Advertisement

Dissecting the Architecture of Bone Strength-Related Phenotypes for Studying Osteoporosis

  • Xiaojing Wang
  • Candace M. Kammerer
Chapter

Abstract

This chapter provides a brief overview of methods being used to dissect the underlying architecture of bone strength-related phenotypes, especially with regard to identifying risk factors for osteoporosis, a complex, common disease. The first section comprises a brief background on the known genetic and environmental factors that influence development of osteoporosis. In the next section, we describe the concept of bone strength and how studies of its components may facilitate our understanding of the etiology of osteoporosis. The advantages and disadvantages of several state-of-art two and three dimensional imaging technologies used for assessment of components of bone strength in human populations are described in the third section. These methods include: dual x-ray absorptiometry (DXA), quantitative computed tomography (QCT), quantitative ultrasound (QUS), and magnetic resonance imagining (MRI). In the fourth section, results from the use of different methods of bone assessment on an Afro-Caribbean population are compared. Finally, we describe how these methods could potentially be extended to study other complex diseases.

Keywords

Obesity Europe Attenuation Estrogen Osteoporosis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

aBMD

Areal bone mineral density

BMI

Body mass index

CSA

Cross-sectional area

DXA

Dual x-ray absorptiometry

ENPP1

Ectonucleotide pyrophosphatase/phosphodiesterase 1

ESR1

Estrogen receptor-α

LRP5

Low density lipoprotein receptor-related protein 5

MRI

Magnetic resonance imagining

QCT

Quantitative computed tomography

QUS

Quantitative ultrasound

SSI

Strength strain index

SXA

Single X-ray absorptiometry

TFS

Tobago Family Study

TGFBR3

Transforming growth factor, beta receptor III

vBMD

Volumetric bone mineral density

WNT

Wingless-type

Notes

Acknowledgments

This work was supported, in part, by grants R03-AR050107 and R01-AR049747 from the National Institute of Arthritis and Musculoskeletal and Skin Diseases.

