Osteoporosis International

, Volume 26, Issue 6, pp 1819–1823 | Cite as

Normal bone mass and normocalcemia in adulthood despite homozygous vitamin D receptor mutations

  • F. M. Damiani
  • R. M. Martin
  • A. C. Latronico
  • B. Ferraz-de-SouzaEmail author
Case Report



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.


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.


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.


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.


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.


Bone health Bone mass Calcium homeostasis Hereditary vitamin D-resistant rickets Vitamin D Vitamin D receptor 



We thank Pedro Henrique S Correa, Jose B Mechica, and Maria Odette R Leite who were responsible for the clinical care of these patients for several years. This work was supported by Sao Paulo Research Foundation (FAPESP) grants 2011/12696-4 and 2012/11231-0.

Conflicts of interest



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Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2015

Authors and Affiliations

  • F. M. Damiani
    • 1
  • R. M. Martin
    • 1
  • A. C. Latronico
    • 1
  • B. Ferraz-de-Souza
    • 1
    Email author
  1. 1.Division of Endocrinology and Laboratory of Medical Investigation 18 - LIM-18Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloSão PauloBrazil

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