Nutraceuticals and Bone Health

  • Jeri W. NievesEmail author
Part of the Nutrition and Health book series (NH)


The use of dietary supplement or nutraceutical in the past month exceeded 50 % in US adults with higher rates in individuals with chronic disease. Although calcium and vitamin D are important, various other nutrients may also provide benefit to the skeleton. The relationship between soy compounds and skeletal health is inconclusive. Dehydroepiandrosterone has not been shown to benefit the skeleton even in elderly with low serum levels. There is no clear skeletal benefit from various antioxidants, flavonoids, carotenoids, omega-3-fatty acids, and various vitamins with only limited observational data and small clinical trials. In addition, in some cases pharmacologic doses have been investigated. High homocysteine may relate to fracture risk, but whether this risk is reduced by any B vitamins is unclear. There is no clear relationship between bone health and nutritional intake of magnesium, boron, strontium, silicon, and phosphorus.


Nutraceuticals Soy B vitamins Magnesium Boron Strontium Silicon and phosphorus Omega 3 DHEA 


  1. 1.
    Nieves JW. Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D. Osteoporos Int. 2013;24:771–86.PubMedGoogle Scholar
  2. 2.
    Rock CL. Multivitamin-multimineral supplements: who uses them? Am J Clin Nutr. 2007;85:277S–9.PubMedGoogle Scholar
  3. 3.
    FDA. Overview of Dietary Supplements. Silver Spring, MD: U.S. Department of Health and Human Services; 2009.Google Scholar
  4. 4.
    Wang YD, Tao MF, Cheng WW, Liu XH, Wan XP, Cui K. Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway. Chin Med J (Engl). 2012;125:1230–5.Google Scholar
  5. 5.
    Ghebre MA, Hart DJ, Hakim AJ, Kato BS, Thompson V, Arden NK, Spector TD, Zhai G. Association between DHEAS and bone loss in postmenopausal women: a 15-year longitudinal population-based study. Calcif Tissue Int. 2011;89:295–302.PubMedCentralPubMedGoogle Scholar
  6. 6.
    Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci U S A. 2000;97:4279–84.PubMedCentralPubMedGoogle Scholar
  7. 7.
    Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf). 1998;49:421–32.Google Scholar
  8. 8.
    von Muhlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R. Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int. 2008;19:699–707.Google Scholar
  9. 9.
    Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf). 2000;53:561–8.Google Scholar
  10. 10.
    Nair KS, Rizza RA, O'Brien P, et al. DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med. 2006;355:1647–59.PubMedGoogle Scholar
  11. 11.
    Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P. Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl). 2002;115:402–4.Google Scholar
  12. 12.
    Corona G, Rastrelli G, Giagulli VA, Sila A, Sforza A, Forti G, Mannucci E, Maggi M. Dehydroepiandrosterone supplementation in elderly men: a meta-analysis study of placebo-controlled trials. J Clin Endocrinol Metab. 2013;98:3615–26.PubMedGoogle Scholar
  13. 13.
    Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer. 2006;55:1–12.PubMedGoogle Scholar
  14. 14.
    Chun OK, Chung SJ, Song WO. Urinary isoflavones and their metabolites validate the dietary isoflavone intakes in US adults. J Am Diet Assoc. 2009;109:245–54.PubMedGoogle Scholar
  15. 15.
    (2010) Dietary Guidelines for Americans, 2010. In Agriculture USDo, Services USDoHaH (eds), 7th ed. US Government Printing Office, Washington, DC.Google Scholar
  16. 16.
    Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, Zheng W. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med. 2005;165:1890–5.PubMedGoogle Scholar
  17. 17.
    Messina M, Ho S, Alekel DL. Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data. Curr Opin Clin Nutr Metab Care. 2004;7:649–58.PubMedGoogle Scholar
  18. 18.
    Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT. The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr. 2010;91:218–30.PubMedCentralPubMedGoogle Scholar
  19. 19.
    Wong WW, Lewis RD, Steinberg FM, et al. Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr. 2009;90:1433–9.PubMedCentralPubMedGoogle Scholar
  20. 20.
    Brink E, Coxam V, Robins S, Wahala K, Cassidy A, Branca F. Long-term consumption of isoflavone-enriched foods does not affect bone mineral density, bone metabolism, or hormonal status in early postmenopausal women: a randomized, double-blind, placebo controlled study. Am J Clin Nutr. 2008;87:761–70.PubMedGoogle Scholar
  21. 21.
