Genetic influences on bone density: physiological correlates of vitamin D receptor gene alleles in premenopausal women.
Common vitamin D receptor (VDR) gene alleles have recently been shown to contribute to the genetic variability in bone mass and bone turnover, however, the physiological mechanisms involved are unknown. To examine this, the response to 7 days of 2 micrograms oral 1,25-dihydroxyvitamin D[1,25-(OH)2D] (calcitriol) stimulation was assessed in 21 premenopausal women, homozygous for one or other of the common VDR alleles (bb, n = 11; BB, n = 10). Indices of bone turnover and calcium homeostasis were measured during 2 weeks. Baseline osteocalcin, 1,25-(OH)2D, type I collagen carboxyterminal telopeptide, and inorganic phosphate levels were significantly higher and spinal bone mineral density was significantly lower in the BB allelic group. After calcitriol administration, similar levels of 1,25-(OH)2D were attained throughout the study in both genotypic groups. The increase in serum osteocalcin levels in the BB group was significantly less than that in the bb group (11% vs. 32%, P = 0.01). The genotype-related baseline difference in osteocalcin levels was not apparent at the similar serum 1,25-(OH)2D levels. By contrast, the baseline differences in phosphate and type I collagen carboxyterminal telopeptide persisted throughout the study. Serum ionized calcium levels did not differ between genotypes, nor did it move out of normal range values. However, parathyroid hormone was less suppressed in the low bone density group (38% vs. 11%, P = 0.01). These data indicate that the VDR alleles are associated with differences in the vitamin D endocrine system and may have important implications in relation to the pathophysiology of osteoporosis.
Howard
G
G
Bone and Mineral Research Division, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney, New South Wales, Australia.
Nguyen
T
T
Morrison
N
N
Watanabe
T
T
Sambrook
P
P
Eisman
J
J
Kelly
P J
PJ
D000328:Adult; D000483:Alleles; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000097:blood / Q000627:therapeutic use; D002118:Calcium / Q000378:metabolism; D003094:Collagen; D024042:Collagen Type I; D005260:Female; D005796:Genes; D006706:Homeostasis; D006720:Homozygote; D006801:Humans; D015675:Osteocalcin / Q000097:blood; D010455:Peptides; D010710:Phosphates / Q000097:blood; D017697:Premenopause / Q000235:genetics* / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics*; D013131:Spine / Q000378:metabolism
D024042:Collagen Type I; D010455:Peptides; D010710:Phosphates; D018167:Receptors, Calcitriol; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D003094:Collagen; D002117:Calcitriol; D002118:Calcium