ARS | Publication request: Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets

Submitted to: Journal of Clinical Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 22, 2011
Publication Date: December 1, 2011
Citation: Tiosano, D., Hadad, S., Chen, Z., Nemirovsky, A., Gepstein, V., Militianu, D., Weisman, Y., Abrams, S.A. 2011. Calcium absorption, kinetics, bone density, and bone structure in patients with hereditary vitamin D-resistant rickets. Journal of Clinical Endocrinology and Metabolism. 96(12):3701-3709.

Interpretive Summary: We studied whether individuals who have a rare inability to use vitamin D, called hereditary vitamin D resistant rickets would be able to absorb calcium normally at different ages. We used stable isotopes to determine that calcium absorption was low in children up to 17 years of age, but then was at or above normal for the next 10 years. These data showed that calcium absorption in this population was highly vitamin D dependent from infancy until the end of adolescence but was not vitamin D dependent after that. We also found that the structure of bone as determined by magnetic resonance imaging (MRI) was normal in this population.

Technical Abstract: 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. 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. 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. 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. 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.