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Rheumatology 2001; 40: 779-793
© 2001 British Society for Rheumatology

Herbal medicines for the treatment of osteoarthritis: a systematic review

L. Long, K. Soeken1 and E. Ernst

Department of Complementary Medicine, School of Postgraduate Medicine and Health Studies, University of Exeter, 25 Victoria Park Road, Exeter EX2 4NT, UK and
1 University of Maryland School of Medicine, Complementary Medicine Program, Kernan Hospital Mansion, 2200 Kernan Drive, Baltimore, MD 21207-6697, USA

Abstract

Objective. Limitations in the conventional medical management of osteoarthritis indicate a real need for safe and effective treatment of osteoarthritis patients. Herbal medicines may provide a solution to this problem. The aim of this article was to review systematically all randomized controlled trials on the effectiveness of herbal medicines in the treatment of osteoarthritis.

Methods. Computerized literature searches were carried out on five electronic databases. Trial data were extracted in a standardized, predefined manner and assessed independently.

Results. Twelve trials and two systematic reviews fulfilled the inclusion criteria. The authors found promising evidence for the effective use of some herbal preparations in the treatment of osteoarthritis. In addition, evidence suggesting that some herbal preparations reduce consumption of non-steroidal anti-inflammatory drugs was found. The reviewed herbal medicines appear relatively safe.

Conclusions. Some herbal medicines may offer a much-needed alternative for patients with osteoarthritis.

KEY WORDS: Osteoarthritis, Degenerative joint disease, Herbal medicine, Phytomedicine.

Osteoarthritis (OA) is a progressive rheumatic disease characterized by the degeneration of articular cartilage. It is the most common of all rheumatic disorders and is destined to become one of the most prevalent and costly diseases in our society [1].

Therapeutic interventions conventionally employed for OA include the use of physiotherapy and antidepressant therapies, patient education [2] and weight control. In addition, drug therapy includes non-opioid analgesics such as paracetamol, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, opioid analgesics and intra-articular steroid injection. Such treatments may prove ineffective in some patients and NSAIDS often have serious adverse effects [3, 4]. Gastrointestinal complications are frequently reported with NSAIDs, with 12000 hospitalizations and about 2000 deaths attributed to NSAID use in the UK every year [1, 3–6]. Hence there appears to be a need for drugs with good efficacy and low toxicity in the treatment of OA. Specifically, there is a need for safe and effective drugs for patients who do not respond well to conventional medical therapy. Such patients are turning increasingly to complementary/alternative medicines (CAM).

The use of CAM by sufferers of rheumatic diseases is highly prevalent and increasing. Arthritis is the sixth most frequently cited health problem treated with CAM in the USA [7]. Individuals who use CAM regularly are more likely to have OA and severe pain [8]. Patients suffering from musculoskeletal problems are likely to be users of herbal treatments [9]. It is therefore important to determine the effectiveness and safety of herbal medicines in the treatment of OA.

The objective of this systematic review is to evaluate the existing evidence from randomized controlled trials (RCTs) of herbal medicines and plant extracts for OA that are either taken orally or applied topically.

Methods

Identification of clinical trials
Systematic literature searches were performed to identify all RCTs of herbal medicines for OA. Computer databases used were Medline, Embase, Biosis, CINAHL and the Cochrane Library (all from their respective inception to May 2000). The search terms used were ‘osteoarthritis’, ‘osteoarthrosis’, ‘degenerative joint disease’, ‘degenerative arthritis’, ‘degenerative arthrosis’, ‘gonarthrosis’ and ‘coxarthrosis’. Herbal search terms used were ‘botanic’, ‘phyto’, ‘herb’ and all their derivatives, together with individual plant and herb names. A manual search for additional trials was performed using the bibliographies of studies and reviews located through the electronic searches and by scanning our own files. In addition, 11 experts and 15 manufacturers in the field were contacted to provide published and unpublished material.

All potential articles (or abstracts if only available as abstracts) were read in full and, if additional information was required, authors were contacted wherever possible.

Inclusion/exclusion criteria
There were no restrictions regarding language or age group in this systematic review. Studies were limited to RCTs of patients with OA. RCTs with any type of objective and/or subjective parameters were considered. Comparative studies of one herbal treatment measured against another active drug were included, as were relevant systematic reviews. Parenterally applied herbal preparations were excluded [10]. Studies focusing exclusively on back pain and osteoarthritic conditions of the spine, including cervical spondylosis, were excluded. Animal studies were excluded, as were trials that were lacking in essential methodological detail, such as dosage descriptions [11]. Trials that did not include baseline data and clinical end-points were also excluded [12]. All articles were read by two reviewers and any disagreements were resolved through discussion.

