A. Rebeca Hernandez-Hernandez1, M. Carola Zillikens1, A. Bosman1, N. M. Appelman‐Dijkstra2, A. M. Boot3, M. H. de Borst4, A. C. van de Ven5, R. T. de Jongh6, A. Bökenkamp7, J. P. van den Bergh8, B. C. J. van der Eerden1, Evert F.S van Velsen1
(1) Department of Internal Medicine, Erasmus MC Bone Center, Erasmus University Medical Center, Rotterdam, The Netherlands.
(2) Department of Internal Medicine, Center for Bone Quality Leiden, Leiden University Medical Center, Leiden, The Netherlands.
(3) Department of Pediatrics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
(4) Department of Internal Medicine, University Medical Center Groningen, Groningen, The Netherlands.
(5) Department of Internal Medicine, Radboud University Medical Center, Nijmegen, The Netherlands.
(6) Department of Internal Medicine, Amsterdam University Medical Center, Vrije Universiteit, Amsterdam, The Netherlands.
(7) Department of Pediatric Nephrology, Amsterdam University Medical Center, Emma Children’s Hospital,, Amsterdam, The Netherlands.
(8) Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands.
X-Linked Hypophosphatemia (XLH), caused by PHEX variants leading to elevated FGF23 and hypophosphatemia, has been epidemiologically linked to an increased overweight/obesity prevalence. However, longitudinal BMI data across childhood and adulthood remains limited. This study describes BMI trajectory patterns over time in a Dutch XLH cohort.
XLH patients from the ORPHOS-NED study were analyzed using combined retrospective/prospective BMI data. Overweight/obesity was defined as BMI ≥25 kg/m² for adults or WHO z-score thresholds for pediatrics (≥1 for ages 5-19; ≥2 for ages 0-5). WHO height z-scores were calculated, and Pearson correlations quantified linear growth-weight relationships. Longitudinal BMI trajectories and sex differences were assessed using repeated measures analysis.
Seventy-seven XLH patients were included (61% female; median age 34 [IQR 28-47] years). Overall, overweight/obesity prevalence was 69% (33.4% with BMI ≥30kg/m²). Among pediatric participants (n=55, median age 4.2 [IQR 1.5-9] years), 34.5% exceeded WHO cutoffs. BMI z-cores and height z-scores showed negative correlation (r= -0.26; p<0.001). BMI trajectories demonstrated significant increases over time (p<0.001) across the entire cohort, with similar patterns in both males and females (p=0.833).
XLH patients showed high overweight/obesity prevalence with significant age-related BMI increases with time across both sexes. An elevated BMI may perpetuate a vicious cycle of worsening mobility and joint dysfunction while representing a potential cardiovascular risk factor. Future research should compare these patterns to population norms and explore genotype influences, functional assessments, patient-reported outcomes, and treatment-stratified trajectories.