Hostname: page-component-76fb5796d-45l2p Total loading time: 0 Render date: 2024-04-25T17:06:18.679Z Has data issue: false hasContentIssue false

Impact of genetic variation on metabolic response of bone to diet

Published online by Cambridge University Press:  07 March 2007

Siobhán Cusack*
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland
Kevin D. Cashman*
Affiliation:
Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland Department of Medicine, University College, Cork, Republic of Ireland
*
*Corresponding author: Professor Kevin D. Cashman, fax +353 21 4270244, k.cashman@ucc.ie
*Corresponding author: Professor Kevin D. Cashman, fax +353 21 4270244, k.cashman@ucc.ie
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

There is compelling evidence to suggest that both the development of bone to peak bone mass at maturity and subsequent loss depend on the interaction between genetic, hormonal, environmental and nutritional factors. The major part (≤80%) of the age-specific variation in bone turnover and bone density is genetically determined. However, the notion of genetic determinant is of little value unless the specific genes that are involved can be identified. Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (α and β), apolipoprotein E, collagen type I α 1 and methylenetetrahydrofolate reductase, amongst many others. However, in general, findings from numerous studies of the association between such genes and various bone variables have been inconsistent. In addition to possible gene—gene interactions it is likely that there are interactions between these genes and certain environmental factors, especially nutrition, that may mediate expression of bone-related phenotypes. While these potential interactions add a level of complexity to our understanding of these apparent genetic effects on bone, identification of a role for genetic factors without knowledge of their interaction with nutrients can do little to advance prevention and treatment of osteoporosis. This information is especially important because, unlike genotype, diet and nutrition can be modified. The aim of the present review is to critically evaluate current knowledge relating to candidate genes for osteoporosis, with particular emphasis on their interaction with nutrients and dietary factors in determining bone health.

Type
Meeting Report
Copyright
Copyright © The Nutrition Society 2003

References

Abrahamsen, B, Madsen, JS, Tofteng, CL, Stilgren, L, Bladbjerg, EM, Kristensen, SR, Brixen, K & Mosekilde, L (2003) A common methylenetetrahydrofolate reductase (C677 T) polymorphism is associated with low bone mineral density and increased fracture incidence after menopause: longitudinal data from the Danish osteoporosis prevention study. Journal of Bone and Mineral Research 18, 723729.CrossRefGoogle Scholar
Ames, SK, Ellis, KJ, Gunn, SK, Copeland, KC & Abrams, SA (1999) Vitamin D receptor gene Fok I polymorphism predicts calcium absorption and bone mineral density in children. Journal of Bone and Mineral Research 14, 740746.CrossRefGoogle Scholar
Arai, H, Myamoto, K, Taketani, Y, Yamamoto, H, Iemori, Y, Morita, K, Tonai, T, Nishisho, T, Mori, S & Takeda, E (1997) A vitamin D receptor gene polymorphism in the translation initiation codon: effect on protein activity and relation to bone mineral density in Japanese women. Journal of Bone and Mineral Research 12, 915921.CrossRefGoogle ScholarPubMed
Arden, NK, Griffiths, GO, Hart, DJ, Doyle, DV & Spector, TD (1996) The association between osteoarthritis and osteoporotic fracture: the Chingford study. British Journal of Rheumatology 35, 12991304.CrossRefGoogle ScholarPubMed
Ban, Y, Tozaki, T, Taniyama, M, Tomita, M & Ban, Y (2001) Lack of association between estrogen receptor ER~ dinucleotide repeat polymorphism and autoimmune thyroid diseases in Japanese patients. BioMed Central Medical Genetics 2, 1.CrossRefGoogle ScholarPubMed
Barger-Lux, MJ, Heany, RP, Hayes, J, Deluca, HF, Johnson, ML & Gong, G (1995) Vitamin D receptor gene polymorphism, bone mass, body size, and vitamin D receptor density. Calcified Tissue International 60, 491495.Google Scholar
