钙化悖论:血管钙化与骨质疏松症共存的研究进展

Research progress on the calcification paradox:coexistence of vascular calcification and osteoporosis

摘要:

钙化是指钙盐在机体组织中异常沉积的病理过程,包括生理性钙化和异位钙化两大类:前者为正常生理现象,常见于牙齿和骨骼的发育与成熟；后者则是钙盐沉积于非骨组织的病理状态,以血管、心肌等部位受累最为典型。临床研究表明,血管钙化(VC)与骨质疏松症(OP)密切相关,这一相互影响的病理现象被称为“钙化悖论”。目前,二者共存的机制尚未完全阐明,但已明确存在多重共同的影响因素,包括钙磷代谢紊乱、慢性炎症反应、激素水平失衡和肠道菌群失调等。此外,VC和OP可以相互调节,促进彼此的发生和发展。一方面,VC可导致血管管腔狭窄,进而影响骨组织的血液灌注,减少骨基质合成；另一方面,骨细胞分泌的各类调节因子和基质囊泡,不仅可调控骨矿化进程,还可通过诱导血管平滑肌细胞(VSMC)向成骨样细胞表型转化,从而促进VC。深入研究“钙化悖论”的潜在分子机制,有望为研发同步改善骨骼和血管健康的药物干预提供新的思路与靶点。

Abstract:

Calcification refers to the pathological process of abnormal deposition of calcium salts in body tissues, which includes two main categories:physiological calcification and ectopic calcification. The former is a normal physiological phenomenon, commonly observed in the development and maturation of teeth and bones; the latter, however, is a pathological condition where calcium salts deposit in non-osseous tissues, most typically affecting blood vessels and the myocardium. Clinical studies have shown that vascular calcification (VC) is closely related to osteoporosis (OP), and this mutually influential pathological phenomenon is referred to as the “calcification paradox”. Currently, the mechanisms underlying their coexistence have not been fully elucidated, but it is well-established that multiple common influencing factors exist, including disorders of calcium and phosphorus metabolism, chronic inflammatory responses, hormonal imbalances, and gut microbiota dysbiosis. Furthermore, VC and OP can regulate each other, promoting the occurrence and progression of both conditions. On the one hand, VC can lead to narrowing of the vascular lumen, thereby affecting blood perfusion in bone tissues and reducing bone matrix synthesis. On the other hand, various regulatory factors and matrix vesicles secreted by bone cells can not only regulate the process of bone mineralization but also promote VC by inducing the phenotypic transdifferentiation of vascular smooth muscle cells (VSMC) into osteoblast-like cells. In-depth research into the underlying molecular mechanisms of the “calcification paradox” holds promise for providing new insights and therapeutic targets for developing drug interventions that simultaneously improve bone and vascular health.