4–6, and monthly for months 7–18.
Effectiveness data was from the single-blind Fitness and Arthritis in Seniors Trial (FAST) RCT. A health care payer perspective was adopted. Limitations of the study include that it only reported results comparing each exercise programme individually with the education control, rather than also comparing the exercise programmes to one another. Also Incremental Cost Effectiveness Ratios (ICERs) were calculated incorrectly.
An Australian study 413 economically evaluated a number of different interventions for the treatment of OA. The population considered varies for the different comparisons. The interventions considered were:
- Comprehensive mass media program for weight loss
- Intensive primary care weight loss program delivered by GP or dietician for overweight or obese
- Intensive primary care weight loss program delivered by GP or dietician for overweight or obese with previous knee injury
- Surgery for obese people
- Lay-led group education
- Primary care: GP or clinical nurse educator plus phone support
- Exercise/strength training
- Home-based basic
- Home-based intensive
- Clinic-based primary care
- Clinic based outpatients
- Specially fitted knee brace
- Non-specific NSAIDs (naproxen, diclofenac)
- COX2s (celecoxib)
- Glucosamine sulfate
- Avocado
- Topical capsaicin/soy unsaponifiable
- Total knee replacement
- Total hip replacement
- Knee arthroscopy with lavage
The paper required published outcomes and costs of the considered interventions to be found. At a minimum the papers used had to include a precise program description and quantitative evidence of effectiveness derived from an acceptable research design and preferably health endpoints, a usual care or placebo control, and a suitable follow-up period. Costs included resources applied to the intervention and to the management of treatment side effects, and for primary prevention estimated savings in ‘downstream’ health care service use. Intervention costs were calculated as the product of program inputs multiplied by current published unit costs.
The paper is limited with regards to its technique applied to compare health outcomes. A ‘transfer to utility’ (TTU) technique was used which has been criticised in the literature.477 This involves transforming health outcome scores found in the original trials into quality adjusted life year (QALY) scores.
One study from the Netherlands investigated behavioural graded activity and usual physiotherapy treatment for 200 patients with osteoarthritis of the hip or knee.89
The behavioural graded activity group received a treatment integrating the concepts of operant conditioning with exercise treatment comprising booster sessions. Graded activity was directed at increasing the level of activity in a time-contingent manner, with the goal of integrating these activities in the daily lives of patients. Treatment consisted of a 12 week period with a maximum of 18 sessions, followed by 5 preset booster moments with a maximum of 7 sessions (in weeks 18, 25, 34, 42 and 55).
The usual care group received treatment according to the Dutch physio guideline for patients with OA of hip and/or knee. This recommends provision of information and advice, exercise treatment and encouragement of coping positively with the complaints. Treatment consisted of a 12 week period with a maximum of 18 sessions and could be discontinued within this 12 weeks period if, according to the physio, all treatment goals had been achieved.
8.1.10. Health economic evidence statements
Home-based exercise Vs Home-based exercise supplemented with class-based exercise
One UK study291 conducted an economic analysis into the effects on supplementing a home-based exercise programme with a class-based programme.
Table 64
McCarthy’s cost-benefit estimates.
These results show that the class-based supplement dominates the home-based intervention alone. However neither the cost or the effect data were statistically significantly different, so cost effectiveness acceptability curves (CEACs) were presented. These showed that for all plausible threshold WTP values the class-based regime was more likely to be cost effective than the home-based regime. The CEAC showed that the probability of the class-based programme being cost-saving was just over 50%. At a WTP of £30,000 the probability of the class-based programme being cost effective was over 70%.
Additional sensitivity analysis was undertaken. When considering only patients for whom complete cost data was available (n=74, 30 in home-based and 44 in class-based) the class-based group had a higher probability of being cost effective (approximately 95% at WTP £20,000 to £30,000). Sensitivity analysis also included adding travel costs to the class-based regime. In this case the class-based programme was still likely (65% probability) to be cost effective compared to the home-based programme with a WTP threshold per additional QALY of £20,000–£30,000. There is considerable uncertainty however with a probability of 30–35% that the class-based programme will not be cost-effective.
It should be noted that as a one-year time horizon is used, the results are biased against the more effective intervention, or the intervention for which benefits are likely to be prolonged the most. This is because these patients will benefit from an increased QALY score for some time going into the future, assuming that the QALY improvement does not disappear immediately after the intervention is stopped.
In conclusion, it is likely that supplementing a home-based exercise programme with a class-based programme will be cost saving or cost effective and will improve outcomes. If travel costs are included this becomes less likely but it is probable that the class-based supplement will remain cost effective.
Exercise vs No Exercise vs Telephone
One 2005 UK study447 compared exercise interventions, no treatment, and telephone interventions, essentially from the health care provider perspective. All costs were reported in pound sterling at 1996 prices.
Table 65
Thomas’s cost-benefit estimates.
It should be noted that this paper has a bias against the exercise intervention if it is assumed that the benefits of the exercise programme continue for some time after the intervention has been stopped. This is because the intervention would no longer be paid for but some of the benefits may remain.
There is no evidence of telephone interventions being more effective than no-telephone interventions, so it is unclear whether adding telephone contact would be cost-effective.
Home-based exercise vs Clinic-based exercise vs Control
An Australian study413 undertakes an economic analysis of a number of different interventions for the treatment of OA, using a ‘transfer-to-utility’ technique which allows each intervention to be analysed with regards to their cost per QALY gain.
Table 66
Segal’s cost-effectiveness estimates.
Note that the effectiveness data these estimates are based on were generally from studies of around 12 weeks, but these estimates calculate costs and QALYs for a one year time period – ie as if the intervention was continued for one full year.
Compared to one another clinic-based exercise in a primary care setting [between one and three 30 minute exercise sessions per week for 12 weeks given on an individual basis by a physiotherapist, which included strengthening and lengthening exercises for muscle functions, mobility, coordination, and elementary movement plus locomotion abilities] is cost effective if there is a WTP per additional QALY gained of between approximately £2,049 and £42,805. For a WTP higher than £42,805 the evidence suggests that intensive home-based exercise may be cost effective. Home-based basic exercise is extendedly dominated by clinic-based exercise in primary care. Clinic-based exercise in an outpatient setting is dominated by clinic-based exercise in primary care.
Aerobic exercise versus resistance exercise versus education control
One US study414 considers the cost effectiveness of aerobic exercise and resistance exercise compared to an education control from the health care payer perspective.
Table 67
Sevick’s cost-effectiveness estimates.
Note that the resistance and aerobic exercise programmes were undertaken in the same setting ie 3 months facility-based and 15 months home-based and cost differences were only from medical referrals and adverse events, despite the fact that weights were used in the resistance exercise group. The authors state that the educational control arm of the study would be equivalent to a ‘no special instruction’ group in the real world. They state that the cost for this would be zero, but that it is possible outcomes would be slightly worse for these patients.
Also, similarly to other studies with relatively short time horizons, and which stop recording outputs as soon as the intervention is stopped, this paper may bias against the intervention as the benefits of the intervention may not disappear as soon as the intervention is discontinued.
In conclusion, aerobic exercise has been shown to result in lower costs than a resistance exercise group and an educational control group in the US, while incurring lower medical costs. Exercise programmes are likely to be cost effective compared to an educational programme involving regular telephone follow-up with patients.
The study89 found that the behavioural graded activity group was less costly than the usual care group, but not statistically significantly so. It is notable that more joint replacement operations took place in the usual care group, and it is unclear whether this is related to the interventions under consideration. The difference in effect of the two treatments was minimal for all outcomes. The study was excluded from the clinical review for this guideline, and given the uncertainty in the results no evidence statements can be made based upon it.
A recent UK study which is soon to be published investigates the Enabling Self-management and Coping with Arthritic knee Pain through Exercise (ESCAPE-knee pain) programme in 418 patients with chronic knee pain (Hurley ref). The interventions studied were:
- Usual primary care
- Usual primary care plus individual rehabilitation (Indiv-ESCAPE)
- Usual primary care plus rehabilitation in groups of about 8 participants (Grp-ESCAPE).
The content and format of ESCAPE was the same for the individual and group patients. They consisted of 12 sessions (twice weekly for 6 weeks) involving self-management advice and exercises to improve lower limb function.
The results of the study suggest that the group patients achieved very similar results as the individual patients, but the group costs were less. The probability that ESCAPE (Indiv and Grp combined) is cost effective compared to usual care based on QALYs, with £20,000 willingness to pay threshold for an additional QALY = 60%
The Probability that ESCAPE (Indiv and Grp combined) is cost effective compared to usual care based on 15% improvement in WOMAC function, with £1,900 willingness to pay threshold for an additional person with a 15% improvement = 90%. With a willingness to pay threshold of £800 the probability is 50%. Based on the WOMAC outcome, the probability of Indiv-ESCAPE being more cost effective than Grp-ESCAPE reached 50% at willingness to pay threshold of £6,000.
8.1.11. From evidence to recommendations
Exercise
The GDG recognised the need to distinguish between exercise therapy aimed at individual joints and general activity-related fitness. Evidence from a large well conducted systematic review385 and one large randomised controlled trial312 for knee osteoarthritis demonstrated the beneficial effects of exercise compared with no exercise. Exercise in this context included aerobic walking, home quadriceps exercise, strengthening and home exercise, aerobic exercise with weight training, and diet with aerobic and resisted exercise. Exercise reduced pain, disability, medication intake and improved physical functioning, stair climbing, walking distance, muscle strength, balance, self-efficacy and mental health and physical functioning (SF-36). The majority of these beneficial outcomes were seen at 18 months.
The strengths of these effects were not evident for hip and hand osteoarthritis. However, there is limited evidence for hip and hand osteoarthritis and the mechanisms of exercise on the hip and hand may be different to those for knee osteoarthritis.159
There is limited evidence for the benefits of one type of exercise over another but delivery of exercise in a class setting supplemented by home exercise may be superior to home exercise alone in terms of pain reduction, improved disability and increased walking speed.292 Classes were also shown to be cost effective. A class based exercise programme was superior to a home exercise alone programme at 12 months for pain, disability and walking speed in knee osteoarthritis.291 This study was conducted in a secondary care setting and patients were referred from primary and secondary care.
There is limited evidence to suggest exercise in water may be beneficial in the short term. There is difficulty in interpreting the study findings (one in pool based sessions in the community in the UK, a second of hydrotherapy in the US) for current practice in the NHS.
Exercise therapies given by health professionals to people and to groups of patients (e.g. exercise classes) may both be effective and locally available. Individual patient preferences can inform the design of exercise programmes.
Adverse events were not consistently studied, but the risk of adverse events is considered low if the suitability of the exercise for the individual is appropriately assessed by a trained health professional.
The GDG considered that the choice between individual and group exercise interventions has to be informed by patient preference, and tailoring it to the individual will achieve longer-term positive behavioural change.
The GDG also considered adding reference to the Expert Patient Programme but NICE guidelines do not specify the service model used to deliver effective interventions, and therefore an open recommendation is made focussing on the intervention shown to be of benefit.
Manual therapy
The majority of studies evaluated manual therapy for osteoarthritis in combination with other treatment approaches, for example exercise. This reflected current practice in physiotherapy, where manual therapy would not be used as a sole treatment for osteoarthritis but as part of a package of care.
There was strong evidence for the benefit of manual therapy alone compared with exercise.193 Again the design of this study reflects usual physiotherapy practice, where there is limited evidence for the benefit of exercise for hip osteoarthritis. The exercise programme was based on that reported by van Barr et al.469 Manual therapy included stretching techniques of the identified shortened muscles around the hip joint and manual traction which was repeated at each visit until the therapist concluded optimal results. Patients were treated twice weekly for 5 weeks with a total of 9 treatments. The duration of this programme is somewhat longer than that usually available in the NHS, however, the benefit of the manual therapy would indicate that such a programme should be considered in people who are not benefiting from home stretching exercises.
There have been few reported adverse events of manual therapy, pain on massage being one.
8.1.12. Recommendations
- 12.
Advise people with osteoarthritis to exercise as a core treatment (see recommendation 6), irrespective of age, comorbidity, pain severity or disability. Exercise should include:
- local muscle strengthening and
- general aerobic fitness.
It has not been specified whether exercise should be provided by the NHS or whether the healthcare professional should provide advice and encouragement to the person to obtain and carry out the intervention themselves. Exercise has been found to be beneficial but the clinician needs to make a judgement in each case on how to effectively ensure participation. This will depend upon the person’s individual needs, circumstances and self-motivation, and the availability of local facilities. [2008]
- 13.
Manipulation and stretching should be considered as an adjunct to core treatments, particularly for osteoarthritis of the hip. [2008]
8.2. Weight loss
8.2.1. Clinical introduction
Excess or abnormal mechanical loading of the joint appears to be one of the main factors leading to the development and progression of osteoarthritis. This is apparent in secondary forms of osteoarthritis, such as that related to developmental dysplasia of the hip. It also occurs in primary osteoarthritis, where abnormal or excess loading may be related to obesity or even relatively minor degrees of mal-alignment (varus or valgus deformity) at the knee.
The association of obesity with the development and progression of osteoarthritis, especially at the knee, provides the justification for weight reduction. Weight loss is usually achieved with either dietary manipulation and/or exercise, where the independent effect of the latter must also be considered.
8.2.2. Methodological introduction
We looked for studies that investigated the efficacy and safety of weight loss versus no weight loss with respect to symptoms, function and quality of life in adults with osteoarthritis. One systematic review and meta-analysis75 and 4 additional RCTs197,311,379,450 were found. One of these RCTs379 was a subgroup analysis of another trial304. 3 RCTs197,311,450 were excluded due to methodological limitations. No relevant cohort or case-control studies were found.
