Efficacy and Safety of Turmeric Extracts for the Treatment of Knee Osteoarthritis: a Systematic Review and Meta-analysis of Randomised Controlled Trials.

PURPOSE OF THE REVIEW: Finding appropriate pharmacological options to treat osteoarthritis (OA) remain challenging. We aimed to determine the efficacy and safety of all types of turmeric extracts for the management of knee OA. RECENT FINDINGS: 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 (SMD - 0.82, 95% CI - 1.17 to - 0.47, I2 = 86.23%) and improved physical function (SMD - 0.75, 95% CI - 1.18 to - 0.33, I2 = 90.05%) compared to placebo but had similar effects compared to NSAIDs. BMI was the major contributor to heterogeneity in the placebo-controlled studies (explained 37.68% and 67.24%, respectively, in the models) and modified the effects of the turmeric on pain and physical function with less improvement with higher BMI (SMD 0.26 95% CI 0.04 to 0.48; SMD 0.48 95% CI 0.21 to 0.74). 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. Turmeric extract is a safe and effective option for the symptomatic management of knee OA, compared to placebo or NSAIDs. However, current evidence from short-term studies is heterogeneous and has moderate risk of bias leading to some uncertainty about the true effect.

Effectiveness of Curcuma longa Extract for the Treatment of Symptoms and Effusion-Synovitis of Knee Osteoarthritis : A Randomized Trial.

BACKGROUND: Current pharmacologic therapies for patients with osteoarthritis are suboptimal. OBJECTIVE: To determine the efficacy of Curcuma longa extract (CL) for reducing knee symptoms and effusion-synovitis in patients with symptomatic knee osteoarthritis and knee effusion-synovitis. DESIGN: Randomized, double-blind, placebo-controlled trial. (Australian New Zealand Clinical Trials Registry: ACTRN12618000080224). SETTING: Single-center study with patients from southern Tasmania, Australia. PARTICIPANTS: 70 participants with symptomatic knee osteoarthritis and ultrasonography-defined effusion-synovitis. INTERVENTION: 2 capsules of CL (n = 36) or matched placebo (n = 34) per day for 12 weeks. MEASUREMENTS: The 2 primary outcomes were changes in knee pain on a visual analogue scale (VAS) and effusion-synovitis volume on magnetic resonance imaging (MRI). The key secondary outcomes were change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and cartilage composition values. Outcomes were assessed over 12 weeks. RESULTS: CL improved VAS pain compared with placebo by -9.1 mm (95% CI, -17.8 to -0.4 mm [P = 0.039]) but did not change effusion-synovitis volume (3.2 mL [CI, -0.3 to 6.8 mL]). CL also improved WOMAC knee pain (-47.2 mm [CI, -81.2 to -13.2 mm]; P = 0.006) but not lateral femoral cartilage T2 relaxation time (-0.4 ms [CI, -1.1 to 0.3 ms]). The incidence of adverse events was similar in the CL (n = 14 [39%]) and placebo (n = 18 [53%]) groups (P = 0.16); 2 events in the CL group and 5 in the placebo group may have been treatment related. LIMITATION: Modest sample size and short duration. CONCLUSION: CL was more effective than placebo for knee pain but did not affect knee effusion-synovitis or cartilage composition. Multicenter trials with larger sample sizes are needed to assess the clinical significance of these findings. PRIMARY FUNDING SOURCE: University of Tasmania and Natural Remedies Private Limited.

Individualized Fracture Risk Feedback and Long-term Benefits After 10 Years.

INTRODUCTION: This study aimed to determine if beneficial effects of individualized feedback of fracture risk on osteoporosis preventive behaviors and bone mineral density observed in a 2-year trial were sustained long-term. METHODS: This was a 10-year follow-up of a 2-year RCT in 470 premenopausal women aged 25-44 years, who were randomized to one of two educational interventions (the Osteoporosis Prevention and Self-Management Course [OPSMC] or an osteoporosis information leaflet) and received tailored feedback of their relative risk of fracture in later life (high versus normal risk groups). Bone mineral density of lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry. Physical activity, dietary calcium intake, calcium and vitamin D supplements, and smoking status were measured by questionnaires. RESULTS: From 2 to 12 years, the high-risk group had a smaller decrease in femoral neck bone mineral density (ß=0.023, 95% CI=0.005, 0.041 g/cm2) but similar lumbar spine bone mineral density change as the normal-risk group. They were more likely to use calcium (relative risk=1.66, 95% CI=1.22, 2.24) and vitamin D supplements (1.99, 95% CI=1.27, 3.11). The OPSMC had no effects on bone mineral density change. Both high-risk (versus normal-risk) and the OPSMC groups (versus leaflet) had a more favorable pattern of smoking behavior change (relative risk=1.85, 95% CI=0.70, 4.89 and relative risk=2.27, 95% CI=0.86, 6.01 for smoking cessation; relative risk=0.33, 95% CI=0.13, 0.80 and relative risk=0.28, 95% CI=0.10, 0.79 for commenced or persistent smoking). CONCLUSIONS: Feedback of high fracture risk to younger women was associated with long-term improvements in osteoporosis preventive behaviors and attenuated femoral neck bone mineral density loss. Therefore, this could be considered as a strategy to prevent osteoporosis. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) NCT00273260.

Threshold Effects of Vitamin D Status on Bone Health in Chinese Adolescents With Low Calcium Intake.

