Systemic effects of abnormal bone resorption on muscle, metabolism, and cognition.
Systemic effects of abnormal bone resorption on muscle, metabolism, and cognition.
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DOI：
10.1016/j.bone.2021.116245
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发表时间：
2021-10
期刊：
影响因子：
4.1
通讯作者：
T. Trivedi;T. Guise
中科院分区：
文献类型：
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作者：
T. Trivedi;T. Guise
骨组织是动态的，经历不断的重塑以维持人体肌肉骨骼的完整性和平衡。最近的证据表明，除了维持局部微环境的内稳态外，骨骼系统地影响其他组织。几种与癌症相关和非癌症相关的骨疾病可局部破坏骨微环境的生理稳态，并间接导致全身功能失调。骨对远端器官功能调节的全身性作用尚未得到广泛探讨。最近的证据表明，骨骼可以通过矿化骨基质释放因子与骨骼肌、胰腺和大脑相互作用。目前可用的骨靶向治疗如双膦酸盐和denosumab抑制骨吸收，降低与骨破坏相关的发病率，提高生存率。双膦酸盐已成为骨转移、骨质疏松和癌症治疗引起的骨病的标准治疗方法。双膦酸盐对肿瘤生长的抑制作用是已知的。然而，我们对双膦酸盐对肌肉无力、高血糖和认知缺陷的影响的了解目前还在不断发展。能够识别异常骨吸收过程中骨和远端器官之间的分子联系，然后治疗这些异常并防止其系统性影响，可以提高生存效益。目前的综述强调了骨吸收与其对肌肉、胰腺和大脑的系统性影响之间的联系。
Skeletal tissue is dynamic, undergoing constant remodeling to maintain musculoskeletal integrity and balance in the human body. Recent evidence shows that apart from maintaining homeostasis in the local microenvironment, the skeleton systemically affects other tissues. Several cancer-associated and noncancer-associated bone disorders can disrupt the physiological homeostasis locally in the bone microenvironment and indirectly contribute to dysregulation of systemic body function. The systemic effects of bone on the regulation of distant organ function have not been widely explored. Recent evidence suggests that bone can interact with skeletal muscle, pancreas, and brain by releasing factors from mineralized bone matrix. Currently available bone-targeting therapies such as bisphosphonates and denosumab inhibit bone resorption, decrease morbidity associated with bone destruction, and improve survival. Bisphosphonates have been a standard treatment for bone metastases, osteoporosis, and cancer treatment–induced bone diseases. The extraskeletal effects of bisphosphonates on inhibition of tumor growth are known. However, our knowledge of the effects of bisphosphonates on muscle weakness, hyperglycemia, and cognitive defects is currently evolving. To be able to identify the molecular link between bone and distant organs during abnormal bone resorption and then treat these abnormalities and prevent their systemic effects could improve survival benefits. The current review highlights the link between bone resorption and its systemic effects on muscle, pancreas, and brain.