Genetics of osteoporosis

Aging Health

Volumn 4, Issue 4, 2008, Pages 365-376

  Riancho, José A ^a   Zarrabeitia, María T ^a   Macías, Jesús González ^a  

^a UNIVERSITY OF CANTABRIA   (Spain)

Author keywords

Aromatase; Bone mineral density; Collagen; Estrogen; Fractures; LRP5; MTHFR; Osteoporosis; Wnt

Indexed keywords

5,10 METHYLENETETRAHYDROFOLATE REDUCTASE (FADH2); ALCOHOL; ANDROGEN RECEPTOR; AROMATASE; ASCORBIC ACID; CALCITONIN; COLLAGEN; COLLAGEN TYPE 1; CORTICOSTEROID; CYANOCOBALAMIN; ESTROGEN; ESTROGEN RECEPTOR; ESTROGEN RECEPTOR ALPHA; ESTROGEN RECEPTOR BETA; HEPARIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; PARATHYROID HORMONE; PYRIDOXINE; RIBOFLAVIN; STEROID 17ALPHA MONOOXYGENASE; SULFOTRANSFERASE; VITAMIN D RECEPTOR; VITAMIN K GROUP; WNT PROTEIN;

BONE DISEASE; BONE MASS; BONE REMODELING; BONE STRENGTH; BONE STRUCTURE; CLINICAL GENETICS; ESTROGEN ACTIVITY; ESTROGEN METABOLISM; FEMALE; FRACTURE; GENE MUTATION; GENOME ANALYSIS; HEREDITY; HERITABILITY; HUMAN; LIFESTYLE; MALE; NUTRITIONAL STATUS; OSTEOPOROSIS; PHYSICAL ACTIVITY; POSTMENOPAUSE OSTEOPOROSIS; REVIEW; SINGLE NUCLEOTIDE POLYMORPHISM;

EID: 50649096333     PISSN: 1745509X     EISSN: 17455103     Source Type: Journal    
DOI: 10.2217/1745509X.4.4.365     Document Type: Review

References (126)

1. Melton LJ: How many women have osteoporosis now? J. Bone Miner. Res. 10, 175-177 (1995).
2. Bonewald LF, Johnson ML: Osteocytes, mechanosensing and Wnt signaling. Bone 42, 606-615 (2008).
3. van Oers RF, Ruimerman R, Tanck E, Hilbers PA, Huiskes R: A unified theory for osteonal and hemi-osteonal remodeling. Bone 42, 250-259 (2008).
4. Hofbauer LC, Heufelder AE: Role of receptor activator of nuclear factor-κB ligand and osteoprotegerin in bone cell biology. J. Mol. Med. 79, 243-253 (2001).
5. Riancho JA, Mundy GR: The role of cytokines and growth factors as mediators of the effects of systemic hormones at the bone local level. Crit. Rev. Eukaryot Gene Expr. 5, 193-217 (1995).
6. Zaidi M: Skeletal remodeling in health and disease. Nat. Med. 13, 791-801 (2007).
7. Baron R, Rawadi G: Wnt signaling and the regulation of bone mass. Curr. Osteoporos. Rep. 5, 73-80 (2007).
8. Johnson ML, Kamel MA: The Wnt signaling pathway and bone metabolism. Curr. Opin. Rheumatol 19, 376-382 (2007).
9. Riggs BL, Melton LJ, Robb RA et al.: A population-based assessment of rates of bone loss at multiple skeletal sites: evidence for substantial trabecular bone loss in young adult women and men. J. Bone Miner. Res. 23, 205-214 (2008).
10. Ralston SH: Genetic control of susceptibility to osteoporosis. J. Clin. Endocrinol Metab. 87, 2460-2466 (2002).
11. Peacock M, Turner CH, Econs MJ, Foroud T: Genetics of osteoporosis. Endocr. Rev. 23, 303-326 (2002).
12. Nguyen TV, Howard GM, Kelly PJ, Eisman JA: Bone mass, lean mass, and fat mass: same genes or same environments? Am. J. Epidemiol. 147, 3-16 (1998).
