Context: X-Linked hypophosphatemia (XLH) is characterized by renal phosphate wasting, with inappropriately low or normal serum 1,25-dihydroxyvitamin D concentrations causing rickets and osteomalacia. Mutations in PHEX result in increased fibroblast growth factor 23 (FGF23) expression, elevating circulating FGF23 concentrations. Treating XLH with phosphate and calcitriol may further increase FGF23 concentrations, based on in vitro and in vivo models.
Objective: The aim of the study was to investigate whether current standard XLH therapies increase circulating FGF23 concentrations.
Design and setting: We conducted a prospective observational study of XLH subjects during routine clinical management at two tertiary referral centers.
Patients: The study included 10 XLH patients (seven children, three adults; age, 2-30 yr) initiating therapy and five XLH patients (age, 18-41 yr) electing not to undergo therapy.
Intervention(s): Oral calcitriol and phosphate were administered.
Main outcome measures: We measured circulating intact FGF23 concentrations.
Results: Baseline circulating FGF23 concentrations were elevated in 14 of 15 subjects, increasing after treatment in most subjects. Follow-up was 14.4 +/- 11.7 months (treatment cohort) and 25 +/- 32 months (nontreatment cohort). FGF23 concentrations increased 132.7 +/- 202.4% from pretreatment to peak during therapy but did not change significantly over time in the nontreatment cohort. FGF23 concentrations were related to phosphate doses (P = 0.04) and nonsignificantly to calcitriol doses (P = 0.06).
Conclusions: Treating XLH with phosphate and calcitriol was associated with concurrent increases in circulating FGF23 concentrations, which may diminish therapeutic effect or contribute to complications of therapy. Because it is unknown whether the degree of FGF23 elevation correlates with disease severity in XLH, further study is needed to determine whether adjusting therapy to minimize effects on FGF23 concentration is warranted.