Hypertonic dextrose injections (prolotherapy) is an emerging treatment for symptomatic knee osteoarthritis (OA) but its efficacy is uncertain. We conducted a systematic review with meta-analysis to synthesize clinical evidence on the effect of prolotherapy for knee OA. Fifteen electronic databases were searched from their inception to September 2015. The primary outcome of interest was score change on the Western Ontario and McMaster Universities Arthritis Index (WOMAC). Three randomized controlled trials (RCTs) of moderate risk of bias and one quasi–randomized trial were included, with data from a total of 258 patients. In the meta-analysis of two eligible studies, prolotherapy is superior to exercise alone by a standardized mean difference (SMD) of 0.81 (95% CI: 0.18 to 1.45, p = 0.012), 0.78 (95% CI: 0.25 to 1.30, p = 0.001) and 0.62 (95% CI: 0.04 to 1.20, p = 0.035) on the WOMAC composite scale; and WOMAC function and pain subscale scores respectively. Moderate heterogeneity exists in all cases. Overall, prolotherapy conferred a positive and significant beneficial effect in the treatment of knee OA. Adequately powered, longer-term trials with uniform end points are needed to better elucidate the efficacy of prolotherapy.

To identify and quantify risk factors for incident knee osteoarthritis (KOA) across the lifespan. This systematic review and meta-analysis identified eligible studies from seven electronic databases and three registries. Longitudinal cohort studies or randomised controlled trials evaluating participants who developed incident symptomatic and/or radiographic KOA were included. Two independent reviewers completed data screening and extraction. Estimates were pooled using a random effects model and reported as odds ratio (OR), hazard ratio (HR), or risk ratio (RR) and corresponding 95% confidence intervals (95% CI). Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to determine the certainty of evidence. Population attributable fractions (PAFs) were calculated, including risk factors significantly associated with radiographic KOA based on the pooled meta-analysis and where we could determine communality scores using existing clinical datasets. We identified 132 studies evaluating >150 risk factors. Higher body mass index (BMI), previous knee injury, older age and high bone mineral density were associated with an increased risk of incident radiographic KOA based on the pooled analysis [OR (95% CI): 1.56 (1.25, 1.95), 3.02 (1.93, 4.71), 1.15 (1.00, 1.33) and 1.82 (1.12, 2.94), respectively], with moderate-to-high certainty. Two risk factors (overweight/obesity and previous knee injury) accounted for 14% of incident radiographic KOA. Other modifiable risk factors including occupational physical activity also contribute to radiographic or symptomatic KOA. Novel strategies addressing known modifiable risk factors including overweight/obesity, knee injuries and occupational physical activity are needed to reduce overall burden of KOA. PROSPERO ID: CRD42023391187 FUNDING: Sydney Musculoskeletal Health, Faculty of Medicine and Health, The University of Sydney.

PURPOSE To test the efficacy of intra-articular hypertonic dextrose prolotherapy (DPT) vs normal saline (NS) injection for knee osteoarthritis (KOA). METHODS A single-center, parallel-group, blinded, randomized controlled trial was conducted at a university primary care clinic in Hong Kong. Patients with KOA (n = 76) were randomly allocated (1:1) to DPT or NS groups for injections at weeks 0, 4, 8, and 16. The primary outcome was the Western Ontario McMaster University Osteoarthritis Index (WOMAC; 0-100 points) pain score. The secondary outcomes were the WOMAC composite, function and stiffness scores; objectively assessed physical function test results; visual analogue scale (VAS) for knee pain; and EuroQol-5D score. All outcomes were evaluated at baseline and at 16, 26, and 52 weeks using linear mixed model. RESULTS Randomization produced similar groups. The WOMAC pain score at 52 weeks showed a difference-in-difference estimate of −10.34 (95% CI, −19.20 to −1.49, P = 0.022) points. A similar favorable effect was shown on the difference-in-difference estimate on WOMAC function score of −9.55 (95% CI, −17.72 to −1.39, P = 0.022), WOMAC composite score of −9.65 (95% CI, −17.77 to −1.53, P = 0.020), VAS pain intensity score of −10.98 (95% CI, −21.36 to −0.61, P = 0.038), and EuroQol-5D VAS score of 8.64 (95% CI, 1.36 to 5.92, P = 0.020). No adverse events were reported. CONCLUSION Intra-articular dextrose prolotherapy injections reduced pain, improved function and quality of life in patients with KOA compared with blinded saline injections. The procedure is straightforward and safe; the adherence and satisfaction were high.