13. Wang X, Kammerer CM, Wheeler VW, Patrick AL, Bunker CH, Zmuda JM: Genetic and environmental determinants of volumetric and areal BMD in multigenerational families of African ancestry: the Tobago Family Health Study. J. Bone Miner. Res. 22, 527-536 (2007).
14. Duncan EL, Cardon LR, Sinsheimer JS, Wass JA, Brown MA: Site and gender specificity of inheritance of bone mineral density. J. Bone Miner. Res. 18, 1531-1538 (2003).
15. Lenchik L, Hsu FC, Register TC et al.: Heritability of spinal trabecular volumetric bone mineral density measured by QCT in the Diabetes Heart Study. Calcif. Tissue Int. 75, 305-312 (2004).
16. Brown LB, Streeten EA, Shapiro JR et al.: Genetic and environmental influences on bone mineral density in pre- and post-menopausal women. Osteoporos. Int. 16, 1849-1856 (2005).
17. Makovey J, Nguyen TV, Naganathan V, Wark JD, Sambrook PN: Genetic effects on bone loss in peri- and postmenopausal women: a longitudinal twin study. J. Bone Miner. Res. 22, 1773-1780 (2007).
18. Havill LM, Mahaney MC, Binkley L, Specker BL: Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD. J. Bone Miner. Res. 22, 737-746 (2007).
19. Chen Y, Gou YF, Lei SF, Wang YB,Deng HW: Genetic and environmental correlations between bone mineral density and bone size in Caucasians. Hum. Biol. 79, 15-24 (2007).
20. Cummings SR, Nevitt MC, Browner WS et al.: Risk factors for hip fracture in white women. N. Engl. J. Med. 332, 767-773 (1995).
21. Kanis JA, Johansson H, Oden A et al.: A Family history of fracture and fracture risk: a meta-analysis. Bone 35, 1029-1037 (2004).
22. Ralston SH, de Crombrugghe B: Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev. 20, 2492-2506 (2006).
23. Michaelsson K, Melhus H, Ferm H, Ahlbom A, Pedersen NL: Genetic liability to fractures in the elderly. Arch. Intern. Med. 165, 1825-1830 (2005).
24. Liu YZ, Liu YJ, Recker RR, Deng HW: Molecular studies of identification of genes for osteoporosis: the 2002 update. J. Endocrinol. 177, 147-196 (2003).
25. Ioannidis JP, Ng My, Sham PC et al.: Meta-analysis of genome-wide scans provides evidence for sex- and site-specific regulation of bone mass. J. Bone Miner. Res. 22, 173-183 (2007).
26. Liu YJ, Shen H, Xiao P et al.: Molecular genetic studies of gene identification for osteoporosis: a 2004 update. J. Bone Miner. Res. 21, 1511-1535 (2006).
27. Morrison NA, Qi JC, Tokita A et al.: Prediction of bone density from vitamin D receptor alleles. Nature 367, 284-287 (1994).
28. Fang Y, Rivadeneira F, van Meurs JB, Pols HA, Ioannidis JP, Uitterlinden AG: Vitamin D receptor gene BsmI and TaqI polymorphisms and fracture risk: a meta-analysis. Bone 39, 938-945 (2006).
29. Fang Y, van Meurs JB, Bergink AP et al.: Cdx-2 polymorphism in the promoter region of the human vitamin D receptor gene determines susceptibility to fracture in the elderly. J. Bone Miner. Res. 18(9), 1632-1641 (2003).
30. Uitterlinden AG, Fang Y, van Meurs JB, Pols HA, van Leeuwen JP: Genetics and biology of vitamin D receptor polymorphisms. Gene 338(2), 143-156 (2004).
31. Uitterlinden AG, Ralston SH, Brandi ML et al.: The association between common vitamin D receptor gene variations and osteoporosis: a participant-level meta-analysis. Ann. Int. Med. 145, 255-264 (2006).