Berg, JP, Falch, JA & Haug, E (1996) Fracture rate, pre- and postmenopausal bone mass and early and late postmenopausal bone loss are not associated with vitamin D receptor genotype in a high-endemic area of osteoporosis. European Journal of Endocrinology 135, 96100.CrossRefGoogle ScholarPubMed
Booth, SL, Tucker, KL, Chen, H, Hannan, MT, Gagnon, DR, Cupples, LA, Wilson, PW, Ordovas, J, Schaefer, EJ, Dawsonhughes, B & Kiel, DP (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. American Journal of Clinical Nutrition 71, 12011208.CrossRefGoogle Scholar
Carling, T, Kindmark, A, Hellman, P, Lundgren, E, Ljunghall, S, Rastad, J, Akerstrom, G & Melhus, H (1995) Vitamin D receptor genotypes in primary hyperparathyroidism. Nature Medicine 1, 13091311.CrossRefGoogle ScholarPubMed
Carling, T, Ridefelt, P, Hellman, P, Rastad, J & Akerstrom, G (1997) Vitamin D receptor polymorphisms correlate to parathyroid cell function in primary hyperparathyroidism. Journal of Clinical Endocrinology and Metabolism 82, 17721775.Google ScholarPubMed
Cashman, KD (2002) Calcium intake, calcium bioavailability and bone health. British Journal of Nutrition 87, Suppl. 2, S169S177.CrossRefGoogle ScholarPubMed
Cassidy, A (1996) Physiological effects of phyto-oestrogens in relation to cancer and other human health risks. Proceedings of the Nutrition Society 55, 399417.CrossRefGoogle ScholarPubMed
Cauley, Ja, Zmuda, JM, Yaffe, K, Kuller, LH, Ferrell, RE, Wisniewski, SR & Cummings, SR (1999) Apolipoprotein E polymorphism: A new genetic marker of hip fracture risk – The study of osteoporotic Fractures. Journal Of Bone and Mineral Research 14, 11751181.Google ScholarPubMed
Cheng, WC & Tsai, KS (1999) The vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in premenopausal women in Taiwan. Osteoporosis International 9, 545549.Google Scholar
Choi, YM, Jun, JK, Choe, J, Hwang, D, Park, SH, Kang, D, Kim, JG, Moon, SY & Lee, JY (2000) Association of the vitamin D receptor start codon polymorphism (Fok I) with bone mineral density in post-menopausal Korean women. Journal of Human Genetics 45, 280283.CrossRefGoogle Scholar
Christian, JC, Yu, PL, Slemenda, CW & Johnston, CC (1989) Heritability of bone mass: a longitudinal study in aging male twins. American Journal of Human Genetics 44, 429433.Google ScholarPubMed
Cooper, GS & Umbach, DM (1996) Are vitamin D receptor polymorphisms associated with bone mineral density? A metaanalysis. Journal of Bone and Mineral Research 11, 18411849.CrossRefGoogle ScholarPubMed
Cotter, A & Cashman, KD (2003) Genistein, a soy-based dietary phytoestrogen, appears to prevent early postmenopausal bone loss as effectively as hormone replacement therapy. Nutrition Reviews (In the Press)CrossRefGoogle Scholar
Dalais, F, Rice, G & Wahlqvist, M (1998) Effects ofdietaryphytoestrogens in postmenopausal women. Climateric 1, 124129.CrossRefGoogle ScholarPubMed
Dawson-Hughes, B, Harris, SS & Finneran, S (1995) Calcium absorption on high and low calcium intakes in relation to vitamin D receptor genotype. Journal of Clinical Endocrinology and Metabolism 80, 36573661.Google ScholarPubMed
de Knijff, P, van den Maagdenberg, AM, Frants, RR & Havekes, LM (1994) Genetic heterogeneity of apolipoprotein E and its influence on plasma lipid and lipoprotein levels. Human Mutation 4, 178194.CrossRefGoogle ScholarPubMed
Deng, HW, Li, J, Li, JL, Johnson, M, Gong, G & Recker, RR (1999) Association of VDR and estrogen receptor genotypes with bone mass in postmenopausal Caucasian women: Different conclusions with different analyses and the implications. Osteoporosis International 9, 499507.CrossRefGoogle ScholarPubMed
Dick, IM, Devine, A, Marangou, A, Dhaliwal, SS, Laws, S, Martins, RN & Prince, RL (2002) Apolipoprotein E4 is associated with reduced calcaneal quantitative ultrasound measurements and bone mineral density in elderly women. Bone 31, 497502.CrossRefGoogle ScholarPubMed
Dohi, Y, Iki, M, Ohgushi, H, Gojo, S, Tabata, S, Kajita, E, Nishino, H & Yonemasu, K (1998) A novel polymorphism in the promoter region for the human osteocalcin gene: the possibility of a correlation with bone mineral density in postmenopausal Japanese women. Journal of Bone and Mineral Research 13, 16331639.CrossRefGoogle ScholarPubMed