The systematic review and meta-analysis75 on weight loss versus no weight loss in patients with knee osteoarthritis. The MA included 5 RCTs (with N=454 participants). All RCTs were methodologically sound. Studies included in the analysis differed with respect to:
- Intervention – weight loss method (4 RCTs exercise and cognitive-behavioural therapy; 1 RCT low-energy diet; 1 RCT Mazindol-weight loss drug + low-energy diet).
- Study size and length.
The one RCT379 not included in the systematic review was methodologically sound and compared weight loss (exercise vs diet vs exercise + diet) vs no weight loss (healthy lifestyle education)in N=316 patients with knee osteoarthritis in an 18-month treatment phase.
8.2.4. From evidence to recommendations
Published data suggest that interventions reducing excess load, including weight loss, lead to improvement in function, providing the magnitude of weight loss is sufficient. In contrast, the effect of weight loss on pain is inconsistent. The only study to show an unequivocal effect on WOMAC pain as a primary outcome measure included exercise as part of the intervention304. Other studies suggest exercise might achieve this outcome in the absence of weight loss (see 7.1), although the exercise alone arm in this study did not achieve a statistically significant reduction in pain.
Furthermore, there is no clear evidence so far that weight loss, either alone or in combination with exercise, can slow disease progression. Although only one of the studies reviewed specifically addressed this question304, it was small (N=84), of relatively short duration and therefore underpowered for this outcome. Nor is there a definite threshold of weight below which the beneficial effect of weight loss on function is reduced or diminished, although all of the studies were restricted to those who were overweight (BMI>26.4 kg.m-2). Also, all of the studies have been conducted in knee osteoarthritis, with consequent difficulties in generalising the results to other joints, where mechanical influence may be less. The other health benefits of sustained weight loss are generally assumed to justify its widespread recommendation, but there is a paucity of trials showing that the kind of sustainable weight loss which would achieve metabolic and cardiovascular health benefits is achievable in clinical practice. The NICE guideline for obesity provides information on this evidence and the most effective weight loss strategies323.
Despite the limitations of the available evidence, the benefits of weight loss in people with osteoarthritis who are overweight are generally perceived to be greater than the risks. The GDG therefore advocate weight loss in all obese and overweight adults with osteoarthritis of the knee and hip who have associated functional limitations.
8.2.5. Recommendations
- 14.
Offer interventions to achieve weight losse as a core treatment (see recommendation 6) for people who are obese or overweight. [2008]
8.3. Electrotherapy
8.3.1. Clinical introduction
Electrotherapy and electrophysical agents include pulsed short-wave therapy (pulsed electromagnetic energy, PEME), interferential therapy, laser, Transcutaneous Electrical Nerve Stimulation (TENS) and ultrasound. All are commonly used to treat the signs and symptoms of OA such as pain, trigger point tenderness and swelling. These modalities involve the introduction of energy into affected tissue resulting in physical changes in the tissue as a result of thermal and non-thermal effects.
Ultrasound
The therapeutic effects of ultrasound have been classifed as relating to thermal and non-thermal effects132. Thermal effects cause a rise in temperature in the tissue and non-thermal effects (cavitation, acoustic streaming) can alter the permeability of the cell membrane20,445 which is thought to produce therapeutic benefits512. The potential therapeutic benefits seen in clinical practice may be more likely in tissue which has a high collagen content, for example a joint capsule rather than cartilage and bone which have a lower collagen content.
Pulsed shortwave therapy (Pulsed electromagnetic energy, PEME)
Pulsed short wave therapy has been purported to work by increasing blood flow, facilitating the resolution of inflammation and increasing deep collagen extensibility411. The application of this type of therapy can also produce thermal and non-thermal effects. The specific effect may be determined by the specific dose.
Transcutaneous Electrical Nerve Stimulation or TENS (also termed TNS)
TENS produces selected pulsed currents which are delivered cutaneously via electrode placement on the skin. These currents can activate specific nerve fibres potentially producing analgesic responses67,70. TENS is recognised as a treatment modality with minimal contraindications480. The term AL-TENS is not commonly used in the UK. It involves switching between high and low frequency electrical stimulation and many TENS machines now do this. The term is more specific to stimulating acupuncture points.
Interferential therapy
Interferential therapy can be described as the transcutaneous application of alternating medium-frequency electrical currents, and may be considered a form of TENS. Interferential therapy may be useful in pain relief, promoting healing and producing muscular contraction282.
Laser
Laser is an acronym for Light Amplification by the Stimulated Emission of Radiation. Therapeutic applications of low intensity or low level laser therapy at doses considered too low to effect any detectable heating of the tissue, have been applied to treat musculoskeletal injury24.
8.3.2. Methodological introduction
We looked for studies that investigated the efficacy and safety of electrotherapy (ultrasound, laser, transcutaneous electrical nerve stimulation [TENS, TNS, AL-TENS], pulsed shortwave diathermy, interferential therapy) versus no treatment, placebo or other interventions with respect to symptoms, function, and quality of life in adults with osteoarthritis. Five systematic reviews and meta-analyses47,206,290,337,384 were found on electrotherapy (laser, electromagnetic fields, ultrasounds and TENS) and 6 additional RCTs23,68,69,339,442,508 on electrotherapy (laser, electromagnetic fields and TENS). Due to the large volume of evidence, trials with a sample size N < 40 were excluded.
The meta-analyses assessed the RCTs for quality and pooled together data for the outcomes of symptoms and function. However, the outcomes of quality of life and adverse events (AEs) were not always reported. Results for quality of life have been taken from the individual RCTs included in this systematic review.
Ultrasound
One SR/MA384 was found on ultrasound in patients with knee or hip osteoarthritis. The MA included 3 RCTs (with N=294 participants) on comparisons between therapeutic ultrasound (continuous or pulsed) versus placebo or galvanic current or shorth wave diathermy (SWD). All RCTs were randomised and of parallel group design. Studies included in the analysis differed with respect to:
- Comparison used (1 RCT placebo – sham ultrasound; 1 RCT short wave diathermy; 1 RCT galvanic current)
- Treatment regimen (stimulation frequency and intensity; placement of electrodes; lengths of stimulation time and how often TENS was applied)
- Trial size, blinding, length, follow-up and quality.
Laser
One SR/MA47 and 2 RCTs442,508 were found that focused on laser therapy.
The MA47 included 7 RCTs (with N=345 participants) on comparisons between laser therapy versus placebo in patients with osteoarthritis. All RCTs were randomised, double-blind and parallel group studies. Studies included in the analysis differed with respect to:
- Site of osteoarthritis (4 RCTs knee, 1 RCT thumb, 1 RCT hand, 1 RCT not specified)
- Type of laser used (2 RCTs He-Ne laser of 632.8 nm; 1 RCT space laser 904 nm; 4 RCTs Galenium-Arsenide laser – either 830 or 860 nm)
- Treatment regimen (4 RCTs 2–3 sessions/week; 1 RCT every day; 1 RCT twice a day; 1 RCT 3 times a week)
- Trial size, length and quality.
The first RCT442 not in the systematic review focused on the outcomes of symptoms, function and AEs in N=60 patients with knee osteoarthritis. The RCT was a single blind, parallel group study and compared low power laser treatment with placebo laser treatment (given once a day, 5 times a week) in a 10 day treatment phase with 6 months follow-up. The second RCT508 not in the systematic review focused on the outcomes of symptoms, function and AEs in N=55 patients with Knee osteoarthritis. The RCT was a triple blind, parallel group study and compared laser acupuncture (laser at acupuncture sites) + exercise with placebo laser acupuncture + exercise (given once a day, 5 times a week) in a 2 week treatment phase with 12 weeks follow-up.
TENS
One SR/MA337 and 3 RCTs68,69,339 were found that focused on TENS.
The MA337 included 7 RCTs (with N=294 participants) that focused on comparisons between TENS and AL-TENS versus placebo in patients with knee osteoarthritis. Studies included in the analysis differed with respect to:
- Type of TENS used (4 RCTs High frequency TENS; 1 RCT Strong burst TENS; 1 RCT High frequency and strong burst TENS; 1 RCT AL-TENS)
- Treatment regimen (modes of stimulation, optimal stimulation levels, pulse frequencies, electrode placements, lengths of stimulation time and how often TENS was applied)
- Trial size, blinding, length, follow-up and quality
- Trial design (4 RCTs were parallel-group studies; 3 RCTs were cross-over studies).
The 3 RCTs68,69,339 not in the systematic review were parallel studies that focused on the outcomes of symptoms, function and QoL in patients with knee osteoarthritis. The 2 studies by Cheing et al68,69 refer to the same RCT with different outcomes published in each paper. This RCT did not mention blinding or ITT analysis but was otherwise methodologically sound. AL-TENS was compared to placebo AL-TENS or exercise (all given 5 days a week) in N=66 patients in a 4 week treatment phase with 4 weeks follow-up. The second RCT339 was methodologically sound (randomised and double-blind) and compared TENS (given 5 times a week) versus intra-articular Hylan GF-20 injection (given once a week) in N=60 patients with knee osteoarthritis in a 3 week treatment phase with 6 months follow-up.
PEMF
Two SRs/MAs206,290 were found on PEMF.
The first MA206 included 3 RCTs (with N=259 participants) that focused on comparisons between PEMF versus placebo PEMF in patients with knee osteoarthritis. All RCTs were high quality, double-blind parallel group studies. Studies included in the analysis differed with respect to:
- Type of electromagnetic field used and treatment regimen (2 RCTs pulsed electromagnetic fields, PEMF, using non-contact devise delivering 3 signals ranging from 5–12Hz frequency at 10 G to 25 G of magnetic energy. These used 9 hours of stimulation over 1 month period; 1 RCT use pulsed electric devise delivering 100 Hz low-amplitude signal via skin surface electrodes for 6–10 hrs/day for 4 weeks)
- Trial size and length.
The second MA290 included 5 RCTs (with N=276 participants) that focused on comparisons between PEMF versus placebo PEMF in patients with Knee osteoarthritis. All RCTs were high quality, randomised, double-blind parallel group studies. Studies included in the analysis differed with respect to:
- Type of electromagnetic field used and treatment regimen (2 RCTs low frequency PEMF ranging from 3–50Hz requiring long durations of treatment range 3–10 hrs/week; 3 RCTs used ‘pulsed short wave’ high frequency devices with shorter treatment durations)
- Trial size and length.
8.3.3. Evidence statements: ultrasound
Table 72
Pain.
Table 73
Patient Function.
Table 74
Global assessment.
8.3.4. Evidence statements: laser
Table 75
Pain.
Table 76
Stiffness.
Table 77
Patient function.
Table 78
Global asssessment.
Table 79
Quality of life.
Table 80
Adverse events.
8.3.5. Evidence statements: TENS
Table 81
Pain.
Table 82
Stiffness.
Table 83
Patient function.
Table 84
Quality of life.
Table 85
Study withdrawals.
8.3.6. Evidence statements: PEMF
Table 86
Pain.
Table 87
Stiffness.
Table 88
Function.
Table 89
Global assessment.
Table 90
Quality of life.
Table 91
Adverse events.
Table 92
Study withdrawals.
8.3.7. From evidence to recommendations
Studies had varying methodological quality and detail on treatment dosages. There was evidence that ultrasound provided no benefit beyond placebo ultrasound or other electrotherapy agents in the treatment of knee and hip osteoarthritis384. There was no evidence for the benefit of laser for pain relief at mixed sites of osteoarthritis from a systematic review48, but a recent study508 points to the benefit of laser at acupuncture points in reducing knee swelling. Evidence for the benefits of pulsed electromagnetic energy for osteoarthritis was limited in knee osteoarthritis290. In the hip and hand no studies were identified. Ultrasound, laser and pulsed electromagnetic energy are well suited for small joints such as hand and foot, but there is insufficient evidence to support their efficacy or clinical effectiveness in osteoarthritis. Further research would be helpful in these areas because it is not clear if efficacy or safety can be extrapolated from knee studies, and a research recommendation is included on this area. Given that there is no evidence on harm caused by laser, ultrasound or pulsed electromagnetic fields the GDG have not made a negative recommendation on these.
There is evidence that TENS is clinically beneficial for pain relief and reduction of stiffness in knee osteoarthritis especially in the short term however this was not shown in a community setting. There is no evidence that efficacy tails off over time, or that periodic use for exacerbations is helpful.
Proper training for people with osteoarthritis in the placing of pads and selection of stimulation intensity could make a difference to the benefit they obtain. Good practice guidance recommends an assessment visit with the health professional with proper training in the selection of stimulation intensity (e.g. low intensity, once a day, 40 minutes duration, 80Hz, 140 microseconds pulse) with reinforcement with an instruction booklet. People with osteoarthritis should be encouraged to experiment with intensities and duration of application if the desired relief of symptoms is not initially achieved. This enables patients control of their symptoms as part of a self-management approach. A further follow up visit is essential allowing the health professional to check patients’ usage of TENS and problem solve. No adverse events or toxicity have been reported with TENS. Contraindications include active implants (pacemakers, devices with batteries giving active medication); the contraindication of the first three months of pregnancy is currently under review (CSP guidelines). Although adverse events from TENS such as local skin reactions and allergies to the adhesive pads are known, they are rare.
As with all therapies adjunctive to the core treatments (see algorithm), it is important that the individual with osteoarthritis is able to assess the benefit they obtain from electrotherapy and take part in treatment decisions.
8.3.8. Recommendations
- 15.
Healthcare professionals should consider the use of transcutaneous electrical nerve stimulation (TENS)f as an adjunct to core treatments for pain relief. [2008]
8.4. Nutraceuticals
8.4.1. Introduction
Nutraceuticals is a term used to cover foods or food supplements thought to have health benefits. The most widely used is glucosamine (sulfate and hydrochloride) which is widely sold in various combinations, compounds, strengths and purities over the counter in the UK. Medical quality glucosamine sulfate and hydrochloride are licensed in the European Union and can be prescribed. These compounds are not licensed by the Food and Drug Administration in the USA, so are marketed there (and on the internet) as health food supplements.
