Osteoporosis and atherosclerosis are leading causes of mortality and morbidity in the Western world. A link between osteoporosis and atherosclerosis was proposed by epidemiologic and laboratory data. In the present study, we investigated skeletal status in postmenopausal women with hypercholesterolemia using quantitative ultrasonometry (QUS). Six hundred healthy postmenopausal subjects were enrolled within a 2-mo period by primary care physicians. Information on lifestyle and calcium intake was collected for each enrolled subject. Subjects (n = 256) were divided into two groups according to lipid profile: normal (n = 180) with serum cholesterol <200 mg/dL and hypercholesterolemic (n = 76) with serum cholesterol >or=200 mg/dL. Hypercholesterolemic subjects were further stratified into two groups, one receiving dietary treatment (n = 34) and the other receiving statin treatment (n = 42). We found a statistically significant reduction in amplitude dependent speed of sound (AD-SoS) in hypercholesterolemic subjects compared with subjects with normal cholesterol (p = 0.006). Calcium intake behaved similarly to AD-SoS (p = 0.0001). No statistical significant difference in AD-SoS were observed between the group on diet treatment versus the group on statin (p = 0.52). Calcium intake was lower in patients on statins treatment compared with subjects on diet treatment only (p < 0.0001). Our data suggest that hypercholesterolemia per se is a risk factor for impaired skeletal status. Our data also call attention to the risk of a poor calcium intake in patient receiving diet to lower plasma cholesterol. Moreover, our data suggest that statins per se may exert a protective effect on bone independently from calcium intake.