Heritable and life-style determinants of bone mineral density

Abstract

Familial resemblance in bone mineral density at five skeletal sites was measured among 160 adult members of 40 families. Each family included a postmenopausal mother, one premenopausal daughter, one son, and the children's father. Similarities in selected life-style factors thought to influence bone density, such as physical activity, smoking, alcohol use, and diet, were also evaluated. Bone density was measured by dual-energy (total body, femoral neck, and lumbar spine) or single-photon (radius and os calcis) absorptiometry. Correlation coefficients between the midparent Z score and offspring Z scores of bone mineral density ranged from 0.22 to 0.52 among daughters and from 0.27 to 0.58 among sons. Adjustment of bone density for age, height, weight, and significant life-style or environmental factors yielded heritability estimates for the five skeletal sites between 0.46 and 0.62. That is, 46-62% of variance in bone density was attributable to heredity. Most estimates derived from the group of daughters were similar to those from the sons. These observations provide support for a significant contribution of heredity to bone density. However, an individual's life-style may account for a potentially large proportion of the nonheritable variance in bone density.

Genetic influences on bone loss in the San Antonio Family Osteoporosis study

“…Numerous family and sibling studies of peak BMD have been performed in a variety of populations, and these studies have universally shown the high heritability of peak BMD [3,8,21,29,30]. Many whole genome linkage scans have also been performed, with QTLs reported at a number of chromosomal regions, though specific QTLs have rarely been replicated across studies [5][6][7]28,[31][32][33][34][35][36], probably due, in part, to genetic heterogeneity among the populations studied.…”

“…The degenerative disorder and associated fragility fractures have devastating effects on health, resulting in substantial morbidity, and increased mortality for hip and vertebral fractures [1]. Bone mineral density (BMD), as the foremost determinant of bone strength and major predictor of future fractures, has been extensively studied to help identify the environmental [2][3][4] and genetic factors [5][6][7][8] influencing risk for osteoporosis.…”

Genetic variation in the RANKL/RANK/OPG signaling pathway is associated with bone turnover and bone mineral density in men

“…Data from twin studies suggest that up to 80% of bone mineral density (BMD) may be explained by genetic factors, but less is known about bone turnover markers. (8)(9)(10) Over the last decade, a number of candidate genes have been linked with both bone density and bone turnover, although those identified typically explain a relatively small proportion of phenotypic variance. The RANKL/RANK/OPG signaling pathway has a critical role in bone remodeling; RANKL interaction with RANK increases production, activity, and survival of osteoclasts, but the effects of RANKL are blocked by osteoprotegerin (OPG), which act as a natural decoy receptor.…”

Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification

“…Both genetic background and environmental factors play important roles in the risk to this disorder. (1) Alterations in collagen can have a spectrum of effects on bone (from osteoporosis to osteogenesis imperfecta), whereas animal models have shown that changes in the noncollagenous proteins of bone also may predispose to osteoporosis-like phenotypes. (2,3) Bone g-carboxyglutamic acid protein, more commonly known as osteocalcin (OC), is the most abundant extracellular matrix protein in bone (4) and constitutes approximately 1% of the total protein in human bone.…”