32. Herynk MH, Fuqua SAW, Estrogen receptor mutations in human disease. Endocr. Rev. 25, 869-898 (2004).
33. Turner RT, Riggs BL, Spelsberg TC: Skeletal effects of estrogen. Endocr. Rev. 15, 275-300 (1994).
34. Khosla S, Melton LJ, Riggs BL: Estrogen and the male skeleton. J. Clin. Endocrinol. Metab. 87, 1443-1450 (2002).
35. Riggs BL, Khosla S, Melton III LJ: Sex steroids and the construction and conservation of adult skeleton. Endocr. Rev. 23, 279-302 (2002).
36. Syed FS, Khosla S: Mechanisms of sex steroid effects on bone. Biochem. Biophys. Res. Commun. 328, 688-696 (2005).
37. Deroo BJ, Korach KS: Estrogen receptors and human disease. J. Clin. Invest. 116, 561-570 (2006).
38. Cranney A, Guyatt G, Griffith L, Wells G, Tugwell P, Rosen C: Summary of meta-analyses of therapies for postmenopausal osteoporosis. Endocr. Rev. 23, 570-578 (2002).
39. Torgerson DJ, Bell-Syer SEM: Hormone replacement therapy and prevention of nonvertebral fractures. A meta-analysis of randomized trials. JAMA 285, 2891-2897 (2001).
40. Gennari L, Merlotti D, Martini G et al.: Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J. Clin. Endocrinol. Metab. 88, 5327-5333 (2003).
41. Khosla S, Melton LJ, III, Atkinson EJ, O'Fallon WM, Klee GG, Riggs BL: Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J. Clin. Endocrinol. Metab. 83, 2266-2274 (1998).
42. Kobayashi S, Inoue S, Hosoi T, Ouchi Y, Shiraki M, Orimo H: Association of bone mineral density with polymorphisin of the estrogen receptor gene. J. Bone Miner. Res. 11, 306-311 (1996).
43. Ioannidis JPA, Ralston SH, Bennett ST et al.: Differential genetics effects of ESR1 gene polymorphisms on osteoporosis outcomes. JAMA 292, 2105-2114 (2004).
44. Ioarmidis JPA, Stavrou I, Trikalinos TA et al.: Association of polymorphisms of the estrogen receptor α gene with bone mineral density and fracture risk in women: a meta-analysis. J. Bone Miner. Res. 17, 2048-2060 (2002).
45. Sano M, Inoue S, Hosoi T et al.: Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis. Biochem. Biophys. Res. Commun. 217, 378-383 (1995).
46. Langdahl BL, Lokke E, Carstens M, Stenkjaer LL, Eriksen EF: A TA repeat polymorphism in the estrogen receptor gene is associated with osteoporotic fractures but polymorphisms in the first intron are not. J. Bone Miner. Res. 15, 2222-2230 (2000).
47. Riancho JA, Zarrabeitia MT, Valero C, Sanudo C, Mijares V, Gonzalez-Macias J: A gene-to-gene interaction between aromatase and estrogen receptors influences bone mineral density. Eur. J. Endocrinol. 155, 53-59 (2006).
48. Gennari L, Merlotti D, De Paola V et al.: Estrogen receptor gene polymorphisms and the genetics of osteoporosis: a HuGE review. Am. J. Epidemiol. 161, 307-320 (2005).
49. Van Meurs JBJ, Schuit SCE, Weel AEAM et al.: Association of 5′ estrogen receptor α gene polymorphisms with bone mineral density, vertebral bone area and fracture risk. Human Molecular Genetics 12, 1745-1754 (2003).
50. Scariano JK, Simplicio SG, Montoya GD, Garry PJ, Baumgartner RN: Estrogen receptor β dinucleotide (CA) repeat polymorphism is significantly associated with bone mineral density in postmenopausal women. Calcif. Tissue Int. 74, 501-508 (2004).
51. Lau HHL, Ho AYY, Luk KDK, Kung AWC: Estrogen receptor β gene polymorphisms are associated with higher bone mineral density in premenopausal, but not postmenopausal southern chinese women. Bone 31, 276-281 (2002).
