Switching from active vitamin D and phosphate supplementation to burosumab significantly corrects lower limb malalignment in pediatric X-linked hypophosphatemia

X-linked hypophosphatemia (XLH) is a rare disorder of renal phosphate wasting and dysregulated active vitamin D metabolism, ultimately presenting as rickets and osteomalacia, among other manifestations. Lower extremity deformity (genu valgum and/or varum) is frequent in this pediatric population. Despite prompt active vitamin D and phosphate supplementation (active D/Pi), many patients require corrective surgery for lower limb malformation. Burosumab has demonstrated improvements in lower limb malalignment in children with XLH in several studies. We expand on those reports by assessing mechanical femoral tibial angle (mFTA) change in patients enrolled in the XLH Disease Monitoring Program (DMP), (NCT03651505) to determine the impact of initiating burosumab treatment after a history of active D/Pi. Included patients had either switched from active D/Pi to burosumab treatment at the discretion of their treating physician or as part of a burosumab clinical trial, or remained on active D/Pi through Year 3 of the DMP. Year 3 radiographs were compared with baseline to assess mFTA change and gauge improvement. Additional multivariate factor analysis examined 24 attributes to determine which had the greatest association with mFTA change. Change in mFTA was assessed for each limb independently. A greater proportion of limbs of patients switching from active D/Pi to burosumab had improved mFTA compared with those remaining on active D/Pi (p < .023). Odds ratios comparing limbs that improved to those that did not showed that switching to burosumab yields a significantly greater chance of improvement than continuing active D/Pi (OR [95% CI]: 4.38 [1.09-17.50]; p = .0469). Factor analysis identified younger age at burosumab initiation (p = .001) and lower baseline height Z-score (p = .006) as being significantly associated with greater change in mFTA Z-score. This study shows that switching to burosumab significantly improves lower limb malalignment in children with XLH over benefits conferred by active D/Pi, with early burosumab initiation providing the greatest benefit.

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Journal
Journal of Bone and Mineral Research
Published
2025-06-13
DOI
https://doi.org/10.1093/jbmr/zjaf079
Citations
1
Primary Topic
Biomedical Research and Pathophysiology
Type
article
Field-Weighted Citation Impact
1.47

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article

Switching from active vitamin D and phosphate supplementation to burosumab significantly corrects lower limb malalignment in pediatric X-linked hypophosphatemia

Kathryn McCrystal Dahir, Suzanne M. Jan de Beur, Andrea Arcari, Michael P. Levine et al.
1 citations
Journal of Bone and Mineral Research
Biomedical Research and Pathophysiology
1.47
article

Switching from active vitamin D and phosphate supplementation to burosumab significantly corrects lower limb malalignment in pediatric X-linked hypophosphatemia

Kathryn McCrystal Dahir, Suzanne M. Jan de Beur, Andrea Arcari, Michael P. Levine, Ingrid A. Holm, Adriana Isabel Meza, Francis H. Glorieux, Zunqiu Chen, Pablo F Florenzano, Janet Crane, Thomas O. Carpenter, Erik Allen Imel, Sasigarn Arunchaiya Bowden, Jill H. Simmons, Laila Tabatabai, Walter Douthat, Carolina Aguiar Moreira, Anthony A. Portale, David Rodriguez‐Buritica, Neil J. Paloian, I. S. Glass, Ambika P. Ashraf, Regina Matsunaga Martin, Anna Ryabets‐Lienhard, Thomas Joseph Weber, Catherine Siener, Eric Gyuricsko, Sanjukta Basak, Bradley P. Dixon, David B. Frumberg, Stan Krolczyk, Steven Wai Ing, Oscar Brunetto, Richard Baquero-Rodríguez, Leanne Marie Ward, Halley M. Wasserman, Gary S. Gottesman, Puja Singh, Sarah Khan, Lisa Dilworth
article en
1 citations

Abstract

X-linked hypophosphatemia (XLH) is a rare disorder of renal phosphate wasting and dysregulated active vitamin D metabolism, ultimately presenting as rickets and osteomalacia, among other manifestations. Lower extremity deformity (genu valgum and/or varum) is frequent in this pediatric population. Despite prompt active vitamin D and phosphate supplementation (active D/Pi), many patients require corrective surgery for lower limb malformation. Burosumab has demonstrated improvements in lower limb malalignment in children with XLH in several studies. We expand on those reports by assessing mechanical femoral tibial angle (mFTA) change in patients enrolled in the XLH Disease Monitoring Program (DMP), (NCT03651505) to determine the impact of initiating burosumab treatment after a history of active D/Pi. Included patients had either switched from active D/Pi to burosumab treatment at the discretion of their treating physician or as part of a burosumab clinical trial, or remained on active D/Pi through Year 3 of the DMP. Year 3 radiographs were compared with baseline to assess mFTA change and gauge improvement. Additional multivariate factor analysis examined 24 attributes to determine which had the greatest association with mFTA change. Change in mFTA was assessed for each limb independently. A greater proportion of limbs of patients switching from active D/Pi to burosumab had improved mFTA compared with those remaining on active D/Pi (p < .023). Odds ratios comparing limbs that improved to those that did not showed that switching to burosumab yields a significantly greater chance of improvement than continuing active D/Pi (OR [95% CI]: 4.38 [1.09-17.50]; p = .0469). Factor analysis identified younger age at burosumab initiation (p = .001) and lower baseline height Z-score (p = .006) as being significantly associated with greater change in mFTA Z-score. This study shows that switching to burosumab significantly improves lower limb malalignment in children with XLH over benefits conferred by active D/Pi, with early burosumab initiation providing the greatest benefit.

Journal of Bone and Mineral ResearchVol. 40(12)
Children's Hospital of Eastern Ontario (CA), Yale University (US), Ultragenyx Pharmaceutical (United States) (US), Indiana University School of Medicine, Indiana University – Purdue University Indianapolis (US)
University of Ottawa, Ultragenyx Pharmaceutical
Good health and well-being
Openalex Percentile: Top 18%
Biomedical Research and Pathophysiology
1.47
DOIOpen Access PDFOpenAlex
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