    Kenny AM, Mangano KM, Abourizk RH, Bruno RS, Anamani DE, Kleppinger A, Walsh SJ, Prestwood KM, Kerstetter JE. Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr. 2009;90:234–42.PubMedCentralPubMedGoogle Scholar
  22. 22.
    Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J. Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med. 2011;171:1363–9.PubMedGoogle Scholar
  23. 23.
    Atmaca A, Kleerekoper M, Bayraktar M, Kucuk O. Soy isoflavones in the management of postmenopausal osteoporosis. Menopause. 2008;15:748–57.PubMedGoogle Scholar
  24. 24.
    Kruse SO, Lohning A, Pauli GF, Winterhoff H, Nahrstedt A. Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med. 1999;65:763–4.PubMedGoogle Scholar
  25. 25.
    Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M. Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. J Clin Endocrinol Metab. 2009;94:3798–805.PubMedCentralPubMedGoogle Scholar
  26. 26.
    Zhang X, Li SW, Wu JF, Dong CL, Zheng CX, Zhang YP, Du J. Effects of ipriflavone on postmenopausal syndrome and osteoporosis. Gynecol Endocrinol. 2010;26:76–80.PubMedGoogle Scholar
  27. 27.
    Lagari VS, Levis S. Phytoestrogens in the prevention of postmenopausal bone loss. J Clin Densitom. 2013;16:445–9.PubMedGoogle Scholar
  28. 28.
    Morabito N, Crisafulli A, Vergara C, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res. 2002;17:1904–12.PubMedGoogle Scholar
  29. 29.
    Marini H, Minutoli L, Polito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007;146:839–47.PubMedGoogle Scholar
  30. 30.
    Marini H, Bitto A, Altavilla D, et al. Breast safety and efficacy of genistein aglycone for post-menopausal bone loss: a follow-up study. J Clin Endocrinol Metab. 2008;93(12):4787–96.PubMedGoogle Scholar
  31. 31.
    Taylor CK, Levy RM, Elliott JC, Burnett BP. The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical and clinical studies. Nutr Rev. 2009;67(7):398–415.PubMedGoogle Scholar
  32. 32.
    Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy A. Effects of isoflavones on breast density in pre- and post-menopausal women: a systematic review and meta-analysis of randomized controlled trials. Hum Reprod Update. 2010;16:745–60.PubMedCentralPubMedGoogle Scholar
  33. 33.
    Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2011;125:315–23.PubMedGoogle Scholar
  34. 34.
    Andres S, Abraham K, Appel KE, Lampen A. Risks and benefits of dietary isoflavones for cancer. Crit Rev Toxicol. 2011;41:463–506.PubMedGoogle Scholar
  35. 35.
    Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J. Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev 2007:CD001395Google Scholar
  36. 36.
    Dew TP, Williamson G. Controlled flax interventions for the improvement of menopausal symptoms and postmenopausal bone health: a systematic review. Menopause. 2013;20:1207–15.PubMedGoogle Scholar
  37. 37.
    Booth NL, Piersen CE, Banuvar S, Geller SE, Shulman LP, Farnsworth NR. Clinical studies of red clover (Trifolium pratense) dietary supplements in menopause: a literature review. Menopause. 2006;13:251–64.PubMedGoogle Scholar
  38. 38.
    Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA, Tidy A. Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int. 2008;14:6–12.PubMedGoogle Scholar
  39. 39.
    Ohta H, Komukai S, Makita K, Masuzawa T, Nozawa S. Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res. 1999;51:178–83.PubMedGoogle Scholar
  40. 40.
    Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, Gennari C, Reginster JY. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482–8.PubMedGoogle Scholar
  41. 41.
    Office of Dietary Supplements, National Institutes of Health, (2010) Accessed 26 July 2010.
  42. 42.
    Klein MA, Hartman TJ. Guidance from an NIH workshop on designing, implementing, and reporting clinical studies of soy interventions. J Nutr. 2009;140:1192S–204.Google Scholar
  43. 43.
    Arnett TR, Dempster DW. Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology. 1986;119:119–24.PubMedGoogle Scholar
  44. 44.
    Bushinsky DA. Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol. 1996;271:F216–22.PubMedGoogle Scholar
  45. 45.
