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Published in:

01-03-2013 | Review

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D

Author: J. W. Nieves

Published in: Osteoporosis International | Issue 3/2013

Abstract

There is a need to understand the role of nutrition, beyond calcium and vitamin D, in the treatment and prevention of osteoporosis in adults. Results regarding soy compounds on bone density and bone turnover are inconclusive perhaps due to differences in dose and composition or in study population characteristics. The skeletal benefit of black cohosh and red clover are unknown. Dehydroepiandrosterone (DHEA) use may benefit elderly individuals with low serum dehydroepiandrosterone-sulfate levels, but even in this group, there are inconsistent benefits to bone density (BMD). Higher fruit and vegetable intakes may relate to higher BMD. The skeletal benefit of flavonoids, carotenoids, omega-3-fatty acids, and vitamins A, C, E and K are limited to observational data or a few clinical trials, in some cases investigating pharmacologic doses. Given limited data, it would be better to get these nutrients from fruits and vegetables. Potassium bicarbonate may improve calcium homeostasis but with little impact on bone loss. High homocysteine may relate to fracture risk, but the skeletal benefit of each B vitamin is unclear. Magnesium supplementation is likely only required in persons with low magnesium levels. Data are very limited for the role of nutritional levels of boron, strontium, silicon and phosphorus in bone health. A nutrient rich diet with adequate fruits and vegetables will generally meet skeletal needs in healthy individuals. For most healthy adults, supplementation with nutrients other than calcium and vitamin D may not be required, except in those with chronic disease and the frail elderly.

National Academy of Sciences IoM (2010) Dietary reference intakes for calcium and vitamin D. IoM,

Foundation NO (2010) Clinician’s guide to prevention and treatment of osteoporosis. Washington, DC

Rock CL (2007) Multivitamin-multimineral supplements: who uses them? Am J Clin Nutr 85:277S–279SPubMed

FDA (2009) Overview of dietary supplements. In. U.S. Department of Health and Human Services, Silver Spring, MD, 20993

Kruse SO, Lohning A, Pauli GF, Winterhoff H, Nahrstedt A (1999) Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med 65:763–764PubMedCrossRef

Chun OK, Chung SJ, Song WO (2009) Urinary isoflavones and their metabolites validate the dietary isoflavone intakes in US adults. J Am Diet Assoc 109:245–254PubMedCrossRef

Messina M, Nagata C, Wu AH (2006) Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 55:1–12PubMedCrossRef

Dietary Guidelines for Americans, (2010). In: Agriculture USDo, Services USDoHaH (eds), 7th edn. US Government Printing Office, Washington, DC

Atmaca A, Kleerekoper M, Bayraktar M, Kucuk O (2008) Soy isoflavones in the management of postmenopausal osteoporosis. Menopause 15:748–757PubMedCrossRef

10.

Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M (2009) Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. J Clin Endocrinol Metab 94:3798–3805PubMedCrossRef

11.

Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, Zheng W (2005) Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med 165:1890–1895PubMedCrossRef

12.

Ma DF, Qin LQ, Wang PY, Katoh R (2008) Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials. Clin Nutr 27:57–64PubMedCrossRef

13.

Messina M, Ho S, Alekel DL (2004) Skeletal benefits of soy isoflavones: a review of the clinical trial and epidemiologic data. Curr Opin Clin Nutr Metab Care 7:649–658PubMedCrossRef

14.

Brink E, Coxam V, Robins S, Wahala K, Cassidy A, Branca F (2008) 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 87:761–770PubMed

15.

Alekel DL, Van Loan MD, Koehler KJ, Hanson LN, Stewart JW, Hanson KB, Kurzer MS, Peterson CT (2010) The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women. Am J Clin Nutr 91:218–230PubMedCrossRef

16.

Levis S, Strickman-Stein N, Ganjei-Azar P, Xu P, Doerge DR, Krischer J (2011) Soy isoflavones in the prevention of menopausal bone loss and menopausal symptoms: a randomized, double-blind trial. Arch Intern Med 171:1363–1369PubMedCrossRef

17.

Kenny AM, Mangano KM, Abourizk RH, Bruno RS, Anamani DE, Kleppinger A, Walsh SJ, Prestwood KM, Kerstetter JE (2009) Soy proteins and isoflavones affect bone mineral density in older women: a randomized controlled trial. Am J Clin Nutr 90:234–242PubMedCrossRef

18.