52. Ichikawa S, Koller DL, Peacock M et al.: Polymorphisms in the estrogen receptor β (ESR2) gene are associated with bone mineral density in Caucasian men and women. J. Clin. Endocrinol. Metab. 90, 5921-5927 (2005).
53. Shearman AM, Karasik D, Gruenthal KM et al.: Estrogen receptor β polymorphisms are associated with bone mass in women and men: The Framingham study. J. Bone Miner. Res. 19, 773-781 (2004).
54. Greendale GA, Chu J, Ferrell R, Randolph JF, Jr., Johnston JM, Sowers MR: The association of bone mineral density with estrogen receptor gene polymorphisms. Am. J. Med. 119(9 Suppl. 1), S79-S86 (2006).
55. Rivadeneira F, van Meurs JB, Kant J et al.: Estrogen receptor β (ESR2) polymorphisms in interaction with estrogen receptor α (ESR1) and insulin-like growth factor I (IGF1) variants influence the risk of fracture in postmenopausal women. J. Bone Miner. Res. 21, 1443-1456 (2006).
56. Gruber CJ, Tschugguel W, Schneeberger C, Huber JC: Mechanisms of disease: production and actions of estrogens. N. Engl. J. Med. 346, 340-352 (2002).
57. McCloskey E: Effects of third-generation aromatase inhibitors on bone. Eur. J. Cancer 42, 1044-1051 (2006).
58. Lester J, Coleman R: Bone loss and the aromatase inhibitors. Br. J. Cancer 93(Suppl. 1), S16-S22 (2005).
59. Riancho JA: Polymorphisms in the CYP19 gene that influence bone mineral density. Pharmacogenomics 8, 339-352 (2007).
60. Zarrabeitia MT, Hernandez JL, Valero C et al.: A common polymorphism in the 5′-untranslated region of the aromatase gene influences bone mass and fracture risk. Eur. J. Endocrinol. 150, 699-704 (2004).
61. Riancho JA, Zarrabeitia MT, Valero C et al.: Aromatase gene and osteoporosis: relationship of ten polymorphic loci with bone mineral density. Bone 36, 917-925 (2005).
62. Enjuanes A, Garcia-Giralt N, Supervia A et al.: A new SNP in a negative regulatory region of the CYP19A1 gene is associated with lumbar spine BMD in postmenopausal women. Bone 38, 738-743 (2006).
63. Masi L, Becherini L, Gennari L et al.: Polymorphism of the aromatase gene in postmenopausal italian women: distribution and correlation with bone mass and fracture risk. J. Clin. Endocrinol, Metab. 86, 2263-2269 (2001).
64. Riancho JA, Valero C, Naranjo A, Morales DJ, Sanudo C, Zarrabeitia MT: Identification of an aromatase haplotype that is associated with gene expression and postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 92, 660-665 (2007).
65. Valero C, Perez-Castrillon JL, Zarrabeitia MT et al.: Association of aromatase and estrogen receptor gene polymorphisms with hip fractures. Osteoporos. Int. 19, 787-792 (2008).
66. Salmen T, Heikkinen AM, Mahonen A et al.: Relation of androgen receptor gene polymorphism to bone mineral density and fracture risk in early postmenopausal women during a 5-year randomized hormone replacement therapy trial. J. Bone Miner. Res. 18, 319-324 (2003).
67. Tofteng CL, Kindmark A, Brandstrom H et al.: Polymorphisms in the CYP19 and AR genes - relation to bone mass and longitudinal bone changes in postmenopausal women with or without hormone replacement therapy. The Danish Osteoporosis Prevention Study. Calcif. Tissue Int. 74, 25-34 (2004).
68. Moron FJ, Mendoza N, Vazquez F et al.: Multilocus analysis of estrogen-related genes in Spanish postmenopausal women suggests an interactive role of ESR1, ESR2 and NRIP1 genes in the pathogenesis of osteoporosis. Bone 39, 213-221 (2006).
