An association exists between adiposity, insulin resistance, and osteoporosis; however, the mechanism of this relationship remains enigmatic. We aimed to determine whether the insulin resistance index (HOMA-IR), serum adiponectin, or leptin levels are associated with bone mineral density (BMD). A cross-sectional, observational study was designed. Eighty-four postmenopausal ambulant women [52.5 (50.0-58.0) years; body mass index (BMI): 29.4 (25.9-33.8) kg/m(2)] referred for osteoporosis screening were enrolled. Anthropometric measures, fasting serum adiponectin and leptin levels, and the HOMA-IR were determined. The relationships between these variables and lumbar, hip, and forearm BMD measured by dual-energy X-ray absorptiometry (DXA) were analyzed. Considering all 84 participants, the HOMA-IR index was 1.82 (1.17-2.86), serum adiponectin was 13.25 (10.49-16.88) mu g/ml, and serum leptin was 19.26 (14.94-24.90) ng/ml. BMI, waist circumference, and leptin positively correlated with hip and lumbar BMD, whereas adiponectin negatively correlated. Multivariate analysis confirmed an inverse relation between serum adiponectin level and femoral neck and lumbar BMD measurements. In total hip and forearm areas, there was no independent association of adipocytokines with BMD measurements. Instead, waist circumference was independently associated with BMD measurements. In conclusion, adiponectin may represent a biomarker in the relationship between visceral fat mass and BMD. However, this association is probably confounded by the specific body composition parameters (i.e., waist circumference, BMI) in postmenopausal women.