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.
Zoledronic Acid是一种第三代含氮双膦酸盐类骨吸收抑制剂。Zoledronic Acid可通过抑制破骨细胞活性和诱导破骨细胞凋亡来减少骨钙释放和降低血钙水平。Zoledronic Acid通过抑制法尼基焦磷酸合成酶活性以阻断甲羟戊酸途径。Zoledronic Acid可用于骨质疏松症、Paget's病（变形性骨炎）、恶性肿瘤骨转移和恶性肿瘤引起的高钙血症的相关研究[1-4]。
在体外，Zoledronic Acid（0-300μM）处理CT26结肠癌细胞24-48h。Zoledronic Acid可抑制细胞增殖、诱导细胞凋亡并调节自噬[5]。在高葡萄糖条件下，Zoledronic Acid（1mM）处理MC3T3-E1细胞7天。Zoledronic Acid显著上调RUNX2、miR-133和miR-204的表达，同时下调MALAT1和miR-20a的表达[6]。
在体内，Zoledronic Acid（5μg/kg）每两天一次皮下注射，用于处理8周龄雌性Balb/c小鼠，持续10天。Zoledronic Acid防止了卡铂引起的骨丢失和肌肉无力[7]。Zoledronic Acid（100μg/kg）单次皮下注射于雄性C57BL/6J小鼠。Zoledronic Acid增加了体重和肌肉重量，改善了肌肉结构损伤，增加了I型肌纤维比例，并上调了β-catenin和AKT蛋白表达以及Wnt3a、Wnt16、Myf5和PI3K的mRNA表达[8]。