More than 30 million adults in the United States have osteoarthritis (OA),1 and its prevalence has increased over the past decade, which is a reflection of the aging US population.2 Although various risk factors are known to be associated with OA, including older age, obesity, and genetic predisposition, the etiology and underlying pathophysiology of OA are unknown. However, the role of pro-inflammatory cytokines, pro-catabolic mediators, and signaling mechanisms are currently being investigated to discover possible novel targeted therapeutics.3
Currently, there is no treatment to halt or reverse the progressive cartilage destruction, and without a cure, the management of OA is focused on symptomatic relief of joint pain with nonpharmacologic and pharmacologic interventions, including physical therapy, weight loss, supportive devices such as crutches and canes, surgery, and various pharmacologic agents that are primarily palliative. Several pharmacologic agents are recommended in available guidelines, including nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen (paracetamol), chondroitin, glucosamine, and intra-articular injection of hyaluronate or corticosteroid, together with various dietary supplements.4,5
Acetaminophen and NSAIDs are perhaps the most commonly used analgesics for the management of OA. However, adverse effects associated with high doses or long-term use of these analgesics, including liver and gastrointestinal injury and increased risk for cardiovascular events, are well documented in the guidelines.5,6 Although newer and better-tolerated NSAIDs are available for treatment of knee joint OA, their long-term use can still be a problem for older people because of challenges of polypharmacy and age-related physiologic changes that can affect drug pharmacokinetics and pharmacodynamics.7,8 Furthermore, a systematic review of 13 randomized trials concluded that paracetamol provides minimal short-term benefit for people with OA.9
“Emerging evidence has challenged the guidelines that recommend paracetamol and NSAIDs to treat OA,” said Xiaoqian Liu, PhD candidate at the Royal North Shore Hospital Institute of Bone and Joint Research, University of Sydney Medical School, and the lead author of the study investigating the efficacy of supplements for people with OA.4 “Paracetamol, irrespective of dose, is not effective for patients with OA.”
Because of the challenges associated with long-term safety and efficacy of analgesics in the treatment of OA, herbal and dietary supplements are increasingly recommended by physicians and used by patients. Several dietary supplements are available, ranging from avocado soybean unsaponifiables, Boswellia serrata extract, and curcumin, to undenatured type II collagen, vitamins D and E, and willow bark extract.10 The challenge physicians and patients face is the paucity of clinical studies, including studies of commonly used agents that do not necessarily have an evidence base to support their safety and efficacy for the treatment of OA. Furthermore, the efficacy and safety of dietary supplements for patients with OA was investigated in a systematic review of 69 eligible studies involving 20 dietary supplements.10 The study found that although the quality of studies included in the analysis was generally very low with respect to experimental design, some supplements can provide, in the short term, but not in the medium or long term, moderate and clinically meaningful treatment effects on pain and function in patients with hand, hip, or knee OA.10
Choosing a supplement to recommend is an ongoing challenge for physicians. Discrepancies in the international guideline recommendations for the use of dietary supplements and wide variations in clinical practice and patient preferences can result in confusion about which supplement to select or recommend. To shed more light on the safety and efficacy of available dietary supplements, Liu and colleagues evaluated 16 supplements identified from 8 systematic reviews or meta-analyses and 9 randomized controlled trials.4 The domains evaluated included treatment effect (pain management), adverse effects, and quality of the evidence. Among the 16 supplements evaluated, the quality of evidence was generally low, although a few studies were of moderate to high quality. Whereas adverse effects were generally low, migraine headache, neck pain, and allergic skin reactions have been reported with some supplements.4
Treatment effects ranged from no effect or small effect to moderate effect to large and clinically meaningful effect. It is, however, important to balance the treatment effect against the quality of the studies and the associated adverse events. Liu and colleagues concluded from their study that there is limited evidence to support the use of Boswellia serrata extract, Pycnogenol®, curcumin, and methylsulfonylmethane and that there is no evidence to support the use of glucosamine and chondroitin.4
Because commonly used analgesics such as paracetamol and NSAIDs have little evidence to support their efficacy for the treatment of OA and there are few well-designed high-quality clinical trials investigating the use of dietary supplements, recommending and choosing analgesics or dietary supplements for patients with OA is very challenging.
“This is the dilemma we are confronted with for treatment of OA,” Liu noted, adding that “sound evidence supported diclofenac (150 mg/day) as the most effective NSAID for OA7; however, serious potential gastrointestinal side effects have challenged its use. In Australia, 69% [of patients with] OA are taking supplements, with fish oil as the most used, although not enough evidence supports their use.”10
“Based on meta-analyses of published studies, including ours,10 we conditionally don’t recommend the use of glucosamine, chondroitin, fish oil, vitamins D and E, willow bark extract, collagen, and rosehip,” Liu stated. “Further robust research is needed before a firm recommendation to use these little-known supplements [can be made].”
- US Centers for Disease Control and Prevention. Osteoarthritis (OA). https://www.cdc.gov/arthritis/basics/osteoarthritis.htm. Updated March 15, 2018. Accessed March 22, 2018.
- Global Burden of Disease Study 2013 Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 301 acute and chronic diseases and injuries in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386(9995):743-800.
- Kim JR, Yoo JJ, Kim HA. Therapeutics in osteoarthritis based on an understanding of its molecular pathogenesis. Int J Mol Sci. 2018;19(3).
- Liu X, Eyles J, McLachlan AJ, Mobasheri A. Which supplements can I recommend to my osteoarthritis patients? [published online March 1, 2018] Rheumatology (Oxford). doi:10.1093/rheumatology/key005
- Bruyère O, Cooper C, Pelletier JP, et al. An algorithm recommendation for the management of knee osteoarthritis in Europe and internationally: a report from a task force of the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Semin Arthritis Rheum. 2014;44(3):253-263.
- Sinusas K. Osteoarthritis: diagnosis and treatment. Am Fam Physician. 2012;85(1):49-56.
- da Costa BR, Reichenbach S, Keller N, et al. Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet. 2017;390(10090):e21-e33.
- Garg Y, Singh J, Sohal HS, Gore R, Kumar A. Comparison of clinical effectiveness and safety of newer nonsteroidal anti-inflammatory drugs in patients of osteoarthritis of knee joint: a randomized, prospective, open-label parallel-group study. Indian J Pharmacol. 2017;49(5):383-389.
- Machado GC, Maher CG, Ferreira PH, et al. Efficacy and safety of paracetamol for spinal pain and osteoarthritis: systematic review and meta-analysis of randomised placebo controlled trials. BMJ. 2015;350:h1225.
- Liu X, Machado GC, Eyles JP, Ravi V, Hunter DJ. Dietary supplements for treating osteoarthritis: a systematic review and meta-analysis. Br J Sports Med. 2018;52(3):167-175.