Glucosamine is an amino sugar and an important precursor in the biochemical synthesis of glycosylated proteins, including glycosaminoglycans. The sulfate moiety of glucosamine sulfate is associated with the amino group. Chondroitin sulfate is a sulfated glycosaminoglycan (GAG) dimer, which can be polymerised to the chain of alternating sugars (N-acetylgalactosamine and glucuronic acid) found attached to proteins as part of a proteoglycan. It is hypothesised that substrate availability (of glucosamine, chondroitin or sulfate itself) may be the limiting factor in the synthesis of the GAG component of cartilage, which provides the rationale for oral supplementation of these compounds in osteoarthritis. The mode of action and both in vitro and in vivo effects of these compounds remain highly controversial, although their safety is rarely disputed. The GDG wished to review the evidence on the use of nutraceuticals in the management of OA.
8.4.2. What is the clinical and cost effectiveness of glucosamine and chondroitin alone or in compound form versus placebo or other treatments in the management of osteoarthritis?
For full details see review protocol in Appendix C.
Table 93
PICO characteristics of review question.
8.4.3. Clinical evidence
We searched for systematic reviews and randomised trials assessing the effectiveness of nutraceuticals in the management of osteoarthritis. The GDG agreed that the evidence should be stratified according to licensing indication of the nutraceuticals in the UK to inform decisions related to recommendations for the NHS.
The GDG noted that any degree of structure modification should be taken as clinically important, thus the MID chosen for structural modification outcomes was the line of no effect or zero
Glucosamine
One Cochrane review which included 25 RCTs was identified for this question 458. In addition, three studies were identified that were published after the Cochrane review 154,165,401. Evidence from these are summarised in the clinical GRADE evidence profile below. See also the study selection flow chart in Appendix D, forest plots in Appendix I, study evidence tables in Appendix G and exclusion list in Appendix J.
Of the 25 RCTs included in the Cochrane review, eight studies had a population with primary osteoarthritis, whilst the remaining studies did not clarify whether the population had primary or secondary OA.
Twenty studies included in the Cochrane review evaluated the use of nutraceuticals in knee OA, and one looked exclusively at people with hip OA. The three papers published after the Cochrane review all had populations with knee OA. Two studies assessed OA at multiple sites and two studies did not specify the site of OA. These studies were not included in the review because the view is that these studies do not add to the GDG’s understanding of how an agent works on the single site and they do not assist in understanding how therapies might help multiple joint patients.
The route of administration of glucosamine differed between studies included in the Cochrane review. Twenty-one studies used an oral route, two used an intra-articular (IA) route, three used an intramuscular (IM) route, one used an intravenous (IV) route, and two studies used multiple routes of administration. The three papers identified that were published after the Cochrane review all used oral route of administration. All studies allowed the use of paracetamol with/without NSAIDS as rescue medication.
The dosage of glucosamine differed between studies included in the Cochrane review. The dose of glusosamine was 1500mg per day in studies administering glucosamine orally, although the division of doses differed between studies. In the RCTs using parenteral routes, the dosage was 400mg once daily in two studies, and twice per week in another study. In the three papers identified published after the Cochrane, one study used 1500mg per day401, one used approximately 500mg per day154 and in the other study it was assumed that 1500mg per day was administered, although this is not clear165.
The studies included in the Cochrane had varying length of follow up, ranging from 3 weeks to 3 years. The mean trial duration was 25.5 weeks. Of the three papers identified that were published after the Cochrane, one had 12 weeks follow up154, one had 24 weeks follow up165 and one had 2 years follow up401.
Data in the meta-analysis has been stratified by joint type and by licensing indication. The GDG indicated that the licensed glucosamine sulfate preparation from the Rottapharm group is available in the UK as Glusartel. All relevant studies assessing licensed glucosamine sulfate were reviewed and stratified accordingly either based on the information provided in the study or as indicated by the Cochrane Review. The GDG are aware of licensed preparations of glucosamine hydrochloride, but none of the retrieved studies has referred to a licensed preparation. No separate analysis of studies with unlicensed preparations of glucosamine sulfate was undertaken as it was recognised that such studies may have potentially involved the use of preparations licensed outside of the UK.
One study that was included in the Cochrane review was only available as a published abstract 392. The study quality had been assessed by the Cochrane group, but the GDG were interested in the effect that this data had on the overall results, therefore a sensitivity analysis was undertaken excluding the Rovati study from glucosamine hydrochloride and sulfate (licensed and unlicensed formulations) versus placebo and glucosamine sulfate (licensed formulation) versus placebo analyses. No sensitivity analysis was undertaken on glucosamine vs NSAID analysis because the Rovati (1997) study was the only study included in this review.
Sensitivity analyses were also conducted where significant heterogeneity was present. This included looking at the different time points for reporting outcomes and if heterogeneity was still present, to conduct sensitivity analyses on studies with very high risk of bias.
Data from Sawitze (2008) and Sawitze (2010) have not been included in the meta-analysis (but are included in the evidence review) due to their data reporting; as only mean values without standard deviations, standard errors or confidence intervals were provided. Furthermore, Sawitze (2008) and (2010) were not adequately randomised studies.
One post-hoc analysis 52 of two RCTs conducted in people with knee OA 344 375 was included in the review; the study had an 8 year observation period. The GDG thought that this study provided important information on long-term joint replacement outcomes that were not captured in the RCT evidence review. Only information on the number of people who had knee replacements could be extracted from this study. The study also reported that the NNT was 12 (indicating that 12 people needed to take glucosamine sulfate to avoid 1 knee replacement). Time to joint replacement was also reported using a Log-rank test; a p value of 0.026 was reported indicating that there is a decreased and delayed cumulative incidence of total knee replacement for people who had previously taken glucosamine sulfate.
One RCT conference abstract343 in hand OA was also identified and its data presented in a seprate GRADE table.
Chondroitin
One meta-analysis which included 22 trials was included in this review376. One study included in the meta-analysis was a non-randomised study and the findings have not been included in the analysis of this review424. In addition, seven studies were identified that were published after the meta-analysis157,229,316,370,402,492,511. One study was identified as a non-randomised post hoc analysis of one of the studies included in the meta-analysis and the findings, although presented in evidence tables, are not included in the analysis402.
Evidence from these are summarised in the clinical GRADE evidence profile below (See tables 5–9). See also the study selection flow chart in Appendix D, forest plots in Appendix I, study evidence tables in Appendix G and exclusion list in Appendix J.
The meta-analysis376 was assessed using the NICE checklist for quality assessment of systematic reviews and was found to meet the inclusion criteria for this review. An adequate risk of bias assessment was undertaken in the meta-analysis and this has been included in this review for reporting risk of bias of the studies included in the meta- analysis. The studies identified after the meta-analysis were assessed for risk of bias using the NICE checklist for quality assessment of randomised trials.
Of the 22 studies included in the meta-analysis, seventeen trials were published as full text articles and five were published as conference abstracts at time of publication of the meta- analysis. Since then, three studies have been published as full text articles 229,285,465 and relevant data has been extracted from these publications and has been included in this review.
Seventeen studies included in the meta- analysis evaluated the use of chondroitin in osteoarthritis of the knee, two looked at knee or hip and one study looked at hip OA. In the trials identified after the meta-analysis, four trials were in knee OA and one was in OA of the hand.
All studies included in the clinical evidence review included unlicensed preparations of chondroitin.
The route of administration of chondrotin in all studies included in this review was oral except for two studies included in the meta-analysis, where chondroitin was administered intra-muscularly238,393. The daily dose of chondroitin taken differed between studies. In the meta-analysis, among studies reporting oral dosing of chondroitin, eight studies had doses of 800mg, six studies had doses of 100mg, six studies had doses of 1200mg, one study had a dose of 1000mg and one study had a dose of 2000mg. Chondroitin was administered on consecutive days in nineteen trials and intermittently in three trials83,275,424. Of the two studies using intra-muscular preparations, one used 150 biological units238 and the dosage was not reported in the other study393. In the studies identified after the meta-analysis, four reported doses of 800 mg daily and one reported a dose of 1200 mg daily. All studies allowed the use of paracetamol with/without NSAIDS as rescue medication.
The studies included in the meta-analysis had varying lengths of follow up, ranging from 13 to 132 weeks with a median duration of 31 weeks. The length of follow up in the trials identified after the meta-analysis ranged from 3 months to 2 years.
Sensitivity analyses were also conducted where significant heterogeneity was present. This included looking at the different time points for reporting outcomes and if heterogeneity was still present, to conduct sensitivity analyses on studies with very high risk of bias.
Glucosamine + Chondroitin
Three studies that compared glucosamine hydrochloride+ chondroitin vs placebo were included in CG5981,98,369. Four studies published after CG59 that compared glucosamine hydrochloride+ chondroitin sulfate to placebo were identified 78,305,401,402. Three of these studies were three- armed trials that also compared glucosamine hydrochloride+ chondroitin sulfate to NSAIDs 78,305,401,402. The NSAID used in all of these studies was Celecoxib. Two of the studies comparing glucosamine hydrochloride+ chondroitin sulfate to NSAIDs could not be meta-analysed due to reasons reported above 401,402. All studies allowed the use of paracetamol with/without NSAIDS as rescue medication.
Table 94
Summary of studies included in the review.
Additional systematic reviews were identified relating to the clinical and cost effectiveness of nutraceuticals. Firstly, a Health Technology Assessment, The clinical effectiveness of glucosamine and chondroitin supplements in slowing or arresting progression of osteoarthritis of the knee: a systematic review and economic evaluation (2009) 39. This HTA comprised a review of systematic reviews and an economic evaluation, in which the Towheed (2005), Reichenbach (2007) and the original guideline (2008) were included. Therefore, the HTA was not used as the basis for the updated meta-analyses conducted for the nutraceuticals review, but was used as a quality assurance tool to cross-refer for any missed studies.
Secondly, a systematic review conducted as part of an assessment of whether the OARSI recommendations should be modified in light of recent evidence was also identified 513. The systematic review identified 64 systematic reviews, 266 RCTs and 21 economic evaluation’s that met the inclusion criteria. Again, the OARSI meta-analyses were not used as the basis for the updated meta-analyses conducted for the nutraceuticals review, as only effect sizes were published and raw data of the individual studies was not available from the published study
The GDG were also aware of a network meta-analysis 481 which compared glucosamine, chondroitin, and their combination with placebo and showed that there was no reduction in joint pain or an impact on narrowing of joint space. The effect sizes of this NMA were not used in our analyses as the study was published in 2010 (and new studies have been published since then) and stratification of results was different from the strata set out in the protocol for this evidence review
Table 95
Glucosamine hydrochloride and sulfate versus placebo (Knee and hip).
Table 96
Glucosamine hydrochloride and sulfate versus placebo- sensitivity analysis according to time points.
Table 97
Glucosamine hydrochloride and sulfate versus placebo- sensitivity analysis according to study quality.
Table 98
Glucosamine hydrochloride and sulfate (licensed and unlicensed) versus placebo- sensitivity analysis with Rovati 1997 removed.
Table 99
Glucosamine hydrochloride and sulfate versus NSAIDs (knee).
Table 100
Glucosamine hydrochloride and sulfate versus NSAIDs- sensitivity analysis according to treatment duration.
Table 101
Glucosamine hydrochloride and sulfate versus NSAIDs- sensitivity analysis according to study quality.
Table 102
Licensed glucosamine sulfate versus placebo (Knee).
Table 103
Licensed glucosamine sulfate versus placebo- sensitivity analysis according to treatment duration.
Table 104
Licensed glucosamine sulfate versus placebo- sensitivity analysis according to study quality.
Table 105
Licensed glucosamine sulfate formulations versus placebo- sensitivity analysis with Rovati 1997 removed.
Table 106
Licensed glucosamine versus placebo- Bruyere (2009) post-hoc analysis of long term joint replacement outcome.
Table 107
Licensed glucosamine sulfate versus NSAIDs (Knee).
Table 108
Licensed glucosamine sulfate versus paracetamol (Knee).
Table 109
Licenced glucosamine sulfate versus paracetamol (Hand).
Table 110
Chondroitin versus placebo (knee).
Table 111
Chondroitin versus placebo (Hip).
Table 112
Chondroitin versus placebo (Hand).
Table 113
Chondroitin versus NSAIDs (knee).
Table 114
Chondroitin versus placebo: Sensitivity analysis on the basis of study quality.
Table 115
Chondroitin versus placebo: Sensitivity analysis based on time points of observation.
Table 9
Glucosamine sulfate or glucosamine hydrochloride and chondroitin sulfate versus placebo (knee).
Table 116
Glucosamine sulfate or glucosamine hydrochloride and chondroitin sulfate versus NSAIDs (Knee).
8.4.4. Economic evidence
Evidence from CG59
Published literature
No studies were found comparing glucosamine and chondroitin alone or in compound form with the relevant comparators.
Original analysis
An original cost effectiveness analysis was conducted for CG59 using five placebo controlled RCTs 78,288,310,344,375 (included in the original guideline review) comparing glucosamine and chondroitin alone or in compound form versus placebo. WOMAC scores were taken from the RCTs and mapped onto EQ-5D using the formula from Barton 200822. Only direct costs of the interventions were considered, assuming one GP appointment. Placebo was assumed to have no costs.
A summary of this CG59 analysis can be found in Appendix M.
Evidence statements have not been drafted for the CG59 analysis as this has not been updated in this guideline update, and more weight was placed by the GDG on cost effectiveness and clinical evidence from the update guideline.
Evidence from update guideline
Published literature
Three studies were identified from the update search that included the relevant interventions and comparisons 410, 39, 52.
Two studies looked at the cost-effectiveness of glucosamine sulfate: one study compared glucosamine with current care 39, this was a decision analytic model with a lifetime horizon, as well as being a UK study part of a health technology assessment. The other study 410 compared glucosamine with paracetamol and also with placebo, this was a Spanish study with an RCT design and a 6 month time horizon.