CONTEXT: There is no consensus on the definition of vitamin D deficiency for bone health based on serum 25-hydroxyvitamin D (25OHD) levels. OBJECTIVE: Our objective was to determine whether thresholds exist for associations between 25OHD levels and bone outcomes and if low 25OHD levels have adverse effects on bone health. DESIGN: This is a cross-sectional study. PARTICIPANTS: This study included secondary school students in Beijing, China, aged 12-15 years. MEASURES: We measured serum 25OHD; bone mineral density (BMD) of total body, hip, and lumbar spine (LS); serum PTH; bone alkaline phosphatase (BAP); and tartrate-resistant acid phosphatase 5b (TRAP5b) in 222 healthy adolescents (111 girls, 111 boys). RESULTS: The prevalence of low 25OHD was 61% (<30 nmol/liter) and 97% (<50 nmol/liter) (mean 25OHD, 30 nmol/liter). Dietary calcium intake was low (294 and 307 mg/d for boys and girls, respectively). In girls, break-points for 25OHD (nmol/liter) were: total body BMD 20 (95% confidence interval [CI], 14-27), hip BMD 25 (17-34), LS BMD 22 (14-30), TRAP5b 37 (22-52), and PTH 31 (23-38). In boys, break-points were: total body BMD 39 (24-55), TRAP5b 33 (20-45), and PTH 35 (27-43); no break-points were identified for hip and LS BMD. No break-points were identified for BAP in either gender. Below these break-points, higher 25OHD is associated with increased total body BMD, reduced PTH, and TRAP5b, whereas above these break-points, no such relationship exists. CONCLUSIONS: Vitamin D deficiency and insufficiency is common in healthy Chinese adolescents. Attaining serum 25OHD levels of more than 20-37 nmol/liter in girls and 33-39 nmol/liter in boys had positive influences on BMD and bone remodelling markers. However, estimates may be affected by low calcium intake and low serum 25OHD levels, with 97% of adolescents having levels below 50 nmol/liter.

Capsaicin for osteoarthritis pain.

UNLABELLED: Capsaicin appears to be effective for osteoarthritis pain but it is uncertain whether the effect has a dose response, is consistent across joints, or changes over time. METHODS: Randomized controlled trials of topical capsaicin use in OA were identified from PubMed, EMBASE, and ISI Web of Knowledge. Effect on pain scores, patient global evaluation of treatment effectiveness and application site burning were assessed by standardised mean differences (SMD), using RevMan. RESULTS: Five double-blind randomized controlled trials and one case-crossover trial of topical capsaicin use were identified. Formulations ranged from 0.025 to 0.075%, and trial durations from 4 to 12 weeks. Trials assessed OA of the knee (n = 3), hand (n = 1), and a mix of joints (n = 2). Capsaicin treatment efficacy (vs. placebo) for change in VAS pain score was moderate, at 0.44 (95% CI 0.25-0.62) over 4 weeks of treatment. There was no heterogeneity between studies, indicating no between-study differences, including effect of OA site or treatment concentration. Two studies reported treatment beyond 4 weeks, with divergent results. One study reported an effect size of -9 mm after 12 weeks, and maximal between-group differences at 4 weeks. A second study reported that between-group differences increased over time, up to 20 weeks. Capsaicin was reported as being safe and well-tolerated, with no systemic toxicity. Mild application site burning affected 35-100% of capsaicin-treated patients with a risk ratio of 4.22 (95% CI 3.25-5.48, n = 5 trials); incidence peaked in week 1, with incidence rates declining over time. CONCLUSIONS: Topical capsaicin treatment four times daily is moderately effective in reducing pain intensity up to 20 weeks regardless of site of application and dose in patients with at least moderate pain and clinical or radiologically defined OA, and is well tolerated.

Moderate vitamin D deficiency is associated with changes in knee and hip pain in older adults: a 5-year longitudinal study.

BACKGROUND: Vitamin D is important for bone, cartilage and muscle function but there are few studies on its association with joint pain. OBJECTIVE: To investigate whether serum vitamin D predicts change in knee and hip pain in older adults. METHODS: Longitudinal population-based cohort study of randomly selected older adults (n=769) aged 50-80 years (mean 62 years); 50% were male. Serum 25-hydroxyvitamin D (25-OHD) was assessed at baseline by radioimmunoassay, and pain at baseline, 2.6 and/or 5 years using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) questionnaire. We used linear regression with adjustment for age, sex, body mass index and season, then further adjusted for potential structural mechanisms (radiographic osteoarthritis, bone marrow lesions, chondral defects and muscle strength). RESULTS: Mean total knee WOMAC score was 3.2 (range 0-39). 4.2% of participants had moderate vitamin D deficiency at baseline (25-OHD 12.5-25 nmol/l). 25-OHD <25 nmol/l predicted change in knee pain (using total WOMAC score) over 5 years (ß=2.41, p=0.002) with a similar effect size for hip pain over 2.4 years (ß=2.20, p=0.083). Results were consistent within pain subscales, and the association was independent of demographic, anthropometric and structural covariates. No association was present when 25-OHD was analysed as a continuous measure. CONCLUSIONS: Moderate vitamin D deficiency independently predicts incident, or worsening of, knee pain over 5 years and, possibly, hip pain over 2.4 years. Therefore correcting moderate vitamin deficiency may attenuate worsening of knee or hip pain in elderly people but giving supplements to those with a higher 25-OHD level is unlikely to be effective.