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For instance, within the hypothalamic–pituitary–bone axis, leptin not only crosses the blood–brain barrier (BBB) to regulate central neural circuits but also modulates osteoblast and osteoclast activity via sympathetic neural pathways, thereby contributing to the dynamic balance of bone remodeling ( Accumulating evidence indicates that patients with intestinal diseases carry a substantial multisystem comorbidity burden involving the gut–bone–brain axis
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