title: 24,25 Dihydroxyvitamin D supplementation corrects hyperparathyroidism and improves skeletal abnormalities in X-linked hypophosphatemic rickets--a clinical research center study.
abstract: Therapy for X-linked hypophosphatemia (XLH) only partially corrects skeletal lesions and is often complicated by hyperparathyroidism. 24,25(OH)2 D3 improves skeletal lesions in a murine model of XLH and suppresses PTH secretion in animals. Therefore, we undertook a placebo-controlled trial of 24,25(OH)2 D3 supplementation to standard treatment in patients with XLH to improve bone disease and reduce hyperparathyroid complications. Fifteen subjects with XLH receiving standard treatment [1,25(OH)2 D3 or dihydrotachysterol plus phosphate] were evaluated, supplemented with placebo, and reevaluated one yr later. 24,25(OH)2 D3 supplementation was then begun and studies repeated after another year. Each patient underwent a detailed evaluation of calcium homeostasis over a 24-h period. Rachitic abnormalities were assessed radiographically in children. Adults underwent bone biopsies. 24,25(OH)2 D3 normalized PTH values in nine subjects (peak PTH was 46.5 +/- 6.6 pmol/L at entry, 42.3 +/- 5.9 pmol/L after placebo, and 23.3 +/- 5.4 pmol/L after 24,25(OH)2 D3). Nephrogenous cAMP decreased at night, coincident with the decrease in PTH, and serum phosphorus was slightly greater with 24,25(OH)2 D3. Radiographic features of rickets improved during 24,25(OH)2 D3 supplementation in children, and osteoid surface decreased in adults. 24,25(OH)2 D3 is a useful adjunct to standard therapy in XLH by effecting correction of hyperparathyroidism and improvement of rickets and osteomalacia.
authors.affiliation: Endocrine Section of the Pediatric, Yale University School of Medicine, New Haven, Connecticut 06520, USA. CarpenteTO@MASPO3.MAS.YALE.EDU
authors.forename: T O
authors.initials: TO
authors.lastname: Carpenter
authors.forename: M
authors.initials: M
authors.lastname: Keller
authors.forename: D
authors.initials: D
authors.lastname: Schwartz
authors.forename: M
authors.initials: M
authors.lastname: Mitnick
authors.forename: C
authors.initials: C
authors.lastname: Smith
authors.forename: A
authors.initials: A
authors.lastname: Ellison
authors.forename: D
authors.initials: D
authors.lastname: Carey
authors.forename: F
authors.initials: F
authors.lastname: Comite
authors.forename: R
authors.initials: R
authors.lastname: Horst
authors.forename: R
authors.initials: R
authors.lastname: Travers
authors.forename: F H
authors.initials: FH
authors.lastname: Glorieux
authors.forename: C M
authors.initials: CM
authors.lastname: Gundberg
authors.forename: A R
authors.initials: AR
authors.lastname: Poole
authors.forename: K L
authors.initials: KL
authors.lastname: Insogna
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D001842:Bone and Bones / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy*; D007015:Hypophosphatemia, Familial / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D016037:Single-Blind Method; D014960:X Chromosome
chemical_list: D015650:24,25-Dihydroxyvitamin D 3