Normal Bone Mass and Normocalcemia in Adulthood Despite Homozygous Vitamin D Receptor Mutations

Overview

Journal Osteoporos Int

Specialties Endocrinology
Orthopedics

Date 2015 Feb 25

PMID 25708797

Citations 4

Authors

F M Damiani

R M Martin

A C Latronico

B Ferraz-de-Souza

Affiliations

Soon will be listed here.

Abstract

Unlabelled: 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.

Introduction: 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.

Citing Articles

Intestinal Vitamin D Receptor Is Dispensable for Maintaining Adult Bone Mass in Mice With Adequate Calcium Intake.

Jiang H, Chanpaisaeng K, Christakos S, Fleet J Endocrinology. 2023; 164(5).

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Transcriptomic Response to 1,25-Dihydroxyvitamin D in Human Fibroblasts with or without a Functional Vitamin D Receptor (VDR): Novel Target Genes and Insights into VDR Basal Transcriptional Activity.

Costa P, Franca M, Katayama M, Carneiro E, Martin R, Folgueira M Cells. 2019; 8(4).

PMID: 30959822 PMC: 6523947. DOI: 10.3390/cells8040318.

Hereditary Vitamin D Resistant Rickets: Clinical, Laboratory, and Genetic Characteristics of 2 Iranian Siblings.

Ghazi A, Zadeh-Vakili A, Yeganeh M, Alamdari S, Amouzegar A, Khorsandi A Int J Endocrinol Metab. 2017; 15(3):e12384.

PMID: 29201067 PMC: 5702004. DOI: 10.5812/ijem.12384.

Nonspecific binding of a frequently used vitamin D receptor (VDR) antibody: important implications for vitamin D research in human health.

Costa P, Franca M, Ferraz-de-Souza B Endocrine. 2016; 54(2):556-559.

PMID: 27393303 DOI: 10.1007/s12020-016-1036-0.

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