Wong WW, Lewis RD, Steinberg FM et al (2009) Soy isoflavone supplementation and bone mineral density in menopausal women: a 2-y multicenter clinical trial. Am J Clin Nutr 90:1433–1439PubMedCrossRef

19.

Evans EM, Racette SB, Van Pelt RE, Peterson LR, Villareal DT (2007) Effects of soy protein isolate and moderate exercise on bone turnover and bone mineral density in postmenopausal women. Menopause 14:481-488

20.

Vupadhyayula PM, Gallagher JC, Templin T, Logsdon SM, Smith LM (2009) Effects of soy protein isolate on bone mineral density and physical performance indices in postmenopausal women—a 2-year randomized, double-blind, placebo-controlled trial. Menopause 16:320–328PubMedCrossRef

21.

Morabito N, Crisafulli A, Vergara C et al (2002) 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 17:1904–1912PubMedCrossRef

22.

Marini H, Minutoli L, Polito F et al (2007) Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med 146:839–847PubMed

23.

Marini H, Bitto A, Altavilla D, et al. (2008) Breast safety and efficacy of genistein aglycone for post-menopausal bone loss: a follow-up study. J Clin Endocrinol Metab 93:4787-4796

24.

Messina M, Redmond G (2006) Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature. Thyroid 16:249–258PubMedCrossRef

25.

Taylor CK, Levy RM, Elliott JC, Burnett BP (2009) The effect of genistein aglycone on cancer and cancer risk: a review of in vitro, preclinical and clinical studies. Nutr Rev 67:398-415

26.

Hooper L, Madhavan G, Tice JA, Leinster SJ, Cassidy A (2010) 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 16:745–760PubMedCrossRef

27.

Dong JY, Qin LQ (2011) Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat 125:315–323PubMedCrossRef

28.

Andres S, Abraham K, Appel KE, Lampen A (2011) Risks and benefits of dietary isoflavones for cancer. Crit Rev Toxicol 41:463–506PubMedCrossRef

29.

Lethaby AE, Brown J, Marjoribanks J, Kronenberg F, Roberts H, Eden J (2007) Phytoestrogens for vasomotor menopausal symptoms. Cochrane Database Syst Rev CD001395

30.

Atkinson C, Oosthuizen W, Scollen S, Loktionov A, Day NE, Bingham SA (2004) Modest protective effects of isoflavones from a red clover-derived dietary supplement on cardiovascular disease risk factors in perimenopausal women, and evidence of an interaction with ApoE genotype in 49–65 year-old women. J Nutr 134:1759–1764PubMed

31.

Booth NL, Piersen CE, Banuvar S, Geller SE, Shulman LP, Farnsworth NR (2006) Clinical studies of red clover (Trifolium pratense) dietary supplements in menopause: a literature review. Menopause 13:251–264PubMedCrossRef

32.

Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA, Tidy A (2008) Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int 14:6–12PubMedCrossRef

33.

Ohta H, Komukai S, Makita K, Masuzawa T, Nozawa S (1999) Effects of 1-year ipriflavone treatment on lumbar bone mineral density and bone metabolic markers in postmenopausal women with low bone mass. Horm Res 51:178–183PubMedCrossRef

34.

Zhang X, Li SW, Wu JF, Dong CL, Zheng CX, Zhang YP, Du J (2010) Effects of ipriflavone on postmenopausal syndrome and osteoporosis. Gynecol Endocrinol 26:76–80PubMedCrossRef

35.

Alexandersen P, Toussaint A, Christiansen C, Devogelaer JP, Roux C, Fechtenbaum J, Gennari C, Reginster JY (2001) Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. Jama 285:1482–1488PubMedCrossRef

36.

Ghebre MA, Hart DJ, Hakim AJ, Kato BS, Thompson V, Arden NK, Spector TD, Zhai G (2011) Association between DHEAS and bone loss in postmenopausal women: a 15-year longitudinal population-based study. Calcif Tissue Int 89:295–302PubMedCrossRef

37.

Office of Dietary Supplements, National Institutes of Health, http://ods.od.nih.gov/factsheets/blackcohosh.asp (2010) http://ods.od.nih.gov/factsheets/blackcohosh.asp Accessed 7/26/10 2010

38.

Qiu SX, Dan C, Ding LS, Peng S, Chen SN, Farnsworth NR, Nolta J, Gross ML, Zhou P (2007) A triterpene glycoside from black cohosh that inhibits osteoclastogenesis by modulating RANKL and TNFalpha signaling pathways. Chem Biol 14:860–869PubMedCrossRef

39.

