Louisa Bloudeau1, Agnès Linglart2, Sacha Flammier1, Aurélie Portefaix3, Aurélia Bertholet-Thomas1, Sanaa Eddiry4, Anna Barosi2, Jean-Pierre Salles4, Valérie Porquet-Bordes4, Anya Rothenbuhler2, Christelle Roger5,6, Justine Bacchetta7,8,9,10. 1. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, Centre de Référence Des Maladies Rénales Rares, Filières Maladies Rares OSCAR, ORKID Et ERK-Net, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, 69500, France. 2. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, Filière de Santé Maladies Rares OSCAR, Endocrinologie Et Diabète de L'enfant, Hôpital Bicêtre Paris-Saclay, Université Paris Saclay, AP-HP, DMU SEA, INSERM U1185, Paris, 94270, France. 3. Centre d'Investigation Clinique, EPICIME-CIC 1407, Hospices Civils de Lyon, Bron, 69500, France. 4. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, CHU de Toulouse, Toulouse, 31059, France. 5. Service de Biochimie Et Biologie Moléculaire, Hôpital Lyon Sud, Pierre-Bénite, 69310, France. 6. Faculté de Médecine Lyon Est, INSERM, UMR 1033, Université Claude Bernard Lyon1, Lyon, 69008, France. 7. Centre de Référence Des Maladies Rares du Calcium Et du Phosphate, Centre de Référence Des Maladies Rénales Rares, Filières Maladies Rares OSCAR, ORKID Et ERK-Net, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron, 69500, France. justine.bacchetta@chu-lyon.fr. 8. Faculté de Médecine Lyon Est, INSERM, UMR 1033, Université Claude Bernard Lyon1, Lyon, 69008, France. justine.bacchetta@chu-lyon.fr. 9. Faculté de Médecine Lyon Est, Université Claude Bernard Lyon 1, Lyon, 69008, France. justine.bacchetta@chu-lyon.fr. 10. Néphrologie, Rhumatologie Et Dermatologie Pédiatriques Hôpital Femme Mère Enfant, 59 boulevard Pinel, Bron Cedex, 69677, France. justine.bacchetta@chu-lyon.fr.
Abstract
BACKGROUND: The underlying mechanisms of obesity in X-linked hypophosphatemia (XLH) are not known. We aimed to evaluate whether FGF21, an endocrine FGF involved in the regulation of carbohydrate-lipid metabolism, could be involved. METHODS: We performed a prospective multicenter cross-sectional study comparing FGF23, Klotho, and FGF21 levels in teenagers with XLH compared to healthy controls (VITADOS cohort) after matching for age, gender, and puberty. Non-parametric tests were performed (results presented as median (min-max)). RESULTS: A total of 40 XLH teenagers (n = 20 Standard Of Care, SOC, n = 20 burosumab) were included. While patients receiving burosumab displayed increased BMI as compared to patients receiving SOC, systolic blood pressure expressed as percentile was progressively and significantly lower when comparing the three groups: 77 (4-99) in SOC, 47 (9-98) in burosumab, and 28 (1-94) in controls (p = 0.007). When compared to patients receiving SOC, patients receiving burosumab displayed significantly increased phosphate and 1,25(OH)2D levels. We found increased Klotho levels in patients receiving burosumab. No differences were found for either carbohydrate-lipid biomarkers or FGF21 between the three groups. A total of 21 XLH patients (53%) had insulin resistance (HOMA > 2.4, N = 10 SOC, N = 11 burosumab). CONCLUSION: FGF21 does not explain obesity/overweight in XLH. Of note, this study was performed in France in 2018-2019, early after the approval authorizing burosumab only in case of severe XLH despite SOC. As such, the data on systolic blood pressure highlighting a possible impact of burosumab to decrease blood pressure as well as increase Klotho levels deserve further studies given their potential effect on long-term cardiovascular risk. A higher resolution version of the Graphical abstract is available as Supplementary information.
BACKGROUND: The underlying mechanisms of obesity in X-linked hypophosphatemia (XLH) are not known. We aimed to evaluate whether FGF21, an endocrine FGF involved in the regulation of carbohydrate-lipid metabolism, could be involved. METHODS: We performed a prospective multicenter cross-sectional study comparing FGF23, Klotho, and FGF21 levels in teenagers with XLH compared to healthy controls (VITADOS cohort) after matching for age, gender, and puberty. Non-parametric tests were performed (results presented as median (min-max)). RESULTS: A total of 40 XLH teenagers (n = 20 Standard Of Care, SOC, n = 20 burosumab) were included. While patients receiving burosumab displayed increased BMI as compared to patients receiving SOC, systolic blood pressure expressed as percentile was progressively and significantly lower when comparing the three groups: 77 (4-99) in SOC, 47 (9-98) in burosumab, and 28 (1-94) in controls (p = 0.007). When compared to patients receiving SOC, patients receiving burosumab displayed significantly increased phosphate and 1,25(OH)2D levels. We found increased Klotho levels in patients receiving burosumab. No differences were found for either carbohydrate-lipid biomarkers or FGF21 between the three groups. A total of 21 XLH patients (53%) had insulin resistance (HOMA > 2.4, N = 10 SOC, N = 11 burosumab). CONCLUSION: FGF21 does not explain obesity/overweight in XLH. Of note, this study was performed in France in 2018-2019, early after the approval authorizing burosumab only in case of severe XLH despite SOC. As such, the data on systolic blood pressure highlighting a possible impact of burosumab to decrease blood pressure as well as increase Klotho levels deserve further studies given their potential effect on long-term cardiovascular risk. A higher resolution version of the Graphical abstract is available as Supplementary information.
Authors: Thomas O Carpenter; Karl L Insogna; Jane H Zhang; Bruce Ellis; Sherril Nieman; Christine Simpson; Elizabeth Olear; Caren M Gundberg Journal: J Clin Endocrinol Metab Date: 2010-08-04 Impact factor: 5.958
Authors: Dieter Haffner; Francesco Emma; Deborah M Eastwood; Martin Biosse Duplan; Justine Bacchetta; Dirk Schnabel; Philippe Wicart; Detlef Bockenhauer; Fernando Santos; Elena Levtchenko; Pol Harvengt; Martha Kirchhoff; Federico Di Rocco; Catherine Chaussain; Maria Louisa Brandi; Lars Savendahl; Karine Briot; Peter Kamenicky; Lars Rejnmark; Agnès Linglart Journal: Nat Rev Nephrol Date: 2019-07 Impact factor: 28.314