Xu Yunxiang, Liu Xueqin, Li Haolan, Liu Hongyuan, Pan Zhanxia, Chen Guizhen
Clinical Medical College of Acupuncture, Moxibustion and Rehabilitation, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
Department of Rehabilitation, Affiliated BaoAn Traditional Chinese Medicine Hospital, Guangzhou University of Chinese Medicine, Shenzhen 518101, China.
J Tradit Chin Med. 2019 Dec;39(6):902-909.
In Traditional Chinese Medicine (TCM), the 'tonifying kidney and benefiting marrow' (TKBM) method is based on the theory that kidney controls bones, while marrow moistens bones. There have been aboundant theoretical studies on kidney controlling bones since Huangdi's Internal Classics. However, there are too few ones about the marrow moistening the bones. Researchers generally use the tonifying kidney method instead of the TKBM method, which causes lack of a unified standard and theoretical basis in evaluating the TKBM method. Herein, we first proposed the hypothesis that deficiency of marrow sea causes osteoporosis. Next, we prove the scientific validity of this hypothesis from the side of the TCM theory on the relationship among kidney, bone and marrow sea physiologically and pathologically. Based on this, we find that the TCM theory provides theoretical basis for deficiency of marrow sea causing osteoporosis. On the other side, Western Medicine theory holds that (a) physiologically, the brain regulates the bone mass via three pathways: the neuro-osteogenic network, neuro-endocrine-bone network, and neuropeptide-bone network; (b) pathologically, brain impacts bone mass via three major passways including the regulation of the sympathetic nervous system, secreting hormones that directly act on bone cells and regulating the synthesis and secretion of hormones in the intermediary organs, and neuropeptides such as neuropeptide Y (NPY), substance P (SP), and calcitonin gene-related peptide (CGRP). Evidences involving estrogen deficiency, sympatheticotonia, or neuropeptides imbalance prove that brain-bone mass regulation plays an important role in the pathogenesis of osteoporosis. Finally, we find that kidney invigoration method can change the concentrations of central neurotransmitters of norepinephrine and glutamate to regulate neuro-osteogenic network, and promote the recovery of ovarian function and have an estrogen-like effect by regulating the hypothalamus-pituitary-ovarian axis, which thus influences bone metabolism without clinically significant estrogen-like side effects, and regulate NPY, CGRP and SP involved in the bone metabolism. These further support our hypothesis by revealing the brain neural mechanism of the TCM kidney invigoration method for preventing and treating osteoporosis. In the future, neuroimaging techniques may be useful in exploring its neural effects and also aid in developing new strategies for treating osteoporosis.
在中医中，“补肾益髓”法基于肾主骨、髓养骨的理论。自《黄帝内经》以来，关于肾主骨已有大量的理论研究。然而，关于髓养骨的研究却很少。研究者们一般采用补肾法而非补肾益髓法，这导致在评估补肾益髓法时缺乏统一的标准和理论依据。在此，我们首次提出髓海不足导致骨质疏松的假说。接下来，我们从中医理论中肾、骨与髓海在生理和病理上的关系方面，证明了这一假说的科学合理性。基于此，我们发现中医理论为髓海不足导致骨质疏松提供了理论依据。另一方面，西医理论认为：（a）在生理上，大脑通过三条途径调节骨量：神经成骨网络、神经内分泌 - 骨网络和神经肽 - 骨网络；（b）在病理上，大脑通过三条主要途径影响骨量，包括交感神经系统的调节、分泌直接作用于骨细胞的激素以及调节中间器官中激素的合成和分泌，以及神经肽如神经肽Y（NPY）、P物质（SP）和降钙素基因相关肽（CGRP）。涉及雌激素缺乏、交感神经张力亢进或神经肽失衡的证据证明，脑 - 骨量调节在骨质疏松的发病机制中起重要作用。最后，我们发现补肾法可改变去甲肾上腺素和谷氨酸等中枢神经递质的浓度，以调节神经成骨网络，并通过调节下丘脑 - 垂体 - 卵巢轴促进卵巢功能恢复并具有雌激素样作用，从而在无临床显著雌激素样副作用的情况下影响骨代谢，并调节参与骨代谢的NPY、CGRP和SP。这些通过揭示中医补肾法防治骨质疏松的脑神经机制，进一步支持了我们的假说。未来，神经成像技术可能有助于探索其神经效应，并有助于开发治疗骨质疏松的新策略。
