Kidney-bone axis: Emerging paradigms in cross-talk between renal function and skeletal health

The kidney-bone axis represents a complex endocrine network that extends beyond traditional mineral metabolism, with profound clinical implications in chronic kidney disease (CKD)-mineral and bone disorder. CKD affects approximately 700 million people worldwide, with 18%-32% developing osteoporosis and experiencing a 2.5-4-fold higher fracture risk compared with the general population. Fracture incidence increases from 15 to 46.3 per 1000 person-years across advancing CKD stages, with dialysis patients exhibiting hip fracture mortality rates 2.4 times higher than those in the general population. Secondary hyperparathyroidism affects 20%-80% of CKD patients depending on disease severity, yet traditional biomarkers such as parathyroid hormone and phosphate provide incomplete prognostic value. Emerging molecular pathways involving fibroblast growth factor-23 and its co-receptor klotho have unveiled novel bone-kidney endocrine mechanisms regulating phosphate homeostasis and bone turnover. Klotho deficiency and elevated fibroblast growth factor-23 levels appear early in CKD and may serve as biomarkers and therapeutic targets for both cardiovascular and renal disease progression. Integrating clinical, molecular, and translational approaches to understand the interactions between kidney and skeletal systems offers promising therapeutic strategies addressing both bone fragility and systemic complications, potentially transforming outcomes for patients with CKD-related bone disorders.