Treatment of children and adults with X-linked hypophosphatemia with calcitriol alone: A prospective open label study

Context Preclinical studies demonstrate that treatment with calcitriol attenuates skeletal complications in mice with X-linked hypophosphatemia (XLH). Objective To assess serum markers of mineral metabolism, nephrocalcinosis, skeletal microarchitecture, growth, and evidence of rickets following calcitriol monotherapy in children and adults with XLH. Design A 1-year prospective single-arm open-label study comparing baseline and 12-month outcomes. Setting Participants were recruited from outpatient endocrinology clinics in the United States. Data were collected in a research unit. Participants Eligible participants were ≥ 4 years old, not pregnant, with baseline 25-hydroxyvitamin D ≥20 ng/mL and normal serum calcium. Intervention Participants were treated with calcitriol, with dose based on serum and urinary calcium concentrations, for 1 year. Main Outcome Measures The primary endpoints were change in serum phosphate and nephrocalcinosis (all participants) and rickets severity score (children). Secondary endpoints included changes in additional markers of mineral metabolism, skeletal microarchitecture parameters via high-resolution peripheral quantitative computed tomography (all participants), and height z-scores (children). Results Serum phosphate did not change over 12 months of optimized calcitriol treatment. Rickets improved in 2 of 4 children with open epiphyses; height z-scores were unchanged. Nephrocalcinosis scores remained stable. Adults had increased cortical thickness at the radius diaphysis (p=0.012). Serum alkaline phosphatase decreased in children (p=0.021) and parathyroid hormone trended lower in both children (p=0.065) and adults (p=0.063). 4 participants developed mild hypercalcemia and 2 developed hypercalciuria which resolved with calcitriol titration. Conclusions Calcitriol monotherapy is safe and well-tolerated in XLH, with modest benefits on laboratory indices of mineral metabolism and rickets.