Neridronate

Neridronate is an aminobisphosphonate. Neridronate induces osteoblast differentiation, enhances alkaline phosphatase activity and mineralized nodule formation. Neridronate inhibits endothelial cell proliferation, fibroblast growth factor-2-induced capillary-like tube formation, and angiogenesis. Neridronate can be used for osteogenesis imperfecta and Paget’s disease of bone^[1][2][3]. In Vitro:Neridronate (≤10^-8-10^-3 M; 0-20 days) at 10^-3 M causes cytotoxicity and cell death in primary human osteoblasts grown in 10% FCS over 20 days, 10^-4 M inhibits proliferation, 10^-5 to 10^-7 M increases viable cell counts, and concentrations ≤10^-8 M have no effect on viability or proliferation^[1].
Neridronate (10^-7-10^-4 M; 4-8 days) at 10^-5 to 10^-7 M increases type I collagen synthesis in primary human osteoblasts grown in 10% FCS after 4 days, while 10^-4 to 10^-6 M reduces synthesis after 8 days^[1].
Neridronate (10^-8-10^-7 M; 10-20 days) at 10^-8 M maximally increases ALKP activity by 50% in primary human osteoblasts grown in 10% FCS after 10 days, and 10^-7 M increases activity by 22% after 20 days^[1].
Neridronate (10^-8-10^-4 M; 4-20 days) at 10^-4 M increases mineralized nodule formation in primary human osteoblasts grown in 2% UG after 4 days, while 10^-7 and 10^-8 M increase formation by 44% and 24%, respectively, after 20 days^[1].
Neridronate (1-50 μM; 24 h) dose-dependently inhibits the proliferation of human umbilical vein endothelial cells, with peak activity at 30 μM after 24 h of treatment^[2].
Neridronate (30 μM; 18 h) disrupts FGF-2-induced capillary-like tube formation by human umbilical vein endothelial cells seeded on Matrigel after 18 h of incubation^[2]. In Vivo:Neridronate (50 μM/embryo; via gelatin sponge on CAM; single administration on day 8 of incubation) significantly reduces FGF-2-induced angiogenesis in the chick embryo CAM assay^[2].