Osteosarcoma is the most common primary malignant tumor of the skeleton in teenagers and young adults and continues to confer a generally poor prognosis in patients who do not respond to chemotherapy or who present with metastatic diseases at diagnosis. The nitrogen-containing zoledronate, the third generation bisphosphonate (BP), effectively inhibits osteoclastic bone resorption and is widely utilized in the treatment of metabolic and metastatic bone diseases nowadays. Owing to an acceptable safety profile and tolerability, zoledronate is the only BP currently approved for the prevention and treatment of skeletal relevant events in patients with metastatic bone lesions, especially bone metastases from advanced renal cell carcinoma and prostate cancer, and breast cancer, due to all solid malignancy. Moreover, zoledronate possesses diverse anti-osteosarcoma properties and may have potential to become an adjunctive treatment for high-grade osteosarcoma to enhance survival rates and to obliterate complications of the chemotherapy. Herein we highlighted the pharmacology of BPs and its underlying molecular mechanisms in osteoclasts and various cancer cells. We further provided the available literature on in vitro studies to illustrate the new insights into the intracellular molecular mechanisms of zoledronate in human osteosarcoma cell lines and in vivo animal models that led to the development and regulatory approval of zoledronate in patients with human osteosarcoma. This review also addresses clinical trials to focus on the efficacy of zoledronate on human osteosarcoma.

骨肉瘤是青少年和年轻人中最常见的骨骼原发性恶性肿瘤，在对化疗无反应或诊断时出现转移性疾病的患者中，骨肉瘤的预后普遍较差。含氮唑来膦酸盐，第三代双膦酸盐（BP），可有效抑制破骨细胞的骨吸收，并已广泛用于当今代谢性和转移性骨疾病的治疗。由于可接受的安全性和耐受性，唑来膦酸盐是目前唯一被批准用于预防和治疗转移性骨病变（尤其是晚期肾细胞癌和前列腺癌以及乳腺癌的骨转移）患者骨骼相关事件的BP。所有实体恶性肿瘤。此外，唑来膦酸盐具有多种抗骨肉瘤特性，可能具有成为高级骨肉瘤的辅助治疗方法，以提高生存率并消除化学疗法的并发症。在本文中，我们重点介绍了破骨细胞和各种癌细胞中BP的药理作用及其潜在的分子机制。我们进一步提供了有关以下方面的可用文献体外研究来阐明唑来膦酸盐在人骨肉瘤细胞系和体内动物模型中的细胞内分子机制的新见解，从而导致唑来膦酸盐在人骨肉瘤患者中的发展和监管批准。这篇综述还涉及​​临床试验，重点关注唑来膦酸盐对人骨肉瘤的疗效。