Data extraction and quality assessment
Data relating to demographic patient information, interventions, outcomes, results, treatment duration, documentation of power calculation and inclusion/exclusion criteria and the assessment of concomitant medications and compliance were extracted by the first author into predefined tables (Tables 1Go and 2) and validated by the other authors. Data relating to adverse effects were extracted into Table 3Go and validated by the last author.


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  		TABLE 1. RCTs of herbal medicines in the treatment of OA

 

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  		TABLE 2. Further methodological details of RCTs

 

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  		TABLE 3. Adverse effects recorded in reviewed randomized controlled trials

 
Methodological quality was assessed using the standard scoring system developed and validated by Jadad et al. [13], with items on random allocation, double-blinding and description of dropouts and withdrawals.

Results

Twelve trials and two systematic reviews fulfilled the above criteria and were included. Key data are summarized in Tables 1Go, 2Go and 3Go.

Articulin-F
A crossover RCT to test the clinical effectiveness of Articulin-F, an Ayurvedic herbomineral formulation containing Withania somnifera root (450 mg), Boswellia serrata oleo-gum resin (100 mg), Curcoma longa rhizome (50 mg) and zinc (50 mg) in the treatment of OA was performed by Kulkarni et al. [14]. The study was double-blind, with a mixed sample of 42 patients attending a rheumatology out-patient clinic who showed symptoms of OA. They were randomly assigned to receive either two capsules of herbomineral formulation or identical placebo capsules 8 h after food. Each treatment was given for a period of 3 months and then (after a washout period of 2 weeks) the patients were transferred to the other treatment for a further 3 months. Treatment with the herbomineral formulation significantly improved the severity of pain (P<0.001) and disability score (P<0.05). Other parameters, including morning stiffness, Ritchie articular index, grip strength and joint score, showed favourable non-significant trends.

Avocado/soybean unsaponifiables
Extract of avocado and soya bean, termed avocado/soybean unsaponifiables (ASU), is made of unsaponifiable fractions of avocado oil and soya bean oil. Preclinical studies suggest that a 1:3 to 2:3 ASU mixture may be active in OA.

In 1997, Blotman et al. [15] conducted a 3-month double-blind, placebo-controlled, parallel-group RCT in a mixed group of out-patients suffering from either hip or knee OA. Thirty-five rheumatologists evaluated the effectiveness of ASU in reducing NSAID consumption. Patients were assigned randomly to take either one capsule of 300 mg ASU or one indistinguishable placebo capsule daily for 3 months. All patients took one of seven predefined NSAIDs during the first 45 days of the trial and were permitted to resume the same treatment, if needed, during the second half of the trial. Effectiveness was measured primarily by the proportion of patients resuming NSAID consumption and the delay before reintake. In the second half of the study (day 45 to day 90), the proportion of patients resuming NSAID therapy and the time spent off the NSAID drug each showed a significant difference in favour of the ASU treatment. Observed reductions in NSAID intake in the treatment group were supported by secondary outcome measures. Patients’ overall ratings were significantly better in the experimental group (P<0.01) and so were improvements in the functional index (P<0.01). Changes in pain [measured on a visual analogue scale (VAS)] over time were similar in the two groups. Improvements were more evident with hip OA than knee OA.

Maheu et al. [16] randomly assigned a mixed sample of 164 patients diagnosed with OA of the knee or hip into two groups receiving either a daily capsule of ASU (300 mg) or a placebo capsule in a 6-month trial. After a 25-day washout period, analgesic or NSAID intake (from a predefined list) was allowed if judged necessary. Effectiveness was measured primarily according to Lequesne's functional index (LFI). Secondary outcome measures included assessment of pain and functional disability, as scored on a 100-mm VAS, and NSAID/ analgesic intake. At the end of the trial, the patients’ and physicians’ overall assessments were scored on a 5-point verbal scale. Intergroup comparisons of changes between baseline and month 6 values for LFI, pain (VAS), functional disability (VAS) and patient's and physician's overall assessments significantly favoured the ASU group. Improvements appeared to be better in patients with hip OA rather than knee OA. Fewer patients in the ASU group required NSAIDs (P=0.054), suggesting that ASU may help to reduce NSAID consumption in patients with OA.

