Skip to main content
Top
Published in: Osteoporosis International 6/2006

01-06-2006 | Original Article

Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study

Authors: M. Lee, S. A. Czerwinski, A. C. Choh, E. W. Demerath, S. S. Sun, W. C. Chumlea, B. Towne, R. M. Siervogel

Published in: Osteoporosis International | Issue 6/2006

Login to get access

Abstract

Introduction

Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures.

Methods

Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure – broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI) – were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures.

Results

Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero.

Conclusion

This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.
Literature
1.
go back to reference National Osteoporosis Foundation (2002) America’s bone health: the state of osteoporosis and low bone mass in our nation. National Osteoporosis Foundation, Washington D.C. National Osteoporosis Foundation (2002) America’s bone health: the state of osteoporosis and low bone mass in our nation. National Osteoporosis Foundation, Washington D.C.
2.
go back to reference Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489PubMedCrossRef Looker AC, Wahner HW, Dunn WL, Calvo MS, Harris TB, Heyse SP, Johnston CC Jr, Lindsay R (1998) Updated data on proximal femur bone mineral levels of US adults. Osteoporos Int 8:468–489PubMedCrossRef
3.
go back to reference Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767PubMedCrossRef Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767PubMedCrossRef
4.
go back to reference Huang QY, Recker RR, Deng HW (2003) Searching for osteoporosis genes in the post-genome era: progress and challenges. Osteoporos Int 14:701–715PubMedCrossRef Huang QY, Recker RR, Deng HW (2003) Searching for osteoporosis genes in the post-genome era: progress and challenges. Osteoporos Int 14:701–715PubMedCrossRef
5.
go back to reference Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017–2022PubMed Gueguen R, Jouanny P, Guillemin F, Kuntz C, Pourel J, Siest G (1995) Segregation analysis and variance components analysis of bone mineral density in healthy families. J Bone Miner Res 10:2017–2022PubMed
6.
go back to reference Deng HW, Chen W-M, Conway T, Zhou Y, Davies KM, Stegman MR, Deng HW, Recker RR (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors. Genet Epidemiol 19:160–177PubMedCrossRef Deng HW, Chen W-M, Conway T, Zhou Y, Davies KM, Stegman MR, Deng HW, Recker RR (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors. Genet Epidemiol 19:160–177PubMedCrossRef
7.
go back to reference Mitchell BD, Kammerer CM, Schneider JL, Perez R, Bauer RL (2003) Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study. Bone 33:839–846PubMedCrossRef Mitchell BD, Kammerer CM, Schneider JL, Perez R, Bauer RL (2003) Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study. Bone 33:839–846PubMedCrossRef
8.
go back to reference Pocock NA, Eisman JA, Hopper JL, Yeaste MG, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults: a twin study. J Clin Invest 80:706–710PubMedCrossRef Pocock NA, Eisman JA, Hopper JL, Yeaste MG, Sambrook PN, Eberl S (1987) Genetic determinants of bone mass in adults: a twin study. J Clin Invest 80:706–710PubMedCrossRef
9.
go back to reference Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561–567PubMed Slemenda CW, Christian JC, Williams CJ, Norton JA, Johnston CC Jr (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561–567PubMed
10.
go back to reference Lee M, Czerwinski SA, Choh AC, Towne B, Demerath EW, Chumlea WC, Sun SS, Siervogel RM (2004) Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study. Bone 35:1157–1163PubMedCrossRef Lee M, Czerwinski SA, Choh AC, Towne B, Demerath EW, Chumlea WC, Sun SS, Siervogel RM (2004) Heritability of calcaneal quantitative ultrasound measures in healthy adults from the Fels Longitudinal Study. Bone 35:1157–1163PubMedCrossRef
11.
go back to reference Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 11:530–534PubMedCrossRef Arden NK, Baker J, Hogg C, Baan K, Spector TD (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 11:530–534PubMedCrossRef
12.
go back to reference Howard GM, Nguyen TV, Harris M, Kelly PJ, Eisman JA (1998) Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study. J Bone Miner Res 13:1318–1327PubMedCrossRef Howard GM, Nguyen TV, Harris M, Kelly PJ, Eisman JA (1998) Genetic and environmental contributions to the association between quantitative ultrasound and bone mineral density measurements: a twin study. J Bone Miner Res 13:1318–1327PubMedCrossRef