Wuttke W, Gorkow C, Seidlova-Wuttke D (2006) Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Menopause 13:185–196PubMedCrossRef

40.

Bebenek M, Kemmler W, von Stengel S, Engelke K, Kalender WA (2010) Effect of exercise and Cimicifuga racemosa (CR BNO 1055) on bone mineral density, 10-year coronary heart disease risk, and menopausal complaints: the randomized controlled Training and Cimicifuga racemosa Erlangen (TRACE) study. Menopause 17:791–800PubMed

41.

Klein MA, Hartman TJ (2009) Guidance from an NIH workshop on designing, implementing, and reporting clinical studies of soy interventions. J Nutr 140:1192S-

42.

Wang YD, Tao MF, Cheng WW, Liu XH, Wan XP, Cui K (2012) Dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway. Chin Med J (Engl) 125:1230–1235

43.

Baulieu EE, Thomas G, Legrain S et al (2000) Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci U S A 97:4279–4284PubMedCrossRef

44.

Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS (1998) 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) 49:421–432CrossRef

45.

von Muhlen D, Laughlin GA, Kritz-Silverstein D, Bergstrom J, Bettencourt R (2008) Effect of dehydroepiandrosterone supplementation on bone mineral density, bone markers, and body composition in older adults: the DAWN trial. Osteoporos Int 19:699–707CrossRef

46.

Villareal DT, Holloszy JO, Kohrt WM (2000) Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol (Oxf) 53:561–568CrossRef

47.

Nair KS, Rizza RA, O’Brien P et al (2006) DHEA in elderly women and DHEA or testosterone in elderly men. N Engl J Med 355:1647–1659PubMedCrossRef

48.

Sun Y, Mao M, Sun L, Feng Y, Yang J, Shen P (2002) Treatment of osteoporosis in men using dehydroepiandrosterone sulfate. Chin Med J (Engl) 115:402–404

49.

Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31:266–300PubMedCrossRef

50.

Welch A, Macgregor A, Jennings A, Fairweather-Tait S, Spector T, Cassidy A (2012) Habitual flavonoid intakes are positively associated with bone mineral density in women. J Bone Miner Res 27:1872–1878PubMedCrossRef

51.

Hardcastle AC, Aucott L, Reid DM, Macdonald HM (2011) Associations between dietary flavonoid intakes and bone health in a Scottish population. J Bone Miner Res 26:941–947PubMedCrossRef

52.

Boyer J, Liu RH (2004) Apple phytochemicals and their health benefits. Nutr J 3:5PubMedCrossRef

53.

Wattel A, Kamel S, Prouillet C, Petit JP, Lorget F, Offord E, Brazier M (2004) Flavonoid quercetin decreases osteoclastic differentiation induced by RANKL via a mechanism involving NF kappa B and AP-1. J Cell Biochem 92:285–295PubMedCrossRef

54.

Woo JT, Nakagawa H, Notoya M, Yonezawa T, Udagawa N, Lee IS, Ohnishi M, Hagiwara H, Nagai K (2004) Quercetin suppresses bone resorption by inhibiting the differentiation and activation of osteoclasts. Biol Pharm Bull 27:504–509PubMedCrossRef

55.

Wattel A, Kamel S, Mentaverri R, Lorget F, Prouillet C, Petit JP, Fardelonne P, Brazier M (2003) Potent inhibitory effect of naturally occurring flavonoids quercetin and kaempferol on in vitro osteoclastic bone resorption. Biochem Pharmacol 65:35–42PubMedCrossRef

56.

Boots AW, Haenen GR, Bast A (2008) Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 585:325–337PubMedCrossRef

57.

Hay AW, Hassam AG, Crawford MA, Stevens PA, Mawer EB, Jones FS (1980) Essential fatty acid restriction inhibits vitamin D-dependent calcium absorption. Lipids 15:251–254PubMedCrossRef

58.

Hogstrom M, Nordstrom P, Nordstrom A (2007) 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 85:803–807PubMed

59.

Rousseau JH, Kleppinger A, Kenny AM (2009) Self-reported dietary intake of omega-3 fatty acids and association with bone and lower extremity function. J Am Geriatr Soc 57:1781–1788PubMedCrossRef

60.

Salari P, Rezaie A, Larijani B, Abdollahi M (2008) A systematic review of the impact of n-3 fatty acids in bone health and osteoporosis. Med Sci Monit 14:37–44

61.