    Ceglia L, Harris SS, Abrams SA, Rasmussen HM, Dallal GE, Dawson-Hughes B. Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. J Clin Endocrinol Metab. 2009;94:645–53.PubMedCentralPubMedGoogle Scholar
  46. 46.
    He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, Dalton RN, Kaski JC, MacGregor GA. Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension. 2010;55:681–8.PubMedGoogle Scholar
  47. 47.
    Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE. Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab. 2009;94:96–102.PubMedCentralPubMedGoogle Scholar
  48. 48.
    Macdonald HM, Black AJ, Aucott L, Duthie G, Duthie S, Sandison R, Hardcastle AC, Lanham New SA, Fraser WD, Reid DM. Effect of potassium citrate supplementation or increased fruit and vegetable intake on bone metabolism in healthy postmenopausal women: a randomized controlled trial. Am J Clin Nutr. 2008;88:465–74.PubMedGoogle Scholar
  49. 49.
    Hanley DA, Whiting SJ. Does a high dietary acid content cause bone loss, and can bone loss be prevented with an alkaline diet? J Clin Densitom. 2013;16:420–5.PubMedGoogle Scholar
  50. 50.
    Nicklas TA, O'Neil CE, Fulgoni 3rd VL. The role of dairy in meeting the recommendations for shortfall nutrients in the American diet. J Am Coll Nutr. 2009;28 Suppl 1:73S–81.PubMedGoogle Scholar
  51. 51.
    Wang MC, Moore EC, Crawford PB, Hudes M, Sabry ZI, Marcus R, Bachrach LK. Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women. Osteoporos Int. 1999;9:532–5.PubMedGoogle Scholar
  52. 52.
    Carpenter TO, DeLucia MC, Zhang JH, Bejnerowicz G, Tartamella L, Dziura J, Petersen KF, Befroy D, Cohen D. A randomized controlled study of effects of dietary magnesium oxide supplementation on bone mineral content in healthy girls. J Clin Endocrinol Metab. 2006;91:4866–72.PubMedCentralPubMedGoogle Scholar
  53. 53.
    Song CH, Barrett-Connor E, Chung JH, Kim SH, Kim KS. Associations of calcium and magnesium in serum and hair with bone mineral density in premenopausal women. Biol Trace Elem Res. 2007;118:1–9.PubMedGoogle Scholar
  54. 54.
    New SA, Robins SP, Campbell MK, Martin JC, Garton MJ, Bolton-Smith C, Grubb DA, Lee SJ, Reid DM. Dietary influences on bone mass and bone metabolism: further evidence of a positive link between fruit and vegetable consumption and bone health? Am J Clin Nutr. 2000;71:142–51.PubMedGoogle Scholar
  55. 55.
    Houtkooper LB, Ritenbaugh C, Aickin M, Lohman TG, Going SB, Weber JL, Greaves KA, Boyden TW, Pamenter RW, Hall MC. Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women. J Nutr. 1995;125:1229–37.PubMedGoogle Scholar
  56. 56.
    Tranquilli AL, Lucino E, Garzetti GG, Romanini C. Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecol Endocrinol. 1994;8:55–8.PubMedGoogle Scholar
  57. 57.
    Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP. Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69:727–36.PubMedGoogle Scholar
  58. 58.
    Ryder KM, Shorr RI, Bush AJ, Kritchevsky SB, Harris T, Stone K, Cauley J, Tylavsky FA. Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc. 2005;53:1875–80.PubMedGoogle Scholar
  59. 59.
    Nielsen FH. Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Magnes Trace Elem. 1990;9:61–9.PubMedGoogle Scholar
  60. 60.
    Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res. 1993;6:155–63.PubMedGoogle Scholar
  61. 61.
    Jackson R, Bassford T, Cauley J, Chen C, La Croix AZ, Sparks A, Wactawski-Wende J (2003) The impact of magnesium intake on fractures: results from the women’s health initiative observational study (WHI-OS). ASBMR.Google Scholar
  62. 62.
    Durlach J, Bac P, Durlach V, Rayssiguier Y, Bara M, Guiet-Bara A. Magnesium status and ageing: an update. Magnes Res. 1998;11:25–42.PubMedGoogle Scholar
  63. 63.
    Rude RK, Olerich M. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int. 1996;6:453–61.PubMedGoogle Scholar
  64. 64.
