Maturitas 67 (2010) 358–362 Contents lists available at ScienceDirect Maturitas journal homepage: www.elsevier.com/locate/maturitas The association between carotid or femoral atherosclerosis and low bone mass in postmenopausal women referred for osteoporosis screening. Does osteoprotegerin play a role? P. Pennisi a , E. Russo b , A. Gaudio a , R. Veca c , F. D’Amico b , R.A. Mangiafico a , M. Laspina a , G. Tringali c , S.S. Signorelli d , C.E. Fiore a,∗ a Department of Internal Medicine, University of Catania, Italy b Geriatric Unit, Barone I. Romeo Hospital, Patti, Italy c Istituto Ricerca Medica Ambientale (I.R.M.A.), Acireale, Italy d Division of Medical Angiology, University of Catania, Italy article info Article history: Received 21 April 2010 Received in revised form 21 July 2010 Accepted 24 July 2010 Keywords: Carotid plaque Femoral plaque Low bone mass Osteoprotegerin 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 osteo- porosis 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). © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction The relation between atherosclerosis and osteoporosis is still debated. Although growing evidence shows that arterial calcifica- tion is associated with low bone mass even after adjustment for age [1–3], and although several potential biological linkages between these two conditions have been suggested [4], the magnitude and nature of this association remain uncertain. Among the potential pathogenetic mechanisms that link osteoporosis to atherosclero- sis, a dysregulation of the OPG/RANK/RANKL system could be one of the most important. Osteoprotegerin (OPG), a member of the tumor necrosis factor (TNF) receptor family, regulates osteoclasto- genesis by inhibiting receptor activator of nuclear factor-B ligand (RANKL)-mediated osteoclastic bone resorption [5]. OPG, produced ∗ Corresponding author at: Clinica Medica OVE, University of Catania, Via Plebisc- ito 628, 95124 Catania, Italy. Tel.: +39 095 7435386; fax: +39 095 316533. E-mail address: carmelo.fiore@tin.it (C.E. Fiore). mainly by osteoblast lineage cells [6], and also by endothelial cells and arterial smooth muscle cells [7], has been implicated in bone metabolism and vascular function [8]. Experimental data and clin- ical observations appear however rather conflicting. OPG-deficient mice, in fact, develop severe osteoporosis with multiple fractures and calcification of the aorta and renal arteries [9]. On the con- trary, in patients with hypertension or advanced cardiovascular disease, serum levels of OPG are higher, associated with cardiovas- cular mortality [10], and predictive of adverse outcomes in patients presenting with an acute coronary syndrome [11]. These findings suggest that elevated OPG levels may represent an insufficient com- pensatory self-defensive mechanism to prevent further vascular damage. This hypothesis may be supported by the observation that in the early stages of vascular damage observed in osteoporotic postmenopausal patients without any known risk factor for car- diovascular disease, serum levels of OPG are within the normal range, and not correlated with arterial stiffness [12]. On the con- trary, OPG levels are positively associated with arterial stiffness in postmenopausal osteoporotic women with atherosclerotic plaques 0378-5122/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.maturitas.2010.07.013