Eccleshall, TR, Garnero, P, Gross, C, Delmas, PD & Feldman, D (1998) Lack of correlation between start codon polymorphism of the vitamin D receptor gene and bone mineral density in premenopausal French women: The OFELY Study. Journal of Bone and Mineral Research 13, 3135.CrossRefGoogle ScholarPubMed
Eisman, Ja (1995) Vitamin D receptor gene alleles and osteoporosis: an affirmative view. Journal of Bone and Mineral Research 10, 12891293.CrossRefGoogle ScholarPubMed
Eisman, Ja (1999) Genetics of osteoporosis. Endocrine Reviews 20, 788804.CrossRefGoogle ScholarPubMed
Eisman, Ja (2001) PharmacogeneticsofthevitaminDreceptorand osteoporosis. Drug Metabolism and Disposition 29, 505512.Google ScholarPubMed
Ensrud, Ke Stone, K, Cauley, JA, White, C, Zmuda, JM, Nguyen, TV, Eisman, Ja Cummings, SR (1999) (The Study Of Osteoporotic Fractures Research Group) Vitamin D receptor gene polymorphisms and the risk of fractures in older women. Journal of Bone and Mineral Research 14, 16371645.CrossRefGoogle Scholar
European Commission (1998) Report on Osteoporosis in the European Community: Action for Prevention Luxembourg Office for Official. Publications for the European CommissionGoogle Scholar
Ferrari, S, Rizzoli, R, Chevalley, T, Slosman, D, Eisman, JA, Bonjour, JP (1995) Vitamin D receptor gene polymorphisms and change in lumbar spine bone mineral density. Lancet 345, 423424.CrossRefGoogle ScholarPubMed
Ferrari, S, Rizzoli, R, Manen, D, Slosman, D & Bonjour, JP (1998) Vitamin D receptor gene start codon polymorphisms (Fok I) and bone mineral density: Interaction with age, dietary calcium, and 3-end region polymorphisms. Journal of Bone and Mineral Research 13, 925930.CrossRefGoogle Scholar
Feskanich, D, Hunter, DJ, Willett, WC, Hankinson, Se Hollis, BW, Hough, HL, Kelsey, KT, Colditz, GA, (1998) Vitamin D receptor genotype and the risk of bone fractures in women. Epidemiology 9, 535539.CrossRefGoogle ScholarPubMed
Francis, RM, Harrington, F, Turner, E, Papiha, SS & Datta, HK (1997) Vitamin D receptor gene polymorphism in men and its effect on bone density and calcium absorption. Clinical Endocrinology 46, 8386.CrossRefGoogle Scholar
Garnero, P, Borel, O Sornay-Rendu E Arlot Me Delmas, PD (1996) Vitamin D receptor gene polymorphisms are not related to bone turnover, rate of bone loss, and bone mass in postmenopausal women: The OFELY Study. Journal of Bone and Mineral Research 11, 827834.CrossRefGoogle Scholar
Genant, HK, Cann, CE, Ettinger, B & Gordan, GS (1982) Quantitative computed tomography of vertebral spongiosa: A sensitive method for detecting early bone loss after oophorectomy. Annals of Internal Medicine 97, 699705.CrossRefGoogle ScholarPubMed
Gennari, L, Becherini, L, Falchetti, A, Masi, L, Massart, F & Brandi, ML (2002) Genetics of osteoporosis: role of steroid hormone receptor gene polymorphisms. Journal of Steroid Biochemistry and Molecular Biology 81, 124.CrossRefGoogle ScholarPubMed
Gennari, L, Becherini, L, Mansani, R, Masi, L, Falchetti, A, Morelli, A, Colli, E, Gonnelli, S, Cepollaro, C & Brandi, ML (1999) Fok I polymorphism at translation initiation site of the vitamin D receptor gene predicts bone mineral density and vertebral fractures in post-menopausal Italian women. Journal of Bone and Mineral Research 14, 13791386.CrossRefGoogle Scholar
Gennari, L, Becherini, L, Masi, L, Mansani, R, Gonnelli, S, Cepollaro, C, Martini, S, Montagnani, A, Lentini, G, Becorpi, AM & Brandi, ML (1998) Vitamin D and estrogen receptor allelic variants in Italian postmenopausal women: Evidence of multiple gene contribution to bone mineral density. Journal of Clinical Endocrinology and Metabolism 83, 939944.CrossRefGoogle ScholarPubMed
Gong, G, Stern, HS, Cheng, SC, Fong, N, Mordeson, J, Deng, HW & Recker, RR (1999) The association of bone mineral density with vitamin D receptor gene polymorphisms. Osteoporosis International 9, 5564.CrossRefGoogle ScholarPubMed
Graafmans, WC, Lips, P, Ooms, ME, Van Leeuwen, JP, Pols, HA, Uitterlinden, AG (1997) The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype. Journal of Bone and Mineral Research 12, 203205.CrossRefGoogle ScholarPubMed
Grant, Sfa Reid, DM, Blake, G, Herd, R, Fogelman, I & Ralston, SH (1996) Reduced bone density and osteoporosis associated with a polymorphic Sp1 site in the collagen type I alpha I gene. Nature Genetics 14, 203205.CrossRefGoogle Scholar