    Orchard TS, Larson JC, Alghothani N, Bout-Tabaku S, Cauley JA, Chen Z, LaCroix AZ, Wactawski-Wende J, Jackson RD. Magnesium intake, bone mineral density, and fractures: results from the Women's Health Initiative Observational Study. Am J Clin Nutr. 2014;99:926–33.PubMedGoogle Scholar
  65. 65.
    Nieves JW. Bone. Maximizing bone health—magnesium, BMD and fractures. Nat Rev Endocrinol. 2014;10:255–6.PubMedGoogle Scholar
  66. 66.
    Nielsen FH. Is boron nutritionally relevant? Nutr Rev. 2008;66:183–91.PubMedGoogle Scholar
  67. 67.
    Nielsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J. 1987;1:394–7.PubMedGoogle Scholar
  68. 68.
    Hunt CD, Herbel JL, Nielsen FH. Metabolic responses of postmenopausal women to supplemental dietary boron and aluminum during usual and low magnesium intake: boron, calcium, and magnesium absorption and retention and blood mineral concentrations. Am J Clin Nutr. 1997;65:803–13.PubMedGoogle Scholar
  69. 69.
    Bisse E, Epting T, Beil A, Lindinger G, Lang H, Wieland H. Reference values for serum silicon in adults. Anal Biochem. 2005;337:130–5.PubMedGoogle Scholar
  70. 70.
    Jugdaohsingh R. Silicon and bone health. J Nutr Health Aging. 2007;11:99–110.PubMedCentralPubMedGoogle Scholar
  71. 71.
    Tucker KL, Jugdaohsingh R, Powell JJ, Qiao N, Hannan MT, Sripanyakorn S, Cupples LA, Kiel DP. Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr. 2009;89:1188–96.PubMedCentralPubMedGoogle Scholar
  72. 72.
    Macdonald HM, Hardcastle AC, Jugdaohsingh R, Fraser WD, Reid DM, Powell JJ. Dietary silicon interacts with oestrogen to influence bone health: evidence from the Aberdeen Prospective Osteoporosis Screening Study. Bone. 2012;50:681–7.PubMedGoogle Scholar
  73. 73.
    Spector TD, Calomme MR, Anderson SH, Clement G, Bevan L, Demeester N, Swaminathan R, Jugdaohsingh R, Berghe DA, Powell JJ. Choline-stabilized orthosilicic acid supplementation as an adjunct to calcium/vitamin D3 stimulates markers of bone formation in osteopenic females: a randomized, placebo-controlled trial. BMC Musculoskelet Disord. 2008;9:85.PubMedCentralPubMedGoogle Scholar
  74. 74.
    Reginster JY, Felsenberg D, Boonen S, et al. Effects of long-term strontium ranelate treatment on the risk of nonvertebral and vertebral fractures in postmenopausal osteoporosis: results of a five-year, randomized, placebo-controlled trial. Arthritis Rheum. 2008;58:1687–95.PubMedGoogle Scholar
  75. 75.
    Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350:459–68.PubMedGoogle Scholar
  76. 76.
    Calvo MS, Carpenter TO. Influence of phosphorus on the skeleton. In: New SA, Bonjour J-P, editors. Nutritional Aspects of Bone Health. Cambridge, UK: Royal Chemistry Society; 2003. p. 229–65.Google Scholar
  77. 77.
    Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP. Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: the Framingham Osteoporosis Study. Am J Clin Nutr. 2006;84:936–42.PubMedGoogle Scholar
  78. 78.
    Pinheiro MM, Schuch NJ, Genaro PS, Ciconelli RM, Ferraz MB, Martini LA. Nutrient intakes related to osteoporotic fractures in men and women—the Brazilian Osteoporosis Study (BRAZOS). Nutr J. 2009;8:6.PubMedCentralPubMedGoogle Scholar
  79. 79.
    Calvo MS, Tucker KL. Is phosphorus intake that exceeds dietary requirements a risk factor in bone health? Ann N Y Acad Sci. 2013;1301:29–35.PubMedGoogle Scholar
  80. 80.
    van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033–41.PubMedGoogle Scholar
  81. 81.
    Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Drevon CA, Gjessing HK, Tell GS. Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med. 2006;166:88–94.PubMedGoogle Scholar
  82. 82.
    Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res. 2005;20:921–9.PubMedGoogle Scholar
  83. 83.
    McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan MT, Cupples LA, Kiel DP. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042–9.PubMedGoogle Scholar
  84. 84.