One study by Bruyere (2009)52 compared chondroitin sulfate with placebo. The study had an RCT design with a time horizon of 24 months, and was from a European perspective.
These are summarised in the economic evidence profile below (Table 117 and Table 118). See also the study selection flowchart in appendix E and study evidence tables in appendix H.
Table 117
Economic evidence profile: Glucosamine sulfate versus other treatments.
Table 118
Economic evidence profile: Chondroitin versus placebo.
The Black study conducted the most robust sensitivity analysis of the three published papers, and found that the QoL gain is the main parameter causing variation in the results.
In the CG59 analysis, WOMAC scores were mapped onto EQ-5D using the model by Barton22 which may be preferable to the mapping method used in Scholtissen 2010 410 and Black 2009 39 where WOMAC scores were mapped onto HUI3.
The clinical studies included in the CG59 economic analysis are in line with the rest of the studies included in this update, therefore the conclusions of the economic analysis are deemed still applicable to the current evidence base.
At the time of writing of CG59, no licensed glucosamine sulfate product was available in the UK (although it was available over the counter) – whereas now there is (the most recent cost from BNF is £18.20 for 1 month supply).
The difference in the cost between the two identified glucosamine studies can partly be explained by the difference in the acquisition costs. According to the Scholtissen paper, glucosamine is cheaper than paracetamol (£0.19 and £0.26 (per day) respectively), whereas in the Black study, glucosamine is costed at approximately £0.61 per day, which is very similar to the UK cost.
In the Bruyere study, the acquisition cost is £1.30 per day (this is the maximum cost – the cost-effectiveness ratio is also calculated based on a minimum cost of chondroitin in Europe, which is £0.81 per day).
Thus the higher drug acquisition costs of the Bruyere paper explain why it has the largest incremental cost-effectiveness ratio of the three papers.
8.4.5. Evidence statements
Clinical
All glucosamine preparations (hydrochloride and sulfate) vs placebo-knee OA
- Fourteen studies with 2218 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing pain (pooled measures across different scales) [VERY LOW ].
- Eight studies with 671 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine and placebo at decreasing pain (pooled measures across different scales) at a follow up of less than three months [VERY LOW ].
- Six studies with 1547 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine and placebo at decreasing pain (pooled measures across different scales) at a follow up of greater than three months [VERY LOW].
- Ten studies with 1867 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing pain measured on the WOMAC scale at both short and long term follow up [MODERATE].
- Ten studies with 1867 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at improving function measured on the WOMAC scale at both short and long term follow up [MODERATE].
- Seven studies with 1240 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing stiffness measured on the WOMAC scale at both short and long term follow up [LOW].
- Three studies with 918 people with knee osteoarthritis showed that that there may be no clinically important difference between all glucosamine preparations and placebo at improving responder rate according to the OMERACT- OARSI criteria at both short term and long term follow up. [VERY LOW].
- One study with 78 people with knee osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at improving responder rate according to the OMERACT- OARSI criteria at follow up less than three months [LOW ].
- Two studies with 840 people with knee osteoarthritis suggested that all glucosamine preparations may be clinically more effective than placebo at improving responder rate according to the OMERACT- OARSI criteria at follow up greater than three months, but there was some uncertainty. [VERY LOW ].
- Thirteen studies with 1790 people with knee osteoarthritis showed that there may be no difference between all glucosamine preparations and placebo with respect to adverse event profile at both short and long term follow up [MODERATE].
All glucosamine preparations (hydrochloride and sulfate) vs placebo-hip OA
- One study with 222 people with hip osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing pain measured on the WOMAC scale at both short and long term follow up [HIGH].
- One study with 222 people with hip osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing pain measured on the WOMAC scale at follow up greater than three months [HIGH].
- One study with 222 people with hip osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at improving function measured on the WOMAC scale at follow up greater than three months [HIGH].
- One study with 222 people with hip osteoarthritis showed that there may be no clinically important difference between all glucosamine preparations and placebo at decreasing stiffness measured on the WOMAC scale at follow up greater than three months [HIGH].
- One study with 222 people with knee osteoarthritis showed all glucosamine preparations and placebo may be similar with respect to adverse event profiles at follow up greater than three months [HIGH].
All glucosamine preparations (hydrochloride and sulfate) vs NSAIDs- knee OA
- Four studies with 997 people with knee osteoarthritis suggested that all glucosamine preparations and NSAIDs may be similarly effective at decreasing pain (pooled measures across different scales) at both short and long term follow up [VERY LOW ].
- Two studies with 206 people with knee osteoarthritis suggested that all glucosamine preparations and NSAIDs may be similarly effective at decreasing pain (pooled measures across different scales) at follow up less than three months [VERY LOW].
- Two studies with 791 people with knee osteoarthritis suggested that all glucosamine preparations and NSAIDs may be similarly effective at decreasing pain (pooled measures across different scales) at follow up greater than three months [VERY LOW].
- Two studies with 345 people with knee osteoarthritis suggested that all glucosamine preparations and NSAIDs may be similarly effective at improving function measured with the Lequesne index at both short and long term follow up [VERY LOW].
- One study with 189 people with knee osteoarthritis showed that all glucosamine preparations and NSAIDs were similarly effective in improving function measured with Lequesne Index at follow up of less than three months [HIGH].
- One study with 156 people with knee osteoarthritis suggested that all glucosamine preparations may be clinically more effective than NSAIDs at improving function measured with the Lequesne index at follow up greater than three months, although there was uncertainty surrounding this effect [MODERATE].
- One study with 635 people with knee osteoarthritis suggested that all glucosamine preparations and NSAIDs may be similarly effective with respect to patient global assessment of disease status at follow up greater than three months, [VERY LOW ].
- Four studies with 580 people with knee osteoarthritis showed that there are fewer patients reporting adverse events (including GI, CV, pruritis and joint swelling) in the all glucosamine preparations group compared to the placebo group at both short and long term follow up [MODERATE].
- Three studies with 415 people with knee osteoarthritis showed that there are fewer patients reporting adverse events (including GI, CV, pruritis and joint swelling) in the all glucosamine preparations group compared to the placebo group at follow up of less than three months [MODERATE].
- One study with 165 people with knee osteoarthritis showed that there are fewer patients reporting adverse events (including GI, CV, pruritis and joint swelling) in the all glucosamine preparations group compared to placebo group at follow up of greater than three months [HIGH].
Licensed glucosamine preparations(evidence only for glucosamine suphate) vs placebo-knee OA
- Five studies with 800 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than placebo at decreasing pain (pooled measures across different scales) at both short and long term follow up, however there was uncertainty surrounding this effect [VERY LOW].
- One conference abstract with 20 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than placebo at decreasing pain (pooled measures across different scales) at both short term follow up, however there was uncertainty surrounding this effect [VERY LOW].
- Four studies with 780 people with knee osteoarthritis suggested that that there may be no clinically important difference between licensed glucosamine preparations and placebo at decreasing pain (pooled measures across different scales) at long term follow up [VERY LOW].
- Three studies with 624 people with knee osteoarthritis showed that there may be no clinically important difference between licensed glucosamine preparations and placebo at decreasing pain measured on the WOMAC scale at follow up of more than three months [MODERATE].
- Three studies with 624 people with knee osteoarthritis showed that there may be no clinically important difference between licensed glucosamine preparations and placebo at improving function measured on the WOMAC scale at a follow up of greater than three months [MODERATE].
- One study with 202 people with knee osteoarthritis showed that that there may be no clinically important difference between licensed glucosamine preparations and placebo at decreasing stiffness measured on the WOMAC scale at follow up greater than three months [MODERATE].
- Five studies with 951 people with knee osteoarthritis suggested that there may be no clinically important difference between licensed glucosamine preparations and placebo at improving function measured with Lequesne index at both short and long term follow up [VERY LOW ].
- Two studies with 383 people with knee osteoarthritis suggested that there may be no clinically important difference between licensed glucosamine preparations and placebo at improving function measured on the Lequesne index at a follow up of less than three months [MODERATE].
- Three studies with 563 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than placebo in improving function measured on the Lequesne index at a follow up of greater than three months, although there was uncertainty surrounding this effect [VERY LOW].
- Two studies with 414 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective at bringing about a change in minimum joint space width loss at follow up greater than three months[LOW].
- One study with 212 people with knee osteoarthritis showed that licensed glucosamine preparations and placebo were similarly effective in maintaining mean joint space width at follow up greater than three months [MODERATE].
- One study with 210 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than placebo at improving responder rate according to the OMERACT OARSI criteria at a follow up of greater than three months, however there was uncertainty surrounding this effect [MODERATE].
- Seven studies with 1211 people with knee osteoarthritis showed that there may be no difference between licensed glucosamine preparations and placebo in the adverse event profile at both short and long term follow up [MODERATE y].
- Three studies with 431 people with knee osteoarthritis suggested that there may be fewer people reporting adverse events in the licensed glucosamine preparations group compared to the placebo group at a follow up of less than three months, although there was uncertainty surrounding this effect. [VERY LOW].
- Four studies with 780 people with knee osteoarthritis showed that there may be no difference between licensed glucosamine preparations and placebo in the adverse event profile at a follow up of greater than three months [MODERATE].
Licensed glucosamine preparations (evidence only for glucosamine sulfate) vs NSAIDs-knee OA
- One study with 156 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than NSAIDs at decreasing pain at follow up of greater than three months; however there is uncertainty surrounding this effect [MODERATE].
- One study with 156 people with knee osteoarthritis suggested that licensed glucosamine preparations may be clinically more effective than NSAIDs at improving function measured with the Lequesne index at follow up of greater than three months; however there is uncertainty surrounding this effect [MODERATE].
- One study with 165 people with knee osteoarthritis showed that there were fewer people reporting adverse events in the licensed glucosamine preparations group compared to the NSAID group at a follow up of greater than three months [HIGH].
Licensed glucosamine preparations (evidence only for glucosamine sulfate) vs paracetamol-knee OA
- One study with 214 people with knee osteoarthritis showed that licensed glucosamine preparations and paracetamol may be similarly effective in decreasing pain measured on the WOMAC scale at follow greater than three months [MODERATE].
- One study with 214 people with knee osteoarthritis showed that licensed glucosamine preparations and paracetamol were similarly effective in improving function measured on the WOMAC scale at follow greater than three months [HIGH].
- One study with 214 people with knee osteoarthritis showed that licensed glucosamine preparations and paracetamol were similarly effective in improving function measured wth the Lequesne index at follow greater than three months [HIGH].
- One study with 214 people with knee osteoarthritis suggested that licensed glucosamine preparations and paracetamolmay similarly effective in improving responder rate according to the OMERACT-OARSI criteria at follow greater than three months [MODERATE].
Chondroitin sulfate vs placebo- knee OA
- Seventeen studies with 2335 people with osteoarthritis of the knee showed that chondroitin was clinically more effective than placebo at decreasing pain measured on the visual analogue scale(VAS) at both short term and long term follow up but there was some uncertainty. [VERY LOW].
- Four studies with 365 people with osteoarthritis of the knee showed that chondroitin was clinically more effective than placebo at decreasing pain measured on the visual analogue scale(VAS)at follow of less than 3 months [LOW].
- Thirteen studies with 1970 people with osteoarthritis of the knee showed that chondroitin may be clinically more effective than placebo at decreasing pain measured on the visual analogue scale(VAS) at follow of greater than 3 months but there was some uncertainty. [VERY LOW].
- Four studies with 1622 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at decreasing pain measured on the WOMAC scale at follow of greater than 3 months [MODERATE].
- One study with 631 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at improving function measured on the WOMAC scale at follow of greater than 3 months [HIGH].
- One study with 631 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at improving stiffness measured on the WOMAC scale at follow of greater than 3 months [HIGH].
- Three studies with 948 people with osteoarthritis of the knee showed that chondroitin may be clinically more effective in bringing about change in minimum joint space width loss at a follow up of more than 13 weeks compared to placebo [MODERATE].
- Two studies with 938 people with osteoarthritis of the knee suggested that there may be no clinically important difference between chondroitin and placebo at improving responder rate according to OMERACT- OARSI criteria at follow up greater than 3 months [MODERATE].
- One study with 116 people with osteoarthritis of the knee suggested that there may be no clinically important difference between chondroitin and placebo at improving quality of life measured by physical component of SF36 scale at follow up less than 3 months [LOW ].
- One study with 116 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at improving quality of life measured by mental component of SF36 scale at follow up less than 3 months [MODERATE].
- One study with 307 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at improving quality of life measured by physical component of SF12 scale at follow up greater than 3 months [MODERATE].
- One study with 307 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo at improving quality of life measured by mental component of SF12 scale at follow up greater than 3 months [MODERATE].
- Two studies with 938 people with osteoarthritis of the knee showed that there may be no clinically important difference between chondroitin and placebo with respect to patient’s global assessment of disease status at follow up greater than 3 [MODERATE].
- Tweleve studies with 2578 people with osteoarthritis of the knee showed that there may be no difference between chondroitin and placebo int the total number of people reporting adverse events (GI, cardiovascular, infections, pruritis and back pain)at short term and long term follow up [MODERATE].
- Two studies with 243 people with osteoarthritis of the knee suggested that there may be no difference between chondroitin and placebo in the number of people reporting adverse events events (GI, cardiovascular, infections, pruritis and back pain) at follow up less than 3 months [VERY LOW].
- Ten studies with 2335 people with osteoarthritis of the knee suggeseted that there may be no difference between chondroitin and placebo in the number of people reporting adverse events events (GI, cardiovascular, infections, pruritis and back pain) at follow up greater than 3 months [Low quality].
Chondroitin sulfate vs. placebo- hip OA
- One study with 104 people with osteoarthritis of the hip suggested that chondroitin may be clinically more effective than placebo at decreasing pain measured on the visual analogue scale(VAS)at follow up greater than 3 months, however there was some uncertainty surrounding this effect [LOW].
