The cross-cultural and chronological evolution of the kidney-bone relationship: from ancient medical insights to modern molecular endocrinology.

چکیده اصلی

The kidney-bone axis constitutes a conserved bidirectional endocrine network that orchestrates skeletal remodeling and systemic mineral homeostasis. Its dysregulation underlies chronic kidney disease-mineral and bone disorder (CKD-MBD), renal osteodystrophy, secondary hyperparathyroidism, and associated vascular calcification, markedly elevating fracture and cardiovascular mortality risks. This review offers a unique cross-cultural and chronological synthesis of the kidney-bone relationship, bridging ancient medical insights with modern molecular endocrinology. Horizontally, we systematically compare the "kidney governing bones" doctrine in Traditional Chinese Medicine (TCM), ancient Greek humoral theory, and Ayurvedic Asthi Dhatu concept, revealing their shared holistic visceral-skeletal paradigm as the primitive prototype of contemporary multi-organ crosstalk, while highlighting distinct interpretive and therapeutic frameworks. Vertically, modern research is delineated into three developmental stages: (1) clinical-pathological observation of renal osteodystrophy and vitamin D-PTH disturbances (19th-early 20th century); (2) core molecular endocrine discoveries centered on the FGF23-Klotho, vitamin D, and OPG/RANKL/PTH signaling axes; and (3) expansion to novel multi-organ networks involving gut microbiota-derived uremic toxins, exosomes, and O-GlcNAc modification. We further summarize the multi-target mechanisms of kidney-tonifying TCM formulas (e.g., Zuogui Pill, Gushudan) and Western interventions, critically analyze translational bottlenecks-including biomarker limitations, stratified therapy challenges, and insufficient high-level clinical evidence-and propose integrated Chinese-Western strategies, multi-omics precision biomarkers, and cross-cultural theoretical fusion to advance personalized management of CKD-MBD and related metabolic bone diseases.

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