    Ravaglia G, Forti P, Maioli F, Servadei L, Martelli M, Brunetti N, Bastagli L, Cucinotta D, Mariani E. Folate, but not homocysteine, predicts the risk of fracture in elderly persons. J Gerontol A Biol Sci Med Sci. 2005;60:1458–62.PubMedGoogle Scholar
  85. 85.
    McLean RR, Jacques PF, Selhub J, Fredman L, Tucker KL, Samelson EJ, Kiel DP, Cupples LA, Hannan MT. Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab. 2008;93:2206–12.PubMedCentralPubMedGoogle Scholar
  86. 86.
    Tucker KL, Hannan MT, Qiao N, Jacques PF, Selhub J, Cupples LA, Kiel DP. Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res. 2005;20:152–8.PubMedGoogle Scholar
  87. 87.
    Dhonukshe-Rutten RA, Lips M, de Jong N, Chin APMJ, Hiddink GJ, van Dusseldorp M, De Groot LC, van Staveren WA. Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr. 2003;133:801–7.PubMedGoogle Scholar
  88. 88.
    Morris MS, Jacques PF, Selhub J. Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone. 2005;37:234–42.PubMedGoogle Scholar
  89. 89.
    Stone KL, Bauer DC, Sellmeyer D, Cummings SR. Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study. J Clin Endocrinol Metab. 2004;89:1217–21.PubMedGoogle Scholar
  90. 90.
    Baines M, Kredan MB, Davison A, Higgins G, West C, Fraser WD, Ranganath LR. The association between cysteine, bone turnover, and low bone mass. Calcif Tissue Int. 2007;81:450–4.PubMedGoogle Scholar
  91. 91.
    Cagnacci A, Bagni B, Zini A, Cannoletta M, Generali M, Volpe A. Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation. Bone. 2008;42:314–20.PubMedGoogle Scholar
  92. 92.
    Cagnacci A, Baldassari F, Rivolta G, Arangino S, Volpe A. Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women. Bone. 2003;33:956–9.PubMedGoogle Scholar
  93. 93.
    Rejnmark L, Vestergaard P, Hermann AP, Brot C, Eiken P, Mosekilde L. Dietary intake of folate, but not vitamin B2 or B12, is associated with increased bone mineral density 5 years after the menopause: results from a 10-year follow-up study in early postmenopausal women. Calcif Tissue Int. 2008;82:1–11.PubMedGoogle Scholar
  94. 94.
    Herrmann M, Stanger O, Paulweber B, Hufnagl C, Herrmann W. Folate supplementation does not affect biochemical markers of bone turnover. Clin Lab. 2006;52:131–6.PubMedGoogle Scholar
  95. 95.
    Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA. 2005;293:1082–8.PubMedGoogle Scholar
  96. 96.
    Zhang H, Tao X, Wu J. Association of homocysteine, vitamin B12, and folate with bone mineral density in postmenopausal women: a meta-analysis. Arch Gynecol Obstet. 2014;289:1003–9.PubMedGoogle Scholar
  97. 97.
    McLean RR, Hannan MT. B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporos Rep. 2007;5:112–9.PubMedGoogle Scholar
  98. 98.
    van Wijngaarden JP, Dhonukshe-Rutten RA, van Schoor NM, et al. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence. BMC Geriatr. 2011;11:80.PubMedCentralPubMedGoogle Scholar
  99. 99.
    Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev. 2010;31:266–300.PubMedCentralPubMedGoogle Scholar
  100. 100.
    Welch A, Macgregor A, Jennings A, Fairweather-Tait S, Spector T, Cassidy A. Habitual flavonoid intakes are positively associated with bone mineral density in women. J Bone Miner Res. 2012;27:1872–8.PubMedGoogle Scholar
  101. 101.
    Hardcastle AC, Aucott L, Reid DM, Macdonald HM. Associations between dietary flavonoid intakes and bone health in a Scottish population. J Bone Miner Res. 2011;26:941–7.PubMedGoogle Scholar
  102. 102.
    Boyer J, Liu RH. Apple phytochemicals and their health benefits. Nutr J. 2004;3:5.PubMedCentralPubMedGoogle Scholar
  103. 103.
    Wattel A, Kamel S, Prouillet C, Petit JP, Lorget F, Offord E, Brazier M. Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. J Cell Biochem. 2004;92:285–95.PubMedGoogle Scholar
  104. 104.
