The Advantage of Gold Microparticles Compared to Nano and Bead Particles for Local Treatment of Osteoarthritis: A Review of Animal and Human Studies

Background: and objectives: Gold-based therapies are increasingly being studied for their potential to alleviate symptoms of osteoarthritis (OA), although their overall ev-idence remains inconclusive. Methods: We conducted a systematic review and meta-analysis (search date: April 7, 2025) across five databases. We included both human and animal cohort studies, as well as randomized controlled trials, that reported on the effects of bead implants (GBI), nanoparticles (AuNP), and gold microparticles (µGold) on osteoarthritic symptoms. The risk of bias was assessed using the Cochrane, CAMARADES, and ROBINS-I tools. When appropriate, log odds ratio, Cohen’s d and Freeman-Tukey proportions were used to estimate effect size under a random-effects model. Results: A total of 22 studies met the inclusion criteria. We analyzed ten studies on GBI, nine on AuNP, and three on µGold, grouping them based on study type. For the 14 randomized controlled studies, the log odds ratio for the number of patients improved with GBI for human knee and cervical OA (two studies) was 1.61 (-1.04, 4.27), p = 0.23. For the number of patients improved with GBI for dog hip OA (three studies), the log odds ratio was 0.86 (-0.06, 1.79), p = 0.07. The effect size for the osteoarthritic score for AuNP in small animal OA (four studies) was -2.48 (-3.80, -1.15), p < 0.001, and for TNF-alpha in AuNP for small animal OA (five studies), it was -2.70 (-4.24, -1.15), p < 0.001. In the eight cohort studies, the success proportion of GBI for dog OA (five studies) was 0.88 (0.77, 0.96), p < 0.001, while for µGold in human OA (three studies), it was 0.75 (0.68, 0.82), p < 0.001. Conclusions: Notably, µGold offers an advantage in localized delivery through single intra-articular administration and greater potential for the release of gold ions compared to both GBI and AuNP. Although the evidence is classified as low to moder-ate and shows a moderate degree of heterogeneity, the results favor the use of GBI, AuNP, and µGold for OA treatment.