Capsaicin
Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is derived from hot chilli peppers. It is used as a topical analgesic for a variety of conditions characterized by pain. A meta-analysis of three double-blind, placebo-controlled RCTs [17–19] (192 capsaicin patients, 190 controls) for the treatment of primary OA with topically applied capsaicin has been published [20]. Trials were abstracted for response data and analysed using both a fixed effects model and a random effects model. The odds ratio (OR) of the response rate of subjects receiving topical capsaicin relative to that of the subjects on placebo was determined and used as the main outcome measure. The response rate difference (RD) was used as the response variable under the random effects model. The results in all three trials favoured capsaicin cream for improvements in pain and articular tenderness, although only one of these trials reached the usual statistically significant level (P=0.05). The meta-analysis showed that capsaicin cream was better than placebo in the treatment of OA [OR=4.36 (95% confidence interval [CI]=2.77, 6.88); RD=0.29 (95% CI=0.2, 0.37)].

An additional RCT not included in this meta-analysis was located [21]. Altman et al. [21] performed a double-blind, parallel, vehicle-controlled, six-centre study with a mixed population of 113 patients suffering from OA of the knee, ankle, elbow, wrist or shoulder. One hundred and thirteen patients were assigned randomly to receive 0.025% capsaicin cream or vehicle cream as placebo. Cream was applied to joints four times daily for 12 weeks. At the end of 12 weeks of treatment, patients’ and physicians’ global (5-point scale) evaluations of pain showed that a significantly greater percentage of capsaicin-treated patients improved compared with vehicle-treated patients (P=0.03), while pain severity as measured by VAS was found to be significantly decreased (P=0.02). Overall, capsaicin-treated patients had significantly greater improvement in tenderness on passive range of motion (4-point scale) (P=0.03) and physician palpation (P=0.01) than vehicle-treated patients. A 5-point severity scale for ‘today's pain’ and secondary outcome measures of morning stiffness using a two-question method and a modified health assessment questionnaire showed no significant differences.

Devil's claw
Devil's claw (Harpagophytum procumbens) is a medicinal plant native to Africa. Its active ingredients are thought to be iridoid glycosides. Guyader [22] conducted a double-blind RCT in which 50 OA patients were given capsules containing 400 mg Harpagophytum extract (with an iridoid glycoside content of 1.5%) or placebo at a dosage of two capsules three times daily for 3 weeks. One month after the beginning of the treatment, the patients were assessed. Outcome was assessed with a 4-point pain intensity score based on pain at rest, on active and passive mobilization, on articular pressure, and on walking and night pain. Administration of the extract was associated with a statistically significant decrease in pain severity. Improvements were more frequent in moderate than in severe cases.

In another placebo-controlled, double-blind RCT in 89 outpatients with pain due to OA, the effectiveness of capsules containing 335 mg of powdered Harpagophytum with an iridoid glycoside content of 3% were assessed at a dosage of two capsules three times daily for 2 months [23]. The clinical parameters, measured on days 0, 30 and 60, were severity of pain (score) and joint mobility determined by measuring finger–floor distances. Results revealed a significant drop in pain intensity and a significant increase in spinal and coxofemoral mobility in the treated group.

Eazmov
Biswas et al. [24] performed a comparative RCT to determine the effectiveness of Eazmov, an Ayurvedic herbal preparation containing Cyperus rotundus, Tinospora cordifolia, Saussurea lappa, Picrorrhiza kurroa and Zingiber officiniale, compared with diclofenac in the treatment of a mixed sample of 60 patients with OA (n=31), non-specific arthritis or rheumatoid arthritis. Patients were allocated randomly to take 1 capsule (50 mg) of either Eazmov or diclofenac three times daily after meals for 6 months. They were assessed weekly for pain severity, morning stiffness, Ritchie articular index, joint score, disability score and grip strength. The clinical efficacy of Eazmov was found to be significantly inferior to that of diclofenac regarding pain severity (P<0.001) and disability scores (P<0.05).

