Role of Bisphosphonates in Vascular Calcification and Bone Metabolism: A Clinical Summary

BACKGROUND: Vascular calcification is known to be a strong risk factor for cardiovascularadverse events and mortality. Atherosclerosis, diabetes, aging, abnormal bone mineral homeostasisand high uremic milieu such as chronic kidney disease are major factors that contribute to theprogression of vascular calcification. Several mechanisms such as the osteoblastic transition of vascularsmooth muscle cells in response to oxidative stress have shed light on the active nature ofvascular calcification, which was once thought to be a passive process. The fine interplay of regulatoryfactors such as PTH, vitamin D3, FGF 23 and klotho reflect the delicate balance between vascularcalcification and bone mineralization. Any disturbance affecting this equilibrium of the bonemineral-vascular axis results in accelerated vascular calcification. Bisphosphonates share similar mechanism of action as statins, and hence several studies were undertakenin humans to verify if the benefits proven to be obtained in animal models extended tohuman models too. This yielded conflicting outcomes which are outlined in this review. This wasattributed mainly to inadequate sample size and flaws in the study design. Therefore, this benefitcan only be ascertained if studies addressing this are undertaken. CONCLUSION: This review seeks to highlight the pathophysiologic phenomena implicated in vascular and valvular calcification and summarize the literature available regarding the use of bisphosphonates in animal and human models. We also discuss novel treatment approaches for vascular calcification,with emphasis on chronic kidney disease and calciphylaxis.