Chondroitin sulfate vs. placebo- hand OA
- One study with 139 people with osteoarthritis of the hand showed that there may be no clinically important difference between chondroitin and placebo at decreasing pain measured on the visual analogue scale (VAS)at follow up of greater than 3 months [HIGH].
- One study with 139 people with osteoarthritis of the hand showed that there may be no clinically important difference between that chondroitin and placebo at improving function measured by the FIHOA score at follow up greater than 3 months [HIGH].
- One study with 162 people with osteoarthritis of the hand showed that three may be no difference between chondroitin and placebo in the number of people reporting adverse events (GI, musculoskeletal, disorders relating to the nervous system, skin and subcutaneous tissue) at follow up of greater than 3 months [HIGH].
Chondroitin sulfate vs NSAIDs-knee OA
- One study with 636 people with osteoarthritis of the knee showed that chondrotin and NSAIDs may be similarly effective at decreasing pain measured on the WOMAC scale at follow up of greater than 3 months [HIGH].
- One study with 636 people with osteoarthritis of the knee showed that chondrotin and NSAIDs may be similarly effective at improving function measured on the WOMAC scale at follow up of greater than 3 months [HIGH].
- One study with 636 people with osteoarthritis of the knee showed that chondrotin and NSAIDs may be similarly effective at decreasing stiffness measured on the WOMAC scale at follow up of greater than 3 months [HIGH].
- One study with 636 people with osteoarthritis of the knee showed that chondrotin and NSAIDs may be similarly effective at improving responder rate according to the OMERACT-OARSI criteria at follow up of greater than 3 months [HIGH].
- One study with 636 people with osteoarthritis of the knee showed that chondrotin and NSAIDs may be similarly effective with respect to patient’s global assessment of disease status at follow up of greater than 3 months [HIGH].
- One study with 636 people with osteoarthritis of the knee suggested that there may be fewer people withdrawing due to adverse events adverse events in the NSAID group compared to the chondroitin group at follow up of greater than 3 months, however there was some uncertainty surrounding this effect [MODERATE].
Glucosamine sulfate or glucosamine hydrochloride and chondroitin sulfate vs. placebo- knee OA
- Two studies with 719 people with knee osteoarthritis showed that there may be no clinically important difference between a combination of glucosamine and chondroitin and placebo in decreasing pain measured on the WOMAC scale at a follow up greater than three months [LOW].
- Two studies with 719 people with knee osteoarthritis showed that there may be no clinically important difference between a combination of glucosamine and chondroitin and placebo in improving function measured on the WOMAC scale at follow up of greater than three months [LOW].
- One study with 630 people with knee osteoarthritis showed that there may be no clinically important difference between a combination of glucosamine and chondroitin and placebo in decreasing stiffness measured on the WOMAC scale at follow up greater than three months [LOW].
- One study with 630 people with knee osteoarthritis showed that there may be no clinically important difference between a combination of glucosamine and chondroitin and placebo with respect to patient’s global assessment of disease status at follow up greater than three months [LOW].
- One study with 630 people with knee osteoarthritis suggested that there may be no clinically important difference between a combination of glucosamine and chondroitin and placebo in improving responder rate according to the OMERACT-OARSI criteria at follow up greater than three months [VERY LOW].
- One study with 93 people with knee osteoarthritis suggested that there may be no clinically important difference between a combination of glucosamine and and placebo in improving function measured with the Lequesne index at follow up greater than three months, but the effect size was too small to be clinically effective and there was some uncertainty [LOW].
- One study with 59 people with knee osteoarthritis suggested that a combination of glucosamine and chondroitin may be clinically more effective than placebo at decreasing pain measured on the visual analogue scale (VAS) at follow up less than three months, however there was uncertainty surrounding this effect. [MODERATE].
- One study with 59 people with knee osteoarthritis suggested that a combination of glucosamine and chondroitin may be clinically more effective than placebo at improving quality of life measured by the physical component of SF36 at follow up of less than three months, however there was uncertainty surrounding this effect [LOW].
- One study with 59 people with knee osteoarthritis suggested that placebo may be clinically more effective than a combination of glucosamine and chondroitin at improving quality of life measured by the mental component of SF36 at follow up of less than three months [MODERATE].
Glucosamine sulfate or glucosamine hydrochloride and chondroitin sulfate vs. NSAIDs- knee OA
- One study with 635 people with knee osteoarthritis showed that a combination of glucosamine and chondroitin and NSAIDs were similarly effective at decreasing pain measured on the WOMAC scale at follow up of greater than three months [LOW].
- One study with 635 people with knee osteoarthritis showed that a combination of glucosamine and chondroitin and NSAIDs were similarly effective at improving function measured on the WOMAC scale at follow up of greater than three months [LOW].
- One study with 635 people with knee osteoarthritis showed that a combination of glucosamine and chondroitin and NSAIDs were similarly effective at decreasing stiffness measured on the WOMAC scale at follow up of greater than three months [LOW].
- One study with 635 people with knee osteoarthritis showed that a combination of glucosamine and chondroitin and NSAIDs were similarly effective at improving patient’s global assessment of disease status at follow up of greater than three months [LOW].
- One study with 635 people with knee osteoarthritis showed that a combination of glucosamine and chondroitin and NSAIDs were similarly effective at improving responder rate according to OMERACT-OARSI criteria at follow up of greater than three months [LOW].
Economic
- One study found that glucosamine sulfate was not cost effective compared with current care (ICER = £21,335). This study was partially applicable with minor limitations.
- One study found that glucosamine sulfate was dominant compared with paracetamol, and cost effective compared with placebo (ICER = £3,950). This study was partially applicable with potentially serious limitations.
- One study found Chondroitin sulfate was not cost effective compared with placebo (ICER = £23,637). This study was partially applicable with potentially serious limitations.
8.4.6. Recommendations and link to evidence
Recommendation |
|
---|---|
Relative values of different outcomes | The GDG considered that pain, function, structure modification and adverse events profile to be the critical outcomes for decision-making. Other important outcomes were stiffness, the OMERACT OARSI responder criteria and the patient’s global assessment. |
Trade off between clinical benefits and harms | The GDG reviewed the evidence for the use of glucosamine and chondroitin in isolation and in combination. The evidence for their use was also considered in relation to the joint involved. The GDG identified the important joints as hip; knee and hand. The effect of the nutraceuticals can be divided into symptom modifying effects, and structure modifying effects. After reviewing the clinical evidence, the GDG felt that the symptom modifying data (e.g. improvement in pain or function) were not positive enough to warrant a change in the recommendation. The GDG noted that any degree of structure modification should be taken as clinically important, thus the MID chosen for structural modification outcomes was the line of no effect or zero. The relative lack of data, inconsistent effects on structural modification, and radiological method of measurement of structure modification were also noted. Glucosamine The GDG considered that there was a no clinically important difference with all glucosamine preparations when compared to placebo in OA of the knee for the critical outcomes of pain, (both for pooled measures of pain and WOMAC) WOMAC function and WOMAC stiffness at both short and long term, and the OMERACT OARSI responder criteria at less than three months. The level of evidence ranged from moderate to very low quality. The GDG considered that despite the evidence for a clinically significant reduction of pooled pain with licensed glucosamine sulfate at less than 3 months, the evidence stemmed from only one study 365 with 20 participants and thus was deemed insufficient as a basis for a recommendation on the analgesic effect of licensed glucosamine sulfate. There was no clinically important difference between glucosamine and placebo in osteoarthritis of the hip in pain, WOMAC pain, WOMAC stiffness or WOMAC function at more than three months. There was no clinically important difference with licensed glucosamine sulfate when compared with placebo in OA of the knee for pain (pooled measures) for long-term outcomes. There was a possible clinical benefit of licenced glucosamine when compared to placebo in OA of the knee for the Lequesne index at more than three months, and the OMERACT-OARSI responder index at more than three months but there was uncertainty in these effects and the evidence ranged from very low to moderate quality. The effect size of licensed glucosamine sulfate was too small to be clinically effective for WOMAC pain, function, and stiffness at more than three months and the evidence was of moderate quality. This was also the case for minimum joint space width, where despite a clinical effect, the evidence ranged from very low to moderate quality. There was a possible clinical benefit with licensed glucosamine sulfate when compared to NSAIDs for pain in OA of the knee (pooled measures in the long term) but there was uncertainty in the effect and the evidence was of moderate quality. Low quality evidence suggested that licensed glucosamine sulfate may be more effective at bringing about a change in minimum joint space width loss at follow up of greater than three months compared to placebo, but moderate quality evidence from one three year study suggested licensed glucosamine sulfate and placebo were similarly effective in maintaining mean joint space width at follow up greater than three months. Overall, the GDG considered that there was no difference in safety between licensed glucosamine sulfate and placebo. One study (Herrero-Beaumont 2007) examined the use of licenced glucosamine sulfate compared to paracetamol in knee osteoarthritis and found no clinically important difference in the reduction of pain as measured by the WOMAC scale, improvement in function as measured on the WOMAC scale and the Lequesne index, or the numbers of responders according to OMERACT-OARSI criteria at 6 months. The evidence ranged from moderate to high quality. One conference abstract (Patru 2012) examined the use of licenced glucosamine sulfate compared to paracetamol in hand osteoarthritis. Little methodological information was available from the abstract and its evidence was deemed of low quality. In the critical outcome of pain, there was similar efficacy of both agents. Glucosamine and chondroitin in combination There was a possible clinical benefit with glucosamine and chondroitin in combination when compared to placebo in osteoarthritis of the knee in decreasing pain as measured by a VAS, and improving the SF-36 physical component at less than 3 months, but no clinically important difference between the two in terms of WOMAC pain, function and stiffness at more than 3 months was shown. As such, the GDG considered that the evidence for an analgesic effect with the use of glucosamine and chondroitin in combination was neglible. Chondroitin The GDG discussed the clinical evidence for chondroitin which showed a possible benefit of chrondroitin over placebo at reducing pain as measured on a visual analogue scale (VAS) at combined short and long term outcomes although there was uncertainty surrounding these effects and the quality of the evidence ranged from low to very low. At short term outcomes alone (<13 weeks) chondroitin is favoured compared to placebo, however the quality of this evidence was low. Moderate quality evidence suggested chondroitin may be more effective in bringing about change in minimum joint space width loss at a follow up of more than 13 weeks compared to placebo. |
Economic considerations | Analysis from the previous guideline looked at the cost-effectiveness of glucosamine or chondroitin compared to placebo. This found that only glucosamine sulfate was cost effective with a cost per QALY below £20,000. However the CG59 analysis was deemed to be simplistic and was assessed as having potentially serious limitations. These include only considering the direct cost of the interventions, not considering adverse events or decrease in use of other medicines due to increased well being. Three cost-effectiveness analyses were identified from the update search for this area. One study by Bruyere (2009) found that chondroitin sulfate was not cost effective compared with placebo. This study had potentially serious limitations as it underestimated the total costs. For this reason, the costs and ICER were recalculated by the NCGC health economist using the data reported in the study and more recent UK costs. The GDG were satisfied by this evidence that chondroitin was not cost effective. Two studies looked at the cost-effectiveness of glucosamine. A study by Black (2009) found glucosamine sulfate was not cost effective compared to usual care. The other study by Scholtissen (2010) found that glucosamine sulfate was cost effective compared to paracetamol and placebo. The GDG placed a higher weighting on the glucosamine study by Black, as this was of higher quality, was a Health Technology Appraisal and was more applicable to the NHS setting (UK study). The difference in the cost per QALY between the two glucosamine studies appeared substantial, the main contributor to this difference are the drug costs from each study. The drug costs in the Scholtissen (2010) study appear very low compared to the other studies and to the actual drug cost in the UK, which would bias the results by making glucosamine more cost effective. Additionally, glucosamine being cheaper than paracetamol in this study does not reflect actual UK drug costs. The possible concern of omitting side effects was discussed, as none of the three studies incorporated the side effects of the drugs. If adverse events were included in the Scholtissen study, then glucosamine may appear even more cost effective compared to paracetamol. It is accepted that nutraceuticals are relatively safe, however it was noted that if the Black paper (where the cost per QALY is just over the threshold of £20,000) included side effects of both intervention and comparator, then the side effects associated with current care (which includes medications) could cause glucosamine to appear more favourable. Additionally, if nutraceuticals reduce the need for other drugs in the future, then excluding this will also bias against glucosamine. Therefore glucosamine might be more cost effective if these factors were taken into account. Although glucosamine may appear cost effective in some studies (Scholtissen and CG59 analysis) or when side effects are taken into account in the Black study, by looking at the results of the clinical review the GDG considered the increase in effectiveness observed with glucosamine was not clinically important and therefore considered the results of the cost-effectiveness analyses driven by negligible and non-significant improvement. Interventions should first be proven effective (compared to placebo) before considering cost effectiveness. The GDG noted the lack of clinical data on structural modification. The decision model in the study by Black (2009) included a health state entitled ‘progression to total knee replacement’. There was a lower probability of progressing to this state for those patients in the glucosamine group (these probabilities were taken from Bruyere (2008), which found a clinically significant decrease and delayed cumulative incidence of total knee replacement for people who had previously taken glucosamine sulfate). As Bruyere (2008) was the only study identified which looked at the outcome of time to joint replacement, the GDG were uncertain about its effects. If this were not included in the Black model, it is likely that the ICER would have been higher. If it is indeed the case that glucosamine reduces the need for joint replacement, then this will have a positive impact on downstream resource use and costs. |
Quality of evidence | Data in the meta-analysis conducted by the GDG was stratified by joint type and by licensing indication. All relevant studies assessing licensed glucosamine sulfate were reviewed and stratified accordingly either based on the information provided in the study or as indicated by the Cochrane Review. The GDG are aware of licensed preparations of glucosamine hydrochloride, but none of the retrieved studies has referred to a licensed preparation. No separate analysis of studies with unlicensed preparations of glucosamine sulfate was undertaken as it was recognised that such studies may have potentially involved the use of preparations licensed outside of the UK. All studies included in the clinical evidence review included unlicensed preparations of chondroitin. The GDG considered the quality of evidence when considering whether any changes to the existing recommendation should be made. All glucosamine preparations when compared to placebo in OA of the knee for the critical outcome of pain showed no clinically important difference in the effect and the evidence ranged from very low to low quality. After examining a sensitivity analysis in the clinical review, which separated high and low quality studies (i.e. low and high risk of bias respectively), the GDG decided that the overall evidence on effectiveness of glucosamine sulfate and chondroitin remained very limited and uncertain. |
Other considerations | The GDG noted that the evidence demonstrated that there was no clinically important difference between chondroitin and placebo in WOMAC pain, stiffness or function at time points greater than 3 months even though low quality short term outcome data demonstrated efficacy compared to placebo at <13 weeks . The GDG felt overall therefore that this did not demonstrate clinical efficacy and chose not to recommend chondroitin products. The GDG also considered that despite the evidence for a clinically significant reduction of pain with licensed glucosamine sulfate in the short term, this evidence stemmed from only one study with 20 patients365 and as such this was deemed insufficient evidence for a positive recommendation. The GDG also noted the lack of data on structural modification. There was limited evidence identified for the time to joint replacement outcome. The GDG noted a study (Bruyere et al, 2008) which followed up patients from two RCTs, and the results showed fewer joint replacement operations in the group who took glucosamine sulfate in the RCTs. The GDG were aware that many combinations and compounds of nutraceuticals are available for purchase as health food supplements and are sold over the counter in a variety of settings. The GDG were concerned that the advice contained within a NICE guideline may influence people with osteoarthritis in their purchasing patterns of these products. The GDG felt that the over the counter preparations were not always regulated in terms of their strength and purity and felt strongly that they should make comment only on products whose content is licensed and regulated as outlined in the BNF and on the advice of the Medicines and Healthcare Regulatory Authority (MHRA). The technical team therefore sought advice from the GDG, including the GDG pharmacist, on the available licensed nutraceuticals in the UK and have considered this evidence when discussing advice for the NHS. The GDG have assumed that Glusartel is the licensed UK equivalent of the Rottapharm preparation, which is mentioned in the Cochrane Review and throughout the studies included in this evidence review. Therefore, in light of the overall limited and uncertain evidence on effectiveness of all glucosamine and chondroitin preperations, the GDG chose not to recommend them for use in the NHS. Research recommendation The GDG agreed to draft a research recommendation on therapies that can modify joint structures resulting in delayed structural progression and improved patient outcomes. For further details on research recommendations, see Appendix N. |
8.5. Acupuncture
8.5.1. Introduction
The Chinese discovered acupuncture about 2000 years ago, and their explanation of how it works has changed over time, as world views evolved. In the 1950s, all these explanations were combined into the system currently known as ‘traditional Chinese acupuncture’. This approach uses concepts that cannot be explained by conventional physiology, but remains the most common form of acupuncture practised throughout the world. In the UK, doctors and physiotherapists are increasingly using acupuncture on the basis of neurophysiological mechanisms, known as ‘Western medical acupuncture’, whereas acupuncturists outside the NHS tend to use traditional Chinese acupuncture, and sometimes add Chinese herbs.
