Markers and regulators of osteoblast and osteoclast activity in children with X-linked hypophosphatemia treated with burosumab

Burosumab is effective for treatment of rickets in children with X-linked hypophosphatemia (XLH). The effects of burosumab on markers and regulators of osteoblast and osteoclast acitivity are largely unknown. In this cross-sectional observational study, we investigated 7 key markers and regulators of osteoblast and osteoclast activity in 107 burosumab-treated children with XLH. We calculated z-scores for bone-specific alkaline phosphatase (BAP), procollagen-1-N-terminal propeptide (P1NP), carboxy-terminal telopeptide of type 1 collagen (CTX), tartrate-resistant acid phosphatase type 5b (TRAP5b), soluble receptor activator of NF-κB ligand (sRANKL), osteoprotegerin (OPG), and sclerostin. The median age at investigation and duration of burosumab treatment were 10.7 and 2.2 yr, respectively, with 18.7% of patients on primary burosumab treatment and 81.3% with prior treatment with phosphate and active vitamin D. Height and body mass index improved by approx. 0.3 z-score from baseline with burosumab treatment, and serum phosphate, 1,25-dihydroxyvitamin D, and alkaline phosphatase improved by 2 z-scores (each p < .01 versus prior burosunab), but phosphate (-1.8 z-score) and calcium (-0.65 z-score) remained reduced (each p < .001 versus age and sex specific reference values). The z-scores for osteoblast (BAP, P1NP) and osteoclast (CTX, TRAP5b) activity markers and for the osteoblast suppressor sclerostin were increased (each p < .001). Standardized sRANKL was reduced (p < .05), while the RANKL inhibitor OPG was increased resulting in a reduced sRANKL/OPG ratio (each p < .001). Multivariate analysis revealed significant associations between serum sclerostin and serum phosphate (negative), serum calcium and vitamin D sufficiency (positive), and primary burosumab treatment with BAP (negative). In this real-world setting, pediatric XLH patients receiving burosumab treatment showed persisting mild hypophosphatemia and increased markers of osteoblast and osteoclast acitivity despite negative counter-regulation of osteoblasts by sclerostin and osteoclasts by OPG/RANKL. Our data suggest a more pronounced normalization osteoblast activity when children are primarily treated with burosumab and underscore the need for adequate vitamin D supplementation.

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Journal
Journal of Bone and Mineral Research
Published
2026-04-24
DOI
https://doi.org/10.1093/jbmr/zjag071
Primary Topic
Parathyroid Disorders and Treatments
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article
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article

Markers and regulators of osteoblast and osteoclast activity in children with X-linked hypophosphatemia treated with burosumab

Angela Hübner, Alexandra Goischke, Dorothée Schmidt, Sabine Heger et al.
Journal of Bone and Mineral Research
Parathyroid Disorders and Treatments
article

Markers and regulators of osteoblast and osteoclast activity in children with X-linked hypophosphatemia treated with burosumab

Angela Hübner, Alexandra Goischke, Dorothée Schmidt, Sabine Heger, Jens Banzer, Norbert Jorch, Olaf Hiort, Ineke Böckmann, Norbert Albers, Gabriele Krauch, Mj Kemper, Ulrike John-Kroegel, Oliver Metzing, Marcus Weitz, Maren Leifheit‐Nestler, Frauke Wilkening, Dieter Haffner, Ute Derichs, Annette Richter-Unruh, Mirko Rehberg, Elmar Schmid, Clemens Freiberg, Elke Wühl, Carmen M Schroder, Miroslav Živičnjak, Inka Baus, Giuseppina Spartà, Katrina EVERS, Carl‐Joachim Partsch, Hagen Staude, Michaela Geßner, Ludwig Patzer, Désirée Dunstheimer, Christof Land, Michaela Marx, Dirk Schnabel, Karina Grohmann-Held, Karl Peter Schlingmann, Kristina Möller, Verena Wagner
article en

