Bone fragility is the determinant of the increased risk of minimal trauma fracture and must be treated with a multimodal approach that includes pharmacological therapy, physical exercise, and adequate nutrition. Pharmacological therapy, to date based on the administration of antiresorptive drugs, such as bisphosphonates and denosumab, or osteoanabolic drugs, such as teriparatide and abaloparatide, has shown to be effective in reducing the risk of fracture in osteoporotic patients. In the context of the cellular and molecular mechanisms that regulate bone metabolism, the discovery of the Wnt signaling pathway and its role in bone tissue homeostasis has allowed the identification of sclerostin as an inhibitor of osteoblastic activity and simultaneously as a stimulator of osteoclastic activity. Therefore, the use of a monoclonal antibody, romosozumab, against this protein has been tested as a potential drug with a dual action, stimulating bone neo-apposition and inhibiting bone resorption. The efficacy of romosozumab has been demonstrated in numerous clinical trials against both placebo and other drugs commonly used in the treatment of patients affected by osteoporosis. The advantages of this drug lie above all in its rapid action which makes it particularly suitable in clinical situations where it is necessary to improve bone strength very quickly due to the imminent risk of fragility fracture. Clinical studies and guidelines suggest romosozumab as an initial drug in an ideal sequential approach from osteoanabolic to antiresorptive drugs. Some aspects of cardiovascular safety remain to be fully investigated, therefore its use in osteoporotic patients at high cardiovascular risk should be avoided until further data become available.

中文翻译：

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抗硬化蛋白抗体：脆性骨折治疗的新领域。

骨脆性是微创骨折风险增加的决定因素，必须采用多模式方法进行治疗，包括药物治疗、体育锻炼和充足的营养。迄今为止，基于抗骨吸收药物（例如双膦酸盐和狄诺塞麦）或骨合成代谢药物（例如特立帕肽和阿巴洛帕肽）的药物治疗已被证明可以有效降低骨质疏松患者骨折的风险。在调节骨代谢的细胞和分子机制的背景下，Wnt信号通路及其在骨组织稳态中的作用的发现使得硬化素被鉴定为成骨细胞活性的抑制剂，同时作为破骨细胞活性的刺激剂。因此，针对这种蛋白质的单克隆抗体 romosozumab 的使用已被测试为具有双重作用的潜在药物，即刺激骨新沉积和抑制骨吸收。romosozumab 的功效已在针对安慰剂和其他常用于治疗骨质疏松症患者的药物的大量临床试验中得到证实。该药物的优点首先在于其快速作用，这使得它特别适合于因脆性骨折迫在眉睫的风险而需要非常快速地提高骨强度的临床情况。临床研究和指南表明，romosozumab 作为从骨合成代谢药物到抗骨吸收药物的理想序贯方法中的初始药物。心血管安全性的某些方面仍有待充分研究，因此在获得进一步数据之前，应避免将其用于具有高心血管风险的骨质疏松患者。