13.
go back to reference Sahota O, San P, Cawte SA, Pearson D, Hosking DJ (2000) A comparison of the longitudinal changes in quantitative ultrasound with dual-energy X-ray absorptiometry: the four-year effects of hormone replacement therapy. Osteoporos Int 11:52–58PubMedCrossRef Sahota O, San P, Cawte SA, Pearson D, Hosking DJ (2000) A comparison of the longitudinal changes in quantitative ultrasound with dual-energy X-ray absorptiometry: the four-year effects of hormone replacement therapy. Osteoporos Int 11:52–58PubMedCrossRef
14.
go back to reference Bauer DC, Gluer CC, Cauley JA, Vogt TM, Ensrud KE, Genant HK, Black DM (1997) Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 157:629–634PubMedCrossRef Bauer DC, Gluer CC, Cauley JA, Vogt TM, Ensrud KE, Genant HK, Black DM (1997) Broadband ultrasound attenuation predicts fractures strongly and independently of densitometry in older women. A prospective study. Study of Osteoporotic Fractures Research Group. Arch Intern Med 157:629–634PubMedCrossRef
15.
go back to reference Frost ML, Blake GM, Fogelman I (2002) A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip. Calcif Tissue Int 71:207–211PubMedCrossRef Frost ML, Blake GM, Fogelman I (2002) A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip. Calcif Tissue Int 71:207–211PubMedCrossRef
16.
go back to reference Khaw KT, Reeve J, Luben R, Bingham S, Welch A, Wareham N, Oakes S, Day N (2004) Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet 363:197–202PubMedCrossRef Khaw KT, Reeve J, Luben R, Bingham S, Welch A, Wareham N, Oakes S, Day N (2004) Prediction of total and hip fracture risk in men and women by quantitative ultrasound of the calcaneus: EPIC-Norfolk prospective population study. Lancet 363:197–202PubMedCrossRef
17.
go back to reference van den Bergh JP, van Lenthe GH, Hermus AR, Corstens FH, Smals AG, Huiskes R (2000) Speed of sound reflects Young’s modulus as assessed by microstructural finite element analysis. Bone 26:519–524PubMedCrossRef van den Bergh JP, van Lenthe GH, Hermus AR, Corstens FH, Smals AG, Huiskes R (2000) Speed of sound reflects Young’s modulus as assessed by microstructural finite element analysis. Bone 26:519–524PubMedCrossRef
18.
go back to reference Bouxsein ML, Radloff SE (1997) Quantitative ultrasound of the calcaneus reflects the mechanical properties of calcaneal trabecular bone. J Bone Miner Res 12:839–846PubMedCrossRef Bouxsein ML, Radloff SE (1997) Quantitative ultrasound of the calcaneus reflects the mechanical properties of calcaneal trabecular bone. J Bone Miner Res 12:839–846PubMedCrossRef
19.
go back to reference Hans D, Srivastav SK, Singal C, Barkmann R, Njeh CF, Kantorovich E, Gluer CC, Genant HK (1999) Does combining the results from multiple bone sites measured by a new quantitative ultrasound device improve discrimination of hip fracture? J Bone Miner Res 14:644–651PubMedCrossRef Hans D, Srivastav SK, Singal C, Barkmann R, Njeh CF, Kantorovich E, Gluer CC, Genant HK (1999) Does combining the results from multiple bone sites measured by a new quantitative ultrasound device improve discrimination of hip fracture? J Bone Miner Res 14:644–651PubMedCrossRef
20.
go back to reference Gluer CC, Hans D (1999) How to use ultrasound for risk assessment: a need for defining strategies. Osteoporos Int 9:193–195PubMedCrossRef Gluer CC, Hans D (1999) How to use ultrasound for risk assessment: a need for defining strategies. Osteoporos Int 9:193–195PubMedCrossRef
21.
go back to reference Knapp K, Andrew T, Macgregor A, Blake GM, Fogelman I, Spector T (2003) An investigation of unique and shared gene effects on speed of sound and bone density using axial transmission quantitative ultrasound and DXA in twins. J Bone Miner Res 18:1525–1530PubMedCrossRef Knapp K, Andrew T, Macgregor A, Blake GM, Fogelman I, Spector T (2003) An investigation of unique and shared gene effects on speed of sound and bone density using axial transmission quantitative ultrasound and DXA in twins. J Bone Miner Res 18:1525–1530PubMedCrossRef
22.
go back to reference Roche AF (1992) Growth, maturation, and body composition: the Fels Longitudinal Study, 1929–1991. Cambridge University Press, Cambridge; New York, NY Roche AF (1992) Growth, maturation, and body composition: the Fels Longitudinal Study, 1929–1991. Cambridge University Press, Cambridge; New York, NY