Jarvinen R, Tuppurainen M, Erkkila AT, Penttinen P, Karkkainen M, Salovaara K, Jurvelin JS, Kroger H (2012) Associations of dietary polyunsaturated fatty acids with bone mineral density in elderly women. Eur J Clin Nutr 66:496–503PubMedCrossRef

62.

Eriksson S, Mellstrom D, Strandvik B (2009) Fatty acid pattern in serum is associated with bone mineralisation in healthy 8-year-old children. Br J Nutr 102:407–412PubMedCrossRef

63.

Weiss LA, Barrett-Connor E, von Muhlen D (2005) Ratio of n-6 to n-3 fatty acids and bone mineral density in older adults: the Rancho Bernardo Study. Am J Clin Nutr 81:934–938PubMed

64.

Orchard TS, Pan X, Cheek F, Ing SW, Jackson RD (2012) A systematic review of omega-3 fatty acids and osteoporosis. Br J Nutr 107(Suppl 2):S253–S260PubMedCrossRef

65.

Marik PE, Flemmer M (2012) Do dietary supplements have beneficial health effects in industrialized nations: what is the evidence? JPEN J Parenter Enteral Nutr 36:159–168PubMedCrossRef

66.

Yang Z, Zhang Z, Penniston KL, Binkley N, Tanumihardjo SA (2008) Serum carotenoid concentrations in postmenopausal women from the United States with and without osteoporosis. Int J Vitam Nutr Res 78:105–111PubMedCrossRef

67.

Wolf RL, Cauley JA, Pettinger M et al (2005) Lack of a relation between vitamin and mineral antioxidants and bone mineral density: results from the Women’s Health Initiative. Am J Clin Nutr 82:581–588PubMed

68.

Barker ME, McCloskey E, Saha S, Gossiel F, Charlesworth D, Powers HJ, Blumsohn A (2005) Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res 20:913–920PubMedCrossRef

69.

Pasco JA, Henry MJ, Wilkinson LK, Nicholson GC, Schneider HG, Kotowicz MA (2006) Antioxidant vitamin supplements and markers of bone turnover in a community sample of nonsmoking women. J Womens Health (Larchmt) 15:295–300CrossRef

70.

Sahni S, Hannan MT, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2009) 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 24:1086–1094PubMedCrossRef

71.

Feskanich D, Singh V, Willett WC, Colditz GA (2002) Vitamin A intake and hip fractures among postmenopausal women. Jama 287:47–54PubMedCrossRef

72.

Melhus H, Michaelsson K, Kindmark A, Bergstrom R, Holmberg L, Mallmin H, Wolk A, Ljunghall S (1998) Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 129:770–778PubMed

73.

Michaelsson K, Lithell H, Vessby B, Melhus H (2003) Serum retinol levels and the risk of fracture. N Engl J Med 348:287–294PubMedCrossRef

74.

Promislow JH, Goodman-Gruen D, Slymen DJ, Barrett-Connor E (2002) Retinol intake and bone mineral density in the elderly: the Rancho Bernardo Study. J Bone Miner Res 17:1349–1358PubMedCrossRef

75.

Ballew C, Galuska D, Gillespie C (2001) 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 16:2306–2312PubMedCrossRef

76.

Chuin A, Labonte M, Tessier D, Khalil A, Bobeuf F, Doyon CY, Rieth N, Dionne IJ (2009) Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int 20:1253–1258PubMedCrossRef

77.

Macdonald HM, New SA, Golden MH, Campbell MK, Reid DM (2004) 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 79:155–165PubMed

78.

Kaptoge S, Welch A, McTaggart A, Mulligan A, Dalzell N, Day NE, Bingham S, Khaw KT, Reeve J (2003) 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 14:418–428PubMedCrossRef

79.

Weber P (1999) The role of vitamins in the prevention of osteoporosis—a brief status report. Int J Vitam Nutr Res 69:194–197PubMedCrossRef

80.

Leveille SG, LaCroix AZ, Koepsell TD, Beresford SA, Van Belle G, Buchner DM (1997) Dietary vitamin C and bone mineral density in postmenopausal women in Washington State, USA. J Epidemiol Community Health 51:479–485PubMedCrossRef

81.

Hernandez-Avila M, Stampfer MJ, Ravnikar VA, Willett WC, Schiff I, Francis M, Longcope C, McKinlay SM, Longscope C (1993) Caffeine and other predictors of bone density among pre- and perimenopausal women. Epidemiology 4:128–134PubMedCrossRef

82.

