The association of body fat mass (FM) with bone mineral mass (BMC) and bone mineral density (BMD) has been attributed to a mechanical load exerted on the skeleton by FM and by the effect of different hormones. The aim of the present study was to determine whether there is a relationship between ghrelin, adiponectin, and leptin with BMC and BMD in healthy postmenopausal women (n = 88; age, 68.9 +/- 6.8 years; body mass index, 27.4 +/- 3.6 kg/m(2)). Body composition, BMC, and BMD were derived by dual-energy X-ray absorptiometry. Waist-to-hip (WHR) and waist-to-thigh (WTR) ratios were also obtained. Ghrelin was associated with total BMC (beta = -0.945; P = 0.0001), total BMD (beta = -0.959; P = 0.0001), lumbar spine BMD (beta = -0.945; P = 0.0001), and femoral neck BMD (beta = -0.957; P = 0.0001), and remained associated (P < 0.041) in different analyses that controlled for measured body composition and hormonal and insulin resistance values. However, the associations between ghrelin and measured bone mineral values were no longer significant (P > 0.149) when adjusted for body fat distribution values (WHR, WTR). Adiponectin was significantly related to total BMC (beta = -0.931; P = 0.0001), total BMD (beta = -0.940; P = 0.0001), lumbar spine BMD (beta = -0.937; P = 0.0001), and femoral neck BMD (beta = -0.940; P = 0.0001) values, and these relationships remained significant (P < 0.019) after adjusting for measured body fat, hormonal, and insulin resistance values but not when adjusted for fat-free mass (FFM; P > 0.106). In addition, significant associations of leptin with total BMC (beta = 0.912; P = 0.0001), total BMD (beta = 0.907; P = 0.0001), lumbar spine BMD (beta = 0.899; P = 0.0001), and femoral neck BMD (beta = 0.906; P = 0.0001) were found. These associations remained significant (P < 0.010) in different analyses that controlled for hormonal and insulin resistance values, but the associations between leptin and bone mineral values were no longer significant (P > 0.145) when adjusted for specific body composition values (WHR, WTR, FM, and FFM). In conclusion, it appears that the influence of plasma ghrelin, adiponectin, and leptin levels on BMC and BMD values is mediated or confounded by the specific body composition parameters in healthy postmenopausal women.