The role of complementary and alternative medicines in the management of osteoarthritis

Osteoarthritis (OA) is a serious disease and a major public health challenge, affecting mainly older adults and the obese population. Despite its enormous disease burden, no approved disease-modifying drugs are available to treat OA. Complementary and alternative medicines (CAMs) are increasingly used in OA treatment with very little evidence of their efficacy. They are generally considered safe and may be an alternative option for OA patients who often have comorbidities and contraindications to modern pharmacological therapies. Aiming to widen the evidence base for CAMs use among OA patients, this thesis investigated the prevalence of the use of CAMs in the Tasmanian population and tested the efficacy of Curcuma longa extract (CL) and vitamin D for the management of knee OA.

In Chapter 4, we first explored the prevalence and correlates of CAM medication use among older adults utilising data from the Tasmania Older Adult Cohort Study (TASOAC, n=1099). Participants aged between 50 and 80 years were selected randomly from the electoral roll in southern Tasmania (total population: n=229,000). Participants were asked to bring all their over-the-counter and prescription medications to the clinic visit and complete a questionnaire with assistance from the research nurse. Correlates of CAM medication use were assessed by comparing CAM medication users and non-users. We found that CAM medications were commonly used among Tasmanian older adults, with 35% of the population using CAM medications either alone or with conventional analgesics. CAM medication users were more likely to be females, better educated, had more joints with OA, and had healthier lifestyles.

In Chapter 5, we conducted a randomised, double-blinded, placebo-controlled trial (CurKOA trial registered in ANZCTR: ACTRN12618000080224) to determine the efficacy of CL for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee OA and knee effusion-synovitis. Seventy participants with symptomatic knee OA and ultrasound-defined effusion-synovitis were included and given two capsules per day of CL (n=36) or matched placebo (n=34) for 12 weeks. Two primary outcomes were changes in knee visual analogue scale (VAS) pain, and effusion-synovitis volume on magnetic resonance imaging (MRI) scans. The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. We found that CL improved VAS pain compared to placebo by -9.1mm but did not change effusion-synovitis volume. CL also improved WOMAC knee pain, but not lateral femoral cartilage T2 relaxation time. The incidence of adverse events was similar in the CL (n=14 (39%)) and placebo (n=18 (53%)) groups.

CL was shown to be modestly effective for relieving knee symptoms in knee OA patients; however, the mechanism of action is unclear. In Chapter 6, we aimed to determine the effects of CL treatment on serum inflammatory markers over 12 weeks and to explore its potential effects on synovitis assessed by contrast-enhanced magnetic resonance imaging (CE-MRI) of the knee. Systemic inflammatory markers (TNF-α, and hs-CRP) and cartilage marker (MMP-3) were measured at baseline and 12-week follow-up. We conducted a sub-study to the CurKOA trial and performed secondary analyses. A subgroup of participants (CL, n=7; placebo, n=5) underwent CE-MRI at baseline and a 12-week follow-up for assessing synovitis. Over 12 weeks, there were no between-group differences in change in hs-CRP, IL-6 levels, and TNF-α. MMP-3 levels decreased in both the CL and placebo groups, with a slightly greater decrease in the placebo group. Synovitis status remained stable for all except two participants, one each in the CL and placebo group, whose synovitis score increased. There was no clinically significant effect of CL treatment on systemic (inflammatory and cartilage) or local synovitis (CE-MRI) biomarkers compared to placebo.

Chapter 7 was a systematic review and meta-analysis of the efficacy and safety of turmeric extracts in knee OA. We aimed to determine the efficacy and safety of all types of turmeric extracts to manage knee OA. Sixteen RCTs of up to 16 weeks duration, including 1810 adults with knee OA were included. Eleven RCTs compared the efficacy of turmeric extracts with placebo and five with active comparators (NSAIDs). The overall risk bias of included RCTs was moderate. Turmeric extracts significantly reduced knee pain, and improved physical function compared to placebo, but had similar effects compared to NSAIDs. No significant between-group differences were reported for either biochemical markers or imaging outcomes. Turmeric extracts had 12% fewer adverse events than NSAIDs and similar rates to placebo.

In Chapter 8, we aimed to investigate the effect of vitamin D supplementation compared to placebo over 2 years on knee symptoms, psychological health, and inflammatory markers over 5 years in patients with knee OA. We also aimed to describe the effect of maintaining sufficient serum vitamin D levels on knee symptoms in knee OA patients over 5 years. As an extension of the Vitamin D Effects on Osteoarthritis trial (VIDEO), participants (n=173) from the Hobart centre of the trial were further followed up at 3.5 years after the cessation of 2-year investigational treatment. Vitamin D supplementation over 2 years or maintaining vitamin D sufficiency for 5 years was not associated with significant differences in change in knee symptom score over 5 years. However, two-year vitamin D supplementation was linked to WOMAC function and psychological improvement among participants who did not report knee surgery. Similarly, knee OA patients without knee surgery maintaining sufficient serum vitamin D levels over 5 years were associated with improvement in knee pain and physical function than those who did not, suggesting a potential beneficial effect of maintaining sufficient serum vitamin D for knee OA.

In conclusion, CAMs were commonly used among Tasmanian older adults, with 35% of the population using CAM medications. A standardised extract of turmeric showed a moderate effect on the symptomatic management of knee OA. Vitamin D supplementation over 2 years was not associated with symptomatic improvement in knee OA patients over 5 years. However, maintaining sufficient vitamin D levels over 5 years may have a significant effect on the improvement of symptoms in knee OA patients without knee surgery.