Freudenheim JL, Johnson NE, Smith EL (1986) 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 44:863–876PubMed

83.

Sowers MR, Wallace RB, Lemke JH (1985) Correlates of mid-radius bone density among postmenopausal women: a community study. Am J Clin Nutr 41:1045–1053PubMed

84.

Odland LM, Mason RL, Alexeff AI (1972) Bone density and dietary findings of 409 Tennessee subjects. 1. Bone density considerations. Am J Clin Nutr 25:905–907PubMed

85.

Hall SL, Greendale GA (1998) The relation of dietary vitamin C intake to bone mineral density: results from the PEPI study. Calcif Tissue Int 63:183–189PubMedCrossRef

86.

Prynne CJ, Mishra GD, O’Connell MA, Muniz G, Laskey MA, Yan L, Prentice A, Ginty F (2006) Fruit and vegetable intakes and bone mineral status: a cross sectional study in 5 age and sex cohorts. Am J Clin Nutr 83:1420–1428PubMed

87.

New SA, Bolton-Smith C, Grubb DA, Reid DM (1997) Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr 65:1831–1839PubMed

88.

Tucker KL, Chen H, Hannan MT, Cupples LA, Wilson PW, Felson D, Kiel DP (2002) Bone mineral density and dietary patterns in older adults: the Framingham Osteoporosis Study. Am J Clin Nutr 76:245–252PubMed

89.

Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2008) High vitamin C intake is associated with lower 4-year bone loss in elderly men. J Nutr 138:1931–1938PubMed

90.

Sahni S, Hannan MT, Gagnon D, Blumberg J, Cupples LA, Kiel DP, Tucker KL (2009) 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 20:1853–1861PubMedCrossRef

91.

Binkley N, Harke J, Krueger D, Engelke J, Vallarta-Ast N, Gemar D, Checovich M, Chappell R, Suttie J (2009) Vitamin K treatment reduces undercarboxylated osteocalcin but does not alter bone turnover, density, or geometry in healthy postmenopausal North American women. J Bone Miner Res 24:983–991PubMedCrossRef

92.

Feskanich D, Weber P, Willett WC, Rockett H, Booth SL, Colditz GA (1999) Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr 69:74–79PubMed

93.

Booth SL, Broe KE, Gagnon DR, Tucker KL, Hannan MT, McLean RR, Dawson-Hughes B, Wilson PW, Cupples LA, Kiel DP (2003) Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr 77:512–516PubMed

94.

Booth SL, Tucker KL, Chen H et al (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 71:1201–1208PubMed

95.

Cheung AM, Tile L, Lee Y et al (2008) Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med 5:e196PubMedCrossRef

96.

Braam LA, Knapen MH, Geusens P, Brouns F, Hamulyak K, Gerichhausen MJ, Vermeer C (2003) Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 73:21–26PubMedCrossRef

97.

Emaus N, Gjesdal CG, Almas B, Christensen M, Grimsgaard AS, Berntsen GK, Salomonsen L, Fonnebo V (2010) Vitamin K2 supplementation does not influence bone loss in early menopausal women: a randomised double-blind placebo-controlled trial. Osteoporos Int 21:1731–1740PubMedCrossRef

98.

Bolton-Smith C, McMurdo ME, Paterson CR, Mole PA, Harvey JM, Fenton ST, Prynne CJ, Mishra GD, Shearer MJ (2007) Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res 22:509–519PubMedCrossRef

99.

Booth SL, Dallal G, Shea MK, Gundberg C, Peterson JW, Dawson-Hughes B (2008) Effect of vitamin K supplementation on bone loss in elderly men and women. J Clin Endocrinol Metab 93:1217–1223PubMedCrossRef

100.

Cockayne S, Adamson J, Lanham-New S, Shearer MJ, Gilbody S, Torgerson DJ (2006) Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 166:1256–1261PubMedCrossRef

101.

Inoue T, Fujita T, Kishimoto H, Makino T, Nakamura T, Sato T, Yamazaki K (2009) Randomized controlled study on the prevention of osteoporotic fractures (OF study): a phase IV clinical study of 15-mg menatetrenone capsules. J Bone Miner Metab 27:66–75PubMedCrossRef

102.

Orimo H, Shiraki M, Tomita A, Morii H, Fujita T, Ohata M (1998) Effects of menatetrenone on the bone and calcium metabolism in osteoporosis: a double-blind placebo-controlled study. J Bone Miner Metab 16:106–112CrossRef

103.