Gross, C, Eccleshall, TR, Malloy, PJ, Villa, ML, Marcus, R & Feldman, D (1996) The presence of a polymorphism at the translation initiation site of the vitamin D receptor gene is associated with low bone mineral density in post-menopausal Mexican-American women. Journal of Bone and Mineral Research 11, 18501855.CrossRefGoogle Scholar
Gross, C, Krishnan, AV, Malloy, PJ, Eccleshall, TR, Zhao, XY & Feldman, D (1998a) The vitamin D receptor gene start codon polymorphism: a functional analysis of Fok1 variants. Journal of Bone and Mineral Research 13, 19.CrossRefGoogle Scholar
Gross, C, Musiol, IM, Eccleshall, TR, Malloy, PJ & Feldman, D (1998b) Vitamin D receptor gene polymorphisms: analysis of ligand binding and hormone responsiveness in cultured skin fibroblasts. Biochemical and Biophysical Research Communications 242, 467473.CrossRefGoogle ScholarPubMed
Gueguen, R, Jouanny, P, Guillemin, F, Knutz, C, Pourel, J & Siset, G (1995) Segregation analysis and variance components analysis on bone mineral density in healthy families. Journal of Bone and Mineral Research 10, 20172022.CrossRefGoogle Scholar
Han, OH, Moon, IG, Kang, YS, Chung, HY, Min, HK & Han, IK (1997) Non association of estrogen receptor genotypes with bone mineral density and estrogen responsiveness to hormone replacement therapy in Korean postmenopausal women. Journal of Clinical Endocrinology and Metabolism 82, 991995.CrossRefGoogle Scholar
Harris, SS, Eccleshall, R, Gross, C, Dawson-Hughes, B & Feldman, D (1997) The vitamin D receptor start codon polymorphism (Fok I) and bone mineral density in pre-menopausal American black and white women. Journal of Bone and Mineral Research 12, 10431048.CrossRefGoogle Scholar
Hassager, C, Jensen, SB & Christiansen, C (1994) Non-responders to hormone replacement therapy for the prevention of postmenopausal bone loss: Do they exist. Osteoporosis International 4, 3641.CrossRefGoogle ScholarPubMed
Hegle, Ra Breslow, JL (1987) Apolipoprotein genetic variation in the assessment of atherosclerosis susceptibility. Genetics Epidemiology 4, 163184.CrossRefGoogle Scholar
Heikkinen, AM, Kroger, H, Niskanen, L, Komulainen, MH, Tyynanen, M, Parviainen, MT, Tuppurainen, MT, Honkanen, R & Saarikoski, S (2000) Does apolipoprotein E genotype relate to BMD and bone markers in postmenopausal women. Maturitas 34, 3341.CrossRefGoogle ScholarPubMed
Hosoi, T, Miyao, M, Inoue, S, Hoshino, S, Shirake, M, Orimo, H & Ouchi, Y (1999) Association study of parathyroid hormone gene polymorphism and bone mineral density in Japanese postmenopausal women. Calcified Tissue International 99, 205208.CrossRefGoogle Scholar
Houston La Grant, SF, Reid, DM & Ralston, SH (1996) Vitamin D receptor polymorphism, bone mineral density, and osteoporotic vertebral fracture: studies in a UK population. Bone 18, 21302134.Google Scholar
Institute Medicine (1997) Dietary Reference Intakes: Calcium, Magnesium, Phosphorus, Vitamin D, and Fluoride. Washington, D.C.: Food and Nutrition Board, National Academy Press.Google Scholar
Institute Medicine (2001) Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium and Zinc. Washington, DC: National Academy Press.Google Scholar
Ioannidis, Jpa Stavrou, I, Trikalinos, TA, Zois, C, Brandi, ML, Gennari, L, Albagha, O, Ralston, SH & Tsatsoulis, A (2002) Association of polymorphisms of the estrogen receptor α gene with bone mineral density and fracture risk in women: a metaanalysis. Journal of Bone and Mineral Research 17, 20482060.CrossRefGoogle ScholarPubMed
Jorgensen, HL, Madsen, JS, Madsen, B, Saleh, MM, Abrahamsen, B, Fenger, M & Lauritzen, JB (2002) Association of a common allelic polymorphism (C677 T) in the methylenetetrahydrofolate reductase gene with a reduced risk of osteoporotic fractures. A case control study in Danish postmenopausal women. Calcified Tissue International 71, 386392.Google Scholar
Kiel, DP, Myers, RH Cupples La Kong, XF, Zhu, XH, Ordovas, J, Schaefer, EJ, Felson, DT, Rush, D, Wilson, PWF, Eisman, JA, Holick, MF (1997) The BsmI vitamin D receptor restriction fragment length polymorphism (bb) influences the effect of calcium intake on bone mineral density. Journal of Bone Mineral Research 12, 10491057.CrossRefGoogle ScholarPubMed
