Zoledronic acid (Zoledronate)

Zoledronic acid (10 µM and 100 µM) causes a significant reduction in the proportions of MCF-7 cells (49.54% and 23.55% of control, respectively) (P < 0.05). Zoledronic acid has little effect on MDA-MB-231 cells at concentrations of 0.1–10 µM, whereas the 100 µM concentration results in a significant reduction in cell number. Zoledronic acid (100 µM) results in a 63.5% reduction in MCF-7 cell number at 72 hours and an 87.1% reduction at 96 hours. Zoledronic acid (10 µM) results in a greater than 4-fold increase in MCF-7 cell apoptosis whereas the 100 µM concentration induces a 6-fold increase in the proportion of apoptotic cells. Zoledronic acid (10 µM) and paclitaxel (2 µM) results in a 5-fold increase in apoptosis (774.8% of control) compared to zoledronic acid alone (155.71%) and a 4-fold increase compared to paclitaxel alone (189.68%). Zoledronic acid-induced apoptosis of MCF-7 breast cancer cells can be inhibited by addition of intermediates of the mevalonate pathway, which is consistent with observations in osteoclasts, macrophages and myeloma cells. ^[1]

Zoledronic acid enhances OPG gene expression and protein secretion by human osteoblasts (hOB) in a dose-dependent fashion with a maximum effect at 10 nM after 72 hours, consistent with the higher biological potency of Zoledronic acid. Zoledronic acid prevents the inhibitory effects of the glucocorticoid dexamethasone on OPG mRNA and protein production in human osteoblasts. Zoledronic acid induces type I collagen secretion and alkaline phosphatase activity by 2- and 4-fold, respectively, in human osteoblasts. ^[2]

Cells were treated with various concentrations of drug for 72 h.

Zoledronic acid (120 ug/kg, s.c.) prevents the formation of lesions, prevents cancellous bone loss and loss of bone mineral density, and reduces osteoclast perimeter in 5T2MM-bearing mice. Zoledronic acid (120 mg/kg, s.c.) also decreases paraprotein concentration, decreases tumor burden, and reduces angiogenesis in 5T2MM-bearing mice. ^[3]