Open Access

Laura Celine Brieger, Stephan Przygodda, Alina Verena Bohlen, Mirko Rehberg, Martin Konrad, Karl Peter Schlingmann, Olaf Hiort, Dorothee Schmidt, Ulrike John-Kroegel, Elke Wuehl, Markus Josef Kemper, Ute Derichs, Ludwig Patzer, Norbert Albers, Desiree Dunstheimer, Sabine Heger, Karina Grohmann-Held, Carmen Schroeder, Norbert Jorch, Elmar Schmid, Hagen Staude, Marcus Weitz, Clemens Freiberg, Angela Huebner, Anke Heitmeyer-Pyper, Giuseppina Sparta, Carl-Joachim Partsch, Michaela Marx, Christof Land, Inka Baus, Frauke Wilkening, Kristina Moeller, Gunter Simic-Schleicher, Susann Empting, Oliver Metzing, Verena Wagner, Martin Holder, Mislav Stjepan Žebec, Dirk Schnabel, Dieter Haffner, Miroslav Zivicnjak

• 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 wasBackground 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.…