Kinyamu, HK, Gallagher, JC, Knezetic, JA, Deluca, HF, Prahl, JM & Lanspa, SJ (1997) Effect of vitamin D receptor genotypes on calcium abosorption, duodenal vitamin D receptor concentration and serum 1,25 dihydroxyvitamin D levels in normal women. Calcified Tissue International 60, 491495.CrossRefGoogle Scholar
Kobayashi, S, Inoue, S, Hosoi, T, Ouchi, Y, Shiraki, M & Orimo, H (1996) Association of bone mineral density with polymorphism of the estrogen receptor gene. Journal of Bone and Mineral Research 11, 306311.CrossRefGoogle ScholarPubMed
Korach, KS (1994) Insights from the study of animals lacking functional estrogen receptor. Science 266, 15241527.CrossRefGoogle Scholar
Krall, Ea Parry, P, Lichter, JB, Dawson-Hughes, B (1995) Vitamin D receptor alleles and rates of bone loss: influence of years since menopause and calcium intake. Journal of Bone Mineral Research 10, 978984.CrossRefGoogle ScholarPubMed
Kuiper, GG, Lemmen, JG, Carlsson, B, Corton, JC, Safe, SH, van der Saag, PT van der Burg, B, Gustafsson, JA, (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139, 42524263.CrossRefGoogle ScholarPubMed
Langdahl, BL, Carstens, M, Stenkjaer, L & Eriksen, EF (2003) Polymorphisms in the transforming growth factor beta 1 gene and osteoporosis. Bone 32, 297310.CrossRefGoogle ScholarPubMed
Langdahl, B, Lokke, E, Carstens, M, Stenkjaer, L & Eriksen, E (2000) A TA repeat polymorphism in the estrogen receptor gene is associated with osteophorotic fractures but polymorphisms in the first exon and intron are not. Journal of Bone and Mineral Research 15, 22222230.CrossRefGoogle Scholar
Langdahl, BL, Knudsen, JY, Jensen, HK, Gregersen, N & Eriksen, EF (1997) A sequence variation: 713–8delC in the transforming growth factor-beta 1 gene has higher prevalence in osteoporotic women than in normal women and is associated with very low bone mass in osteoporotic women and increased bone turnover in both osteoporotic and normal women. Bone 20, 289294.CrossRefGoogle ScholarPubMed
Lau, HHL, Ho, AYY, Luk, KDK & Kung, AWC (2002) Estrogen receptor ~ gene polymorphisms are associated with higher bone mineral density in premenopausal, but not postmenopausal southern Chinese women. Bone 31, 276281.CrossRefGoogle Scholar
Lucotte, G, Mercier, G & Burkel, A (1999) The vitamin D receptor Fok I start codon polymorphism and bone mineral density in osteoporotic post-menopausal French women. Clinical Genetics 56, 221224.CrossRefGoogle Scholar
Mahley, RW, Weisgraber, KH, Innerarity, TL & Rall, SC (1991) Genetic defects in lipoprotein metabolism. Elevation of atherogenic lipoproteins caused by impaired catabolism. Journal of the American Medical Association 265, 7883.CrossRefGoogle ScholarPubMed
Mahonen, A, Turunen, AM, Kroger, H & Maenpaa, PH (1997) Estrogen receptor polymorphism is associated with bone mineral density in perimenopausal Finnish women. Journal of Bone and Mineral Research 12 T614Google Scholar
Mannz, V & Ralston, SH (2003) Meta-analysis of COL1A1 Sp1 polymorphism in relation to bone mineral density and osteoporotic fracture. Bone 32, 711717.CrossRefGoogle Scholar
Masi, L, Climaz, R, Simonini, G, Bindi, G, Stagi, S, Gozzini, A, Malentacchi, C, Brandi, ML & Falcini, F (2002) Association of low bone mass with vitamin D receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis. Journal of Rheumatology 29, 22252231.Google ScholarPubMed
Miyamoto, K, Taketani, E, Arai, E, Yamamoto, H, Iemori, Y, Chikamori, M, Morita, K, Takeda, E, Tohnai, T & Nishisho, T (1996) A novel polymorphism in the vitamin D receptor gene and bone mineral density: Study of vitamin D receptor expression and function in COS-7 cells. Journal of Bone and Mineral Research 11 Suppl. S116Google Scholar
Miyao, M, Morita, H, Hosoi, T, Kurihara, H, Inoue, S, Hoshino, S, Shiraki, M, Yazaki, Y & Ouchi, Y (2000) Association of methylenetetrahydrofolatereductase (MTHFR)polymorphismwithbone mineral density in postmenopausal Japanese women. Calcified Tissue International 66, 190194.CrossRefGoogle Scholar
Mizunuma, H, Hosoi, T, Okano, H, Soda, M, Tokizawa, T, Kagami, I, Miyamoto, S, Ibuki, Y, Inoue, S, Shiraki, M & Ouchi, Y (1997) Estrogen receptor gene polymorphism and bone mineral density at the lumbar spine of pre- and postmenopausal women. Bone 21, 379383.CrossRefGoogle ScholarPubMed
