Bone turnover and phosphate metabolism in children with Prader–Willi syndrome: results from two tertiary centers

Prader–Willi syndrome (PWS) is a rare genetic disorder characterized by impaired growth, altered body composition, and reduced bone mineral accrual. However, the relationships between skeletal maturation, bone turnover, and phosphate homeostasis during childhood remain insufficiently understood. This study explored bone turnover, somatotropic function, skeletal maturation, and phosphate metabolism in children with PWS compared with healthy peers. In this two-center retrospective case–control study, 40 children and adolescents with molecularly confirmed PWS and 40 age- and sex-matched healthy controls were evaluated between January 2016 and May 2026. Anthropometric measurements, bone age, somatotropic axis parameters, bone turnover markers, and indices of phosphate metabolism were analyzed using multivariable-adjusted models, correlation analyses, regression models, and exploratory receiver operating characteristic analyses. Compared with controls, children with PWS showed a pattern of lower circulating bone turnover markers characterized by significantly lower osteocalcin, C-terminal telopeptide of type I collagen, bone-specific alkaline phosphatase, and insulin-like growth factor I, together with a reduced molar insulin-like growth factor I/insulin-like growth factor-binding protein-3 ratio and delayed skeletal maturation. Phosphate metabolism was characterized by higher serum phosphorus, tubular reabsorption of phosphate, and tubular maximum reabsorption of phosphate per glomerular filtration rate, accompanied by lower fibroblast growth factor 23, ionized calcium, and 25-hydroxyvitamin D. Within the PWS group, bone turnover markers correlated with bone age. In exploratory analyses, growth hormone treatment status was not significantly associated with insulin-like growth factor I or major bone turnover markers; however, interpretation was limited by incomplete information regarding treatment dose, duration, age at initiation and adherence. Exploratory receiver operating characteristic analysis identified bone age delay (AUC = 0.847) and bone-specific alkaline phosphatase (AUC = 0.842) as the strongest discriminators of PWS versus control status within the study population. Children and adolescents with PWS showed cross-sectional differences in skeletal maturation, bone turnover, and phosphate homeostasis compared with healthy controls. These findings should be considered exploratory and require confirmation in longitudinal studies incorporating detailed growth hormone exposure, bone density, and body composition assessments.