69. Mendoza N, Moron FJ, Vazquez F et al.: Weighting the effect of CYP19A gene in bone mineral density of postmenopausal women. Bone 38, 951-953 (2006).
70. Valero C, Zarrabeitia MT, Hernandez JL, Zarrabeitia MT, González-Macías J, Riancho, JA: Bone mass in young adults: relationship with gender, weight, and genetic factors. J. Intern. Med. 258, 554-562 (2005).
71. Labrie F, Belanger A, Cusan L, Gómez JL, Candas B: Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J. Clin. Endocrinol. Metab. 82, 2396-2402 (1997).
72. Johnson ML, Harnish K, Nusse R, Van Hul W: LRP5 and Writ signaling: a union made for bone. J. Bone Miner. Res. 19, 1749-1757 (2004).
73. Gordon MD, Nusse R, Wnt signaling: multiple pathways, multiple receptors, and multiple transcription factors. J. Biol. Chem. 281, 22429-22433 (2006).
74. Li X, Zhang Y, Kang H et al.: Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J. Biol. Chem. 280, 19883-19887 (2005).
75. Adaimy L, Chouery E, Megarbane H et al.: Mutation in WNT10A is associated with an autosomal recessive ectodermal dysplasia: the odomo-onycho-dermal dysplasia. Am. J. Hum. Genet. 81, 821-828 (2007).
76. Balemans W, Van Hul W: The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes. Endocrinology 148(6), 2622-2629 (2007).
77. Balemans W, Van Hul W: Human genetics of SOST. J. Musculoskelet. Neuronal. Interact. 6, 355-356 (2006).
78. Grundberg E, Lau EM, Lorentzson M et al.: Large-scale association study between two coding LRP5 gene polymorphisms and bone phenotypes and fractures in men. Osteoporos. Int. 19, 829-837 (2008).
79. Kiel DP, Ferrari SL, Cupples LA et al.: Genetic variation at the low-density lipoprotein receptor-related protein 5 (LRP5) locus modulates Wnt signaling and the relationship of physical activity with bone mineral density in men. Bone 40, 587-596 (2007).
80. Urano T, Shiraki M, Ezura Y et al.: Association of a single-nucleotide polymorphism in low-density lipoprotein receptor-related protein 5 gene with bone mineral density. J. Bone Miner. Metab. 22, 341-345 (2004).
81. Xiong DH, Lei SF, Yang F et al.: Low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms are associated with bone mass in both Chinese and whites. J. Bone Miner. Res. 22, 385-393 (2007).
82. Ferrari S, Deutsch S, Choudhury U et al.: Polymorphisms in the low-density lipoprotein-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites. Am. J. Human Genet. 74, 866-875 (2004).
83. van Meurs JB, Trikalinos TA, Ralston SH et al.: Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis. JAMA 299, 1277-1290 (2008).
84. Giroux S, Elfassihi L, Cole DE, Rousseau F: Replication of associations between LRP5 and ESRRA variants and bone density in premenopausal women. Osteoporos. Int. (2008).
85. Giroux S, Elfassihi L, Cardinal G, Laflamme N, Rousseau F: LRP5 coding polymorphisms influence the variation of peak bone mass in a normal population of French-Canadian women. Bone 40, 1299-1307 (2007).
86. Saarinen A, Valimaki VV, Valimaki MJ et al.: The A1330V polymorphism of the low-density lipoprotein receptor-related protein 5 gene (LRP5) associates with low peak bone mass in young healthy men. Bone 40, 1006-1012 (2007).
87. Koay MA, Tobias JH, Leary SD, Steer CD, Vilarino-Guell C, Brown MA. The effect of LRP5 polymorphisms on bone mineral density is apparent in childhood. Calcif. Tissue Int. 81, 1-9 (2007).
88. Cheung CL, Huang QY, Chan V, Kung AW: Association of low-density lipoprotein receptor-related protein 5 (LRP5) promoter SNP with peak bone mineral density in Chinese women. Human Heredity 65, 232-239 (2008).