Acupuncture involves treatment with needles, and is most commonly used for pain relief. They will be either manipulated to produce a particular ‘needle sensation’, or stimulated electrically (electroacupuncture) for up to 20 minutes. Some practitioners also use moxa, a dried herb which is burned near the point to provide heat. A course of treatment usually consists of six or more sessions during which time, if a response occurs, pain relief gradually accumulates.
The potential mechanisms of action of acupuncture are complex in terms of neurophysiology, and involve various effects including the release of endogenous opioids.
Research into acupuncture has also proved complex. As with surgery and physiotherapy, it is impossible to blind the practitioner and it is difficult to blind the participant. The GDG wished to review the evidence regarding the use of acupuncture in the management of osteoarthritis.
8.5.2. What is the clinical and cost-effectiveness of acupuncture versus sham treatment ( sham control) and other interventions in the management of osteoarthritis?
For full details see review protocol in Appendix C. Outcomes for this review were grouped and evaluated at two time points:
- Short term- Time points less than 3 months and closest to 8 weeks after baseline
- Long term- Time points greater than or equal to 26 weeks after baseline
Trials which assessed outcomes at less than 6 weeks follow-up were excluded from this review as less than this length of follow-up was not considered adequate to assess the effectiveness of acupuncture for OA.
8.5.3. Clinical evidence
We searched for randomised trials comparing the effectiveness of acupuncture versus sham ( sham control) treatment or other interventions for the management of OA.
One Cochrane review278 on the use of acupuncture for the management of peripheral joint arthritis was identified and was updated as part of this review The Cochrane review included 16 RCTs. Of these, 10 RCTs compared acupuncture to sham acupuncture. Nine of these RCTs were in people with OA of the knee and one was in people with OA of the hip.. In addition, six additional RCTs were identified since the publication of the Cochrane review215, 216, 226, 253, 261, 432.
Of the six additional studies identified since publication of the Cochrane review four were found to compare acupuncture to sham acupuncture 215,226,261,432. Of the other two studies one 215 compared acupuncture to transcutaneous electrical nerve stimulation (TENS) and the other 253 compared acupuncture to usual care (which included any appointments, medications and interventions sought by participants from any health practitioner). All the studies evaluated acupuncture based on traditional Chinese acupuncture points. Of these, one reported Knee Society Scores for pain and function and the results are presented separately261. Another RCT presented the results in graphs and did not report standard deviations or standard errors for any of the values215. The data for this RCT have not been included in the meta-analysis, although the information is presented in the evidence tables.
In addition to the Cochrane review and updated studies, an Individual Patient Data Meta-Analysis 474 was also identified. This IPD involved analysis of acupuncture vs. sham acupuncture and acupuncture versus no acupuncture on people with OA. This study included only high quality studies with adequate allocation concealment and studies that reported results at more than four weeks follow up. Both fixed effects and random effects coefficients were calculated. For the comparison of acupuncture versus sham acupuncture the effect sizes quoted from each constituent trial were imputed into our meta-analysis at the appropriate time point for each trial, as the effect sizes quoted in the IPD are likely to represent a more accurate estimate than those quoted in the original trials due to the nature of the IPD analysis.
We set out to conduct sensitivity analysis for studies where blinding was adequate, as undertaken by the Cochrane review. Among the studies comparing acupuncture to sham acupuncture, some trials additionally reported the assessment of blinding by the participants150,226,404,432,498. When acupuncture and sham were found to be indistinguishable, the sham was confirmed to have achieved blinding. A sensitivity analysis was carried out with these trials in the meta-analyses. The results of the sensitivity analysis are presented in a separate table (see Table 121).
Table 119
Clinical evidence profile: Acupuncture versus sham acupuncture-Knee OA.
Table 120
Acupuncture versus sham acupuncture-Hip OA.
Table 121
Acupuncture versus sham-Sensitivity analysis with trials judged to have adequate blinding -Knee OA.
Table 122
Acupuncture vs. waiting list control or other active treatments-Knee OA.
Table 123
Acupuncture vs. waiting list control or other active treatments-Hip OA.
8.5.4. Economic evidence
Evidence from CG59
Published literature
One study499 comparing acupuncture plus usual care versus usual care was included in CG59. This paper has now been supplemented with a more detailed paper from the same study found in the update search 377,488. This study looked at the cost-effectiveness of acupuncture plus usual care, compared with usual care. This was a German study with a time horizon of 3 months (follow up and treatment duration). This is summarised in the economic evidence profile below (Table 124).
Table 124
Economic evidence profile: Acupuncture as an adjunct based on pragmatic trials.
Original analysis
An original cost-effectiveness analysis was conducted for CG59 using four RCTs 32,400,404,498 (included in the original guideline review) comparing acupuncture or electro-acupuncture with sham acupuncture. WOMAC scores were taken from the RCTs and mapped onto EQ-5D using the formula from Barton 2008. Only direct costs of the interventions were considered, either a 30 or 20 minute session with a physiotherapist and the cost of the needles.
A summary of this analysis can be found in Appendix M.
Evidence statements have not been drafted for the CG59 analysis as this has not been updated in this guideline update, and more weight was placed by the GDG on cost effectiveness and clinical evidence from the update guideline.
Evidence from update guideline
Published literature
One study488 was found, which looked at the cost effectiveness of acupuncture plus advice and exercise, compared with advice and exercise. This was a UK study, with a treatment duration of 6 weeks, with a follow up duration of 12 months.
This is summarised in the economic evidence profile below (Table 124). See also the study selection flow chart in Appendix E and study evidence tables in Appendix H
The two studies comparing acupuncture as an adjunct have a similar QALY gain, even though Whitehurst has a time horizon four times longer than that of Reinhold.
Explanations for this are: the length of the treatment duration (3 months for Reinhold and only 6 weeks for Whitehurst).
The clinical review shows that there was a very small difference in the WOMAC pain score (Table 122) in the Foster trial150 (which is the effectiveness data source for Whitehurst). Thus helping to explain why the QALY gain is smaller than that of the Reinhold study, despite a longer time horizon.
8.5.5. Evidence statements
Clinical
Acupuncture vs. Sham (short term)
- Ten studies with 2290 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in decreasing pain measured on the WOMAC scale [LOW].
- Five studies with 800 people with osteoarthritis of the knee suggested that acupuncture may be clinically more effective than sham acupuncture in decreasing pain measured on the visual analogue scale (VAS) however there was some uncertainty [VERY LOW].
- One study with 55 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in decreasing pain measured on the Knee Society Score [LOW].
- Ten studies with 2285 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving function measured on the WOMAC scale [LOW ].
- One study with 55 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving function measured on the Knee Society score [LOW].
- Six studies with 603 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in decreasing stiffness measured on the WOMAC scale [VERY LOW].
- One study with 68 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life measured on the EuroQoL [LOW].
- One study with 455 people with osteoarthritis of the knee showed that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the physical subscale of SF12) [HIGH].
- One study with 455 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the mental subscale of SF12) [HIGH].
- Two studies with 556 people with osteoarthritis of the knee showed that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the physical subscale of SF36), [HIGH].
- One with 218 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the mental subscale of SF36) [HIGH].
Acupuncture vs. Sham (Long term)
- Four studies with 1400 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in decreasing pain measured on the WOMAC scale [HIGH].
- Four studies with 1400 people with osteoarthritis of the knee showed that acupuncture and sham acupuncture may be similarly effective at improving function measured on the WOMAC scale [HIGH].
- Two studies with 896 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective at improving stiffness measured on the WOMAC scale [HIGH].
- One study with 678 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the physical subscale of SF12) [HIGH].
- One study with 678 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the mental subscale of SF12) [HIGH].
- Two studies with 501 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly in improving quality of life (measured on the physical subscale of SF36) [HIGH].
- One with 218 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective in improving quality of life (measured on the mental subscale of SF36) [HIGH].
- One study with 369 people with osteoarthritis of the knee suggested that acupuncture and sham acupuncture may be similarly effective at improving responder rate on the OMERACT-OARSI criteria, [LOW].
- One study with 52 people with osteoarthritis of the hip suggested that acupuncture and sham acupuncture may be similarly effective in decreasing pain measured on the WOMAC scale [LOW].
- One study with 52 people with osteoarthritis of the hip suggested that acupuncture and sham acupuncture may be similarly effective in improving function measured on the WOMAC scale [LOW].
Acupuncture vs. waiting list control or other active treatment (short term)
- Seven studies with 893 people with osteoarthritis of the knee showed that acupuncture was clinically more effective than waiting list control in decreasing pain measured on the WOMAC pain scale [LOW].
- One study with 294 people with osteoarthritis of the knee suggested that acupuncture was clinically more effective than supervised osteoarthritis education in decreasing pain measured on the WOMAC pain scale, but there was some uncertainty. [LOW].
- One study with 218 people with osteoarthritis of the knee suggested that as an adjunct to exercise-based physiotherapy and exercise-based physiotherapy alone may be similarly effective in decreasing pain measured on the WOMAC pain scale [LOW].
- One study with 121 people with osteoarthritis of the knee suggested that acupuncture and home exercise and advice leaflet may be similarly effective in decreasing pain measured on the WOMAC pain scale [LOW].
- One study with 120 people with osteoarthritis of the knee suggested that acupuncture and supervised exercise alone may be similarly effective in decreasing pain measured on the WOMAC pain scale [MODERATE].
- One study with 624 people with osteoarthritis of the knee suggests that acupuncture may be more clinically effective than physician consultations with a physiotherapy co-intervention in decreasing pain measured on the WOMAC pain scale, but there was some uncertainty [LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and TENS may be similarly effective in decreasing pain measured on the WOMAC pain scale[LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and acupuncture with TENS may be similarly effective in decreasing pain measured on the WOMAC pain scale [VERY LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and TENS may be clinically more effective than waiting list control in decreasing pain measured on the WOMAC pain scale, but there was some uncertainty [VERY LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture with TENS and TENS alone may be similarly effective in decreasing pain measured on the WOMAC pain scale [VERY LOW].
- Three studies with 261 people with osteoarthritis of the knee suggested that acupuncture may be clinically more effective than waiting list control in decreasing pain measured on a VAS scale, but there was some uncertainty [VERY LOW].
- One study with 121 people with osteoarthritis of the knee suggested that acupuncture and home exercises + advice leaflet may be similarly effective at decreasing pain measured on a VAS scale result [LOW].
- One study with 120 people with osteoarthritis of the knee suggested that acupuncture and supervised exercise may be similarly effective at decreasing pain measured on a VAS scale [LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture may be clinically more effective than TENS in decreasing pain measured on a VAS scale, but there was some uncertainty [VERY LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and acupuncture + TENS may be similarly effective in decreasing pain measured on a VAS scale [VERY LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and TENS and waiting list control may be similarly effective in decreasing pain measured on a VAS scale, but there was some uncertainty [VERY LOW].