Ginger
Sixty-seven patients with OA of the hip or knee were randomized to three treatment periods of 3 weeks each in a placebo-controlled crossover study of ginger extracts and ibuprofen [25]. Either 170 mg capsules of ginger extract (Eurovita Extract 33, EV.ext-33), 400 mg ibuprofen tablets or placebo were administered three times daily. There was an initial 1-week washout period, with no washout period between the three treatments. Acetaminophen was administered as a rescue drug for pain relief during the study. VAS for pain assessment, the Lequesne index (LI) for either hip or knee, and range of motion were assessed at study entry and after each treatment period, including the initial washout period. Consumption of acetaminophen was recorded. A highly significant ranking of effectiveness (VAS) of the three treatment periods was found, as follows: ibuprofen >ginger extract>placebo (P<0.0001). The same trend was found for acetaminophen consumption (P<0.01) and LI. Significant differences in these tests between ibuprofen and ginger extract as well as ibuprofen and placebo were shown. No differences between ginger extract and placebo were observed.

Gitadyl
Gitadyl is a herbal preparation containing 110 mg feverfew, 90 mg American aspen and 60 mg milfoil. Thirty-five patients who were taking NSAIDs for mild to moderate OA underwent a 2-week washout phase before being randomized to receive Gitadyl (three tablets daily) or ibuprofen (400 mg three times daily) administered for 2x21 days in a double-blind, crossover RCT with the double-dummy technique [26]. Patients were allowed to take dextropropoxyphene as a rescue medication for pain relief. The number of tablets taken was recorded and used to assess change in condition. The primary outcome measures of pain (when resting and working) and walking ability were assessed using a symptom score on a scale of 1–4 (none, mild, moderate, strong). A non-significant trend of symptom reduction was observed in both groups, with no significant difference between groups. Gastrointestinal complaints were more frequent in patients treated with ibuprofen.

Phytodolor
Phytodolor, a fixed herbal formulation containing alcoholic extracts of Populus tremula, Fraxinus excelsior and Solidago virgaurea, has been shown to be effective in various rheumatic diseases, including OA. A systematic review of all double-blind RCTs for rheumatic conditions [27] included six trials for the treatment of OA fulfilling this review's inclusion criteria [28–31; M. Bernhardt, B. Kiemel and U. Dormehl, unpublished results; M. Bernhardt, A. Keimel, G. Belucci and P. Spasojevie, unpublished results]. These trials demonstrate significant results for pain reduction [M. Bernhardt, B. Kiemel and U. Dormehl, unpublished results; M. Bernhardt, A. Keimel, G. Belucci and P. Spasojevie, unpublished results], mobility [31] and NSAID consumption [28, 29] with administration of Phytodolor. They also suggest that Phytodolor is as effective as NSAIDs but has fewer adverse effects [30, 31; M. Bernhardt, A. Keimel, G. Belucci and P. Spasojevie, unpublished results].

Reumalex
Mills et al. [32] conducted a double-blind RCT with patients suffering from chronic stable arthritic conditions, predominantly OA. Eighty-two patients with OA or rheumatoid arthritis, with moderate disability and pain, were randomly allocated to two groups. One group took two tablets of Reumalex (a herbal medicine containing 100 mg Pulv White Willow bark, 40 mg Pulv Guaiacum Resin BHP, 35 mg Pulv Black Cohosh BHP, 25 mg Pulv Ext Sarsparilla 4:1 and 17 mg Pulv Ext Poplar Bark 7:1) equivalent to 20–40 mg salicylic acid per day while the other took two indistinguishable placebo tablets for a 2-month period. Subjects with OA (n=51) showed a statistically significant difference in pain compared with placebo as measured by the Arthritis Impact Measurement Scales (AIMS) score (P<0.05). Use of a modified Ritchie score showed no intergroup difference. Mean mobility and function scores remained, on average, unchanged throughout the study. There were no differences in analgesic consumption, which was monitored as a secondary outcome measure.

Stinging nettle
Twenty-seven patients with OA pain at the base of the thumb or index finger were randomized to receive topical treatment with stinging nettle leaf (Urtica dioica) followed by placebo treatment using white deadnettle (Lamium album) leaf or vice versa in a double-blind crossover RCT [33]. White deadnettle leaf looks like a stinging nettle leaf but has no sting. Stinging nettle leaf was applied daily for 1 week to the painful area. After a 5-week washout period, the placebo treatment was applied for a 1-week period. After 1 week of treatment with nettle sting, reductions in both pain (VAS) and disability (Stanford Health Assessment Questionnaire) were significantly larger than with placebo (P=0.026 and P=0.0027 respectively). No significant differences in either score were observed following the 5-week washout period. There was a non-significant decline in daily use of analgesic and anti-inflammatory drugs following 1 week of treatment with stinging nettle.

