title: Normal bone mass and normocalcemia in adulthood despite homozygous vitamin D receptor mutations.
abstract: Adding to the debate around vitamin D's effects on skeletal health, we report the long-term follow-up of two patients with severe vitamin D receptor mutations, who had normal bone mass acquisition and normalization of calcemia around puberty, suggesting that vitamin D might not be essential for skeletal health in adulthood.
  
  
  BACKGROUND
  Vitamin D plays a pivotal role in calcium homeostasis, and the consequences of vitamin D insufficiency for skeletal health, as well as the importance of its supplementation, are a matter of great interest. Individuals bearing homozygous vitamin D receptor (VDR) defects present with severe hypocalcemic rickets in early infancy due to vitamin D resistance.
  
  
  METHODS
  Here, we report the follow-up of two patients with hereditary vitamin D-resistant rickets (HVDRR), focusing on bone mass acquisition and evolution of calcemia.
  
  
  RESULTS
  Patient 1 is a 30-year-old male bearing a homozygous p.Arg30* nonsense mutation in the VDR DNA-binding domain, who presented at 6 months. From 9 years of age, treatment requirement decreased progressively. Follow-up with DXA showed normal bone mass acquisition. In adulthood, he maintains normocalcemia without calcium supplementation and has no signs of bone fragility. Patient 2 is a 37-year-old female with milder HVDRR and alopecia due to a homozygous p.Gly319Val mutation in the VDR ligand-binding domain. Around puberty, hypercalciuria and kidney stones were detected, resulting in suspension of treatment. Follow-up with DXA revealed normal bone mass, and she maintained normocalcemia without supplementation during gestation and lactation.
  
  
  CONCLUSIONS
  The long-term follow-up of HVDRR provides insights into the role of vitamin D in human calcium homeostasis and bone health. The normalization of calcemia and normal bone mass acquisition despite a permanently dysfunctional VDR suggest that vitamin D might not be essential for skeletal health in adulthood. Extrapolation of these findings may have implications in broader clinical settings, especially considering widespread vitamin D supplementation.
authors.affiliation: Division of Endocrinology and Laboratory of Medical Investigation 18 - LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 sala 3324 (LIM-18), São Paulo, SP, 01246-903, Brazil.
authors.forename: F M
authors.initials: FM
authors.lastname: Damiani
authors.affiliation: Division of Endocrinology and Laboratory of Medical Investigation 18 - LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 sala 3324 (LIM-18), São Paulo, SP, 01246-903, Brazil.
authors.forename: R M
authors.initials: RM
authors.lastname: Martin
authors.affiliation: Division of Endocrinology and Laboratory of Medical Investigation 18 - LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 sala 3324 (LIM-18), São Paulo, SP, 01246-903, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Latronico
authors.affiliation: Division of Endocrinology and Laboratory of Medical Investigation 18 - LIM-18, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av Dr Arnaldo, 455 sala 3324 (LIM-18), São Paulo, SP, 01246-903, Brazil. bruno.ferraz@hc.fm.usp.br.
authors.forename: B
authors.initials: B
authors.lastname: Ferraz-de-Souza
mesh_terms: D000328:Adult; D015519:Bone Density / Q000235:genetics*; D002118:Calcium / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006934:Hypercalcemia / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation; D010375:Pedigree; D018167:Receptors, Calcitriol / Q000235:genetics*; D012279:Rickets / Q000097:blood / Q000235:genetics
chemical_list: D018167:Receptors, Calcitriol; D002118:Calcium
keywords: Bone health; Bone mass; Calcium homeostasis; Hereditary vitamin D-resistant rickets; Vitamin D; Vitamin D receptor