The role of proinflammatory IL-17 cytokine was studied in postmenopausal bone loss between 31 osteopenic and 41 osteoporotic women. The effect of serum IL-17A, soluble receptor activator of NF-κB (sRANK) ligand, and osteoprotegerin (OPG) levels on lumbar bone mineral densities was measured. The results demonstrated an increased IL-17A-mediated sRANK ligand elevation in postmenopausal osteoporotic bone loss.IL-17 proinflammatory cytokine is a new inducer of bone loss. Postmenopausal osteoporosis represents a cross talk between estrogen deprivation and increased immune reactivity. The role of IL-17 was studied in the bone loss of postmenopausal osteoporosis.Serum IL-17A, sRANK ligand, and OPG levels were investigated on bone mineral densities (BMDs) in the total lumbar (L1-L4) region in 18 pre- and 72 postmenopausal women. IL-17A, sRANK ligand, OPG levels, and BMDs were measured with enzyme-linked immunosorbent assay (ELISA) and dual-energy X-ray absorptiometry (DXA).Increased serum IL-17A, sRANK ligand, and OPG levels were demonstrated in postmenopausal osteoporotic women compared to osteopenic women (3.65 ± 0.61 vs 3.31 ± 0.43 ng/ml for IL-17A, P < 0.007; 2.88 ± 0.84 vs 2.49 ± 0.61 ng/ml for sRANK ligand, P < 0.027; and 1.43 ± 0.07 vs 1.39 ± 0.07 ng/ml for OPG, P < 0.038). In postmenopausal women, IL-17A levels correlated inversely with total lumbar BMDs (P < 0.008, r = -0.279) and positively with sRANK ligand levels (P < 0.0001, r = 0.387) or the ratio of sRANK ligand and OPG (P < 0.013, r = 0.261), but did not with OPG levels alone.Increased IL-17A levels are involved in postmenopausal osteoporosis, playing a role in the bone-resorpting processes.