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Zoledronic acid is a third-generation heterocyclic nitrogen-containing bisphosphonate that inhibits the prenylation of GTPases critical to the signaling events related to osteoclast-mediated bone resorption. It has a high affinity for hydroxyapatite (Ki = 3.47 μM) and binds directly to mineralized bone where it decreases bone resorption by inhibiting osteoclast proliferation and inducing osteoclast apoptosis. At μM concentrations, zoledronic acid demonstrates antitumor effects in vitro against breast, prostate, and myeloma cancer cells by inducing cytostasis and prevents bone metastases through its inhibitory effects on adhesion molecules, tumor cell invasion, and angiogenesis. Zoledronic acid has been used in the treatment of osteoporosis, Paget's disease, metastatic bone disease, multiple myeloma, hypercalcemia of malignancy, and skeletal-related events associated with metastatic castrate-resistant prostate cancer.

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