Genetic determinants of bone mass acquisition and risk for osteoporosis

Rubin, Laurence A.; Patel, Millan S.; Cole, David E. C.

doi:10.1002/(sici)1098-2299(200003)49:3<216::aid-ddr12>3.0.co;2-a

Cited by 4 publications

(2 citation statements)

References 93 publications

(76 reference statements)

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“…However, a pattern of genetic influences over bone mass is beginning to materialize, based primarily on cross-sectional evidence, although some genetic studies of longitudinal changes in BMD in older adults are being conducted (see [52]). Comparisons of heritabilities of bone mass in younger and older twin pairs suggest that bone mass may be under tighter genetic control in early life than in later life [51,56,57]. Based on the residual heritability of a number of other early childhood traits such as birth weight, recumbent length and basicranial skeletal dimensions, it would be expected that the heritability of bone mass at birth and during early childhood is high [7,14,54,61,63].…”

Section: Discussionmentioning

confidence: 99%

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

Duren

Sherwood

Choh

et al. 2007

Bone

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The genetic influences on bone mass likely change throughout the life span, but most genetic studies of bone mass regulation have focused on adults. There is, however, a growing awareness of the importance of genes influencing the acquisition of bone mass during childhood on lifelong bone health. The present investigation examines genetic influences on childhood bone mass by estimating the residual heritabilities of different measures of second metacarpal bone mass in a sample of 600 10-year-old participants from 144 families in the Fels Longitudinal Study. Bivariate quantitative genetic analyses were conducted to estimate genetic correlations between cortical bone mass measures, and measures of bone growth and development. Using a maximum likelihood-based variance components method for pedigree data, we found a residual heritability estimate of 0.71 for second metacarpal cortical index. Residual heritability estimates for individual measures of cortical bone (e.g., lateral cortical thickness, medial cortical thickness) ranged from 0.47 to 0.58, at this prepubertal childhood age. Low genetic correlations were found between cortical bone measures and both bone length and skeletal age. However, after Bonferonni adjustment for multiple testing, ρ G was not significantly different from 0 for any of these pairs of traits. Results of this investigation provide evidence of significant genetic control over bone mass largely independent of maturation while bones are actively growing and before rapid accrual of bone that typically occurs during puberty.

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Section: Discussionmentioning

confidence: 99%

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

Duren

Sherwood

Choh

et al. 2007

Bone

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“…Until now, the nature of the changing landscape of heritability of bone traits over much of the life span in humans was largely unknown, mainly because estimated values from various published studies differed on the basis of factors such as bone site or sex studied. Comparisons of heritabilities of bone mass in younger and older twin pairs have suggested that bone mass may be under tighter genetic control in early life than in later life (Smith et al, 1973;Slemenda et al, 1991;Rubin et al, 2000). Similarly, from residual heritability of a number of other early childhood traits such as birth weight, recumbent length, and basicranial skeletal dimensions, it would also be expected that the heritability of bone mass at birth and during early childhood is high (Wilson, 1976;Fischbein and Nordqvist, 1978;Towne et al, 1993;Clausson et al, 2000;Sherwood et al, 2004).…”

Section: The Genetic Landscapementioning

confidence: 99%

Skeletal growth and the changing genetic landscape during childhood and adulthood

Duren

Šešelj

Froehle

et al. 2012

American J Phys Anthropol

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Growth, development, and decline of the human skeleton are of central importance to physical anthropology. All processes of skeletal growth (longitudinal growth as well as gains and losses of bone mass) are subject to environmental and genetic influences. These influences, and their relative contributions to the phenotype, can be asserted at any stage of life. We present here the gross phenotypic and genetic landscapes of four skeletal traits, and show how they vary across the life span. Phenotypic sex differences are found in bone diameter and cortical index (a ratio of cortical thickness over bone diameter) at a very early age and continue throughout most of life. Sexual dimorphism in summed cortical thickness and bone length, however, is not evident until shortly after the pubertal growth spurt. Genetic contributions (heritability) to these skeletal phenotypes are generally moderate to high. Bone length and bone diameter (which both scale with body size) tend to have the highest heritability, with heritability of bone length fairly stable across ages (with a notable dip in early childhood) and that of bone diameter peaking in early childhood. The bone traits summed cortical thickness and cortical index, that may better reflect bone mass, a more plastic phenomenon, have slightly lower genetic influences, on average. Results from our phenotypic and genetic landscapes serve three key purposes: demonstration of the integrated nature of the genetic and environmental underpinnings of skeletal form; identification of periods of bone’s relative sensitivity to genetic and environmental influences; and stimulation of hypotheses predicting the effects of exposure to environmental variables on the skeleton, given variation in the underlying genetic architecture.

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Animal Models in Osteoporosis Research

Kimmel

2002

Principles of Bone Biology

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Genetic determinants of bone mass acquisition and risk for osteoporosis

Cited by 4 publications

References 93 publications

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

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

Skeletal growth and the changing genetic landscape during childhood and adulthood

Animal Models in Osteoporosis Research

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