Morabito, N, Crisafulli, A, Vergara, C, Gaudio, A, Lasco, A, Frisina, N D'anna R Corrado, F, Pizzoleo, MA, Cincotta, M, Altavilla, D, Ientile, R & Squadrito, F (2002) Effects of genistein and hormonereplacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. Journal of Bone and Mineral Research 17, 19041912.CrossRefGoogle Scholar
Morrison Na Qi, JC, Tokita, A, Kelly, PJ, Crofts, L, Nguyen, TV, Sambrook, PN, Eisman, Ja (1994) Prediction of bone density from vitamin D receptor alleles. Nature 367, 284287.CrossRefGoogle Scholar
Morrison, Na Qi, JC, Tokita, A, Kelly, PJ, Crofts, L, Nguyen, TV, Sambrook, PN, Eisman, Ja (1997) Prediction of bone density from vitamin D receptor alleles. Nature 387 106CrossRefGoogle Scholar
Mosselman, S, Polman, J & Dijkema, R (1996) ER- b : identification and characterisation of a novel human estrogen receptor. FEBS Letters 392, 4953.CrossRefGoogle Scholar
Murray, Re McGuigan, F Grant, Sfa Reid, DM & Ralston, SM (1997) Polymorphisms of the interleukin-6 gene are associated with bone mineral density. Bone 21, 8992.CrossRefGoogle ScholarPubMed
Nguyen, TV, Jones, G, Sambrook, PN, White, CP, Kelly, PJ, Eisman, JA, (1995) Effects of estrogen exposure and reproductive factors on bone mineral density and osteoporotic fractures. Journal of Clinical Endocrinology and Metabolism 80, 27092714.Google Scholar
Norman, AW (1990) Intestinal calcium absorption: a vitamin Dhormone-mediated adaptive response. American Journal of Clinical Nutrition 51, 290300.CrossRefGoogle ScholarPubMed
Norris, RJ (1992) Medical costs of osteoporosis. Bone 13, S11S12.CrossRefGoogle ScholarPubMed
Ogawa, S, Hosoi, T, Shiraki, M, Orimo, H, Emi, M, Muramatsu, M, Ouchi, Y & Inoue, S (2000) Association of estrogen receptor beta gene polymorphism with bone mineral density. Biochemical and Biophysical Research Communications 269, 537541.CrossRefGoogle ScholarPubMed
Ongphiphadhanakul, B, Chanprasertyothin, S, Payatikul, P, Tung, SS, Piaseu, N, Chailurkit, L, Chansirikarn, S, Puavilai, G & Rajatanavin, R (2000) Oestrogen-receptor-alpha gene polymorphism affects response in bone mineral density to oestrogen in postmenopausal women. Clinical Endocrinology 52, 581585.CrossRefGoogle Scholar
Ongphiphadhanakul, B, Rajatanavin, R, Chanprasertyothin, S, Piaseu, N, Chailurkit, L, Sirisriro, R & Komind, R (1998) Estrogen receptor gene polymorphism is associated with bone mineral density in premenopausal women but not in post menopausal women. Journal of Endocrinological Investigation 21, 487493.CrossRefGoogle ScholarPubMed
Peacock, M (1995) Vitamin D receptor alleles and osteoporosis: a contrasting view. Journal of Bone and Mineral Research 10, 12941297.CrossRefGoogle ScholarPubMed
Pluijm, SM, Dik, MG, Jonker, C, Deeg, DJ, Van Kamp, GJ & Lips, P (2002) Effects of gender and age on the association of apolipoprotein E epsilon4 with bone mineral density, bone turnover and the risk of fractures in older people. Osteoporosis International 13, 701709.CrossRefGoogle ScholarPubMed
Pocock, Na Eisman, Ja Hopper, JL, Yeates, MG, Sambrook, PN & Eberl, S (1987) Genetic determinants of bone mass in adults. A twin study. Journal of Clinical Investigation 80, 706710.CrossRefGoogle ScholarPubMed
Potter, S, Baum, J, Teng, H, Stillman, R, Shay, N & Erdman, J (1998) Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. American Journal of Clinical Nutrition 68, 1375S1379S.CrossRefGoogle ScholarPubMed
Ralston, SH (2003) Genetic determinants of susceptibility to osteoporosis. Current Opinion in Pharmacology 3, 286290.CrossRefGoogle ScholarPubMed
Rapuri, PB, Gallagher, JC, Kinyamu, HK & Ryschon, KL (2001) Caffeine intake increases the rate of bone loss in elderly women and interacts with vitamin D receptor genotypes. American Journal of Clinical Nutrition 74, 694700.CrossRefGoogle ScholarPubMed
Riggs, L & Melton, LJ (1986) Involutional osteoporosis. New England Journal of Medicine 314, 16761686.CrossRefGoogle ScholarPubMed
Riis, BJ, Thomsen, K, Strom, V & Christiansen, C (1987) The effect of percutaneous estradiol and natural progesterone on postmenopausal bone loss. American Journal of Obstetrics and Gynecology 156, 6165.CrossRefGoogle ScholarPubMed
