Genetic Determinants of Bone Mass

Abstract

A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1_α1, TGF-β₁, interleukin-6, calcitonin receptor, α₂-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, β₃-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.

Gender and Race/Ethnicity Differences in Lead Dose Biomarkers

“…34,35 Because of a growing literature that suggests the toxicokinetics of lead may be modified by genetic polymorphisms, 36,37 we also evaluated associations with 2 genes thought relevant to deposition or release of lead or calcium from bone: apolipoprotein E, APOE, and vitamin D receptor, VDR (by using 2 restriction enzymes, Bsm I and Fok I). [38][39][40][41] Genotyping was performed in the laboratory of the Malaria Institute in the Bloomberg School of Public Health by standard methods.…”

Quantitative genetics of cortical bone mass in healthy 10-year-old children from the Fels Longitudinal Study

“…Bone accumulation dominates during childhood and peaks in early adulthood, while bone loss typically dominates later in life. Investigations of bone mass, both genetic and non-genetic, have traditionally focused on two definable aspects of this process; peak bone mass [21,22,44], and osteoporosis [3,47,48]. It is important to note that both are influenced by genetic and environmental factors, and their interactions, prior to the attainment of peak bone mass or onset of osteoporosis.…”

Immune System Modifications Induced in a Mouse Model of Chronic Exposure to90Sr

“…These authors proposed that IGF-I increases strontium absorption by maintaining the structural integrity of the intestine and the sensitivity of the intestine to 1,25(OH) 2 D and increasing the synthesis of calcium-binding protein in that tissue. IGF-I also acts by stimulating the synthesis of 1,25(OH) 2 D in the kidney (Audi et al 1999;Fatayerji et al 2000).…”