Objective To investigate the value of serum receptor activator of nuclear factor kappa B ligand (RANKL)/osteoprotegrin (OPG) ratio in osteoporotic fracture (OPF) of patients with rheumatoid arthritis (RA). Methods Three hundred and eighty four RA patients with mean age of (49±14)y (16-82) admitted in the First Affiliated Hospital of Anhui Medical University from 2010 to 2013 and 158 sex- and age-matched healthy subjects were enrolled in the study. OPF was diagnosed by X-ray examination and BMDs of femur and lumbar spine 2-4 (L2-4) were measured by dual energy X-ray absorptiometry. Levels of RANKL and OPG in the peripheral blood of 220 RA patients and 100 normal subjects were detected by ELISA method. Results Eighty-two cases of OPF was diagnosed in 384 RA patients (21.35%), the rate was higher than that in controls (3.80%, 6/158, χ2=25.371, P<0.01). The peripheral blood levels of RANKL (0.150±0.143 vs. 0.101±0.066, t=4.178, P<0.01), OPG (0.457±0.293 vs. 0.359±0.216, t=3.347, P=0.001) and ratio of RANKL/OPG (0.41±0.35 vs. 0.34±0.20, t=2.111, P=0.036) in RA patients were significantly higher than those in control group. In comparison with normal controls, BMDs of all detected regions in RA were decreased significantly (P<0.01). The incidence of osteoporosis in RA (121/327, 37%) was higher than that in normal controls (22/158, 13.92%) (χ2=27.291, P<0.01). RA patients with OPF had higher age (t=4.377, P<0.01), longer duration of disease (t=2.612, P=0.009), higher RANKL level (t=3.554, P=0.001), higher RANKL/OPG ratio (t=2.651, P=0.010), higher health assessment questionnaires (HAQ) score (t=2.418, P=0.016), lower serum calcium level (t=2.183, P=0.030), lower hemoglobin level (t=2.125, P=0.036), higher Sharp score in hands X-ray examination (t=2.747, P=0.007), worse X-ray stage (χ2=7.856, P=0.049), higher glucocorticoid utilization rate (χ2=9.066, P=0.003) and higher incidence of osteoporosis (χ2=38.186, P<0.01), compared with patients without OPF. RA patients taking corticosteroids had higher incidence of osteoporosis (χ2=7.489, P=0.006) and higher incidence of OPF (χ2=9.066, P=0.003). Logistic regression analysis showed that age (OR=1.029, P=0.039, 95%CI: 1.001-1.057)and the occurrence of osteoporosis (OR=3.159, P=0.001, 95%CI: 1.562-6.385), RANKL/OPG ratio(OR=3.516, P=0.013, 95%CI: 1.305-9.647) were risk factors for RA patients with OPF. Conclusion A higher incidence of OPF is prevalent in RA patients, and age, osteoporosis, taking glucocorticoids and RANKL/OPG ratio are risk factors for OPF in RA patients. Key words: Arthritis, rheumatoid; Fractures, bone; Osteoporosis; Receptor activator of nuclear factor kappa B