Current treatment of
X-linked hypophosphatemia (XLH) employs the combined administration of oral
phosphate and
1,25-dihydroxyvitamin D3 [
1,25-(OH)2D3]. Although this
drug regimen significantly improves the
clinical course of the disease in children, the value of medical treatment in symptomatic adults with XLH has not been established. We, therefore, investigated the clinical, biochemical, and histological responses to
phosphate and 1,25-(OH)2D3 in 16 symptomatic adult patients with XLH followed for a mean of 4.2 yr. Eighty-seven percent of the patients had an improvement in bone or
joint pain with
therapy. There was a significant increase in mean serum
phosphate (from 0.61 +/- 0.03 to 0.77 +/- 0.03 mmol/L) and urinary
calcium excretion (from 2.45 +/- 0.38 to 4.39 +/- 0.44 mmol/day) with treatment. Pretreatment bone biopsies demonstrated findings characteristic of
osteomalacia, including abnormally increased osteoid volume and decreased
mineral apposition rates. Treatment was accompanied by a significant decrease in osteoid thickness as well as a reduction in mean osteoid volume. However,
therapy did not completely normalize these parameters. Disease severity, as assessed by histomorphometric parameters, did not correlate with any pretreatment serum or urinary biochemical measurement, but did seem to correlate with symptom score. Although most patients tolerated
therapy without difficulty, 1 patient developed tertiary
hyperparathyroidism during treatment and
renal insufficiency that progressed despite cessation of
therapy. This study provides evidence that
therapy with oral
phosphate and 1,25-(OH)2D3 in symptomatic adults with XLH can result in significant clinical and histomorphometric improvement.