Genetic Factors in Determining Bone Mass

Smith, David M.; Nance, Walter E.; Kang, Kae Won; Christian, Joe C.; Johnston, C. Conrad

doi:10.1172/jci107476

Cited by 524 publications

(214 citation statements)

References 12 publications

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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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show abstract

“…Evidence from twin and family studies suggests that between 50% and 85% of the variance in peak bone mass is genetically determined, depending on skeletal site and the age of the subjects studied (Smith et al 1973;Pocock et al 1987;Krall and Dawson-Hughes 1993;Gueguen et al 1995). Heritability studies have also shown evidence of significant genetic effects on other key determinants of osteoporotic fracture risk, including quantitative ultrasound properties of bone (Arden et al 1996), femoral neck geometry (Arden et al 1996), muscle strength (Arden and Spector 1997), bone turnover markers (Hunter et al 2001), and body mass index (Kaprio et al 1995).…”

Section: Genetic Influences On Osteoporosismentioning

confidence: 99%

Genetic regulation of bone mass and susceptibility to osteoporosis

Ralston¹,

Crombrugghe²

2006

Genes Dev.

291

229

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Osteoporosis is a common disease with a strong genetic component characterized by reduced bone mass and increased risk of fragility fractures. Twin and family studies have shown that the heritability of bone mineral density (BMD) and other determinants of fracture risksuch as ultrasound properties of bone, skeletal geometry, and bone turnover-is high, although heritability of fracture is modest. Many different genetic variants of modest effect size are likely to contribute to the regulation of these phenotypes by interacting with environmental factors such as diet and exercise. Linkage studies in rare Mendelian bone diseases have identified several previously unknown genes that play key roles in regulating bone mass and bone turnover. In many instances, subtle polymorphisms in these genes have also been found to regulate BMD in the general population. Although there has been extensive progress in identifying the genetic variants that regulate susceptibility to osteoporosis, most of the genes and genetic variants that regulate bone mass and susceptibility to osteoporosis remain to be discovered.Osteoporosis is characterized by reduced bone mass, alterations in the microarchitecture of bone tissue, reduced bone strength, and an increased risk of fracture (Kanis et al. 1994). Osteoporosis is a common condition that affects up to 30% of women and 12% of men at some point in life. The prevalence of osteoporosis increases with age due to an imbalance in the rate at which bone is removed and replaced during the bone remodeling cycle, which is an important physiological process that is essential for maintenance of a healthy skeleton. Many factors influence the risk of osteoporosis-including diet, physical activity, medication use, and coexisting diseases-but one of the most important clinical risk factors is a positive family history, emphasizing the importance of genetics in the pathogenesis of osteoporosis. In this article, we first review the evidence for a genetic contribution to osteoporosis and related phenotypes, and discuss the mechanisms by which mutations and polymorphisms in genes that regulate susceptibility to osteoporosis affect major signaling pathways in bone. Genetic influences on osteoporosisGenetic factors have long been recognized as playing an important role in the pathogenesis of osteoporosis. Evidence from twin and family studies suggests that between 50% and 85% of the variance in peak bone mass is genetically determined, depending on skeletal site and the age of the subjects studied (Smith et al. 1973;Pocock et al. 1987;Krall and Dawson-Hughes 1993;Gueguen et al. 1995). Heritability studies have also shown evidence of significant genetic effects on other key determinants of osteoporotic fracture risk, including quantitative ultrasound properties of bone (Arden et al. 1996), femoral neck geometry (Arden et al. 1996), muscle strength (Arden and Spector 1997), bone turnover markers (Hunter et al. 2001), and body mass index (Kaprio et al. 1995). The role of genetic factors in the pathogenesis of bon...

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“…As displayed in figures of postflight BMD changes, some crew members recover within the first year after return while others do not recover until much later. Factors that contribute to this variability in recovery are likely to include nutrition [15,16], skeletal muscle reconditioning [17], and genetics [18,19]; some of these factors may delay the ability and motivation of crew members to become ambulatory and thus mechanically load their skeletons. It is interesting to note that two of the three outliers for BMD loss in the proximal femur (greater than a 15% deficit in femoral neck and trochanter) were older than the average age of, or in space longer than the average duration for, long-duration crew members; the missions corresponding to these outliers also represented their first long-duration flight.…”

Section: Introductionmentioning

confidence: 99%

Recovery of spaceflight-induced bone loss: Bone mineral density after long-duration missions as fitted with an exponential function

Sibonga

Evans

Sung

et al. 2007

Bone

191

106

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The loss of bone mineral in NASA astronauts during spaceflight has been investigated throughout the more than 40 years of space travel. Consequently, it is a medical requirement at NASA Johnson Space Center (JSC) that changes in bone mass be monitored in crew members by measuring bone mineral density (BMD) with dual-energy x-ray absorptiometry (DXA) before and after flight on astronauts who serve on long-duration missions (4-6 months). We evaluated this repository of medical data to track whether there is recovery of bone mineral that was lost during spaceflight.Our analysis was supplemented by BMD data from cosmonauts (by convention, a space traveler formally employed by the Russia Aviation and Space Agency or by the previous Soviet Union) who had also flown on long-duration missions. Data from a total of 45 individual crew members -a small number of whom flew on more than one mission -were used in this analysis.Changes in BMD (between 56 different sets of pre-and postflight measurements) were plotted as a function of time (days after landing). Plotted BMD changes were fitted to an exponential mathematical function that estimated: i) BMD change on landing day (day 0) and ii) the number of days after landing when 50% of the lost bone would be recovered ("50% recovery time") in the lumbar spine, trochanter, pelvis, femoral neck and calcaneus. In sum, averaged losses of bone mineral after long-duration spaceflight ranged between 2-9% across all sites with our recovery model predicting a 50% restoration of bone loss for all sites to be within 9 months.Recovery of spaceflight-induced bone loss 3

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Genetic Factors in Determining Bone Mass

Cited by 524 publications

References 12 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

Genetic regulation of bone mass and susceptibility to osteoporosis

Recovery of spaceflight-induced bone loss: Bone mineral density after long-duration missions as fitted with an exponential function

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