    Woo JT, Nakagawa H, Notoya M, Yonezawa T, Udagawa N, Lee IS, Ohnishi M, Hagiwara H, Nagai K. Quercetin suppresses bone resorption by inhibiting the differentiation and activation of osteoclasts. Biol Pharm Bull. 2004;27:504–9.PubMedGoogle Scholar
  105. 105.
    Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit JP, Fardelonne P, Brazier M. Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol. 2003;65:35–42.PubMedGoogle Scholar
  106. 106.
    Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;585:325–37.PubMedGoogle Scholar
  107. 107.
    Hay AW, Hassam AG, Crawford MA, Stevens PA, Mawer EB, Jones FS. Essential fatty acid restriction inhibits vitamin D-dependent calcium absorption. Lipids. 1980;15:251–4.PubMedGoogle Scholar
  108. 108.
    Hogstrom M, Nordstrom P, Nordstrom A. n-3 Fatty acids are positively associated with peak bone mineral density and bone accrual in healthy men: the NO2 Study. Am J Clin Nutr. 2007;85:803–7.PubMedGoogle Scholar
  109. 109.
    Rousseau JH, Kleppinger A, Kenny AM. Self-reported dietary intake of omega-3 fatty acids and association with bone and lower extremity function. J Am Geriatr Soc. 2009;57:1781–8.PubMedGoogle Scholar
  110. 110.
    Salari P, Rezaie A, Larijani B, Abdollahi M. A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Med Sci Monit. 2008;14:RA37–44.PubMedGoogle Scholar
  111. 111.
    Jarvinen R, Tuppurainen M, Erkkila AT, Penttinen P, Karkkainen M, Salovaara K, Jurvelin JS, Kroger H. Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women. Eur J Clin Nutr. 2012;66:496–503.PubMedGoogle Scholar
  112. 112.
    Eriksson S, Mellstrom D, Strandvik B. Fatty acid pattern in serum is associated with bone mineralisation in healthy 8-year-old children. Br J Nutr. 2009;102:407–12.PubMedGoogle Scholar
  113. 113.
    Weiss LA, Barrett-Connor E, von Muhlen D. Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr. 2005;81:934–8.PubMedGoogle Scholar
  114. 114.
    Mangano K, Kerstetter J, Kenny A, Insogna K, Walsh SJ. An investigation of the association between omega 3 FA and bone mineral density among older adults: results from the National Health and Nutrition Examination Survey years 2005-2008. Osteoporos Int. 2014;25:1033–41.PubMedCentralPubMedGoogle Scholar
  115. 115.
    Orchard TS, Pan X, Cheek F, Ing SW, Jackson RD. A systematic review of omega-3 fatty acids and osteoporosis. Br J Nutr. 2012;107 Suppl 2:S253–60.PubMedCentralPubMedGoogle Scholar
  116. 116.
    Yang Z, Zhang Z, Penniston KL, Binkley N, Tanumihardjo SA. Serum carotenoid concentrations in postmenopausal women from the United States with and without osteoporosis. Int J Vitam Nutr Res. 2008;78:105–11.PubMedCentralPubMedGoogle Scholar
  117. 117.
    Wolf RL, Cauley JA, Pettinger M, et al. Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr. 2005;82:581–8.PubMedGoogle Scholar
  118. 118.
    Barker ME, McCloskey E, Saha S, Gossiel F, Charlesworth D, Powers HJ, Blumsohn A. Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res. 2005;20:913–20.PubMedGoogle Scholar
  119. 119.
    Pasco JA, Henry MJ, Wilkinson LK, Nicholson GC, Schneider HG, Kotowicz MA. Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women. J Womens Health (Larchmt). 2006;15:295–300.Google Scholar
  120. 120.
    Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Protective effect of total carotenoid and lycopene intake on the risk of hip fracture: a 17-year follow-up from the Framingham Osteoporosis Study. J Bone Miner Res. 2009;24:1086–94.PubMedCentralPubMedGoogle Scholar
  121. 121.
    Dai Z, Wang R, Ang LW, Low YL, Yuan JM, Koh WP. Protective effects of dietary carotenoids on risk of hip fracture in men: the Singapore Chinese Health Study. J Bone Miner Res. 2014;29:408–17.PubMedGoogle Scholar
  122. 122.
    Feskanich D, Singh V, Willett WC, Colditz GA. Vitamin A intake and hip fractures among postmenopausal women. JAMA. 2002;287:47–54.PubMedGoogle Scholar
  123. 123.
