title: Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets.
abstract: BACKGROUND
  Hereditary 1,25-dihydroxyvitamin D-resistant rickets (HVDRR) is caused by mutations in the vitamin D receptor gene. Children with HVDRR suffer from severe hypocalcemia and rickets that are treatable with extremely high-dose calcium supplements. Surprisingly, spontaneous recovery of calcium metabolism occurs after the end of puberty without the need for further calcium supplementation.
  
  
  OBJECTIVE
  To evaluate the role of vitamin D receptor in intestinal calcium absorption and bone, we investigated intestinal fractional calcium absorption (FCA), bone calcium accretion (Vo+), bone mineral density (BMD), and bone structure parameters in HVDRR patients from infancy into adulthood.
  
  
  METHODS
  Seventeen HVDRR patients aged 1.5-37 yr were investigated. FCA and Vo+ were determined by stable-calcium isotopes. BMD was determined by dual-energy x-ray absorptiometry and bone structure by high-resolution magnetic resonance imaging.
  
  
  RESULTS
  FCA in patients aged 1.5-17 yr was 34.9 ± 11.2% compared with 57.3 ± 2.0% in age-matched controls (P < 0.00004), whereas in patients aged 18-26 yr, it was 82.0 ± 7.8 and 53.6 ± 1.2% in controls (P < 0.001). FCA of patients older than 29 yr was comparable to controls. Patients aged 18-26 yr had higher Vo+ than controls (P < 0.02). Patients under 18 and over 29 yr of age had Vo+ comparable to controls. Femoral-neck BMD Z-score was -2.38 ± 0.3 in patients under 18 yr and 0.28 ± 0.87 in postpubertal patients (P < 0.0001). Bone structure by high-resolution magnetic resonance imaging and bone parameters of HVDRR patients and controls were similar.
  
  
  CONCLUSIONS
  Evidence from HVDRR patients reveals that calcium absorption is highly vitamin D dependent during infancy until the end of puberty, after which there is a period of about 10 yr in which mechanisms other than vitamin D-dependent ones are substantially involved in calcium absorption.
authors.affiliation: Division of Pediatric Endocrinology, Meyer Children's Hospital, Rambam Health Care Campus, Haifa 31096, Israel. d_tiosano@rambam.health.gov.il
authors.forename: Dov
authors.initials: D
authors.lastname: Tiosano
authors.forename: Salim
authors.initials: S
authors.lastname: Hadad
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Chen
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Nemirovsky
authors.forename: Vardit
authors.initials: V
authors.lastname: Gepstein
authors.forename: Daniela
authors.initials: D
authors.lastname: Militianu
authors.forename: Yosef
authors.initials: Y
authors.lastname: Weisman
authors.forename: Steven A
authors.initials: SA
authors.lastname: Abrams
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015519:Bone Density / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D053098:Familial Hypophosphatemic Rickets / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D018167:Receptors, Calcitriol / Q000378:metabolism
chemical_list: D018167:Receptors, Calcitriol; D002118:Calcium