Zoledronic Acid is a third-generation nitrogen-containing bisphosphonate bone resorption inhibitor. Zoledronic Acid reduces bone calcium release and lowers blood calcium levels by inhibiting osteoclast activity and inducing osteoclast apoptosis. Zoledronic Acid blocks the mevalonate pathway by inhibiting farnesyl pyrophosphate synthase activity. Zoledronic Acid can be used in research related to osteoporosis, Paget's disease, bone metastases of malignant tumors, and hypercalcemia caused by malignant tumors[1-4].
In vitro, CT26 colon cancer cells were treated with Zoledronic Acid (0-300μM) for 24-48 hours. Zoledronic Acid inhibited cell proliferation, induced apoptosis, and regulated autophagy[5]. Under high glucose conditions, MC3T3-E1 cells were treated with Zoledronic Acid (1mM) for 7 days. Zoledronic Acid significantly upregulated the expression of RUNX2, miR-133, and miR-204, while downregulating the expression of MALAT1 and miR-20a[6].
In vivo, female Balb/c mice were subcutaneously injected with Zoledronic Acid (5μg/kg) every other day for 10 days. Zoledronic Acid prevented carboplatin-induced bone loss and muscle weakness[7]. Male C57BL/6J mice received a single subcutaneous injection of Zoledronic Acid (100μg/kg). Zoledronic Acid increased body weight and muscle mass, improved muscle structural damage, increased the proportion of type I muscle fibers, and upregulated the protein expression of β-catenin and AKT, as well as the mRNA expression of Wnt3a, Wnt16, Myf5, and PI3K[8].
References:
[1] Cheer SM, Noble S. Zoledronic acid. Drugs. 2001;61(6):799-805; discussion 806.
[2] Finianos A, Aragon-Ching JB. Zoledronic acid for the treatment of prostate cancer. Expert Opin Pharmacother. 2019 Apr;20(6):657-666.
[3] Karpuz S. Zoledronic acid-induced severe lymphopenia. Osteoporos Int. 2023 Sep;34(9):1653-1655.
[4] Ishikawa T. Differences between zoledronic acid and denosumab for breast cancer treatment. J Bone Miner Metab. 2023 May;41(3):301-306.
[5] Zhu J, Liu M, Liu Y, et al. Zoledronic Acid Regulates Autophagy and Induces Apoptosis in Colon Cancer Cell Line CT26. Biomed Res Int. 2017;2017:7203584.
[6] Chen HL, Hu JP, Li JF, et al. Zoledronic acid epigenetically alleviates high-glucose-suppressed osteogenic differentiation of MC3T3-E1 cells. Eur Rev Med Pharmacol Sci. 2023 Aug;27(16):7576-7581.
[7] Hain BA, Jude B, Xu H, et al. Zoledronic Acid Improves Muscle Function in Healthy Mice Treated with Chemotherapy. J Bone Miner Res. 2020 Feb;35(2):368-381.
[8] Li W, Xu M, Shi X, et al. Effect of zoledronic acid on muscle metabolism in mice with osteoporosis combined with sarcopenia. BMC Musculoskelet Disord. 2024 Nov 21;25(1):937.