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Observational Study
. 2025 Oct;40(10):3187-3200.
doi: 10.1007/s00467-025-06841-y. Epub 2025 Jun 10.

Growth dynamics of transversal body dimensions and proportions, with related clinical determinants in children with X-linked hypophosphatemia treated with phosphate supplements and active vitamin D

Laura Celine Brieger  1 , Stephan Przygodda  1 , Alina Verena Bohlen  1 , Mirko Rehberg  2 , Martin Konrad  3 , Karl Peter Schlingmann  3 , Olaf Hiort  4 , Dorothee Schmidt  4 , Ulrike John-Kroegel  5 , Elke Wuehl  6 , Markus Josef Kemper  7 , Ute Derichs  8 , Ludwig Patzer  9 , Norbert Albers  10 , Desiree Dunstheimer  11 , Sabine Heger  12 , Karina Grohmann-Held  13 , Carmen Schroeder  13 , Norbert Jorch  14 , Elmar Schmid  15 , Hagen Staude  16 , Marcus Weitz  17 , Clemens Freiberg  18 , Angela Huebner  19 , Anke Heitmeyer-Pyper  20 , Giuseppina Sparta  21 , Carl-Joachim Partsch  22 , Michaela Marx  23 , Christof Land  24 , Inka Baus  25 , Frauke Wilkening  26 , Kristina Moeller  27 , Gunter Simic-Schleicher  28 , Susann Empting  29 , Oliver Metzing  30 , Verena Wagner  31 , Martin Holder  32 , Mislav Stjepan Žebec  33 , Dirk Schnabel  34 , Dieter Haffner  1 , Miroslav Zivicnjak  35 ; on behalf of; German Society for Pediatric Nephrology (GPN); German Society for Pediatric; Adolescent Endocrinology, Diabetology (DGKED)
Affiliations
Observational Study

Growth dynamics of transversal body dimensions and proportions, with related clinical determinants in children with X-linked hypophosphatemia treated with phosphate supplements and active vitamin D

Laura Celine Brieger et al. Pediatr Nephrol. 2025 Oct.

Abstract

Background: Children with X-linked hypophosphatemia (XLH) present with rickets, leg deformities, and growth failure. Bone stability depends on balanced bone growth in both length and width. Data on body proportions, including transverse body dimensions, in children with XLH treated with phosphate supplements and active vitamin D are lacking.

Methods: Six major transverse body dimensions of the trunk and extremities, and the frame index (FI), i.e., ratio between bicondylar humerus diameter and height, were measured annually along with clinical characteristics in 109 pediatric patients with XLH, all on supplementation therapy, participating in a prospective multicenter observational study conducted since 1998. Associations between anthropometric and clinical parameters were investigated using linear mixed-effects models.

Results: Children with XLH exhibited persistent hypophosphatemia and elevated alkaline phosphatase z scores despite supplementation treatment. This was associated with disproportionate transversal skeletal growth, which was most pronounced during adolescence (13-17 years). Bicondylar diameter z scores (tubular bone width) and FI progressively increased with age (each p < 0.05). In addition, FI was identified as a superior indicator of stunting when compared to other measures of transversal dimensionality across all age groups. In young children (2-6 years), transversal growth was most synchronized and associated most strongly with clinical characteristics.

Conclusions: Our data show disproportionate growth in transversal body dimensions despite supplementation treatment in children with XLH, suggesting compensatory widening of tubular bones as adaptation for mineral loss caused by persisting rickets. The FI can be used as a general indicator of bone health in children with XLH in clinical practice and trials.

Keywords: Alkaline phosphatase; Body disproportion; Frame index; Phosphate; Rickets; Transversal body dimension; XLH.

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Conflict of interest statement

Declarations. Ethical approval: The study received appropriate ethics committee approval from the Institutional Review Board at each site and was performed in accordance with the Declaration of Helsinki. Consent to participate: Written informed consent was obtained from all parents/guardians, with consent or assent from patients where age-appropriate. Competing interests: D.H., O.H., and D.S. received speaker fees, consultation fees, and research grants from Kyowa Kirin. M.R. received speaker fees and consultation fees from Kyowa Kirin. U.J-K. and L.P. received speaker fees from Kyowa Kirin. All other authors declare no conflict of interest.

Figures

None
A higher resolution version of the Graphical abstract is available as Supplementary information
Fig. 1
Fig. 1
Mean z scores of transversal body diameters (bicondylar humerus, bicondylar femur, anterior–posterior chest, biacromial, transverse chest, biiliocristal diameter) as well as frame index and stature across the observed age range in 109 children with XLH. Dotted lines are for illustrative purposes only
Fig. 2
Fig. 2
Mean z scores of transversal body diameters (biacromial, transverse chest, anterior–posterior chest, bicondylar humerus, bicondylar femur, biiliocristal diameter) clustered into three age groups of 109 children with XLH. Data are presented for the three age cohorts (2–6, 7–12, and 13–17 years) as age- and sex-dependent zscores. Error bars represent 95% confidence interval. Dotted lines are for illustrative purposes only, representing changes in patterns of transversal morphology across the three observed age groups
See this image and copyright information in PMC

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