ESPN 53rd Annual Meeting

ESPN 2021


 
X-linked hypophosphatemia, obesity and cardiovascular parameters: data from the XLH21 study
LOUISA BLOUDEAU 1 AGNèS LINGLART 1 SACHA FLAMMIER 1 AURéLIE PORTEFAIX 1 JEAN-PIERRE SALLES 1 ANYA ROTHENBUHLER 1 CHRISTELLE ROGER 1 JUSTINE BACCHETTA 1

1- REFERENCE CENTER OF RARE DISEASES OF CALCIUM AND PHOSPHATE, RARE DISEASES FRENCH NETWORK OSCAR
 
Introduction:

 

There is an over-incidence of obesity in X-linked hypophosphatemia (XLH), but the underlying  pathophysiological mechanisms are not yet known. The objective of this study was to evaluate whether FGF21, another endocrine FGF involved in the regulation of carbohydrate-lipid metabolism, could be involved.

Material and methods:

 

We performed a prospective multicenter cross-sectional study comparing circulating FGF23, Klotho and FGF21 levels in teenagers with XLH compared to healthy controls (HC, VITADOS cohort) after a 1:1 matching on age, gender and puberty (XLH21, NCT03596554; VITADOS NCT01832623). Non-parametric tests were performed, results are presented as median (min-max).

Results:

 

A total of 40 teenagers with XLH (N=20 with standard of care, SOC, N=20 with burosumab) were included. Whilst patients receiving burosumab displayed decreased SDS for height and increased BMI as compared to patients receiving SOC, systolic blood pressure expressed as percentile progressively and significantly decreased when comparing the three groups: 77(4-99) in SOC, 47(9-98) in burosumab, and 28(0.5-94) in HC (p=0.007). When compared to patients receiving SOC, patients receiving burosumab displayed significantly increased phosphate, 1-25-D and Klotho levels. No differences were found for either carbohydrate-lipid biomarkers or FGF21 between the three groups. In HC, FGF23 and FGF21 were positively associated (R=0.586, p=0.002), but this association was lost in XLH patients. A total of 21 XLH patients (53%) had insulin-resistance (HOMA>2.4, N=10 SOC, N=11 burosumab); there were no differences for FGF21, phosphate and Klotho levels between these two sub-groups.

Conclusions:

 

FGF21 does not explain obesity/overweight in XLH teenagers. This study was performed in France in 2018-2019, early after the approval authorizing the treatment of patients with 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 deserve further studies given their potential impact on long-term cardiovascular risk.