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Abstract: Atherosclerosis and osteoporosis appear to be epidemiologically correlated. Most (but not all) animal and clinical studies suggest that osteoprotegerin (OPG) may represent a possible molecular link between bone loss and vascular calcification. The aim of this study was to investigate the association of OPG with bone mineral density (BMD) and vascular plaques, in order to contribute to a better understanding of the link between atherosclerosis and osteoporosis. The study population consisted of 100 consecutive postmenopausal women referred for routine osteoporosis screening. BMD was evaluated by dual-energy X-ray absorptiometry. Presence of carotid or femoral plaques was examined by ultrasonography. OPG was measured by enzyme immunoassay. Seventy-two subjects had low bone mass and were categorized as osteopenic (32) or osteoporotic (40). Fifty-two subjects had one or more atherosclerotic plaques at carotid or femoral level. Both lumbar spine and femoral BMD were associated with the number of plaques (r =−0.5370; p <0.0001, and r =−0.4423; p =0.0012, respectively), however only spine BMD remained significantly associated with the number of plaques after adjustment. OPG serum values showed a significant association with age (r 2 =0.057; p =0.042). The association between OPG and the number of plaques was significant only in patients with concomitant involvement of carotid and femoral districts (r 2 =0.758; p <0.0001). [ABSTRACT FROM AUTHOR]