Serum Levels Of Opg, Rankl, And Rankl/Opg Ratio In Patients With Ankylosing Spondylitis: A Systematic Review And Meta-Analysis

Objectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS).Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model.Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD=0.401, 95%CI=0.026-0.777, p =0.036; RANKL: SMD=1.116, 95%CI=0.510-1.723, p <0.001; RANKL/OPG ratio: SMD=0.691, 95%CI=0.084-1.299, p =0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease 8years, and BASDAI score >4points subgroups showed increased RANKL levels compared to controls.Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients.