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Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men

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Abstract

Summary

We investigated 383 bone candidate genes for associations between single nucleotide polymorphisms and vertebral trabecular volumetric bone mineral density (vBMD) and cross-sectional area (CSA) in 2,018 Caucasian men aged ≥65 years. SNPs in TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE were associated with vBMD and SNPs in CYP11B1, DVL2, DLX5, WNT4, and PAX7 were associated with CSA in independent study samples (p < 0.005).

Inroduction

Vertebral bone mineral density and cross-sectional area are important determinants of vertebral bone strength. Little is known about the specific genetic variants that influence these phenotypes in humans.

Methods

We investigated the potential genetic variants associated with vertebral trabecular volumetric BMD and CSA measured by quantitative computed tomography. We initially tested for association between these phenotypes and 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes in 862 community-dwelling Caucasian men aged ≥65 years in the Osteoporotic Fractures in Men Study.

Results

SNP associations were then validated by genotyping an additional 1,156 randomly sampled men from the same cohort. We identified 11 SNPs in 10 genes (TGFBR3, SOST, KL, CALCR, LEP, CSF1R, PTN, GNRH2, FGFR2, and MEPE) that were consistently associated with trabecular vBMD and five SNPs in five genes (CYP11B1, DVL2, DLX5, WNT4, and PAX7) that were consistently associated with CSA in both samples (p < 0.005).

Conclusion

None of the SNPs associated with trabecular vBMD were associated with CSA. Our findings raise the possibility that at least some of the loci for vertebral trabecular BMD and bone size may be distinct.

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References

  1. Khosla S, Amin S, Orwoll E (2008) Osteoporosis in men. Endocr Rev 29(4):441–464

    Article  PubMed  CAS  Google Scholar 

  2. Szulc P (2006) Bone density, geometry, and fracture in elderly men. Curr Osteoporos Rep 4(2):57–63

    Article  PubMed  Google Scholar 

  3. Yu W, Gluer CC, Grampp S, Jergas M, Fuerst T, Wu CY, Lu Y, Fan B, Genant HK (1995) Spinal bone mineral assessment in postmenopausal women: a comparison between dual X-ray absorptiometry and quantitative computed tomography. Osteoporos Int 5(6):433–439

    Article  PubMed  CAS  Google Scholar 

  4. Guglielmi G, Grimston SK, Fischer KC, Pacifici R (1994) Osteoporosis: diagnosis with lateral and posteroanterior dual X-ray absorptiometry compared with quantitative CT. Radiology 192(3):845–850

    PubMed  CAS  Google Scholar 

  5. Liu G, Peacock M, Eilam O, Dorulla G, Braunstein E, Johnston CC (1997) Effect of osteoarthritis in the lumbar spine and hip on bone mineral density and diagnosis in elderly men and women. Osteoporos Int 7:564–569

    Article  PubMed  CAS  Google Scholar 

  6. Reid IR, Evans MC, Ames R, Wattie DJ (1991) The influence of osteophytes and aortic calcification on spinal mineral density in postmenopausal women. J Clin Endocrinol Metab 72:1372–1374

    Article  PubMed  CAS  Google Scholar 

  7. Orwoll ES, Oviatt SK, Mann T (1990) The impact of osteophytic and vascular calcifications on vertebral mineral density measurements in men. J Clin Endocrinol Metab 70(4):1202–1207

    Article  PubMed  CAS  Google Scholar 

  8. Ito M, Hayashi K, Yamada M, Uetani M, Nakamura T (1993) Relationship of osteophytes to bone mineral density and spinal fracture in men. Radiology 189(2):497–502

    PubMed  CAS  Google Scholar 

  9. Wang X, Kammerer CM, Wheeler VW, Patrick AL, Bunker CH, Zmuda JM (2007) 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 22(4):527–536

    Article  PubMed  Google Scholar 

  10. Wang X, Kammerer CM, Wheeler VW, Patrick AL, Bunker CH, Zmuda JM (2007) Pleiotropy and heterogeneity in the expression of bone strength-related phenotypes in extended pedigrees. J Bone Miner Res 22(11):1766–1772

    Article  PubMed  Google Scholar 

  11. 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(4):305–312

    Article  PubMed  CAS  Google Scholar 

  12. Klein RF, Turner RJ, Skinner LD, Vartanian KA, Serang M, Carlos AS, Shea M, Belknap JK, Orwoll ES (2002) Mapping quantitative trait loci that influence fermoral cross-sectional area in mice. J Bone Miner Res 17:1752–1760

    Article  PubMed  CAS  Google Scholar 

  13. Bouxsein ML, Uchiyama T, Rosen CJ, Shultz KL, Donahue LR, Turner CH, Sen S, Churchill GA, Müller R, Beamer WG (2004) Mapping quantitative trait loci for vertebral trabecular bone volume fraction and microarchitecture in mice. J Bone Miner Res 19(4):587–599

    Article  PubMed  CAS  Google Scholar 

  14. Turner CH, Hsieh YF, Muller R, Bouxsein ML, Rosen CJ, McCrann ME, Donahue LR, Beamer WG (2001) Variation in bone biomechanical properties, microstructure, and density in BXH recombinant inbred mice. J Bone Miner Res 16(2):206–213

    Article  PubMed  CAS  Google Scholar 

  15. Beamer WG, Shultz KL, Donahue LR, Churchill GA, Sen S, Wergedal JR, Baylink DJ, Rosen CJ (2001) Quantitative trait loci for femoral and lumbar vertebral bone mineral density in C57BL/6J and C3H/HeJ inbred strains of mice. J Bone Miner Res 16(7):1195–1206

    Article  PubMed  CAS  Google Scholar 

  16. Sheng MH, Baylink DJ, Beamer WG, Donahue LR, Lau KH, Wergedal JE (2002) Regulation of bone volume is different in the metaphyses of the femur and vertebra of C3H/HeJ and C57BL/6J mice. Bone 30(3):486–491

    Article  PubMed  Google Scholar 

  17. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA, Belmont JW, Boudreau A, Hardenbol P, Leal SM, Pasternak S, Wheeler DA, Willis TD, Yu F, Yang H, Zeng C, Gao Y, Hu H, Hu W, Li C, Lin W, Liu S, Pan H, Tang X, Wang J, Wang W, Yu J, Zhang B, Zhang Q, Zhao H, Zhao H, Zhou J, Gabriel SB, Barry R, Blumenstiel B, Camargo A, Defelice M, Faggart M, Goyette M, Gupta S, Moore J, Nguyen H, Onofrio RC, Parkin M, Roy J, Stahl E, Winchester E, Ziaugra L, Altshuler D, Shen Y, Yao Z, Huang W, Chu X, He Y, Jin L, Liu Y, Shen Y, Sun W, Wang H, Wang Y, Wang Y, Xiong X, Xu L, Waye MM, Tsui SK, Xue H, Wong JT, Galver LM, Fan JB, Gunderson K, Murray SS, Oliphant AR, Chee MS, Montpetit A, Chagnon F, Ferretti V, Leboeuf M, Olivier JF, Phillips MS, Roumy S, Sallee C, Verner A, Hudson TJ, Kwok PY, Cai D, Koboldt DC, Miller RD, Pawlikowska L, Taillon-Miller P, Xiao M, Tsui LC, Mak W, Song YQ, Tam PK, Nakamura Y, Kawaguchi T, Kitamoto T, Morizono T, Nagashima A, Ohnishi Y et al (2007) A second generation human haplotype map of over 3.1 million SNPs. Nature 449(7164):851–861

    Article  PubMed  CAS  Google Scholar 

  18. Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML KS (2005) Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study—a large observational study of the determinants of fracture in older men. Contemp Clin Trials 25(5):569–585

    Article  Google Scholar 

  19. Blank JB, Cawthon PM, Carrion-Petersen ML, Harper L, Johnson JP, Mitson E, Delay RR (2005) Overview of recruitment for the osteoporotic fractures in men study (MrOS). Contemp Clin Trials 26(5):557–568

    Article  PubMed  Google Scholar 

  20. Marshall LM, Lang TF, Lambert LC, Zmuda JM, Ensrud KE, Orwoll ES (2006) Dimensions and volumetric BMD of the proximal femur and their relation to age among older U.S. men. J Bone Miner Res 21(8):1197–1206

    Article  PubMed  Google Scholar 

  21. Lang T, LeBlanc A, Evans H, Lu Y, Genant H, Yu A (2004) Cortical and trabecular bone mineral loss from the spine and hip in long-duration spaceflight. J Bone Miner Res 19(6):1006–1012

    Article  PubMed  Google Scholar 

  22. The International HapMap Project (2003) Nature 426(6968):789–796

    Article  Google Scholar 

  23. Roeder K, Bacanu SA, Sonpar V, Zhang X, Devlin B (2005) Analysis of single-locus tests to detect gene/disease associations. Genet Epidemiol 28(3):207–219

    Article  PubMed  Google Scholar 

  24. Cardon LR, Bell JI (2001) Association study designs for complex diseases. Nat Rev Genet 2(2):91–99

    Article  PubMed  CAS  Google Scholar 

  25. Falush D, Stephens M, Pritchard JK (2003) Inference of population structure using multilocus genotype data: linked loci and correlated allele frequencies. Genetics 164(4):1567–1587

    PubMed  CAS  Google Scholar 

  26. Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38(8):904–909

    Article  PubMed  CAS  Google Scholar 

  27. van Bezooijen RL, ten Dijke P, Papapoulos SE, Löwik CW (2005) SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev 16(3):319–327

    Article  PubMed  Google Scholar 

  28. ten Dijke P, Krause C, de Gorter DJ, Löwik CW, van Bezooijen RL (2008) Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am 90(Suppl 1):31–35

    Article  PubMed  Google Scholar 

  29. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D'Agostin D, Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S, Sarosi I, Kostenuik PJ, Lacey DL, Simonet WS, Ke HZ, Paszty C (2008) Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 23(6):860–869

    Article  PubMed  Google Scholar 

  30. Loots GG, Kneissel M, Keller H, Baptist M, Chang J, Collette NM, Ovcharenko D, Plajzer-Frick I, Rubin EM (2005) Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease. Genome Res 15(7):928–935

    Article  PubMed  CAS  Google Scholar 

  31. Balemans W, Cleiren E, Siebers U, Horst J, Van Hul W (2005) A generalized skeletal hyperostosis in two siblings caused by a novel mutation in the SOST gene. Bone 36(6):943–947

    Article  PubMed  CAS  Google Scholar 

  32. Uitterlinden AG, Arp PP, Paeper BW, Charmley P, Proll S, Rivadeneira F, Fang Y, Van Meurs JB, Britschgi TB, Latham JA, Schatzman RC, Pols HA, Brunkow ME (2004) Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am J Hum Genet 75(6):1032–1045

    Article  PubMed  CAS  Google Scholar 

  33. Styrkarsdottir U, Halldorsson BV, Gretarsdottir S, Gudbjartsson DF, Walters GB, Ingvarsson T, Jonsdottir T, Saemundsdottir J, Snorradóttir S, Center JR, Nguyen TV, Alexandersen P, Gulcher JR, Eisman JA, Christiansen C, Sigurdsson G, Kong A, Thorsteinsdottir U, Stefansson K (2009) New sequence variants associated with bone mineral density. Nat Genet 41(1):15–17

    Article  PubMed  CAS  Google Scholar 

  34. Richards JB, Rivadeneira F, Inouye M, Pastinen TM, Soranzo N, Wilson SG, Andrew T, Falchi M, Gwilliam R, Ahmadi KR, Valdes AM, Arp P, Whittaker P, Verlaan DJ, Jhamai M, Kumanduri V, Moorhouse M, van Meurs JB, Hofman A, Pols HA, Hart D, Zhai G, Kato BS, Mullin BH, Zhang F, Deloukas P, Uitterlinden AG, Spector TD (2008) Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371(9623):1505–1512

    Article  PubMed  CAS  Google Scholar 

  35. Masi L, Becherini L, Colli E, Gennari L, Mansani R, Falchetti A, Becorpi AM, Cepollaro C, Gonnelli S, Tanini A, Brandi ML (1998) Polymorphisms of the calcitonin receptor gene are associated with bone mineral density in postmenopausal Italian women. Biochem Biophys Res Commun 248(1):190–195

    Article  PubMed  CAS  Google Scholar 

  36. Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, de Vernejoul MC (1998) Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 7(13):2129–2133

    Article  PubMed  CAS  Google Scholar 

  37. Tsai FJ, Chen WC, Chen HY, Tsai CH (2003) The ALUI calcitonin receptor gene polymorphism (TT) is associated with low bone mineral density and susceptibility to osteoporosis in postmenopausal women. Gynecol Obstet Investig 55(2):82–87

    Article  CAS  Google Scholar 

  38. Zofková I, Zajícková K, Hill M, Krepelová A (2003) Does polymorphism C1377T of the calcitonin receptor gene determine bone mineral density in postmenopausal women? Exp Clin Endocrinol Diab 111(7):447–449

    Article  Google Scholar 

  39. Nakamura M, Morimoto S, Zhang Z, Utsunomiya H, Inagami T, Ogihara T, Kakudo K (2001) Calcitonin receptor gene polymorphism in japanese women: correlation with body mass and bone mineral density. Calcif Tissue Int 68(4):211–215

    Article  PubMed  CAS  Google Scholar 

  40. Kang BY, Kim JY, Lee KO (2007) Association between an AluI polymorphism in the calcitonin receptor gene and quantitative ultrasound parameters in Korean men. Med Princ Pract 16(5):389–393

    Article  PubMed  Google Scholar 

  41. Bandrés E, Pombo I, González-Huarriz M, Rebollo A, López G, García-Foncillas J (2005) Association between bone mineral density and polymorphisms of the VDR, ERalpha, COL1A1 and CTR genes in Spanish postmenopausal women. J Endocrinol Investig 28(4):312–321

    Google Scholar 

  42. Wolfe LA, Fling ME, Xue Z, Armour S, Kerner SA, Way J, Rimele T, Cox RF (2003) In vitro characterization of a human calcitonin receptor gene polymorphism. Mutat Res 522(1–2):93–105

    PubMed  CAS  Google Scholar 

  43. Kawaguchi H, Manabe N, Miyaura C, Chikuda H, Nakamura K, Kuro-o M (1999) Independent impairment of osteoblast and osteoclast differentiation in klotho mouse exhibiting low-turnover osteopenia. J Clin Invest 104(3):229–237

    Article  PubMed  CAS  Google Scholar 

  44. Zarrabeitia MT, Hernández JL, Valero C, Zarrabeitia AL, Ortiz F, Gonzalez-Macias J, Riancho JA (2007) Klotho gene polymorphism and male bone mass. Calcif Tissue Int 80(1):10–14

    Article  PubMed  CAS  Google Scholar 

  45. Riancho JA, Valero C, Hernández JL, Ortiz F, Zarrabeitia A, Alonso MA, Peña N, Pascual MA, González-Macías J, Zarrabeitia MT (2007) Association of the F352V variant of the Klotho gene with bone mineral density. Biogerontology 8(2):121–127

    Article  PubMed  CAS  Google Scholar 

  46. Yamada Y, Ando F, Niino N, Shimokata H (2005) Association of polymorphisms of the androgen receptor and klotho genes with bone mineral density in Japanese women. J Mol Med 83(1):50–57

    Article  PubMed  CAS  Google Scholar 

  47. Kawano K, Ogata N, Chiano M, Molloy H, Kleyn P, Spector TD, Uchida M, Hosoi T, Suzuki T, Orimo H, Inoue S, Nabeshima Y, Nakamura K, Kuro-o M, Kawaguchi H (2002) Klotho gene polymorphisms associated with bone density of aged postmenopausal women. J Bone Miner Res 17(10):1744–1751

    Article  PubMed  CAS  Google Scholar 

  48. Xiong DH, Liu XG, Guo YF, Tan LJ, Wang L, Sha BY, Tang ZH, Pan F, Yang TL, Chen XD, Lei SF, Yerges LM, Zhu XZ, Wheeler VW, Patrick AL, Bunker CH, Guo Y, Yan H, Pei YF, Zhang YP, Levy S, Papasian CJ, Xiao P, Lundberg YW, Recker RR, Liu YZ, Liu YJ, Zmuda JM, Deng HW (2009) 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 84:388–398

    Article  PubMed  CAS  Google Scholar 

  49. Richards JB, Kavvoura FK, Rivadeneira F, Styrkársdóttir U, Estrada K, Halldórsson BV, Hsu YH, Zillikens MC, Wilson SG, Mullin BH, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra BA, Pols HA, Sigurdsson G, Thorsteinsdottir U, Soranzo N, Williams FM, Zhou Y, Ralston SH, Thorleifsson G, van Duijn CM, Kiel DP, Stefansson K, Uitterlinden AG, Ioannidis JP, Spector TD (2009) Collaborative meta-analysis: associations of 150 candidate genes with osteoporosis and osteoporotic fracture. Ann Intern Med 151(8):528–537

    PubMed  Google Scholar 

  50. Rivadeneira F, Styrkársdottir U, Estrada K, Halldórsson BV, Hsu YH, Richards JB, Zillikens MC, Kavvoura FK, Amin N, Aulchenko YS, Cupples LA, Deloukas P, Demissie S, Grundberg E, Hofman A, Kong A, Karasik D, van Meurs JB, Oostra B, Pastinen T, Pols HA, Sigurdsson G, Soranzo N, Thorleifsson G, Thorsteinsdottir U, Williams FM, Wilson SG, Zhou Y, Ralston SH, van Duijn CM, Spector T, Kiel DP, Stefansson K, Ioannidis JP, Uitterlinden AG (2009) Twenty bone-mineral-density loci identified by large-scale meta-analysis of genome-wide association studies. Nat Genet 41:1199–1206

    Article  PubMed  CAS  Google Scholar 

  51. Harris SE, Gluhak-Heinrich J, Harris MA, Yang W, Bonewald LF, Riha D, Rowe PS, Robling AG, Turner CH, Feng JQ, McKee MD, Nicollela D (2007) DMP1 and MEPE expression are elevated in osteocytes after mechanical loading in vivo: theoretical role in controlling mineral quality in the perilacunar matrix. J Musculoskelet Neuronal Interact 7(4):313–315

    PubMed  CAS  Google Scholar 

  52. Lu C, Huang S, Miclau T, Helms JA, Colnot C (2004) Mepe is expressed during skeletal development and regeneration. Histochem Cell Biol 121(6):493–499

    Article  PubMed  CAS  Google Scholar 

  53. Nampei A, Hashimoto J, Hayashida K, Tsuboi H, Shi K, Tsuji I, Miyashita H, Yamada T, Matsukawa N, Matsumoto M, Morimoto S, Ogihara T, Ochi T, Yoshikawa H (2004) Matrix extracellular phosphoglycoprotein (MEPE) is highly expressed in osteocytes in human bone. J Bone Miner Metab 22(3):176–184

    Article  PubMed  CAS  Google Scholar 

  54. Petersen DN, Tkalcevic GT, Mansolf AL, Rivera-Gonzalez R, Brown TA (2000) Identification of osteoblast/osteocyte factor 45 (OF45), a bone-specific cDNA encoding an RGD-containing protein that is highly expressed in osteoblasts and osteocytes. J Biol Chem 275(46):36172–36180

    Article  PubMed  CAS  Google Scholar 

  55. Gowen LC, Petersen DN, Mansolf AL, Qi H, Stock JL, Tkalcevic GT, Simmons HA, Crawford DT, Chidsey-Frink KL, Ke HZ, McNeish JD, Brown TA (2003) Targeted disruption of the osteoblast/osteocyte factor 45 gene (OF45) results in increased bone formation and bone mass. J Biol Chem 278(3):1998–2007

    Article  PubMed  CAS  Google Scholar 

  56. Yang X, Tare RS, Partridge KA, Roach HI, Clarke NM, Howdle SM, Shakesheff KM, Oreffo RO (2003) Induction of human osteoprogenitor chemotaxis, proliferation, differentiation, and bone formation by osteoblast stimulating factor-1/pleiotrophin: osteoconductive biomimetic scaffolds for tissue engineering. J Bone Miner Res 18(1):47–57

    Article  PubMed  CAS  Google Scholar 

  57. Tare RS, Oreffo RO, Clarke NM, Roach HI (2002) Pleiotrophin/osteoblast-stimulating factor 1: dissecting its diverse functions in bone formation. J Bone Miner Res 17(11):2009–2020

    Article  PubMed  CAS  Google Scholar 

  58. Passos-Bueno MR, Serti Eacute AE, Jehee FS, Fanganiello R, Yeh E (2008) Genetics of craniosynostosis: genes, syndromes, mutations and genotype–phenotype correlations. Front Oral Biol 12:107–143

    Article  PubMed  Google Scholar 

  59. Marie PJ, Kaabeche K, Guenou H (2008) Roles of FGFR2 and twist in human craniosynostosis: insights from genetic mutations in cranial osteoblasts. Front Oral Biol 12:144–159

    Article  PubMed  Google Scholar 

  60. Cohen MM Jr (2006) Role of leptin in regulating appetite, neuroendocrine function, and bone remodeling. Am J Med Genet A 140(5):515–524

    PubMed  Google Scholar 

  61. Felix R, Hofstetter W, Cecchini MG (1996) Recent developments in the understanding of the pathophysiology of osteopetrosis. Eur J Endocrinol 134(2):143–156

    Article  PubMed  CAS  Google Scholar 

  62. Cheng CK, Leung PC (2005) Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr Rev 26(2):283–306

    Article  PubMed  CAS  Google Scholar 

  63. Ajlouni KM, Arnaout MA, Qoussous Y (1996) Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency with skeletal abnormalities. J Endocrinol Investig 19(5):316–319

    CAS  Google Scholar 

  64. Baron R, Rawadi G, Roman-Roman S (2006) Wnt signaling: a key regulator of bone mass. Curr Top Dev Biol 76:103–127

    Article  PubMed  CAS  Google Scholar 

  65. Robledo RF, Rajan L, Li X, Lufkin T (2002) The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development. Genes Dev 16(9):1089–1101

    Article  PubMed  CAS  Google Scholar 

  66. Buckingham M (2007) Skeletal muscle progenitor cells and the role of Pax genes. C R Biol 330(6–7):530–533

    Article  PubMed  CAS  Google Scholar 

  67. Weedon MN, Lango H, Lindgren CM, Wallace C, Evans DM, Mangino M, Freathy RM, Perry JR, Stevens S, Hall AS, Samani NJ, Shields B, Prokopenko I, Farrall M, Dominiczak A, Initiative DG, Consortium WTCC, Johnson T, Bergmann S, Beckmann JS, Vollenweider P, Waterworth DM, Mooser V, Palmer CN, Morris AD, Ouwehand WH, Consortium CG, Zhao JH, Li S, Loos RJ, Barroso I, Deloukas P, Sandhu MS, Wheeler E, Soranzo N, Inouye M, Wareham NJ, Caulfield M, Munroe PB, Hattersley AT, McCarthy MI, Frayling TM (2008) Genome-wide association analysis identifies 20 loci that influence adult height. Nat Genet 40(5):575–583

    Article  PubMed  CAS  Google Scholar 

  68. Li X, Masinde G, Gu W, Wergedal J, Mohan S, Baylink DJ (2002) Genetic dissection of femur breaking strength in a large population (MRL/MpJ x SJL/J) of F2 Mice: single QTL effects, epistasis, and pleiotropy. Genomics 79(5):734–740

    Article  PubMed  CAS  Google Scholar 

  69. Masinde GL, Wergedal J, Davidson H, Mohan S, Li R, Li X, Baylink DJ (2003) Quantitative trait loci for periosteal circumference (PC): identification of single loci and epistatic effects in F2 MRL/SJL mice. Bone 32(5):554–560

    Article  PubMed  CAS  Google Scholar 

  70. Karasik D, Ferrari SL (2008) Contribution of gender-specific genetic factors to osteoporosis risk. Ann Hum Genet 72(Pt 5):696–714

    Article  PubMed  CAS  Google Scholar 

  71. Glüer C, Genant H (1989) Impact of marrow fat on accuracy of quantitative CT. J Comput Assist Tomogr 13(6):1023–1035

    Article  PubMed  Google Scholar 

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Acknowledgments

Genotyping was supported by grant R01-AR051124 from The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). The Osteoporotic Fractures in Men (MrOS) Study is supported by National Institutes of Health funding. The following institutes provide support: the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), the National Institute on Aging (NIA), the National Center for Research Resources (NCRR), and NIH Roadmap for Medical Research under the following grant numbers: U01 AR45580, U01 AR45614, U01 AR45632, U01 AR45647, U01 AR45654, U01 AR45583, U01 AG18197, U01-AG027810, and UL1 RR024140. Laura Yerges was supported as a pre-doctoral fellow on National Institute on Aging T32-AG000181-16. This publication was also made possible by grant number UL1-RR024153 from the National Center for Research Resources (NCRR), a component of the NIH and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

Conflicts of interest

None.

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Authors and Affiliations

  1. Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA

    J. M. Zmuda, L. M. Yerges-Armstrong, S. P. Moffett, J. A. Cauley, A. Kuipers & C. S. Nestlerode

  2. Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA

    L. Klei

  3. Statistics, Carnegie Mellow University, Pittsburgh, PA, USA

    K. Roeder

  4. Genetics, University of Pittsburgh, Pittsburgh, PA, USA

    J. M. Zmuda, C. M. Kammerer & R. E. Ferrell

  5. Medicine, University of Minnesota, Minneapolis, MN, USA

    K. E. Ensrud

  6. Medicine, Oregon Health and Science University, Portland, OR, USA

    E. S. Orwoll

  7. Stanford University, Palo Alto, CA, USA

    A. R. Hoffman

  8. University of Alabama at Birmingham, Birmingham, AL, USA

    C. E. Lewis

  9. Radiology, University of California, San Francisco, CA, USA

    T. F. Lang

  10. Department of Family and Preventive Medicine, University of California San Diego, La Jolla, CA, USA

    E. Barrett-Connor

  11. Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, 130 DeSoto St, Pittsburgh, PA, 15261, USA

    J. M. Zmuda

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  1. J. M. Zmuda
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for the Osteoporotic Fractures in Men (MrOS) Study Group

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Correspondence to J. M. Zmuda.

Additional information

Laura M. Yerges-Armstrong and Susan P. Moffett contributed equally to this work.

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Zmuda, J.M., Yerges-Armstrong, L.M., Moffett, S.P. et al. Genetic analysis of vertebral trabecular bone density and cross-sectional area in older men. Osteoporos Int 22, 1079–1090 (2011). https://doi.org/10.1007/s00198-010-1296-0

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  • DOI: https://doi.org/10.1007/s00198-010-1296-0

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