Shiraki M, Shiraki Y, Aoki C, Miura M (2000) Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res 15:515–521PubMedCrossRef

104.

Iwamoto J, Sato Y, Takeda T, Matsumoto H (2009) High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res 29:221–228PubMedCrossRef

105.

Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP (1999) Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr 69:727–736PubMed

106.

Arnett TR, Dempster DW (1986) Effect of pH on bone resorption by rat osteoclasts in vitro. Endocrinology 119:119–124PubMedCrossRef

107.

Bushinsky DA (1996) Metabolic alkalosis decreases bone calcium efflux by suppressing osteoclasts and stimulating osteoblasts. Am J Physiol 271:F216–F222PubMed

108.

He FJ, Marciniak M, Carney C, Markandu ND, Anand V, Fraser WD, Dalton RN, Kaski JC, MacGregor GA (2010) Effects of potassium chloride and potassium bicarbonate on endothelial function, cardiovascular risk factors, and bone turnover in mild hypertensives. Hypertension 55:681–688PubMedCrossRef

109.

Ceglia L, Harris SS, Abrams SA, Rasmussen HM, Dallal GE, Dawson-Hughes B (2009) Potassium bicarbonate attenuates the urinary nitrogen excretion that accompanies an increase in dietary protein and may promote calcium absorption. J Clin Endocrinol Metab 94:645–653PubMedCrossRef

110.

Dawson-Hughes B, Harris SS, Palermo NJ, Castaneda-Sceppa C, Rasmussen HM, Dallal GE (2009) Treatment with potassium bicarbonate lowers calcium excretion and bone resorption in older men and women. J Clin Endocrinol Metab 94:96–102PubMedCrossRef

111.

Macdonald HM, Black AJ, Aucott L, Duthie G, Duthie S, Sandison R, Hardcastle AC, Lanham New SA, Fraser WD, Reid DM (2008) 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 88:465–474PubMed

112.

van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM et al (2004) Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 350:2033–2041PubMedCrossRef

113.

Gjesdal CG, Vollset SE, Ueland PM, Refsum H, Drevon CA, Gjessing HK, Tell GS (2006) Plasma total homocysteine level and bone mineral density: the Hordaland Homocysteine Study. Arch Intern Med 166:88–94PubMedCrossRef

114.

Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA (2005) Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 20:921–929PubMedCrossRef

115.

McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, Hannan MT, Cupples LA, Kiel DP (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042–2049PubMedCrossRef

116.

Ravaglia G, Forti P, Maioli F, Servadei L, Martelli M, Brunetti N, Bastagli L, Cucinotta D, Mariani E (2005) Folate, but not homocysteine, predicts the risk of fracture in elderly persons. J Gerontol A Biol Sci Med Sci 60:1458–1462PubMedCrossRef

117.

Tucker KL, Hannan MT, Qiao N, Jacques PF, Selhub J, Cupples LA, Kiel DP (2005) Low plasma vitamin B12 is associated with lower BMD: the Framingham Osteoporosis Study. J Bone Miner Res 20:152–158PubMedCrossRef

118.

Dhonukshe-Rutten RA, Lips M, de Jong N, Chin APMJ, Hiddink GJ, van Dusseldorp M, De Groot LC, van Staveren WA (2003) Vitamin B-12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men. J Nutr 133:801–807PubMed

119.

Morris MS, Jacques PF, Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37:234–242PubMedCrossRef

120.

Stone KL, Bauer DC, Sellmeyer D, Cummings SR (2004) Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study. J Clin Endocrinol Metab 89:1217–1221PubMedCrossRef

121.

McLean RR, Jacques PF, Selhub J, Fredman L, Tucker KL, Samelson EJ, Kiel DP, Cupples LA, Hannan MT (2008) Plasma B vitamins, homocysteine, and their relation with bone loss and hip fracture in elderly men and women. J Clin Endocrinol Metab 93:2206–2212PubMedCrossRef

122.

Refsum H, Nurk E, Smith AD, Ueland PM, Gjesdal CG, Bjelland I, Tverdal A, Tell GS, Nygard O, Vollset SE (2006) The Hordaland Homocysteine Study: a community-based study of homocysteine, its determinants, and associations with disease. J Nutr 136:1731S–1740SPubMed

123.

Baines M, Kredan MB, Davison A, Higgins G, West C, Fraser WD, Ranganath LR (2007) The association between cysteine, bone turnover, and low bone mass. Calcif Tissue Int 81:450–454PubMedCrossRef

124.

