Objective To investigate the significance of test of receptor activator of nuclear factor?kappa B(NF?κB)ligand(RANKL)in serum and urine for the diagnosis of osteoporosis. Methods A total of 53 patients with osteoporosis(the experimental group)and 45 healthy controls(the normal control group)were recruited in this study. The expression levels of RANKL in serum and urine was measured and compared by enzyme?linked immunosorbent assay. Results The serum and urine levels of RANKL in the experimental group were significantly higher than those in the normal control group(P<0.01). The areas under receiver operating characteristic(ROC)curve of serum and urine RANKL were 0.898 and 0.734, respectively. The combined detection of serum and urine RANKL and Ca2+reached a high sensitivity of 89.5%and a specificity of 86.1%for diagno?sis of osteoporosis. Conclusion RANKL may be closely associated with the progression of osteoporosis. Serum and urine RANKL test may be help?ful in the diagnosis of osteoporosis.