- One study with 16 people with osteoarthritis of the knee suggested that acupuncture and TENS may be clinically more effective than TENS alone in decreasing pain measured on a VAS scale, but there was some uncertainty [VERY LOW].
- Five studies with 852 people with osteoarthritis of the knee suggested that acupuncture may be clinically more effective than waiting list control in improving function as measured with the WOMAC function scale, [LOW].
- One study with 294 people with osteoarthritis of the knee suggested that acupuncture may be more clinically effective than supervised osteoarthritis education in improving function as measured with the WOMAC function scale, but there was some uncertainty [LOW].
- One study with 218 people with osteoarthritis of the knee suggested that acupuncture + exercise-based physiotherapy program and an exercise-based physiotherapy program alone may be similarly effective at improving function as measured with the WOMAC function scale [MODERATE].
- One study with 121 people with osteoarthritis of the knee suggested that acupuncture and home exercise or advice leaflet may be similarly effective at improving function as measured with the WOMAC function scale[LOW].
- In one study with 120 people with osteoarthritis of the knee acupuncture and supervised exercise may be similarly effective at improving function as measured with the WOMAC function scale [MODERATE].
- One study with 623 people with osteoarthritis of the knee showed that acupuncture was clinically more effective than physician consultations with a physiotherapy co-intervention in improving function as measured with the WOMAC function scale [MODERATE].
- Four studies with 579 people with osteoarthritis of the knee showed that acupuncture was clinically more effective than waiting list control at improving stiffness as measured with the WOMAC stiffness scale [VERY LOW].
- One study with 73 people with osteoarthritis of the knee suggested that acupuncture may be clinically more effective than waiting list control at improving function as measured with the Lequesne Index, but there was some uncertainty [HIGH].
- One study with 30 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective at improving quality of life measured by EQ5D [VERY LOW].
- One study with 455 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective at improving quality of life measured by SF12-physical component, [MODERATE].
- One study with 455 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective at improving quality of life measured by SF12-mental component, [HIGH].
- Two studies with 499 people with osteoarthritis of the knee shows that acupuncture was clinically more effective than waiting list control at improving quality of life measured by SF36 physical component [HIGH].
- One study with 294 people with osteoarthritis of the knee suggested that acupuncture and supervised osteoarthritis education may be similarly effective at improving quality of life measured by SF36 Physical component, [LOW].
- Two studies with 499 people with osteoarthritis of the knee showed that acupuncture and waiting list control may be similarly effective at improving quality of life measured by SF36-Mental component at follow up of less than three months from baseline, but [HIGH].
Acupuncture vs. waiting list control or other active treatment (Long term)
- One study with 30 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective in reduction of pain measured by WOMAC pain [VERY LOW].
- One study with 250 people with osteoarthritis of the knee suggests that acupuncture may be clinically more effective than supervised osteoarthritis education in reduction of pain measured by WOMAC Pain scale, but there was some uncertainty [LOW].
- One study with 213 people with osteoarthritis of the knee suggests that acupuncture and exercise-based physiotherapy compared to exercise-based physiotherapy alone are similarly effective at reducing pain measured by WOMAC pain scale [MODERATE].
- One study with 625 people with osteoarthritis of the knee suggests that acupuncture may be clinically more effective than physician consultation with a physiotherapy co-intervention in reduction of pain measured by WOMAC Pain scale but there is some uncertainty [LOW].
- One study with 30 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective in improving function measured by WOMAC function scale [VERY LOW].
- One study with 250 people with osteoarthritis of the knee suggests that acupuncture may be clinically more effective than supervised osteoarthritis education at improving function measured by WOMAC function scale but there was some uncertainty [LOW].
- One study with 218 people with osteoarthritis of the knee suggested that acupuncture and exercise based physiotherapy and exercise based physiotherapy program alone are similarly effective at improving function measured by WOMAC function scale [MODERATE].
- One study with 625 people with osteoarthritis of the knee suggests that acupuncture may be clinically more effective than physician consultations with a physiotherapy co-intervention at improving function measured by WOMAC function scale, but there was some uncertainty [LOW].
- One study with 30 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective at improving stiffness measured by WOMAC stiffness scale [VERY LOW ].
- One study with 624 people with osteoarthritis of the knee suggested that acupuncture and physician consultations with a physiotherapy co-intervention may be similarly effective at improving stiffness measured by WOMAC Stiffness scale, but [LOW].
- One study with 30 people with osteoarthritis of the knee suggested that acupuncture and waiting list control are similarly effective at improving quality of life as measured by EQ5D [VERY LOW].
- One study with 624 people with osteoarthritis of the knee suggested that acupuncture and physician consultations with a physiotherapy co-intervention may be similarly effective in improving quality of life as measured with the SF12 Physical component, but there was some uncertainty [LOW].
- One study with 624 people with osteoarthritis of the knee suggested that acupuncture and physician consultations with a physiotherapy intervention are similarly effective at improving quality of life measured by SF12 Mental component [MODERATE].
- One study with 317 people with osteoarthritis of the knee showed that acupuncture was clinically more effective than waiting list control in improving quality of life measured by SF36 Physical component [MODERATE].
- One study with 294 people with osteoarthritis of the knee showed that and supervised osteoarthritis education may be similarly effective in improving quality of life measured by SF36 Physical component [LOW].
- One study with 624 people with osteoarthritis of the knee suggested that acupuncture and physician consultations with a physiotherapy co-intervention was similarly effective at improving quality of life measured by SF36 Physical component [MODERATE].
- One study with 317 people with osteoarthritis of the knee suggested that acupuncture and waiting list control may be similarly effective in improving quality of life measured by SF36 Mental component, [MODERATE].
- One study with 360 people with osteoarthritis of the knee showed that acupuncture was clinically more effective than supervised osteoarthritis education in improving OMERACT-OARSI responder rate although there was some uncertainty [MODERATE].
Hip OA
- One study with 75 people with osteoarthritis of the hip showed that acupuncture was clinically more effective that waiting list control in reducing pain measured with the WOMAC pain scale at follow up of less than three months from baseline [MODERATE].
- One study with 75 people with osteoarthritis of the hip showed that acupuncture was clinically more effective that waiting list control in improving function measured with the WOMAC function scale at follow up of less than three months from baseline [MODERATE].
- One study with 75 people with osteoarthritis of the hip showed that acupuncture was clinically more effective that waiting list control in improving joint stiffness measured with the WOMAC stiffness scale at follow up of less than three months from baseline [MODERATE].
- One study with 75 people with osteoarthritis of the hip showed that acupuncture was clinically more effective that waiting list control in improving quality of life measured by SF36 Physical component at follow up of less than three months from baseline [MODERATE].
- One study with 75 people with osteoarthritis of the hip suggested that acupuncture and waiting list control may be similarly effective in improving quality of life measured by SF36 mental component at follow up of less than three months from baseline, but [LOW].
Economic
- One cost-utility analysis found that acupuncture + usual care compared with usual care was cost effective (£13,354 per QALY gained). This study was assessed as partially applicable with minor limitations.
- One cost-utility analysis found that acupuncture + advice and exercise compared with advice and exercise was cost effective (£3,889 per QALY gained). This study was assessed as directly applicable with minor limitations.
8.5.6. Recommendations and link to evidence
Recommendations |
|
---|---|
Relative values of different outcomes | The GDG considered pain and function to be the critical outcomes for decision-making. Other important outcomes were stiffness, OMERACT OARSI responder criteria and the patient’s global assessment. |
Trade-off between clinical benefits and harms | The GDG considered the comparison of acupuncture to sham acupuncture to be the most appropriate clinical comparison to assess the benefits and harms of acupuncture. Results were stratified by joint and data were available on knee and hip for this review. In looking at interventions appropriate controls are needed. When the GDG considered the evidence for the efficacy of a given therapy, the primary comparison for decision making involved looking at active therapies versus placebo, and in the case of device studies versus sham control. They then also considered other comparators where placebo or sham were not available or inappropriate, such as when looking at toxicity and cost effectiveness. The GDG understand and were aware of the considerable effect size of contextual response in clinical trials and in practice for all therapies. Where possible we tried to discern the specific treatment efficacy element that relates to the treatment rather than contextual response. Where such trials exist as to allow for the effective measurement of contextual response they must form the primary comparator for decision making, to ensure we are recomending a therapy with a scientifically proven treatment response. The GDG therefore believe that sham is the appropriate comparator to elicit the specific treatment efficacy for acupuncture. Knee OA No clinically important difference was found between acupuncture and sham acupuncture in OA of the knee in the critical outcomes of pain reduction (WOMAC scale, and the knee pain severity score), functional improvement (WOMAC and function knee society score) and reduction of stiffness (WOMAC stiffness scale) at short and long term time points. (Short term-time points less than 3 months and closest to 8 weeks after baseline and long term-time points greater than or equal to 26 weeks after baseline). This finding remained in a sensitivity analysis, which assessed only studies that had conducted adequate blinding. Five studies suggested that acupuncture may be clinically more effective than sham acupuncture in decreasing pain measured on a visual analogue scale (VAS) at short term time points, however there was some uncertainty surrounding this effect and when selecting those studies which had adequate blinding this effect disappeared and no clinically important difference between acupuncture and sham acupuncture was demonstrable. Hip OA No clinically important difference was found between acupuncture and sham acupuncture in OA of the hip in the critical outcomes of pain reduction (VAS) or functional improvement (Lequesne index). Overall, even though there was no evidence that acupuncture was harmful, the efficacy data failed to reach the level of a clinically important difference of acupuncture over sham acupuncture. This led the GDG to support a ‘do not offer acupuncture’ recommendation. |
Economic considerations | It is widely accepted that large pragmatic randomised trials are the best study design on which to base an economic evaluation, as this will capture the cost-effectiveness of an intervention as it would be used in practice, compared to what is currently standard care or in addition/as an adjunct to standard care. The cost-effectiveness of acupuncture versus sham acupuncture is not of interest, since we are interested in the benefits and opportunity costs that would occur in practice. Furthermore the incremental cost of acupuncture versus sham acupuncture could be zero, since the staff time, etc involved would most likely be the same. However, an intervention must first be shown to have a clinical benefit, and the best comparator to prove this would be a placebo or sham where possible in order to identify the magnitude of effect over and above the contextual or placebo response. Only if effect has been proven above placebo/sham, should cost-effectiveness evidence looking at an intervention as an adjunct be considered. The CG59 analysis was based on a sham comparison. However given that no costs were included in the sham acupuncture arm, then this should be interpreted as a comparison with usual care, but using sham acupuncture controlled trials. 3 out of 4 studies from the analysis showed acupuncture was not cost effective. This analysis was not updated in this guideline update and was rated as having potentially serious limitations. As mentioned above, economic evaluations based on pragmatic trials are preferred, therefore more weight was placed on the two economic evaluations (based on pragmatic trials) identified from the update search:
In summary, although pragmatic trials are the most suitable to assess the cost-effectiveness of any health intervention, it is also reasonable to expect that each intervention has a proven clinical effect over and above any contextual effect. As noted above this has not yet been proven in the case of acupuncture for osteoarthritis. |
Quality of evidence | One Cochrane review on the use of acupuncture for the management of peripheral joint arthritis was identified and was updated as part of this review. In addition, six RCTs were identified since the publication of the Cochrane review. The Cochrane review only included studies that concerned exclusively participants with OA of one or more of the peripheral joints (i.e. knee, hip, and hand). The Cochrane review included 16 RCTs. Of these, 10 RCTs compared acupuncture to sham acupuncture. Nine of these RCTs were in people with OA of the knee and one was in people with OA of the hip. Knee Acupuncture vs. sham Ten studies were included; and the following outcomes were reported at short term: WOMAC pain, VAS pain, Knee Society Score pain, WOMAC function, KSS function, WOMAC stiffness, and EUROQOL, which all ranged from very low to low quality evidence. For SF12 and SF36, the evidence ranged from moderate to high quality. Acupuncture and sham acupuncture were similarly effective for all outcomes. Outcomes that were reported at long term follow up were: WOMAC Pain, WOMAC function, WOMAC stiffness, SF12, SF36. These all ranged from moderate to high quality evidence and OMERACT-OARSI responder criteria was of low quality. The main limitation was that there was ineffective blinding of sham acupuncture in three studies, and the effect of this was investigated by carrying out sensitivity analysis. The results of the sensitivity analysis are discussed above in the trade off between clinical benefits and harms section for each individual joint An Individual Patient Data (IPD) meta-analysis 474 was also identified. This IPD involved analysis of acupuncture vs. sham acupuncture and acupuncture vs. no acupuncture on people with OA. This analysis included only high quality studies with adequate allocation concealment and studies that reported results at more than 4 weeks follow up. Where applicable the effect sizes were transposed into our own meta-analysis to provide the most accurate estimate of overall effect size. Risk of bias was assessed with GRADE on the basis of the evidence for an outcome across studies. Acupuncture vs. waiting list control or other active treatment Overall, eleven studies compared acupuncture to waiting list control or other active treatment. The short term efficacy outcomes of WOMAC pain, VAS pain, WOMAC function WOMAC stiffness and Lequesne index were all of low or very low quality; all of the efficacy outcomes apart from Lequesne index indicated that acupuncture was more clinically effective than waiting list control. The remaining quality of life outcomes of SF12 and SF36 were of moderate and high quality and all apart from the mental health component of SF36 indicated that people who had acupuncture had an increased quality of life compared to waiting list controls. For long term outcomes, WOMAC pain, function, stiffness and EQ5D were all low or very low quality outcomes and indicated no difference between acupuncture and waiting list. Long term follow up SF36 outcomes were of high quality and indicated that acupuncture groups had a higher quality of life than waiting list control. For all other active treatment comparisons there was only one study included for each comparison. Acupuncture was compared to supervised exercise, supervised OA education, exercise and physiotherapy program, home exercise/advice leaflet and physician consultation. WOMAC pain and function outcomes were reported for all of the comparisons listed, and the quality of the evidence for these outcomes was either moderate or low. For active comparisons, such as exercise and physiotherapy, the acupuncture group and the comparison group tended to be similarly clinically effective. For comparisons such as education and physician consultation, the acupuncture group appeared to gain more clinical benefit than the comparison group. One very small study215 assessed acupuncture+/− TENS vs. TENS or waiting list control in a three arm trial. Short term outcomes of WOMAC pain and VAS pain were reported and the evidence was either low or very low quality The individual patient data meta-analysis mentioned above also conducted an IPD meta-analysis on acupuncture vs. no acupuncture in people with OA. Hip One study compared acupuncture to sham acupuncture. Both VAS pain and function outcomes were of low quality and showed no clinical difference between acupuncture and sham acupuncture. The study had a high number of dropouts and ITT analysis was not conducted. One study compared acupuncture to waiting list control. Short term outcomes were reported for pain, function, stiffness and SF36 Physical and Mental components. SF36 Mental component was low quality, all other outcomes were moderate quality. All outcomes favoured acupuncture, though with uncertainty around the point estimate. It was unclear whether the study was blinded and whether participants received the same co-interventions. |
Other considerations | The co-opted acupuncturist expert pointed out that the majority of the evidence base in acupuncture use Chinese acupuncture points within a Western medicine context. Although the selection of needling points may follow the traditional Chinese system, the majority of studies in the literature described the delivery of the whole acupuncture session using a Western medicine approach to the diagnosis and patient experience of the effects of the acupuncture. The GDG therefore felt that the included studies were applicable to acupuncture practices in the UK. The GDG discussed the fact that although there was some evidence supporting acupuncture it generally came from lower quality evidence. There was concern over the issues of blinding of participants and the GDG also noted the findings of sensitivity analyses conducted to determine whether this impacted on outcome measurement. They particularly noted that the finding from the limited evidence which reported acupuncture as possibly being clinically more effective than sham acupuncture, in decreasing as pain measured on the visual analogue scale (VAS) for knee OA at short term time points, disappeared when sensitivity analysis was conducted related to adequate blinding, and no clinically important difference between acupuncture and sham acupuncture was then demonstrable. In light of the above, the GDG discussed the effect that the contextual factors of the provision of acupuncture, such as of increased clinician interaction time and exercise, may have in addition to the actual needling. The GDG agreed that it was therefore difficult to determine the efficacy of acupuncture beyond the contextual effect, and this factor also contributed to the above recommendation. The GDG did not feel it appropriate to make a recommendation for the use of acupuncture in OA when it was uncertain about its clinical effectiveness in the first instance, although the health economics evidence indicated that acupuncture was cost-effective as an adjunct. There was no new evidence to consider as a result of the research recommendation made in the last guideline which sought to establish whether a specific group of people would particularly benefit from this intervention to inform a future recommendation and therefore the GDG could not be more specific in their recommendation in this regard. Research recommendation The GDG agreed to draft a research recommendation on identification of predictors of response to individual treatments in people with osteoarthritis. For further details on research recommendations, see Appendix N. |
8.6. Aids and devices
8.6.1. Clinical introduction
Walking aids are commonly prescribed for hip and knee OA and their mechanism of efficacy is assumed to be via a biomechanical effect. Chan et al conducted a small trial of cane use (on either side) and examined walking speed and cadence as mediators of effect64. Van der Esch et al identified that 44% of an OA cohort possessed a walking aid (commonly canes), and that being older and greater pain and disability were determinants of use470. Non-use is associated with negative views of walking aids, suggesting that careful attention is needed to prescription and discussing clients’ attitudes to cane use.