89. Koller DL, Ichikawa S, Johnson ML et al.: Contribution of the LRP5 gene to normal variation in peak BMD in women. J. Bone Miner. Res. 20, 75-80 (2005).
90. Balemans W, Foernzler D, Parsons C et al.: Lack of association between the SOST gene and bone mineral density in perimenopausal women: analysis of five polymorphisms. Bone 31, 515-519 (2002).
91. Uitterlinden AG, Arp PP, Paeper BW et al.: Polymorphisms in the sclerosteosis/van Buchem disease gene (SOST) region are associated with bone-mineral density in elderly whites. Am. J. Hum. Genet. 75, 1032-1045 (2004).
92. Fazzalari NL, Kuliwaba JS, Atkins GJ, Forwood MR, Findlay DM: The ratio of messenger RNA levels of receptor activator nuclear κB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J. Bone Miner. Res. 16, 1015-1027 (2001).
93. Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T: Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/ osteoprotegerin. Biochem. Biophys. Res. Commun. 247, 610-615 (1998).
94. Lei SF, Jiang H, Deng FY, Deng HW: Searching for genes underlying susceptibility to osteoporotic fracture: current progress and future prospect. Osteoporos. Int. 18, 1157-1175 (2007).
95. Arko B, Prezelj J, Komel R, Hudler P, Marc J: Sequence variations in the osteoprotegerin gene promoter in patients with postmenopausal osteoporosis. J. Clin. Endocrinol. Metab. 87, 4080-4084 (2002).
96. Browner WS, Lui LY, Cummings SR: Associations of serum osteoprotegerin levels with diabetes, stroke, bone density, fractures, and mortality in elderly women. J. Clin. Endocrinol. Metab. 86, 631-637 (2001).
97. Choi JY, Shin A, Park SK et al.: Genetic polymorphisms of OPG, RANK, and ESR1 and bone mineral density in Korean postmenopausal women. Calcif. Tissue Int. 77, 152-159 (2005).
98. Kim JG, Kim JH, Kim JY et al.: Association between osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK), and RANK ligand (RANKL) gene polymorphisms and circulating OPG, soluble RANKL levels, and bone mineral density in Korean postmenopausal women. Menopause 14 (5), 913-918 (2007).
99. Koh JM, Park BL, Kim DJ et al.: Identification of novel RANK polymorphisms and their putative association with low BMD among postmenopausal women. Osteoporos. Int. 18(3), 323-331 (2007).
100. Hsu YH, Niu T, Terwedow HA et al.: Variation in genes involved in the RANKL/RANK/OPG bone remodeling pathway are associated with bone mineral density at different skeletal sites in men. Hum. Genet. 118 (5), 568-577 (2006).
101. Grant SF, Reid DM, Blake G, Herd R, Fogelman I, Ralston SH: Reduced bone density and osteoporosis associated with a polymorphic Sp1 binding site in the collagen type I α1 gene. Nat. Genet. 14, 203-205 (1996).
102. Garcia-Giralt N, Enjuanes A, Bustamante M et al.: In vitro functional assay of alleles and haplotypes of two COL1A1-promoter SNPs. Bone 36, 902-908 (2005).
103. Mann V, Hobson EE, Li B et al.: A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J. Clin. Invest. 107, 899-907 (2001).
104. Mann V, Ralston SH: Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 32, 711-717 (2003).
105. Efstathiadou Z, Tsatsoulis A, Ioannidis JP: Association of collagen Iα 1 Sp1 polymorphism with the risk of prevalent fractures: a meta-analysis. J. Bone Miner. Res. 16, 1586-1592 (2001).
106. Ralston SH, Uitterlinden AG, Brandi ML et al.: Large-scale evidence for the effect of the COLIA1 Sp1 polymorphism on osteoporosis outcomes: the GENOMOS study. PLoS Med. 3, E90 (2006).
107. Nieves JW: Osteoporosis: the role of micronutrients. Am. J. Clin. Nutrit. 81, 1232S-1239S (2005).
108. Yazdanpanah N, Zillikens MC, Rivadeneira F et al.: Effect of dietary B vitamins on BMD and risk of fracture in elderly men and women: the Rotterdam study. Bone 41, 987-994 (2007).