Cagnacci A, Bagni B, Zini A, Cannoletta M, Generali M, Volpe A (2008) Relation of folates, vitamin B12 and homocysteine to vertebral bone mineral density change in postmenopausal women. A five-year longitudinal evaluation. Bone 42:314–320PubMedCrossRef

125.

Cagnacci A, Baldassari F, Rivolta G, Arangino S, Volpe A (2003) Relation of homocysteine, folate, and vitamin B12 to bone mineral density of postmenopausal women. Bone 33:956–959PubMedCrossRef

126.

Rejnmark L, Vestergaard P, Hermann AP, Brot C, Eiken P, Mosekilde L (2008) 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 82:1–11PubMedCrossRef

127.

Herrmann M, Stanger O, Paulweber B, Hufnagl C, Herrmann W (2006) Folate supplementation does not affect biochemical markers of bone turnover. Clin Lab 52:131–136PubMed

128.

Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K (2005) Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. Jama 293:1082–1088PubMedCrossRef

129.

McLean RR, Hannan MT (2007) B vitamins, homocysteine, and bone disease: epidemiology and pathophysiology. Curr Osteoporos Rep 5:112–119PubMedCrossRef

130.

van Wijngaarden JP, Dhonukshe-Rutten RA, van Schoor NM et al (2011) 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 11:80PubMedCrossRef

131.

Nicklas TA, O’Neil CE, Fulgoni VL 3rd (2009) The role of dairy in meeting the recommendations for shortfall nutrients in the American diet. J Am Coll Nutr 28(Suppl 1):73S–81SPubMed

132.

Wang MC, Moore EC, Crawford PB, Hudes M, Sabry ZI, Marcus R, Bachrach LK (1999) Influence of pre-adolescent diet on quantitative ultrasound measurements of the calcaneus in young adult women. Osteoporos Int 9:532–535PubMed

133.

Carpenter TO, DeLucia MC, Zhang JH, Bejnerowicz G, Tartamella L, Dziura J, Petersen KF, Befroy D, Cohen D (2006) A randomized controlled study of effects of dietary magnesium oxide supplementation on bone mineral content in healthy girls. J Clin Endocrinol Metab 91:4866–4872PubMedCrossRef

134.

Song CH, Barrett-Connor E, Chung JH, Kim SH, Kim KS (2007) Associations of calcium and magnesium in serum and hair with bone mineral density in premenopausal women. Biol Trace Elem Res 118:1–9PubMedCrossRef

135.

New SA, Robins SP, Campbell MK, Martin JC, Garton MJ, Bolton-Smith C, Grubb DA, Lee SJ, Reid DM (2000) 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 71:142–151PubMed

136.

Houtkooper LB, Ritenbaugh C, Aickin M, Lohman TG, Going SB, Weber JL, Greaves KA, Boyden TW, Pamenter RW, Hall MC (1995) Nutrients, body composition and exercise are related to change in bone mineral density in premenopausal women. J Nutr 125:1229–1237PubMed

137.

Tranquilli AL, Lucino E, Garzetti GG, Romanini C (1994) Calcium, phosphorus and magnesium intakes correlate with bone mineral content in postmenopausal women. Gynecol Endocrinol 8:55–58PubMedCrossRef

138.

Ryder KM, Shorr RI, Bush AJ, Kritchevsky SB, Harris T, Stone K, Cauley J, Tylavsky FA (2005) Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects. J Am Geriatr Soc 53:1875–1880PubMedCrossRef

139.

Nielsen FH (1990) Studies on the relationship between boron and magnesium which possibly affects the formation and maintenance of bones. Magnes Trace Elem 9:61–69PubMedCrossRef

140.

Stendig-Lindberg G, Tepper R, Leichter I (1993) Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res 6:155–163PubMed

141.

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 p 31

142.

Durlach J, Bac P, Durlach V, Rayssiguier Y, Bara M, Guiet-Bara A (1998) Magnesium status and ageing: an update. Magnes Res 11:25–42PubMed

143.

Rude RK, Olerich M (1996) Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int 6:453–461PubMedCrossRef

144.

Nielsen FH (2008) Is boron nutritionally relevant? Nutr Rev 66:183–191PubMedCrossRef

145.

Nielsen FH (1998) The justification for providing dietary guidance for the nutritional intake of boron. Biol Trace Elem Res 66:319–330PubMedCrossRef

146.

Sutherland B, Strong P, King JC (1998) Determining human dietary requirements for boron. Biol Trace Elem Res 66:193–204PubMedCrossRef

147.