References

  1. Bates DW, Black DM, Cummings SR. Clinical use of bone densitometry: clinical applications. JAMA. 2002;288:1898–900.PubMedCrossRefGoogle Scholar
  2. Borah B, Gross GJ, Dufresne TE, Smith TS, Cockman MD, Chmielewski PA, Lundy MW, Hartke JR, Sod EW. Three-dimensional microimaging (MRmicroI and microCT), finite element modeling, and rapid prototyping provide unique insights into bone architecture in osteoporosis. Anat Rec. 2001;265:101–10.PubMedCrossRefGoogle Scholar
  3. Bouxsein ML. Bone quality: where do we go from here? Osteoporos Int. 2003;14(Suppl 5):S118–27.PubMedCrossRefGoogle Scholar
  4. Bouxsein ML. Technology insight: noninvasive assessment of bone strength in osteoporosis. Nat. Clin. Pract Rheumatol. 2008;4:310–8.PubMedCrossRefGoogle Scholar
  5. Bunker CH, Zmuda JM, Patrick AL, Wheeler VW, Weissfeld JL, Kuller LH, Cauley JA. High bone density is associated with prostate cancer in older Afro-Caribbean men: Tobago prostate survey. Cancer Causes Control. 2006;17:1083–9.PubMedCrossRefGoogle Scholar
  6. Chen Y, Shen H, Yang F, Liu PY, Tang N, Recker RR, Deng HW. Choice of study phenotype in osteoporosis genetic research. J Bone Miner Metab. 2009;27:121–6.PubMedCrossRefGoogle Scholar
  7. Felsenberg D, Boonen S. The bone quality framework: determinants of bone strength and their interrelationships, and implications for osteoporosis management. Clin Ther. 2005;27:1–11.PubMedCrossRefGoogle Scholar
  8. Genant HK, Lang TF, Engelke K, Fuerst T, Gluer C, Majumdar S, Jergas M. Advances in the noninvasive assessment of bone density, quality, and structure. Calcif Tissue Int. 1996;59(Suppl 1):S10–5.PubMedCrossRefGoogle Scholar
  9. Guglielmi G, Grimston SK, Fischer KC, Pacifici R. Osteoporosis: diagnosis with lateral and posteroanterior dual x-ray absorptiometry compared with quantitative CT. Radiology. 1994;192:845–50.PubMedGoogle Scholar
  10. Holroyd C, Cooper C, Dennison E. Best Practice & Research Clinical Endocrinology & Metabolism. Clin Endocrinol Metab. 2008;22:671–85.Google Scholar
  11. Hong J, Hipp JA, Mulkern RV, Jaramillo D, Snyder BD. Magnetic resonance imaging measurements of bone density and cross-sectional geometry. Calcif Tissue Int. 2000;66:74–8.PubMedCrossRefGoogle Scholar
  12. Irwin M, Alvarez-Reeves M, Cadmus L, Mierzejewski E, Mayne S, Yu H, Chung G, Jones B, Knobf M, Dipietro L. Exercise improves body fat, lean mass, and bone mass in breast cancer survivors. Obesity. 2009;17:1534–41.PubMedCrossRefGoogle Scholar
  13. Johnell O, Oden A, De Laet C, Garnero P, Delmas PD, Kanis JA. Biochemical indices of bone turnover and the assessment of fracture probability. Osteoporos Int. 2002;13:523–6.PubMedCrossRefGoogle Scholar
  14. Jouanny P, Guillemin F, Kuntz C, Jeandel C, Pourel J. Environmental and genetic factors affecting bone mass. Similarity of bone density among members of healthy families. Arthritis Rheum. 1995;38:61–7.PubMedCrossRefGoogle Scholar
  15. Karasik D, Cupples LA, Hannan MT, Kiel DP. Genome screen for a combined bone phenotype using principal component analysis: the Framingham study. Bone. 2004;34:547–56.PubMedCrossRefGoogle Scholar
  16. Kiel DP, Demissie S, Dupuis J, Lunetta KL, Murabito JM, Karasik D. Genome-wide association with bone mass and geometry in the Framingham Heart Study. BMC Med Genet. 2007;8(Suppl 1):S14.PubMedCrossRefGoogle Scholar
  17. McCreadie BR, Goldstein SA. Biomechanics of fracture: is bone mineral density sufficient to assess risk?. J Bone Miner Res 2000;15:2305–8.PubMedCrossRefGoogle Scholar
  18. Nguyen TV, Howard GM, Kelly PJ, Eisman JA. Bone mass, lean mass, and fat mass: same genes or same environments? Am J Epidemiol. 1998;147:3–16.PubMedCrossRefGoogle Scholar
  19. Ongphiphadhanakul B. Osteoporosis: the role of genetics and the environment. Forum Nutr. 2007;60:158–67.PubMedCrossRefGoogle Scholar
  20. Peacock M, Turner CH, Econs MJ, Foroud T. Genetics of osteoporosis. Endocr Rev. 2002;23:303–26.PubMedCrossRefGoogle Scholar
  21. Petit MA, Beck TJ, Kontulainen SA. Examining the developing bone: What do we measure and how do we do it? J Musculoskelet Neurol Interact. 2005;5:213–24.Google Scholar
  22. Prior SJ, Roth SM, Wang X, Kammerer C, Miljkovic-Gacic I, Bunker CH, Wheeler VW, Patrick AL, Zmuda JM. Genetic and environmental influences on skeletal muscle phenotypes as a function of age and sex in large, multigenerational families of African heritage. J Appl Physiol. 2007;103:1121–7.PubMedCrossRefGoogle Scholar
  23. Rizzoli R, Bonjour JP, Ferrari SL. Osteoporosis, genetics and hormones. J Mol Endocrinol. 2001;26:79–94.PubMedCrossRefGoogle Scholar
  24. Siu WS, Qin L, Leung KS. pQCT bone strength index may serve as a better predictor than bone mineral density for long bone breaking strength. J Bone Miner Metab. 2003;21:316–22.PubMedCrossRefGoogle Scholar
  25. Taes YE, Lapauw B, Vanbillemont G, Bogaert V, Bacquer DD, Zmierczak H, Goemaere S, Kaufman J-M. Fat Mass Is Negatively Associated with Cortical Bone Size in Young Healthy Male Siblings. J Clin Endocrinol Metab. 2009;94:2325–31.PubMedCrossRefGoogle Scholar
  26. Wang X, Kammerer CM, Wheeler VW, Patrick AL, Bunker CH, Zmuda JM. Genetic and environmental determinants of volumetric and areal BMD in multi-generational families of African ancestry: the Tobago Family Health Study. J Bone Miner Res. 2007a;22:527–36.PubMedCrossRefGoogle Scholar
  27. Wang X, Kammerer CM, Wheeler VW, Patrick AL, Bunker CH, Zmuda JM. Pleiotropy and heterogeneity in the expression of bone strength-related phenotypes in extended pedigrees. J Bone Miner Res. 2007b;22:1766–72.PubMedCrossRefGoogle Scholar
  28. Wang X, Kammerer CM, Anderson S, Lu A comparison of principal component analysis and factor analysis strategies for uncovering pleiotropic factors Genet. Genet Epidemiol 2009;33:325–31.PubMedCrossRefGoogle Scholar
  29. Xiong DH, Liu XG, Guo YF, Tan LJ, Wang L, Sha BY, Tang ZH, Pan F, Yang TL, Chen XD, Deng HW. Genome-wide association and follow-up replication studies identified ADAMTS18 and TGFBR3 as bone mass candidate genes in different ethnic groups. Am J Hum Genet. 2009;84:388–98.PubMedCrossRefGoogle Scholar
  30. Xu XH, Xiong DH, Liu XG, Guo Y, Chen Y, Zhao J, Recker RR, Deng HW. Association analyses of vitamin D-binding protein gene with compression strength index variation in Caucasian nuclear families. Osteoporos Int. 2010;21(1):99–107.PubMedCrossRefGoogle Scholar
  31. Zmuda JM, Yerges LM, Kammerer CM, Cauley JA, Wang X, Nestlerode CS, Wheeler VW, Patrick AL, Bunker CH, Moffett SP, Ferrell RE. Association analysis of WNT10B with bone mass and structure among individuals of African ancestry. J Bone Miner Res. 2009;24:437–47.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Center for Craniofacial and Dental Genetics, School of Dental MedicineUniversity of PittsburghPittsburghUSA

Personalised recommendations