Carla Caffarelli, Andrea Montagnani, Ranuccio Nuti, Stefano Gonnelli

Epidemiologic and clinical data have suggested the existence of a biologic linkage between the bone system and the vascular system. Bisphosphonates (BPs) are effective inhibitors of bone resorption and are currently considered the drugs of choice for the prevention and treatment of osteoporosis and related fractures. Data from several publications have suggested that BPs may also be effective in reducing the atherosclerotic process and vascular calcification, but the results of these studies are contrasting. This review aimed to allow a better understanding of the relationships between BPs and atherosclerosis in humans. Electronic databases of Pubmed-Medline, Cochrane Library and SCOPUS from inception to June 30, 2016 were searched. The full texts of the articles potentially eligible were carefully assessed and reviewed. Finally, 20 studies were found to be eligible and were included in the systematic review. All included studies were published between 2000 and 2014. In several studies, etidronate limited the progression of aortic and coronary calcification in hemodialysis patients, whereas the nitrogen-containing-BPs given orally did not significantly reduce vascular calcifications in patients with chronic kidney disease, kidney trasplant or in those with osteoporosis. Nitrogen-containing-BPs present favorable effects both on vessel wall thickness and on arterial elasticity due to both a reduction in serum lipids and the interaction of BPs with the bone tissue, with the consequent release of bone turnover markers and cytokines into the bloodstream. To sum up, the BPs seem to have the potential of influencing atherosclerosis and calcium homeostasis at the level of vascular walls with several possible mechanisms which may differ according to the type, potency, dosage and administration route of BPs. Additional studies are needed to specifically address the mechanism by which BP use could influence cardiovascular morbidity and mortality.