Serum Levels of Lipocalin Are Lower in Adolescents With X-Linked Hypophosphatemia

Abstract Individuals with X-linked hypophosphatemia (XLH) are at greater risk for being overweight or obese. It has generally been assumed that the primary reason for this is impaired mobility due to accelerated osteoarthritis, abnormal biomechanics of ambulation, pseudofractures and enthesopathy. These known complications limit the ability of patients with XLH to engage in regular aerobic exercise. Whether there are underlying metabolic abnormalities that also put patients with XLH at greater risk for excessive weight gain is largely unknown. A recent French study1 confirmed that patients with XLH, especially adolescents, have a predilection to obesity. Evidence suggests that elevated circulating levels of fibroblast growth factor 23 (FGF23) are associated with an increase in fat mass and dyslipidemia in elderly normal individuals. Whether the elevated levels of FGF23 in XLH play a direct pathogenic role in the risk for excessive weight gain in XLH is unclear. Lipocalin (LCN2) has recently received considerable attention as a factor regulating energy consumption and specifically is postulated to be anorexigenic and improve insulin sensitivity. We therefore measured circulating levels of LCN2, leptin and insulin in 32 patients with XLH, ages 2–60 y.o., all of whom were being treated with burosumab and 40 Cntrl subjects, matched for age, sex, and BMI or weight/height z-score for children and adolescents. Serum was obtained from excess sample from clinical 25-hydroxy vitamin D testing in our laboratory. All patients were de-identified for the study. In 7 adults with XLH 20–60 y.o. (mean age 35) and 11 Cntrls (mean age 41), mean values for BMI, LCN2, leptin and insulin levels in the two group were as follows, (XLH vs. Cntrl); BMI: 36 vs. 34 kg/m2, LCN2: 83 vs. 108 ng/mL, leptin: 26 vs. 39 ng/mL, insulin: 19 vs. 20 µIU/mL. The pediatric patients were separated into two groups: 2–10 and 11–18 y.o.. In the 2–10 y.o. group the mean values were (XLH vs. Cntrl); age: 5.5 y.o. vs. 5.8 y.o., weight/height Z-score: 0.8 vs. 1.1, LCN2: 47 vs. 60, leptin: 2.2. vs. 6.7, and insulin: 8.4 vs. 13. In the 11–18 group, mean values were (XLH vs. Cntrl); age: 14 y.o. vs. 14 y.o., weight/height Z-score: 1.0 vs. 1.2, LCN2: 65 vs. 105, leptin: 24 vs.19, and insulin: 17 vs. 48. In all age groups LCN2 was lower in the patients with XLH than Cntrls and this difference reached significance in the adolescents with XLH (p=0.04). No other parameters were significantly different among the groups. Since all patients with XLH were treated with burosumab it is unlikely that a direct effect of excess FGF23 production explains this finding. We conclude that reduced expression of lipocalin in adolescents with XLH may contribute to their risk for obesity.1Lecoq et.al. Obesity and Impaired Glucose Metabolism in Adult Patients with X-Linked Hypophosphatemia, J, Endo. Soc. 2020 https://doi.org/10.1210/jendso/bvaa046.1355