Willow bark
Schmid et al. [34] randomized 78 hospital in-patients suffering from OA of the knee or hip joints to receive two tablets twice daily of either willow bark extract (corresponding to 240 mg salicin per day) or placebo tablets for a 2-week period. Drug effectiveness was measured primarily by the pain dimension of the WOMAC OA index [35]. All patients also received regular physical therapy following standard procedures. A statistically significant advantage of the active treatment over placebo was observed (P=0.047). Secondary outcome measures of physical function were better in the treatment group compared with placebo, although this was not statistically significant and no differences in stiffness were observed between the two groups during the study period. A significant positive effect of the active medication was confirmed by overall assessments both by the physician and by the patients (P<0.01). No significant correlation was observed between the different physical therapy methods and the primary outcome measure, suggesting that the observed medication effect was not influenced by the physical therapy. No relevant differences between outcome were observed in knee and hip OA.

Discussion

The review found promising evidence in the form of RCTs for the use of some herbal preparations in reducing pain and improving mobility, function and disability in OA. While there is no compelling evidence for significant clinically relevant benefits for Eazmov [24], Gitadyl [26] or ginger extract [25], there is weak evidence, in the form of single RCTs, for mild to moderate relief of symptoms using Reumalex [32], willow bark [34], common stinging nettle [33] and the Ayurvedic herbal preparation Articulin-F [14]. There is promising evidence for devil's claw [22, 23] and ASU [15, 16] and moderately strong evidence for Phytodolor [27] and capsaicin cream [20, 21] for the relief of OA symptoms. [‘Weak evidence’ describes herbs with a single RCT with significant results; ‘promising evidence’ describes herbs with two trials that produced favourable outcomes; ‘moderately strong evidence’ describes herbs with three or more favourable trials.]

All of the individually reviewed trials were found to be of high methodological quality as assessed by the Jadad scale [13]; trials were considered to be of high quality if they attained 3 out of a maximum of 5 points. However, seven of the 12 RCTs reviewed were unreplicated studies and as such can only provide weak evidence for effectiveness. Although all 12 trials were generally found to be of good methodological quality, failure to implement or state inclusion/exclusion criteria [22], compliance [23, 26], withdrawals [14, 23, 24] and power calculation [14, 21–24, 26, 32, 34] were evident. Some RCTs did not distinguish between patients with mild and severe forms of OA [e.g. 14, 23] or differing joint location [e.g. 14, 23, 32], yet this would be important for assessing the effectiveness of herbal medicines in patients presenting with mild or moderate symptoms, as some treatments appear less effective in severe cases, e.g. devil's claw [22]. Differentiation between joint locations of OA would be important as treatments may be more effective for OA in one particular joint rather than another, e.g. hip joints tended to respond more favourably than knee joints to ASU treatment [15, 16]. Many of the studies used different diagnostic criteria for inclusion, only three trials distinguishing between primary (idiopathic) and post-traumatic (secondary) OA [15, 16, 21]. Other studies did not mention the concomitant use of NSAIDs, analgesics or other medications during trials [22, 23]. This is particularly important if adverse effects are noted which could be attributed to NSAIDs or the test medication.

Promising evidence from two RCTs showed that ASU could significantly improve hip or knee OA symptoms and reduce patients’ NSAID consumption [15, 16]. ASU was found to have a delayed (by 2 months) treatment effect that resulted in improved pain and function. This suggests that ASU is an effective slow-acting drug for OA. There is growing evidence, mainly in the form of in vitro studies, that ASU may stimulate the deposition and repair of extracellular matrix components. Although the active ingredient(s) of ASU remain unknown, ASU has been shown to have an inhibitory effect on various interleukins [36–38], prostaglandin E2 production [38] and collagenase synthesis [38]. ASU stimulates collagen synthesis in articular chondrocyte cultures [38] and may promote transforming growth factor ß-induced matrix repair mechanisms in articular cartilage [39]. Furthermore, ASU increased the production of plasminogen activator inhibitor 1, an effect that could help in blocking the plasmin cascade that leads to metalloproteinase activation [39]. Although the clinical evidence for ASU is promising, it is noteworthy that both RCTs published to date originate from the same research group. Independent replication would seem to be a precondition before acceptance of this therapy.

Extracts of devil's claw have been shown in two RCTs to reduce pain and increase mobility significantly in patients with OA [22, 23]. However, in neither study were concomitant medications mentioned. In vitro experiments have shown the iridoid glycoside harpagoside to be an active component of devil's claw, while in vivo experiments indicate that the plant extract elicits significant antioxidant activity which may be responsible for its reported experimental and clinical anti-inflammatory action [40].

