Assessment of calciprotein particle formation by AUC of the absorbance change: effect of FYB-931, a novel bisphosphonate compound

Abstract

Objective: Ectopic calcification such as vascular calcification, involves the formation of calciprotein particle (CPP), that is, colloidal particle of calcium phosphate bound to serum protein. In this study, a novel parameter for CPP formation was introduced, thereby the effect of FYB-931, a bisphosphonate compound was evaluated.

Methods: CPP formation in rat serum was assessed by the area under the curve (AUC) of the change in absorbance over time, and the commonly used T50, as indices. In vivo, the rats were treated with vitamin D3 to induce vascular calcification and then intravenously administered FYB-931 or etidronate thrice weekly for 2 weeks.

Key findings: In vitro, FYB-931 was the most potent inhibitor of CPP formation and it also inhibited the maximum response of CPP formation at higher concentrations. The AUC of the change in absorbance provided obvious dose-dependency, while T50 did not. FYB-931 dose-dependently prevented aortic calcification in vivo as well as CPP formation ex vivo more potently than etidronate. AUC showed a stronger correlation with the degree of aortic calcification than T50.

Conclusions: The AUC in CPP formation can be an alternative parameter that reflects calcification. Based on the findings, FYB-931 has potential as an anti-calcifying agent.

Keywords: area under the curve; bisphosphonate; calcification; calciprotein particle formation; rat.