Brain neural effects of the 'tonifying kidney and benefiting marrow' method in the treatment of osteoporosis.

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.