Phytodolor has been shown to relieve many OA symptoms, particularly pain, in a reasonably large number of double-blind RCTs of good methodological quality [27], as assessed by the Jadad score [13]. Two RCTs showed that Phytodolor was as clinically effective as conventional NSAIDs while two other RCTs showed a reduction in NSAID consumption with Phytodolor treatment. Caveats associated with the included trials are discussed by the author, although the question of potential publication bias for this registered commercial herbal preparation is not explored in the review. The alcoholic extracts of Phytodolor's constituents (Populus tremula, Fraxinus excelsior and Solidago virgaurea) are proportioned in the ratio of 3:1:1. The active ingredients of Phytodolor are salicin, salicyl alcohol, phenolcarbon acids, flavonoids, triterpensaponines and coumarin derivatives and the herbal mixture is standardized to 1 mg/ml of salicin, 0.07 mg/ml of total flavonoids and 0.14 mg/ml of isofraxidine. The mechanism of action of Phytodolor is proposed to lie in the inhibition of arachidonic acid metabolism via the cyclooxygenase and lipoxygenase pathways, leading to suppression of mediators of inflammation, such as prostaglandin E2 [41].

Topically applied capsaicin is proposed to exert its action by stimulating a subpopulation of nociceptive pain neurones. Exposure to capsaicin brings about the depletion of substance P, neurones subsequently becoming insensitive to all other exposure, including exposure to capsaicin itself [43, 44].

The incidence of adverse effects for these herbal medicines appears to be low, and they may offer a much-needed alternative for individuals with long-term chronic OA (Tables 3 and 4 ). Hundreds of herbal remedies are used for treating OA, and the research literature reflects only a small percentage of them. It is recommended that all herbal treatments promoted for OA are submitted to rigorous scientific scrutiny. Future RCTs of herbs for OA should distinguish between patients with mild and severe forms of the condition so that mild to moderate benefits of herbal preparations are not missed. In addition, differentiation or stratification according to joint location of OA is recommended so that herbal preparations potentially suitable for the particular treatment of certain joint locations of OA can be distinguished. Some of the studies reviewed included outcome measures such as grip strength, walking time and joint tenderness, which are considered unreliable measures of OA by the WHO (World Health Organization) and OARSI (Osteoarthritis Research Society International) [45, 46]. Future studies should use the recommended core of outcome measures [46].


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  		TABLE 4. Adverse effects listed in the literature

 
The question arises of the clinical relevance and implications of the findings summarized in this review. It seems that herbal remedies that have been shown to be effective could be employed in order to lower or stop the consumption of NSAIDs and to reduce the incidence of adverse effects of NSAIDs. This would, at the same time, generate long-term safety data, which are urgently needed, for these herbal medicines.

It is concluded that a number of herbal medicines may be effective for the treatment of symptoms, especially pain, associated with OA. Considering the large number of people suffering from OA and the known adverse effects associated with NSAID use, this area is under-researched and would seem to merit further attention.

Acknowledgments

We thank Barker Bausell and Brian Berman, University of Maryland School of Medicine, Complementary Medicine Program, Baltimore, USA for their useful comments.