People with more severe hip and knee OA are commonly provided with or obtain long-handled reachers, personal care aids (eg sock aids to reduce bending), bath aids, chair and bed raisers, raised toilet seats, perch stools, half steps and grab rails, additional stair rails and may also have home adaptations to improve access internally and externally. Wielandt et al highlighted the importance of carefully matching assistive devices to the patients’ needs489. Factors significantly associated with assistive technology (AT) non-use are: poor perceptions of AT and their benefits; anxiety; poor ability to recall AT training; poor perception of disability/illness; and lack of choice during the selection process. Many people do obtain AT without professional advice and may waste money if their choice is inappropriate due to lack of information.
Splints are commonly used for hand problems, especially OA of the thumb base. Practical advice is given to balance activity and rest during hand use; to avoid repetitive grasp, pinch and twisting motions; and to use appropriate assistive devices to reduce effort in hand function (eg using enlarged grips for writing, using small non-slip mats for opening objects, electric can openers).
8.6.2. Methodological introduction
Footwear, bracing and walking aids
We looked for studies that investigated the efficacy and safety of aids and devices compared to other aids and devices or no intervention/usual care with respect to symptoms, function, quality of life. One Cochrane systematic review and meta-analysis50 was found on braces and insoles and 20 additional RCTs19,33,51,64,96,190,191,201,331,359,366,382,451–455,479,485,486 were found on shoes, insoles, canes, braces, strapping, splinting and taping. Two of these studies452,453 were reports of the same RCT, showing mid-study results452 and end-of study results453. One study359 reports the long-term results of an RCT273 (mid-study results) that was included in the Cochrane systematic review. Five RCTs33,190,201,382,486 were excluded due to methodological limitations. Therefore overall, 12 RCTs were found in addition to the Cochrane review.
The Cochrane MA50 included 4 RCTs (with N=444 participants) that on insoles and braces in people with knee osteoarthritis. Studies were all randomised, parallel-group design but were inadequately blinded (single blind or blinding not mentioned). The RCTs included in the analysis differed with respect to:
- Interventions and comparisons
- Trial size, length, follow-up and quality.
The Cochrane meta-analysis assessed the RCTs for quality and pooled together all data for the outcomes of symptoms and function. However, the outcome of quality of life was not reported because quality of life was not assessed by the individual RCTs included in this systematic review.
The 13 RCTs not included in the Cochrane systematic review differed with respect to:
- osteoarthritis site (11 RCTs knee, 2 RCTs thumb)
- Interventions and comparisons
- Trial size, blinding, length and follow-up.
Assistive devices
We looked for studies that investigated the efficacy and safety of assistive devices versus no devices with respect to symptoms, function and quality of life in adults with osteoarthritis. 1 RCT430 was found on assistive devices and assessed the outcomes of pain and function. Four additional observational studies280,436,440,472 were found on usage and assessment of the effectiveness of assistive devices.
The included RCT was a randomised, single-blind parallel group study.
The 4 observational studies differed with respect to osteoarthritis site, study design, sample size and outcomes measured.
8.6.3. Evidence statements: footwear, bracing and walking aids
Table 125
Symptoms:pain.
Table 126
Symptoms: stiffness.
Table 127
Symptoms: function.
Table 128
Global assessment.
Table 129
Quality of life.
Table 130
Adverse events.
Table 131
Analgesic use.
Table 132
Withdrawals.
Table 133
Structural changes.
8.6.4. Evidence statements: assistive devices
Table 134
Symptoms: pain.
Table 135
Symptoms: function.
Table 136
Use of assistive devices.
Table 137
Patient satisfaction / views of devices.
8.6.5. From evidence to recommendations
There is a paucity of well designed trials in this area, and the GDG considered various additional sources of evidence, including non-controlled studies. Evidence generally showed that aids and devices are well accepted by many people with OA who report high satisfaction with use.
There are limited data for the effectiveness of insoles (either wedged or neutral) in reducing the symptoms of knee OA. However in the absence of well-designed trial data and given the low cost of the intervention, the GDG felt that attention to footware with shock-absorbing properties was worth consideration.
There is some evidence for the effectiveness of walking aids and assistive devices (such as braces) for hip and knee OA. Walking aids (ipsi- or contralateral cane use) can significantly improve stride length and cadence.
There is some evidence for the effectiveness of aids/ devices for hand OA. Thumb splints (of any design) can help reduce pain from thumb OA and improve hand function. There are many different designs of thumb CMC splint for OA described in the literature, frequently accompanied by biomechanical rationales for which is most effective. As yet it is unclear which design/s are considered most comfortable to patients, and thus will be worn long-term, and what degree of splint rigidity/ support is required at what stage of OA in order to effectively improve pain and function. The best study to date479 has included exercises within the trial design which confounds identifying whether it was splinting or exercise which was most effective. Clinically, patients are commonly provided with both a splint and exercise regime.
The role of Disability Equipment Assessment Centres was discussed. It was noted that the MDA regularly publishes reports on assistive devices.
Referral: Hand osteoarthritis
This evidence suggests that those people with hand pain, difficulty and frustration with performing daily activities and work tasks should be referred to occupational therapy for splinting, joint protection training and assistive device provision. This may be combined with hand exercise training. People should be referred early particularly if work abilities are affected.
Referral: Lower Limb
Provision of rehabilitation and physical therapies is commonly recommended in guidelines. Physiotherapists and occupational therapists may be able to help with provision and fitting of appropriate aids and devices. Insoles are commonly provided by podiatrists and orthotists but may also be provided by physiotherapists and occupational therapists. Referral for, or direct local provision of footwear advice should always be considered.
8.6.6. Recommendations
- 18.
Offer advice on appropriate footwear (including shock-absorbing properties) as part of core treatments (see recommendation 6) for people with lower limb osteoarthritis. [2008]
- 19.
People with osteoarthritis who have biomechanical joint pain or instability should be considered for assessment for bracing/joint supports/insoles as an adjunct to their core treatments. [2008]
- 20.
Assistive devices (for example, walking sticks and tap turners) should be considered as adjuncts to core treatments for people with osteoarthritis who have specific problems with activities of daily living. If needed, seek expert advice in this context (for example, from occupational therapists or Disability Equipment Assessment Centres). [2008]
8.7. Invasive treatments for knee osteoarthritis
8.7.1. Clinical introduction
In clinical practice arthroscopic lavage, debridement and tidal irrigation are invasive procedures offered to patients who are failing medical management, predominantly for knee osteoarthritis. There is no general consensus on which patients should be offered these procedures.
Arthroscopy usually involves a day-stay hospital admission with general anaesthesia and the insertion of a fibre-optic instrument into the knee, allowing thorough inspection of pathology. The joint is irrigated with a sizable volume of fluid, a process known as lavage, which may remove microscopic and macroscopic debris resulting from cartilage breakdown, as well as removing the pro-inflammatory effects of this material. This procedure may be associated with debridement, the surgical “neatening” of obviously frayed cartilage or meniscal surfaces.
Tidal irrigation refers to the process of irrigating the joint and does not require general anaesthesia – rather a needle is inserted in the knee under local anaesthesia and a large volume of fluid run into the knee and then allowed to drain out. The rationale is the same as for arthroscopic lavage.
Evaluating these therapies is difficult due to the lack of standardised referral criteria, the absence of many randomised trials and the lack of standardisation of co-therapies including exercises.
8.7.2. Methodological introduction
We looked for studies that investigated the efficacy and safety of arthroscopic lavage (with or without debridement) compared with tidal irrigation and placebo (sham procedure) with respect to symptoms, function, and quality of life in adults with osteoarthritis. Ten RCTs 318 44,66,99,162,202,212,231,302,373 were found on the outcomes of symptoms, function and quality of life, no data for AEs was reported. No relevant cohort or case-control studies were found. Two RCTs202,302 were excluded as evidence due to methodological limitations.
The eight included RCTs were methodologically sound and were similar in terms of:
- Osteoarthritis site (all looked at knee osteoarthritis)
- Osteoarthritis diagnosis (radiologically)
- Trial design (parallel group).
However, they differed with respect to:
- Interventions and comparisons
- Trial size and length
8.7.3. Evidence statements
Table 138
Pain.
Table 139
Stiffness.
Table 140
Function.
Table 141
Global Assessment.
Table 142
Quality of life.
Table 143
Use of rescue medication / analgesia.
Table 144
Other.
8.7.4. From evidence to recommendations
Arthroscopic lavage and debridement are surgical procedures that have become widely used. Tidal irrigation, through large bore needles, has been practiced by physicians to a limited degree. These procedures have limited risks, though arthroscopy usually involves a general anaesthetic. These procedures are offered to patients when usual medical care is failing or has failed and the next option, knee arthroplasty, appears too severe, for a variety of reasons, for either the patient or the medical advisor.
Arthroscopy may be indicated for true locking, caused by meniscal lesions or loose bodies in the knee joint. These situations are uncommon in patients with osteoarthritis of the knee.
Many procedures in medicine have a large placebo effect and when assessing minimalistic surgical procedures it can be very difficult to separate this placebo effect from the surgical procedure itself.
8.7.5. Recommendations
- 21.
Do not refer for arthroscopic lavage and debridementg as part of treatment for osteoarthritis, unless the person has knee osteoarthritis with a clear history of mechanical locking (as opposed to morning joint stiffness, 'giving way' or X-ray evidence of loose bodies). [2008, amended 2014]
Footnotes
- e
See Obesity: guidance on the prevention, identification, assessment and management of overweight and obesity in adults and children (NICE clinical guideline 43).
- f
TENS machines are generally loaned to the person by the NHS for a short period, and if effective the person is advised where they can purchase their own.
- g
This recommendation is a refinement of the indication in Arthroscopic knee washout, with or without debridement, for the treatment of osteoarthritis (NICE interventional procedure guidance 230). The clinical and cost-effectiveness evidence for this procedure was reviewed for the original guideline (published in 2008), which led to this more specific recommendation on the indication for which arthroscopic lavage and debridement is judged to be clinically and cost effective.
- Non-pharmacological management of osteoarthritis - OsteoarthritisNon-pharmacological management of osteoarthritis - Osteoarthritis
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