109. Riancho JA, Valero C, Zarrabeitia MT: MTHFR polymorphism and bone mineral density: meta-analysis of published studies. Calcif. Tissue Int. 79, 289-293 (2006).
110. Abrahamsen B, Jorgensen HL, Nielsen TL et al.: MTHFR c.677C>T polymorphism as an independent predictor of peak bone mass in Danish men - results from the Odense Androgen Study. Bone 38, 215-219 (2006).
111. Li M, Lau EM, Woo J: Methylenetetrahydrofolate reductase polymorphism (MTHFR C677T) and bone mineral density in Chinese men and women. Bone 35, 1369-1374 (2004).
112. Miyao M, Morita H, Hosoi T et al.: Association of methylenetetrahydrofolate reductase (MTHFR) polymorphism with bone mineral density in postmenopausal Japanese women. Calcif. Tissue Int. 66, 190-194 (2000).
113. Bathum L, von Bornemann-Hjelmorbg J, Christiansen L, Madsen JS, Skytthe A, Christensen K: Evidence for an association of methylene tetrahydrofolate reductase polymorphism C677T and an increased rsik of fractures: results from a population-based Danish study. Osteoporos. Int. 15, 659-664 (2004).
114. Jorgensen HL, Madsen JS, Madsen B et al.: Association of a common allelic polymorphism (C677T) in the methylene tetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A case control study in danish postmenopausal women. Calcif. Tissue Int. 71, 386-392 (2002).
115. Valero C, Alonso MA, Zarrabeitia MT, Viadero C, Hernandez JL, Riancho JA: MTHFR C677T polymorphism and osteoporotic fractures. Horm. Metab. Res. 39, 543-547 (2007).
116. McLean RR, Karasik D, Selhub J et al.: Association of a common polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene with bone phenotypes depends on plasma folate status. J. Bone Miner. Res. 19, 410-418 (2004).
117. Yazdanpanah N, Uitterlinden AG, Zillikens MC et al.: Low dietary riboflavin but not folate predicts increased fracture risk in postmenopausal women homozygous for the MTHFR 677 T allele. J. Bone Miner. Res. 23, 86-94 (2008).
118. Abrahamsen B, Madsen JS, Tofteng CL et al.: Are effects of MTHFR (C677T) genotype on BMD confined to women with low folate and riboflavin intake? Analysis of food records from the Danish osteoporosis prevention study. Bone 36, 577-583 (2005).
119. Xiong DH, Zhao LJ, Xiao P et al.: Robust and comprehensive analysis of 20 osteoporosis candidate genes by very high-density single-nucleotide polymorphism screen among 405 white nuclear families identified significant association and gene-gene interaction. J. Bone Miner. Res. 21, 1678-1695 (2006).
120. Sims AM, Shephard N, Carter K et al.: Genetic analyses in a sample of individulas with high or low bone density demonstrates association with multiple Wnt pathway genes. J. Bone Miner. Res. 23, 459-506 (2008).
121. 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. 8(Suppl. 1), S14 (2007).
122. Birney E, Stamatoyannopoulos JA, Dutta A et al.: Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project. Nature 447, 799-816 (2007).
123. Richards JB, Rivadeneira F, Inouye M et al.: Bone mineral density, osteoporosis, and osteoporotic fractures: a genome-wide association study. Lancet 371, 1505-1512 (2008).
124. Styrkarsdottir U, Halldorsson BV, Gretarsdottir S et al.: Multiple genetic loci for bone mineral density and fractures. N. Engl. J. Med. 358, 2355-2365 (2008).
125. Chanock SJ, Manolio T, Boehnke M et al.: Replicating genotype-phenotype associations. Nature 447, 655-660 (2007).
126. Manolio TA, Rodriguez LL, Brooks L et al.: New models of collaboration in genome-wide association studies: the Genetic Association Information Network. Nat. Genet. 39, 1045-1051 (2007).