F M Damiani1, R M Martin1, A C Latronico1, B Ferraz-de-Souza2. 1. 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. 2. 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.
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.
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 Dinsufficiency 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 humancalcium 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.
Entities:
Keywords:
Bone health; Bone mass; Calcium homeostasis; Hereditary vitamin D-resistant rickets; Vitamin D; Vitamin D receptor
Authors: Bram C J van der Eerden; Josine C van der Heyden; Jan Piet van Hamburg; Marijke Schreuders-Koedam; Patrick S Asmawidjaja; Sabine M de Muinck Keizer-Schrama; Annemieke M Boot; Erik Lubberts; Stenvert L S Drop; Johannes P T M van Leeuwen Journal: Bone Date: 2014-09-06 Impact factor: 4.398
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