Notes

Corresponding author: L. Long Back

References

  1. Brooks PM, March LA. New insights into osteoarthritis. Med J Aust1995;163:367–9.[Medline]
  2. Weinberger MTWM, Booher P, Katz BP. Can the provision of information to patients with osteoarthritis improve functional status? A randomised controlled trial. Arthritis Rheum1989;32:1577–83.[Web of Science][Medline]
  3. Tramer MR, Moore RA, Reynolds DJ, McQuay HJ. Quantitative estimation of rare adverse events which follow a biological progression: a new model applied to chronic NSAID use. Pain2000;85:169–82.[Web of Science][Medline]
  4. Buchanan W. Implications of NSAID therapy in elderly in-patients. J Rheumatol1990;4:29–32.
  5. Caradoc-Davies T. Non-steroidal anti-inflammatory drugs, arthritis and gastrointestinal bleeding in elderly in-patients. Age Ageing1984;13:295–8.[Abstract/Free Full Text]
  6. Perneger TV, Whelton PK, Klag MJ. Risk of kidney failure associated with the use of acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs. N Engl J Med1994;331:1675–9.[Abstract/Free Full Text]
  7. Astin JA. Why patients use alternative medicine. J Am Med Assoc1998;279:1548–53.[Abstract/Free Full Text]
  8. Rao JK, Mihaliak K, Kroenke K, Bradley J, Tierney WM, Weinberger M. Use of complementary therapies for arthritis among patients of rheumatologists. Ann Intern Med1999;131:409–16.[Abstract/Free Full Text]
  9. Ernst E. Usage of complementary therapies in rheumatology: A systematic review. Clin Rheumatol1998;17:301–5.[Web of Science][Medline]
  10. Stange R, Moser C, Goedings P, Mansmann U, Buehring M. Randomised trial with mistletoe injections for osteoarthritis of the knee in comparison to treatment with diclofenac. Forsch Komplementarmed2000; 7:29–58.
  11. Chopra A, Lavin P, Chitre D, Patwardhan B, Polisson R. A clinical study of Ayurvedic (Asian Indian) medicine in OA knees. Arthritis Rheum1998;41(Suppl.):S198.
  12. Ferraz MB, Periera RB, Iwata NM, Atra E. Tipi. A popular analgesic tea: double-blind cross-over trial in osteoarthritis. Clin Exp Rheumatol1991;9:205–12.[Medline]
  13. Jadad AR, Moore RA, Carrol D et al. Assessing the quality of reports of randomised clinical trials: is blinding necessary? Control Clin Trials1996;17:1–12.[Web of Science][Medline]
  14. Kulkarni RR, Patki PS, Jog VP, Gandage SG, Patwardhan B. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol1991;33:91–5.[Web of Science][Medline]
  15. Blotman F, Maheu E, Wulwik A, Caspard H, Lopez A. Efficacy and safety of avocado/soybean unsaponifiables in the treatment of symptomatic osteoarthritis of the knee and hip. A prospective, multicenter, three-month, randomized, double-blind, placebo-controlled trial. Rev Rhum Engl Ed1997;64:825–34.[Medline]
  16. Maheu E, Mazieres B, Valat JP et al. Symptomatic efficacy of avocado/soybean unsaponifiables in the treatment of osteoarthritis of the knee and hip: a prospective, randomized, double-blind, placebo-controlled, multicenter clinical trial with a six-month treatment period and a two-month follow-up demonstrating a persistent effect. Arthritis Rheum1998;41:81–91.[Medline]
  17. Deal CL, Schnitzer TJ, Lipstein E et al. Treatment of arthritis with topical capsaicin: a double-blind trial. Clin Ther1991;13:383–93.[Web of Science][Medline]
  18. McCarthy GM, McCarty DL. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J Rheumatol1992;19:604–7.[Medline]
  19. Schinitzer TJ, Morton C, Coker C, Flynn P. Effectiveness of reduced applications of topical capsaicin (0.025%) in osteoarthritis. Arthritis Rheum1992;35:S132.
  20. Zhang WY, Li Wan Po A. The effectiveness of topically applied capsaicin. A meta-analysis. Eur J Clin Pharmacol1994;46:517–22.[Web of Science][Medline]
  21. Altman RD, Aven A, Holmburg CE et al. Capsaicin cream 0.025% as monotherapy for osteoarthritis: A double-blind study. Semin Arthritis Rheum1994;23(Suppl.):25–33.
  22. Guyader M. Les plantes antirhumatismales. Etude historique et pharmacologique, et étude clinique du nébulisat d’Harpagophytum procumbens DC chez 50 patients arthrosiques suivis en service hospitalier. Paris: Université Pierre et Marie Curie, 1984, PhD thesis.
  23. Lecomte A, Costa JP. Harpagophytum dans l'arthrose: Etudes en double insu contre placebo. 37°2 Le Magazine1992;15:27–30.
