Influence of Iguratimod on Bone Metabolism in Patients with Rheumatoid Arthritis: A Meta-analysis

BACKGROUND: Influence of iguratimod on bone mineral density (BMD) and biomarkers of bone metabolism in patients with rheumatoid arthritis (RA) remains not determined. Accordingly, a meta-analysis was performed for systematical evaluation. METHODS: Relevant randomized controlled trials (RCTs) were retrieved by searching of PubMed, Embase, Cochrane's Library, China National Knowledge Infrastructure (CNKI), and Wanfang databases. A random-effect model was used to pool the results. RESULTS: In total, 24 RCTs including 2439 patients with RA contributed to the meta-analysis. Pooled results showed that compared to methotrexate alone, additional use of iguratimod 25 mg Bid for 12∼24 weeks significantly improved lumbar-spine BMD (mean difference [MD]: 0.12, 95% confidence interval [CI]: 0.04 to 0.20, p=0.002, I(2) = 39%) in patients with RA. Moreover, treatment with iguratimod was associated with increased serum osteoprotegerin (MD: 180.36 pg/ml, 95% CI: 122.52 to 238.20, p < 0.001, I(2) = 48%), and decreased serum receptor activator for nuclear factor kappa-B ligand (MD: −10.65 pmol/l, 95% CI: −15.59 to −5.72, p < 0.001, I(2) = 53%). In addition, iguratimod was associated with increased bone formation markers such as the serum N-terminal middle molecular fragment of osteocalcin (MD: 4.23 ng/ml, 95% CI: 3.74 to 4.71, p < 0.001, I(2) = 35%) and total procollagen type I amino-terminal propeptide (MD: 9.10 ng/ml, 95% CI: 7.39 to 10.80, p < 0.001, I(2) = 86%), but decreased the bone resorption marker such as serum β-C terminal cross-linking telopeptide of type 1 collagen (MD: −0.18 pg/ml, 95% CI: −0.21 to −0.14, p < 0.001, I(2) = 70%). CONCLUSIONS: Iguratimod could prevent the bone loss and improve the bone metabolism in patients with RA.