Liver transplantation-related osteoporosis and fragility fractures: pathogenic pathways, risk stratification and...

Liver transplantation (LT) serves as the definitive treatment for end-stage liver disease. Yet, osteoporosis (OP) and fragility fractures remain frequently overlooked skeletal complications that may impair the long-term prognosis of recipients. This review systematically summarizes recent evidence regarding epidemiological characteristics, multifactorial pathogenic pathways, risk stratification approaches, and advances in targeted interventions for LT-related bone disorders. Skeletal damage distributes across pre-transplant waiting, early post-transplant acute and long-term chronic phases; rapid bone loss and elevated fracture risk potentially peak within the first year after LT. Pre-transplant hepatic dysfunction-induced malnutrition, endocrine disturbance, and chronic inflammation lay baseline skeletal impairment. In contrast, perioperative high-dose glucocorticoids, calcineurin inhibitor toxicity, surgical denervation, and ischemia-reperfusion injury may jointly drive substantial elevation of bone turnover in the early post-transplant stage. Long-term cortical bone repair deficiency could be attributed to persistent secondary hyperparathyroidism, post-transplant diabetes, and genetic susceptibility. Dual-energy X-ray absorptiometry remains the standard bone mineral density diagnostic tool, while vertebral computed tomography attenuation value and simplified clinical scoring systems support auxiliary risk stratification for skeletal health. Generalized nutritional and lifestyle interventions combined with anti-resorptive agents form mainstream management schemes; DKK-1/Wnt/β-catenin pathway-targeted therapy shows potential as a novel intervention direction. Pediatric LT recipients feature unique bone maturation characteristics that require age-specific evaluation criteria, though unified standardized protocols remain insufficient. Current clinical practice suffers from inadequate bone health screening and pharmacotherapy coverage. Further prospective trials are warranted to validate optimized stratified screening algorithms and individualized targeted regimens for high-risk LT populations.