Osteoprotegerin as an independent marker of subclinical atherosclerosis in osteoporotic postmenopausal women.

Osteoprotegerin (OPG) appears to represent the molecular link between bone resorption and vascular calcification, and may help to explain the high prevalence of atherosclerosis and osteoporosis in postmenopausal women. We investigated a possible association between serum OPG levels and arterial stiffness in postmenopausal women with osteoporosis. 70 postmenopausal women with osteoporosis and cardiovascular risk factors but without coronary artery disease were evaluated for metabolic, inflammatory parameters and serum OPG levels. Pulse wave velocity (PWV) and augmentation index (AIx) were performed as a simple noninvasive recording of the two artery sites pressure waveform using SphygmoCor (version 7.1, AtCor Medical, Sydney, Australia). Serum OPG levels were significantly, positively associated with AIx (r=0.39, p=0.003) and with PWV (r=0.81, p<0.0001). No association between OPG levels and hemodynamic variables or measures of glucose metabolism was observed. Among inflammatory markers, OPG was significantly, positively associated with fibrinogen (r=0.323, p=0.015). In a multiple linear regression analysis, OPG was independent predictor of PWV (standardized beta=0.75, p<0.0001) and AIx (standardized beta=0.41, p=0.01). Serum OPG is potentially an independent predictor of early vascular adverse changes in osteoporotic postmenopausal women.

Effect of long-term treatment with risedronate on arterial compliance in osteoporotic patients with cardiovascular risk factors.

Accumulating evidence suggests that osteoporosis and coronary artery disease have epidemiologic similarities. Moreover, the anti-atherogenic effects of bisphosphonates have been observed in vitro and in animal models. The present study investigated the effect of risedronate on indices of arterial compliance, serum osteoprotegerin (OPG) level, inflammatory and metabolic parameters in osteoporotic women with cardiovascular risk factors. In an open label, prospective study 68 postmenopausal osteoporotic women were evaluated for the study. Patients received risedronate orally in a dose of 35 mg per week, daily supplements of calcium and cholecalciferol during 6month treatment period. Patients were evaluated for lipid profile, HbA1C, insulin, C-peptide, fibrinogen, hs-CRP and plasma osreoprotegerin. Arterial elasticity was evaluated using pulse wave contour analysis (HDI CR 2000, Eagan, Minnesota). Large artery elasticity index (LAEI) increased from 9.86+/-3.66 to 11.54+/-">+/-3.16 ml/mm HgX10 (p<0.0001) during treatment period. Small artery elasticity index (SAEI) increased from 2.64+/-1.10 to 3.28+/-1.16 ml/mm HgX100 (p<0.0001). Systemic vascular resistance (SVR) decreased from 1876.12+/-457.72 to 1646.12+/-260.17 dyn/s/cm(- 5) (p<0.013). Metabolic parameters did not change during the treatment period. Plasma osteoprotegerin was significantly, positively correlated to SVR at baseline (r=0.36, p=0.045). At the final visit, OPG was marginally inversely associated with LAE (r=- 0.312, p=0.09), and significantly, positively associated with total vascular impedance (r=0.43, p=0.015). In conclusion, prolonged treatment with risedronate improved arterial elasticity of small and large arteries, and decreased SVR. These beneficial vascular effects were not related to changes in cardiovascular risk factors and may be attributed to direct effects of risedronate on the vascular wall.