23.
go back to reference Lohman T, Martorell R, Roche AF (1988) Anthropometric standardization reference manual. Human Kinetics, Champaign, IL, U S A Lohman T, Martorell R, Roche AF (1988) Anthropometric standardization reference manual. Human Kinetics, Champaign, IL, U S A
24.
go back to reference Baecke JAH, Burema J, Frijters JER (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936–942PubMed Baecke JAH, Burema J, Frijters JER (1982) A short questionnaire for the measurement of habitual physical activity in epidemiological studies. Am J Clin Nutr 36:936–942PubMed
25.
go back to reference Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211PubMedCrossRef Almasy L, Blangero J (1998) Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Hum Genet 62:1198–1211PubMedCrossRef
26.
go back to reference Almasy L, Dyer TD, Blangero J (1997) Bivariate quantitative trait linkage analysis: Pleiotropy versus co-incident linkages. Genet Epidemiol 14:953–958PubMedCrossRef Almasy L, Dyer TD, Blangero J (1997) Bivariate quantitative trait linkage analysis: Pleiotropy versus co-incident linkages. Genet Epidemiol 14:953–958PubMedCrossRef
27.
go back to reference Brown LB, Streeten EA, Shuldiner AR, Almasy LA, Peyser PA, Mitchell BD (2004) Assessment of sex-specific genetic and environmental effects on bone mineral density. Genet Epidemiol 27:153–161PubMedCrossRef Brown LB, Streeten EA, Shuldiner AR, Almasy LA, Peyser PA, Mitchell BD (2004) Assessment of sex-specific genetic and environmental effects on bone mineral density. Genet Epidemiol 27:153–161PubMedCrossRef
28.
go back to reference Nguyen TV, Livshits G, Center JR, Yakovenko K, Eisman JA (2003) Genetic determination of bone mineral density: evidence for a major gene. J Clin Endocrinol Metab 88:3614–3620PubMedCrossRef Nguyen TV, Livshits G, Center JR, Yakovenko K, Eisman JA (2003) Genetic determination of bone mineral density: evidence for a major gene. J Clin Endocrinol Metab 88:3614–3620PubMedCrossRef
29.
go back to reference Karasik D, Cupples LA, Hannan MT, Kiel DP (2004) Genome screen for a combined bone phenotype using principal component analysis: the Framingham study. Bone 34:547–556PubMedCrossRef Karasik D, Cupples LA, Hannan MT, Kiel DP (2004) Genome screen for a combined bone phenotype using principal component analysis: the Framingham study. Bone 34:547–556PubMedCrossRef
30.
go back to reference Deng HW, Mahaney MC, Williams JT, Li J, Conway T, Davies KM, Li J-L, Deng HW, Recker RR (2002) Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases. Genet Epidemiol 22:12–25PubMedCrossRef Deng HW, Mahaney MC, Williams JT, Li J, Conway T, Davies KM, Li J-L, Deng HW, Recker RR (2002) Relevance of the genes for bone mass variation to susceptibility to osteoporotic fractures and its implications to gene search for complex human diseases. Genet Epidemiol 22:12–25PubMedCrossRef
31.
go back to reference Lenchik L, Hsu FC, Register TC, Lohman KK, Freedman BI, Langefeld CD, Bowden DW, Carr JJ (2004) Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Calcif Tissue Int 75:305–312PubMedCrossRef Lenchik L, Hsu FC, Register TC, Lohman KK, Freedman BI, Langefeld CD, Bowden DW, Carr JJ (2004) Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Calcif Tissue Int 75:305–312PubMedCrossRef
32.
go back to reference Slemenda CW, Turner CH, Peacock M, Christian JC, Sorbel J, Hui SL, Johnston CC (1996) The genetics of proximal femur geometry, distribution of bone mass and bone mineral density. Osteoporos Int 6:178–182PubMedCrossRef Slemenda CW, Turner CH, Peacock M, Christian JC, Sorbel J, Hui SL, Johnston CC (1996) The genetics of proximal femur geometry, distribution of bone mass and bone mineral density. Osteoporos Int 6:178–182PubMedCrossRef
33.
go back to reference Gluer CC, Vahlensieck M, Faulkner KG, Engelke K, Black D, Genant HK (1992) Site-matched calcaneal measurements of broad-band ultrasound attenuation and single X-ray absorptiometry: do they measure different skeletal properties? J Bone Miner Res 7:1071–1079PubMed Gluer CC, Vahlensieck M, Faulkner KG, Engelke K, Black D, Genant HK (1992) Site-matched calcaneal measurements of broad-band ultrasound attenuation and single X-ray absorptiometry: do they measure different skeletal properties? J Bone Miner Res 7:1071–1079PubMed
34.