  24. Biswas NR, Biswas K, Pandey M, Pandy RM. Treatment of osteoarthritis, rheumatoid arthritis and non-specific arthritis with a herbal drug: A double-blind, active drug controlled parallel study. JK Pract1998;5:129–32.
  25. Bliddal H, Rosetzky A, Schlichting P et al. A randomized, placebo-controlled, cross-over study of ginger extracts and ibuprofen in osteoarthritis. Osteoarthritis Cartilage2000;8:9–12.[Web of Science][Medline]
  26. Ryttig K, Schlamowitz PV, Warnoe O, Wilstrup F. Gitadyl versus ibuprofen in patients with osteoarthrosis. The result of a double-blind, randomized crossover study. Ugeskr Laeg1991;153:2298–9.[Medline]
  27. Ernst E. The efficacy of Phytodolor® for the treatment of musculoskeletal pain—a systematic review of randomized clinical trials. Nat Med J1999;2:14–6.
  28. Huber VB. Therapie degenerativer rheumatischer Erkrankungen. Fortschr Med1991;109:248–50.[Medline]
  29. Schadler W. Phytodolor N zur Behandlung aktivierter Arthrosen. Rheuma1988;8:280–90.
  30. Baumann D, Focke G, Kornosoff G. Phytodolor bei Patienten mit aktivierter Gonarthrose, Koxathrose bzw. Schulter-Arm-Syndrom. Multizentrische randomisierte Doppelblindstudie versus Diclofenac-Natrium. Darmstadt: Steigerwald GmbH. Interner Forschungsbericht, 1989.
  31. Hawel R. Phytodolor vs Diclofenac bei rheumatischen Erkrankungen. Darmstadt: Steigerwald GmbH. Interner Forschungsbericht, 1991.
  32. Mills SY, Jacoby RK, Chacksfield M, Willoughby M. Effect of a proprietary herbal medicine on the relief of chronic arthritic pain: a double blind study. Br J Rheumatol1996;35:874–8.[Abstract/Free Full Text]
  33. Randall C, Randall H, Dobbs F, Hutton C, Sanders H. Randomized controlled trial of nettle sting for treatment of base-of-thumb pain. J R Soc Med2000;93:305–9.[Abstract/Free Full Text]
  34. Schmid B, Tschirdewahn B, Kotter I et al. Analgesic effects of willow bark extract in osteoarthritis: results of a clinical double-blind trial. FACT: Focus Alternative Complementary Ther1998;3:86.
  35. Bellamy N, Buchanan W, Goldsmith C, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol1988;15:1833–40.[Web of Science][Medline]
  36. Mauviel A, Daireux M, Hartmann DJ, Galera P, Loyau G, Pujol JP. Effets des insaponifiables d'avocat et de soja (PIAS) sur la production de collagene par des cultures de synoviocytes, chondrocytes articularies et fibroblasts dermiques. Rev Rhum Mal Osteoartic1989;56:207–11.[Medline]
  37. Mauviel A, Loyau G, Pujol JP. Effet des insaponofiables d'avocat/soja (Piascledine) sur l'activite collagenolytique de cultures de synoviocytes rhumatoides humains et de chondrocytes articulaires de lapin traites par l'interleukine 1. Rev Rhum Mal Osteoartic1991;58:241–5.[Medline]
  38. Henrotin Y, Labasse A, Zheng SX et al. Effects of three avocado/soybean unsaponifiable mixtures on human articular chondrocyte metabolism. Arthritis Rheum1996;39:S227.
  39. Boumediene K, Felisaz N, Bogdanowicz P, Galera P, Guillou GB, Pujol JP. Avocado/soya unsaponifiables enhance the expression of transforming growth factor beta1 and beta2 in cultured articular chondrocytes. Arthritis Rheum1999;42:148–56.[Medline]
  40. Bhattacharya A, Bhattacharya SK. Anti-oxidant activity of Harpagophytum procumbens (devil's claw). Br J Phytother1999;5:68–71.
  41. Chrubasik S, Junck H, Breitschwerdt H, Conradt CH, Zappe H. Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomised placebo-controlled double-blind study. Eur J Anaesthesiol1999;16:118–29.[Medline]
  42. Bach GJ, Chubasik S. Wirksamkeit eines Kombinationspraparates aus Zitterpappel, Goldrute und Esche bei rheumatishen Beschwerden. Rheumatherapie mit Phytopharmaka1997:131.
  43. Fusco BM, Giacovazzo M. Peppers and pain. The promise of capsaicin. Drugs1997;53:909–14.[Web of Science][Medline]
  44. Baron R. Capsaicin and nociception: from basic mechanisms to novel drugs. Lancet2000;356:785–6.[Medline]
  45. Guidelines for the clinical investigations of drugs used in rheumatic diseases. European Drug Guidelines, Series 5. Copenhagen: World Health Organization, Regional Office for Europe, European League Against Rheumatism 1985 March:21–4.
  46. Bellamy N, Kirwan J, Boers M et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip and hand osteoarthritis. Consensus development at OMERACT III. J Rheumatol1997;24:799–802.[Web of Science][Medline]
Submitted 25 September 2000; Accepted 31 January 2001


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