Salamone, LM, Cauley, JA, Zmuda, J Pasagian-Macaulay A Epstein, RS, Ferrell, RE, Black, DM & Kuller, LH (2000) Apolipoprotein E gene polymorphism and bone loss: estrogen status modifies the influence of apolipoprotein E on bone loss. Journal of Bone and Mineral Research 15, 308314.CrossRefGoogle ScholarPubMed
Salamone, LM, Glynn, NW, Black, DM, Ferrell, Re Palermo, L, Epstein, RS, Kuller, LH, Cauley, Ja (1996) Determinants of premenopausal bone mineral density: The interplay of genetic and lifestyle factors. Journal of Bone Mineral Research 11, 15571565.CrossRefGoogle ScholarPubMed
Salmen, T, Heikkinen, AM, Mahonen, A, Kroger, H, Komulainen, M, Saarikoski, S, Honkanen, R & Maenpaa, PH (2000a) Early postmenopausal bone loss is associated with Pvu I estrogen receptor gene polymorphism in Finnish women: effect of hormone replacement therapy. Journal of Bone and Mineral Research 15, 315321.CrossRefGoogle Scholar
Salmen, T, Heikkinen, A, Mahonin, A, Kroger, H, Komulainen, M, Saarikoski, S, Honkanen, R & Maenpaa, PH (2000b) The protective effect of hormone-replacement therapy on fracture risk is modulated by estrogen receptor ~ genotype in early postmenopausal women. Journal of Bone and Mineral Research 15, 24792486.CrossRefGoogle ScholarPubMed
Sanada, M, Nakagawa, H, Kodama, I, Sakasita, T & Ohama, K (1998) Apolipoprotein E phenotype associations with plasma lipoproteins and bone mass in postmenopausal women. Climacteric 1, 188195.CrossRefGoogle ScholarPubMed
Sano, M, Inoue, S, Hosoi, T, Ouchi, Y, Emi, M, Shiraki, M & Orimo, H (1995) Association of estrogen receptor dinucleotide repeat polymorphism with osteoporosis. Biochemical and Biophysical Research Communications 217, 378383.CrossRefGoogle ScholarPubMed
Saupe, J, Shearer, MJ & Kohlmeier, M (1993) Phylloquinone transport and its influence on α-carboxylation residues of osteocalcin in patients on maintenance haemodialysis. American Journal of Clinical Nutrition 58, 204208.CrossRefGoogle Scholar
Shiekh, M, Ramirez, A, Emmett, M, Santa, C & Fordtran, J (1988) Role of vitamin D dependent and vitamin D independent mechanisms in absorption of food calcium. Journal of Clinical Investigation 81, 126132.CrossRefGoogle Scholar
Shiraki, M, Shiraki, Y, Aoki, C, Hosoi, T, Inoue, S, Kaneki, M & Ouchi, Y (1997) Association of bone mineral density and apolipoprotein E phenotype. Journal of Bone Mineral Research 12, 14381445.CrossRefGoogle ScholarPubMed
Simopoulos, AP (1995) Genetic variation and nutrition. Nutrition Today 30, 157167.CrossRefGoogle Scholar
Slemenda, CW, Christian, JC, Williams, CJ, Norton, Ja Johnston, CC (1991) Genetic determinants of bone mass in adult women; a re-evaluation of the model and the potential importance of gene interaction on heritability estimates. Journal of Bone and Mineral Research 6, 651657.CrossRefGoogle Scholar
Smith, EP, Boyd, J, Frank, GR, Takahasi, H, Cohen, RM, Specker, B, Williams, TC, Lubahn, DB & Korach, KS (1994) Estrogen resistance caused by a mutation in the estrogenreceptor gene in a man. New England Journal of Medicine 331, 10561061.CrossRefGoogle ScholarPubMed
Sowers, M, Willing, M, Burns, T, Deschenes, S, Hollis, B, Crutchfield, M & Jannusch, M (1999) Genetic markers, bone mineral density and serum osteocalcin levels. Journal of Bone and Mineral Research 14, 14111419.CrossRefGoogle ScholarPubMed
Stevenson, JC, Cust, MP, Gangar, KF, Hillard, TC, Lees, B, Whitehead, MI, (1990) Effects of transdermal versus oral hormone replacement therapy on bone density in spine and proximal femur in postmenopausal women. Lancet 336, 265269.CrossRefGoogle Scholar
Stewart, TL & Ralston, SH (2000) Role of genetic factors in the pathogenesis of osteoporosis. Journal of Endocrinology 166, 235245.CrossRefGoogle ScholarPubMed
Stulc, T, Ceska, R, Horinek, A & Stepan, J (2000) Bone mineral density in patients with apolipoprotein E type 2/2 and 4/4 genotype. Physiology Research 49, 435439.Google ScholarPubMed
Takacs, I, Speer, G, Bajnok, E, Tabak, A, Nagy, Z, Horvath, C Kovacs Lakatos, P (2002) Lack of association between calcium-sensing receptor gene 'A986' polymorphism and bone mineral density in Hungarian postmenopausal women. Bone 30, 849852.CrossRefGoogle Scholar
Thompson, E (2001) Detection of human genetic linkage: foundations. Theoretical Population Biology 60, 203213.CrossRefGoogle ScholarPubMed
