Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone
Abstract Background X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in mos...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-022-02562-9 |
| _version_ | 1798019140269637632 |
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| author | Diana-Alexandra Ertl Justin Le Lorier Andreas Gleiss Séverine Trabado Candace Bensignor Christelle Audrain Volha Zhukouskaya Régis Coutant Jugurtha Berkenou Anya Rothenbuhler Gabriele Haeusler Agnès Linglart |
| author_facet | Diana-Alexandra Ertl Justin Le Lorier Andreas Gleiss Séverine Trabado Candace Bensignor Christelle Audrain Volha Zhukouskaya Régis Coutant Jugurtha Berkenou Anya Rothenbuhler Gabriele Haeusler Agnès Linglart |
| author_sort | Diana-Alexandra Ertl |
| collection | DOAJ |
| description | Abstract Background X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies. Results Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH)2D increased dramatically under burosumab therapy. Conclusion To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height. |
| first_indexed | 2024-04-11T16:35:56Z |
| format | Article |
| id | doaj.art-699a007222eb4987bb113e9ef42cf39a |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-11T16:35:56Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-699a007222eb4987bb113e9ef42cf39a2022-12-22T04:13:50ZengBMCOrphanet Journal of Rare Diseases1750-11722022-11-0117111210.1186/s13023-022-02562-9Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormoneDiana-Alexandra Ertl0Justin Le Lorier1Andreas Gleiss2Séverine Trabado3Candace Bensignor4Christelle Audrain5Volha Zhukouskaya6Régis Coutant7Jugurtha Berkenou8Anya Rothenbuhler9Gabriele Haeusler10Agnès Linglart11AP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalCenter for Medical Statistics, Informatics, and Intelligent Systems, Medical University of ViennaDepartment of Molecular Genetics, Pharmacogenetics and Hormonology, Inserm U1185 and University Paris Saclay, AP-HP Bicêtre Paris-Saclay HospitalCHU Dijon Bourgogne, Pediatric HospitalAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalDepartment of Pediatric Endocrinology and Diabetes, CHU AngersAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalDepartment of Pediatrics and Adolescent Medicine, Division of Pulmonology, Allergology and Endocrinology, Medical University of ViennaAP-HP, Reference Center for Rare Disorders of the Calcium and Phosphate Metabolism, Filière OSCAR and Platform of Expertise for Rare Diseases Paris-Sud, Bicêtre Paris-Saclay HospitalAbstract Background X-linked hypophosphatemia (XLH) is characterized by increased serum concentrations of fibroblast growth factor 23 (FGF23), hypophosphatemia and insufficient endogenous synthesis of calcitriol. Beside rickets, odonto- and osteomalacia, disproportionate short stature is seen in most affected individuals. Vitamin D analogs and phosphate supplements, i.e., conventional therapy, can improve growth especially when started early in life. Recombinant human growth hormone (rhGH) therapy in XLH children with short stature has positive effects, although few reports are available. Newly available treatment (burosumab) targeting increased FGF23 signaling leads to minimal improvement of growth in XLH children. So far, we lack data on the growth of XLH children treated with concomitant rhGH and burosumab therapies. Results Thirty-six patients received burosumab for at least 1 year after switching from conventional therapy. Of these, 23 received burosumab alone, while the others continued rhGH therapy after switching to burosumab. Children treated with burosumab alone showed a minimal change in height SDS after 1 year (mean ± SD 0.0 ± 0.3 prepubertal vs. 0.1 ± 0.3 pubertal participants). In contrast, rhGH clearly improved height during the first year of treatment before initiating burosumab (mean ± SD of height gain 1.0 ± 0.4); patients continued to gain height during the year of combined burosumab and rhGH therapies (mean ± SD height gain 0.2 ± 0.1). As expected, phosphate serum levels normalized upon burosumab therapy. No change in serum calcium levels, urinary calcium excretion, or 25-OHD levels was seen, though 1,25-(OH)2D increased dramatically under burosumab therapy. Conclusion To our knowledge, this is the first study on growth under concomitant rhGH and burosumab treatments. We did not observe any safety issue in this cohort of patients which is one of the largest in Europe. Our data suggest that continuing treatment with rhGH after switching from conventional therapy to burosumab, if the height prognosis is compromised, might be beneficial for the final height.https://doi.org/10.1186/s13023-022-02562-9X-linked hypophosphatemia (XLH)BurosumabGrowthRecombinant human growth hormoneChildren |
| spellingShingle | Diana-Alexandra Ertl Justin Le Lorier Andreas Gleiss Séverine Trabado Candace Bensignor Christelle Audrain Volha Zhukouskaya Régis Coutant Jugurtha Berkenou Anya Rothenbuhler Gabriele Haeusler Agnès Linglart Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone Orphanet Journal of Rare Diseases X-linked hypophosphatemia (XLH) Burosumab Growth Recombinant human growth hormone Children |
| title | Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone |
| title_full | Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone |
| title_fullStr | Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone |
| title_full_unstemmed | Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone |
| title_short | Growth pattern in children with X-linked hypophosphatemia treated with burosumab and growth hormone |
| title_sort | growth pattern in children with x linked hypophosphatemia treated with burosumab and growth hormone |
| topic | X-linked hypophosphatemia (XLH) Burosumab Growth Recombinant human growth hormone Children |
| url | https://doi.org/10.1186/s13023-022-02562-9 |
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