Introduction
Osteoarthritis (OA) is the most prevalent joint disease worldwide and is the 11th cause of years lived with disability according to the 2010 WHO global burden of disease report.1 Roughly 80% of the OA disease burden is secondary to knee OA (KOA) which impacts over 300 million people worldwide and 19% of Americans above the age of 45.2 3 Current best practice management is often characterised as palliative and reactive, rather than a combination of shared decision-making coupled with proactive and preventive measures that are the goal of chronic disease management in today’s environment.
Rather than simply a ‘wear-and-tear’ disease, it is now recognised that OA involves mechanical, inflammatory and metabolic factors. Advances in the methodology of DNA sequencing have also advanced our understanding of the genetics and epigenetics of the disease.4 The underlying process of KOA includes a variety of factors, including biomechanical forces, pro-inflammatory mediators, metabolic dysregulation and alterations in local tissue metabolism.5 Following the initial loss of cartilage integrity, compositional changes in the joint allow increased susceptibility to damage from physical impact.6 As joint damage continues, chondrocyte activity increases leading to secondary degradation and pro-inflammatory mediators throughout the synovium.7 Protein complexes such as NF-kB which contribute to joint homoeostasis then become upregulated leading to increased cytokine activity.6 Taken together, these factors suggest that inflammation plays a greater role in the pathogenesis of OA than previously appreciated.
OA is a complex chronic disease that is frequently compounded by the presence of multiple comorbidities. In recognition of the various underlying aetiologies of KOA and coexistence of comorbidities, recent efforts have focussed on identifying specific phenotypes with distinct features that could potentially aid in molecular targeting of disease management. For example, Dell’Isola et al8 proposed six phenotypes including chronic pain, inflammation, metabolic syndrome, bone and cartilage metabolism, mechanical overload and minimal joint disease. On the other hand, van der Esch et al9 suggested phenotypes based on lower extremity muscle strength, body habitus and psychological components of KOA pain. To date, there have not been any validated guidelines grouping patients with KOA into specific phenotypes. Despite this lack of consensus, inflammation is a common feature of many of these emerging phenotypic classification systems.
Given the recognition that inflammation may play a critical role in the pathogenesis and progression of OA, particularly that of post-traumatic OA, it is not surprising that researchers and clinicians have turned to strategies to address this feature of the disease as a way to manage symptoms and ideally slow its progression. A recent review summarises the current evidence for the role of diet and nutrition in patients with OA.10 Both the Osteoarthritis Research Society International (OARSI) and American College of Rheumatology (ACR) have published recent recommendations on conservative treatment of KOA.11 12 There is near-uniform consensus on the use of exercise, weight loss, topical non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroid injections and hyaluronic acid injections from both societies. In the OARSI statement, expert consensus was derived from a review of 60 popular treatments and a subsequent meta-analysis. Interestingly, the ACR report did evaluate some nutraceuticals and recommended that there was insufficient evidence for the vast majority including glucosamine, vitamin D, chondroitin sulfate and fish oil.11 A previous meta-analysis by Liu et al published in the British Journal of Sports Medicine examined the use of various nutraceutical supplements in which two randomised controlled trials (RCTs) evaluating turmeric were included. Though the author noted positive outcomes with turmeric therapy, no recommendations could be provided due to limitations in quantity and quality of the data reviewed.13
Turmeric is a spice from the ginger family that is widely used in Indo-Asian cuisine and traditional eastern medicine. Curcumin is one of the active components in turmeric making up roughly 3% to 10% of the turmeric powder which can be extracted.14 The isolated curcumin extract (CE) has anti-inflammatory properties similar to that of non-steroidal anti-inflammatories.15 It has been shown that CE affects the signalling of pro-inflammatory cytokines such as interleukins, phospholipase A2, 5-lipoxygenase enzyme and COX-2 by influencing NF kappa Beta activity.16 Its anti-inflammatory properties may be particularly important at the chondrocyte level where curcumin has been shown to have an inhibitory effect on macrophage inhibitory factor-induced upregulation of matrix metalloproteinase MMP-1 (interstitial collagenase) and MMP-3 (stromelysin) enzymes.17 These enzymes when activated in synovial fibroblasts accelerate catabolic changes of the articular cartilage and subsequent development of OA.
To date, there has been one systematic review assessing the therapeutic effects of turmeric in patients with either OA or rheumatoid arthritis.18 This review highlighted the potential benefits of this supplement and evaluated a Pain Visual Analogue Score and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as primary outcomes. Eight RCTs were included and judged to exhibit low-to-moderate risk of bias. The authors concluded that there was evidence supporting the use of turmeric extract in treatment of arthritis but, a lack of sufficient power to draw definitive conclusions. Given the promise of their conclusions and the increasing recognition of inflammation and its role in the pathogenesis of OA, our goal was to evaluate the efficacy of turmeric in the treatment of patients with KOA exclusively. Our primary purpose was to determine whether turmeric affects pain and physical function in individuals with KOA exclusively. Second, we investigated the therapeutic responses of turmeric in studies that compared its efficacy to NSAID treatment.