Background: Virtual reality (VR) in different immersive conditions has been increasingly used as a nonpharmacological method for managing chronic musculoskeletal pain. Objective: We aimed to assess the effectiveness of VR-assisted active training versus conventional exercise or physiotherapy in chronic musculoskeletal pain and to analyze the effects of immersive versus nonimmersive VR on pain outcomes. Methods: This systematic review of randomized control trials (RCTs) searched PubMed, Scopus, and Web of Science databases from inception to June 9, 2024. RCTs comparing adults with chronic musculoskeletal pain receiving VR-assisted training were included. The primary outcome was pain intensity; secondary outcomes included functional disability and kinesiophobia. Available data were pooled in a meta-analysis. Studies were graded using the Cochrane Risk-of-Bias Tool version 2. Results: In total, 28 RCTs including 1114 participants with some concerns for a high risk of bias were identified, and 25 RCTs were included in the meta-analysis. In low back pain, short-term outcomes measured post intervention showed that nonimmersive VR is effective in reducing pain (standardized mean difference [SMD] –1.79, 95% CI –2.72 to –0.87; P<.001), improving disability (SMD –0.44, 95% CI –0.72 to –0.16; P=.002), and kinesiophobia (SMD –2.94, 95% CI –5.20 to –0.68; P=.01). Intermediate-term outcomes measured at 6 months also showed that nonimmersive VR is effective in reducing pain (SMD –8.15, 95% CI –15.29 to –1.01; P=.03), and kinesiophobia (SMD –4.28, 95% CI –8.12 to –0.44; P=.03) compared to conventional active training. For neck pain, immersive VR reduced pain intensity (SMD –0.55, 95% CI –1.02 to –0.08; P=.02) but not disability and kinesiophobia in the short term. No statistical significances were detected for knee pain or other pain regions at all time points. In addition, 2 (8%) studies had a high risk of bias. Conclusions: Both nonimmersive and immersive VR–assisted active training is effective in reducing back and neck pain symptoms. Our study findings suggest that VR is effective in alleviating chronic musculoskeletal pain. Trial Registration: PROSPERO CRD42022302912; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=302912

Hypertonic dextrose prolotherapy (DPT) has been reported to be effective for temporomandibular disorders (TMDs) in clinical trials but its overall efficacy is uncertain. To conduct a systematic review with meta-analysis of randomized controlled trials (RCTs) to synthesize evidence on the effectiveness of DPT for TMDs. Eleven electronic databases were searched from their inception to October, 2020. The primary outcome of interest was pain intensity. Secondary outcomes included maximum inter-incisal mouth opening (MIO) and disability score. Studies were graded by “Cochrane risk of bias 2” tool; if data could be pooled, a meta-analysis was performed. Ten RCTs (n = 336) with some to high risk of bias were included. In a meta-analysis of 5 RCTs, DPT was significantly superior to placebo injections in reducing TMJ pain at 12 weeks, with moderate effect size and low heterogeneity (Standardized Mean Difference: − 0.76; 95% CI − 1.19 to − 0.32, I² = 0%). No statistically significant differences were detected for changes in MIO and functional scores. In this systematic review and meta-analysis, evidence from low to moderate quality studies show that DPT conferred a large positive effect which met criteria for clinical relevance in the treatment of TMJ pain, compared with placebo injections.Protocol registration at PROSPERO: CRD42020214305.