Tofteng, CL, Jensen, JEB, Abrahamsen, B, Odum, L & Brot, C (2002) Two polymorphisms in the vitamin D receptor gene – association with bone mass and 5-year change in bone mass with or without hormone-replacement therapy in postmenopausal women: the Danish osteoporosis prevention study. Journal of Bone and Mineral Research 17, 15351544.CrossRefGoogle ScholarPubMed
Uitterlinden, AG, Fang, Y, Bergink, AP, Van Meurs, JBJ, Van Leeuwen, HPTM, Pols, HAP, (2002) The role of vitamin D receptor gene polymorphisms in bone biology. Molecular and Cellular Endocrinology 197, 1521.CrossRefGoogle ScholarPubMed
Uitterlinden, AG, Pols, HA, Burger, H, Huang, Q, Van Daele, PL, Van Duijn, CM, Hofman, A, Birkenhager, JC, Van Leeuwen, JP (1996) A large-scale population-based study of the association of vitamin D receptor gene polymorphisms with bone mineral density. Journal of Bone and Mineral Research 11, 12411248.CrossRefGoogle ScholarPubMed
Uitterlinden, AG, Weel, AE, Burger, H, Fang, Y, Van Dujin, CM, Hofman, A, Van Leeuwen, JP, Pols, HA, (2001) Interaction between the vitamin D receptor gene and collagen type I alpha I gene in susceptibility for fracture. Journal of Bone and Mineral Research 16, 379385.CrossRefGoogle Scholar
Vandevyver, C, Vanhoof, J, Declerck, K, Stinissen, P, Vandervorst, C, Michiels, L, Cassiman, JJ, Boonen, S, Raus, J & Geusens, P (1999) Lack of association between estrogen receptor genotypes and bone mineral density, fracture history, or muscle strength in elderly women. Journal of Bone and Mineral Research 14, 15761582.CrossRefGoogle ScholarPubMed
Verbeek, W, Gombart, AF, Shiohara, M, Campbell, M & Koeffler, HP (1997) Vitamin D receptor: no evidence for allele-specific mRNA stability in cells which are heterozygous for the Taq 1 restriction enzyme polymorphism. Biochemical and Biophysical Communications 238, 7780.CrossRefGoogle ScholarPubMed
Vermeer, C, Jie, K-SG & Knapen, MHJ (1995) Role of vitamin K in bone metabolism. Annual Reviews in Nutrition 15, 122.CrossRefGoogle ScholarPubMed
Vink, JM & Boomsma, DI (2002) Gene finding strategies. Biological Psychology 61, 5371.CrossRefGoogle ScholarPubMed
Von Muhlen, DG, Barrett-Connor, E, Schneider, DL, Morin, PA, Parry, P (2001) Osteoporosis and apolipoprotein E genotype in older adults: The Rancho Bernardo study. Osteoporosis International 12, 332335.CrossRefGoogle ScholarPubMed
Willing, M, Sowers, M, Aron, D, Clark, MK, Burns, T, Bunten, C, Crutchfield, M D'agostino D Jannausch, M (1998) Bone mineral density and its changes in white women: Estrogen and vitamin D receptor genotypes and their interaction. Journal of Bone and Mineral Research 13, 695705.CrossRefGoogle ScholarPubMed
Windahl, SH, Vidal, O, Andersson, G, Gustafsson, Ja Ohlsson, C (1999) Increased cortical bone mineral content but unchanged trabecluar bone mineral density in female ER~(-/-) mice. Journal of Clinical Investigation 104, 895901.CrossRefGoogle Scholar
Wishart, JM, Horowitz, M, Need, AG, Scopacasa, F, Morris, HA, Clifton, PM & Nordin, C (1997) Relations between calcium intake, calcitriol, polymorphisms of the vitamin D receptor gene, and calcium absorption in premenopausal women. American Journal of Clinical Nutrition 65, 798802.CrossRefGoogle ScholarPubMed
Wood, RJ & Fleet, JC (1998) The genetics of osteoporosis: vitamin D receptor polymorphisms. Annual Reviews of Nutrition 18, 233258.CrossRefGoogle ScholarPubMed
Yamada, Y, Ando, F, Niino, N & Shimokata, H (2002) Association of a polymophism of the matrix metallproteinase-1 gene with bone mineral density. Matrix Biology 21, 389392.CrossRefGoogle Scholar
Yokoyama, K, Shigematsu, T, Tsukada, T, Ogura, Y, Takemoto, F, Hara, S, Yamada, Y, Kawaguchi, Y & Hosoya, T (1998) Apa I polymorphism in the vitamin D receptor gene may affect the parathyroid response in Japanese with end-stage renal disease. Kidney International 53, 454458.CrossRefGoogle ScholarPubMed
Zittermann, A (2003) Vitamin D in preventive medicine: are we ignoring the evidence. British Journal of Nutrition 89, 552572.CrossRefGoogle ScholarPubMed
Zmuda, JM, Cauley, JA, Danielson Me Wolf, RL, Ferrell, Re, (1997) Vitamin D receptor gene polymorphisms, bone turnover, and rates of bone loss in older African-American women. Journal of Bone and Mineral Research 12, 14461452.CrossRefGoogle ScholarPubMed