Abstract

Burosumab is effective for treatment of rickets in children with X-linked hypophosphatemia (XLH). The effects of burosumab on markers and regulators of osteoblast and osteoclast acitivity are largely unknown. In this cross-sectional observational study, we investigated 7 key markers and regulators of osteoblast and osteoclast activity in 107 burosumab-treated children with XLH. We calculated z-scores for bone-specific alkaline phosphatase (BAP), procollagen-1-N-terminal propeptide (P1NP), carboxy-terminal telopeptide of type 1 collagen (CTX), tartrate-resistant acid phosphatase type 5b (TRAP5b), soluble receptor activator of NF-κB ligand (sRANKL), osteoprotegerin (OPG), and sclerostin. The median age at investigation and duration of burosumab treatment were 10.7 and 2.2 yr, respectively, with 18.7% of patients on primary burosumab treatment and 81.3% with prior treatment with phosphate and active vitamin D. Height and body mass index improved by approx. 0.3 z-score from baseline with burosumab treatment, and serum phosphate, 1,25-dihydroxyvitamin D, and alkaline phosphatase improved by 2 z-scores (each p < .01 versus prior burosunab), but phosphate (-1.8 z-score) and calcium (-0.65 z-score) remained reduced (each p < .001 versus age and sex specific reference values). The z-scores for osteoblast (BAP, P1NP) and osteoclast (CTX, TRAP5b) activity markers and for the osteoblast suppressor sclerostin were increased (each p < .001). Standardized sRANKL was reduced (p < .05), while the RANKL inhibitor OPG was increased resulting in a reduced sRANKL/OPG ratio (each p < .001). Multivariate analysis revealed significant associations between serum sclerostin and serum phosphate (negative), serum calcium and vitamin D sufficiency (positive), and primary burosumab treatment with BAP (negative). In this real-world setting, pediatric XLH patients receiving burosumab treatment showed persisting mild hypophosphatemia and increased markers of osteoblast and osteoclast acitivity despite negative counter-regulation of osteoblasts by sclerostin and osteoclasts by OPG/RANKL. Our data suggest a more pronounced normalization osteoblast activity when children are primarily treated with burosumab and underscore the need for adequate vitamin D supplementation.

Journal of Bone and Mineral Research
University of Mannheim (DE), American Academy of Child and Adolescent Psychiatry (US), Heidelberg University (DE), Universitätsmedizin Greifswald (DE), University Hospital Augsburg (DE), University Hospital Heidelberg (DE), Temple Street Children's University Hospital (IE), Christian-Albrechts-Universität zu Kiel (DE), Medizinische Hochschule Hannover (DE), Universität Greifswald (DE), Kinderkrankenhaus auf der Bult (DE), Universitätsklinikum Erlangen (DE), Helios Hospital Schwerin (DE), University Hospital Münster (DE), Krankenhaus St. Elisabeth und St. Barbara (DE), Evangelisches Krankenhaus Bielefeld (DE), Kinderkrebs-Zentrum Hamburg (DE), Universitätsmedizin Göttingen (DE), Asklepios Fachkliniken München-Gauting (DE), University Children's Hospital Tübingen (DE), University Children’s Hospital Basel (CH), University Children's Hospital Zurich (CH), KfH Kuratorium für Dialyse und Nierentransplantation (DE), Jena University Hospital (DE), Bochum University of Applied Sciences (DE), Hematology Oncology Associates (US), Klinikum Links der Weser (DE), Marienhospital Osnabrück (DE), University Hospital Cologne (DE), Endokrinologikum (DE), University Hospital Carl Gustav Carus (DE), Asklepios Kliniken Hamburg (DE), University of Rostock (DE), University of Göttingen (DE), Technische Universität Dresden (DE), Charité - Universitätsmedizin Berlin (DE), Heidelberg University (US), University of Lübeck (DE)
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Parathyroid Disorders and Treatments
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