go back to reference Wu C, Hans D, He Y, Fan B, Njeh CF, Augat P, Richards J, Genant HK (2000) Prediction of bone strength of distal forearm using radius bone mineral density and phalangeal speed of sound. Bone 26:529–533PubMedCrossRef Wu C, Hans D, He Y, Fan B, Njeh CF, Augat P, Richards J, Genant HK (2000) Prediction of bone strength of distal forearm using radius bone mineral density and phalangeal speed of sound. Bone 26:529–533PubMedCrossRef
35.
go back to reference Frost ML, Blake GM, Fogelman I (2001) Does the combination of quantitative ultrasound and dual-energy X-ray absorptiometry improve fracture discrimination? Osteoporos Int 12:471–477PubMedCrossRef Frost ML, Blake GM, Fogelman I (2001) Does the combination of quantitative ultrasound and dual-energy X-ray absorptiometry improve fracture discrimination? Osteoporos Int 12:471–477PubMedCrossRef
36.
go back to reference Langton CM, Langton DK (2000) Comparison of bone mineral density and quantitative ultrasound of the calcaneus: site-matched correlation and discrimination of axial BMD status. Br J Radiol 73:31–35PubMed Langton CM, Langton DK (2000) Comparison of bone mineral density and quantitative ultrasound of the calcaneus: site-matched correlation and discrimination of axial BMD status. Br J Radiol 73:31–35PubMed
37.
go back to reference Kang C, Speller R (1998) Comparison of ultrasound and dual energy X-ray absorptiometry measurements in the calcaneus. Br J Radiol 71:861–867PubMed Kang C, Speller R (1998) Comparison of ultrasound and dual energy X-ray absorptiometry measurements in the calcaneus. Br J Radiol 71:861–867PubMed
38.
go back to reference Gluer CC, Eastell R, Reid DM, Felsenberg D, Roux C, Barkmann R, Timm W, Blenk T, Armbrecht G, Stewart A, Clowes J, Thomasius FE, Kolta S (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 19:782–793PubMedCrossRef Gluer CC, Eastell R, Reid DM, Felsenberg D, Roux C, Barkmann R, Timm W, Blenk T, Armbrecht G, Stewart A, Clowes J, Thomasius FE, Kolta S (2004) Association of five quantitative ultrasound devices and bone densitometry with osteoporotic vertebral fractures in a population-based sample: the OPUS Study. J Bone Miner Res 19:782–793PubMedCrossRef
39.
go back to reference Hans D, Arlot ME, Schott AM, Roux JP, Kotzki PO, Meunier PJ (1995) Do ultrasound measurements on the os calcis reflect more the bone microarchitecture than the bone mass?: a two-dimensional histomorphometric study. Bone 16:295–300PubMedCrossRef Hans D, Arlot ME, Schott AM, Roux JP, Kotzki PO, Meunier PJ (1995) Do ultrasound measurements on the os calcis reflect more the bone microarchitecture than the bone mass?: a two-dimensional histomorphometric study. Bone 16:295–300PubMedCrossRef
40.
go back to reference Langton CM, Njeh CF, Hodgskinson R, Currey JD (1996) Prediction of mechanical properties of the human calcaneus by broadband ultrasonic attenuation. Bone 18:495–503PubMedCrossRef Langton CM, Njeh CF, Hodgskinson R, Currey JD (1996) Prediction of mechanical properties of the human calcaneus by broadband ultrasonic attenuation. Bone 18:495–503PubMedCrossRef
41.
go back to reference Sakata S, Barkmann R, Lochmuller EM, Heller M, Gluer CC (2004) Assessing bone status beyond BMD: evaluation of bone geometry and porosity by quantitative ultrasound of human finger phalanges. J Bone Miner Res 19:924–930PubMedCrossRef Sakata S, Barkmann R, Lochmuller EM, Heller M, Gluer CC (2004) Assessing bone status beyond BMD: evaluation of bone geometry and porosity by quantitative ultrasound of human finger phalanges. J Bone Miner Res 19:924–930PubMedCrossRef
42.
go back to reference Cortet B, Boutry N, Dubois P, Legroux-Gerot I, Cotten A, Marchandise X (2004) Does quantitative ultrasound of bone reflect more bone mineral density than bone microarchitecture? Calcif Tissue Int 74:60–67PubMedCrossRef Cortet B, Boutry N, Dubois P, Legroux-Gerot I, Cotten A, Marchandise X (2004) Does quantitative ultrasound of bone reflect more bone mineral density than bone microarchitecture? Calcif Tissue Int 74:60–67PubMedCrossRef
43.
go back to reference Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Sinauer, Sunderland, MA, U S A Lynch M, Walsh B (1998) Genetics and analysis of quantitative traits. Sinauer, Sunderland, MA, U S A
Metadata
Title
Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study
Authors
M. Lee
S. A. Czerwinski
A. C. Choh
E. W. Demerath
S. S. Sun
W. C. Chumlea
B. Towne
R. M. Siervogel
Publication date
01-06-2006
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 6/2006
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-006-0075-4

Other articles of this Issue 6/2006

Osteoporosis International 6/2006 Go to the issue