    Melhus H, Michaelsson K, Kindmark A, Bergstrom R, Holmberg L, Mallmin H, Wolk A, Ljunghall S. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med. 1998;129:770–8.PubMedGoogle Scholar
  124. 124.
    Michaelsson K, Lithell H, Vessby B, Melhus H. Serum retinol levels and the risk of fracture. N Engl J Med. 2003;348:287–94.PubMedGoogle Scholar
  125. 125.
    Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E. Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res. 2002;17:1349–58.PubMedGoogle Scholar
  126. 126.
    Ballew C, Galuska D, Gillespie C. High serum retinyl esters are not associated with reduced bone mineral density in the Third National Health and Nutrition Examination Survey, 1988-1994. J Bone Miner Res. 2001;16:2306–12.PubMedGoogle Scholar
  127. 127.
    Wu AM, Huang CQ, Lin ZK, Tian N, Ni WF, Wang XY, Xu H, Chi YL. The relationship between vitamin a and risk of fracture: meta-analysis of prospective studies. J Bone Miner Res. 2014;29(9):2032–9.PubMedGoogle Scholar
  128. 128.
    Chuin A, Labonte M, Tessier D, Khalil A, Bobeuf F, Doyon CY, Rieth N, Dionne IJ. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. 2009;20:1253–8.PubMedGoogle Scholar
  129. 129.
    Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM. Nutritional associations with bone loss during the menopausal transition: evidence of a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr. 2004;79:155–65.PubMedGoogle Scholar
  130. 130.
    Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J. Effects of dietary nutrients and food groups on bone loss from the proximal femur in men and women in the 7th and 8th decades of age. Osteoporos Int. 2003;14:418–28.PubMedGoogle Scholar
  131. 131.
    Weber P. The role of vitamins in the prevention of osteoporosis—a brief status report. Int J Vitam Nutr Res. 1999;69:194–7.PubMedGoogle Scholar
  132. 132.
    Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner DM. Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health. 1997;51:479–85.PubMedCentralPubMedGoogle Scholar
  133. 133.
    Hernandez-Avila M, Stampfer MJ, Ravnikar VA, Willett WC, Schiff I, Francis M, Longcope C, McKinlay SM, Longscope C. Caffeine and other predictors of bone density among pre- and perimenopausal women. Epidemiology. 1993;4:128–34.PubMedGoogle Scholar
  134. 134.
    Freudenheim JL, Johnson NE, Smith EL. Relationships between usual nutrient intake and bone-mineral content of women 35-65 years of age: longitudinal and cross-sectional analysis. Am J Clin Nutr. 1986;44:863–76.PubMedGoogle Scholar
  135. 135.
    Sowers MR, Wallace RB, Lemke JH. Correlates of mid-radius bone density among postmenopausal women: a community study. Am J Clin Nutr. 1985;41:1045–53.PubMedGoogle Scholar
  136. 136.
    Odland LM, Mason RL, Alexeff AI. Bone density and dietary findings of 409 Tennessee subjects. 1. Bone density considerations. Am J Clin Nutr. 1972;25:905–7.PubMedGoogle Scholar
  137. 137.
    Hall SL, Greendale GA. The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int. 1998;63:183–9.PubMedGoogle Scholar
  138. 138.
    Prynne CJ, Mishra GD, O'Connell MA, Muniz G, Laskey MA, Yan L, Prentice A, Ginty F. Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Am J Clin Nutr. 2006;83:1420–8.PubMedGoogle Scholar
  139. 139.
    New SA, Bolton-Smith C, Grubb DA, Reid DM. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997;65:1831–9.PubMedGoogle Scholar
  140. 140.
    Tucker KL, Chen H, Hannan MT, Cupples LA, Wilson PW, Felson D, Kiel DP. Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. Am J Clin Nutr. 2002;76:245–52.PubMedGoogle Scholar
  141. 141.
    Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL. High vitamin C intake is associated with lower 4-year bone loss in elderly men. J Nutr. 2008;138:1931–8.PubMedCentralPubMedGoogle Scholar
  142. 142.
    Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL. Protective effect of total and supplemental vitamin C intake on the risk of hip fracture—a 17-year follow-up from the Framingham Osteoporosis Study. Osteoporos Int. 2009;20:1853–61.PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Department of EpidemiologyHelen Hayes Hospital and Columbia UniversityNew YorkUSA

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