Nielsen FH, Hunt CD, Mullen LM, Hunt JR (1987) Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J 1:394–397PubMed

148.

Hunt CD, Herbel JL, Nielsen FH (1997) 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 65:803–813PubMed

149.

Jugdaohsingh R (2007) Silicon and bone health. J Nutr Health Aging 11:99–110PubMed

150.

Micronutrients Po, Nutrients SoURLo, Interpretation o, Intakes UoDR, Intakes SCotSEoDR (2001) Dietary reference intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. The National Academies Press, Washington, DC

151.

McNaughton SA, Bolton-Smith C, Mishra GD, Jugdaohsingh R, Powell JJ (2005) Dietary silicon intake in post-menopausal women. Br J Nutr 94:813–817PubMedCrossRef

152.

Bisse E, Epting T, Beil A, Lindinger G, Lang H, Wieland H (2005) Reference values for serum silicon in adults. Anal Biochem 337:130–135PubMedCrossRef

153.

Jugdaohsingh R, Tucker KL, Qiao N, Cupples LA, Kiel DP, Powell JJ (2004) Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort. J Bone Miner Res 19:297–307PubMedCrossRef

154.

Tucker KL, Jugdaohsingh R, Powell JJ, Qiao N, Hannan MT, Sripanyakorn S, Cupples LA, Kiel DP (2009) Effects of beer, wine, and liquor intakes on bone mineral density in older men and women. Am J Clin Nutr 89:1188–1196PubMedCrossRef

155.

Meunier PJ, Roux C, Seeman E et al (2004) The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med 350:459–468PubMedCrossRef

156.

Reginster JY, Felsenberg D, Boonen S et al (2008) 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 58:1687–1695PubMedCrossRef

157.

Calvo MS, Carpenter TO (2003) Nutritional aspects of bone health. In: Bonjour SINJ-P (ed) Influence of phosphorus on the skeleton. Royal Chemistry Society, Cambridge, UK, pp 229–265

158.

Tucker KL, Morita K, Qiao N, Hannan MT, Cupples LA, Kiel DP (2006) Colas, but not other carbonated beverages, are associated with low bone mineral density in older women: the Framingham Osteoporosis Study. Am J Clin Nutr 84:936–942PubMed

159.

Pinheiro MM, Schuch NJ, Genaro PS, Ciconelli RM, Ferraz MB, Martini LA (2009) Nutrient intakes related to osteoporotic fractures in men and women—the Brazilian Osteoporosis Study (BRAZOS). Nutr J 8:6PubMedCrossRef

160.

Meier C, Kranzlin ME (2011) Calcium supplementation, osteoporosis and cardiovascular disease. Swiss Med Wkly 141:w13260PubMed

161.

Reid IR, Bolland MJ, Avenell A, Grey A (2011) Cardiovascular effects of calcium supplementation. Osteoporos Int 22:1649–1658PubMedCrossRef

162.

Burckhardt P (2011) Potential negative cardiovascular effects of calcium supplements. Osteoporos Int 22:1645–1647PubMedCrossRef

163.

Shea B, Wells G, Cranney A et al (2002) Meta-analyses of therapies for postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for the prevention of postmenopausal osteoporosis. Endocr Rev 23:552–559PubMedCrossRef

164.

Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A (2007) Use of calcium or calcium in combination with vitamin D supplementation to prevent fractures and bone loss in people aged 50 years and older: a meta-analysis. Lancet 370:657–666PubMedCrossRef

165.

Chung M, Balk EM, Brendel M, et al. (2009) Vitamin D and calcium: a systematic review of health outcomes. Evid Rep Technol Assess (Full Rep) 1–420

166.

Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B (2005) Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. Jama 293:2257–2264PubMedCrossRef

167.

Spangler M, Phillips BB, Ross MB, Moores KG (2011) Calcium supplementation in postmenopausal women to reduce the risk of osteoporotic fractures. Am J Health Syst Pharm 68:309–318PubMedCrossRef

168.

Reid IR, Bolland MJ, Grey A (2008) Effect of calcium supplementation on hip fractures. Osteoporos Int 19:1119–1123PubMedCrossRef

169.

Foundation NO (2008) Clinicians guide for prevention and treatment of osteoporosis. NOF, Washington, DC

170.

Heaney RP, Dowell MS, Hale CA, Bendich A (2003) Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr 22:142–146PubMed

171.

Bischoff HA, Stahelin HB, Dick W et al (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351PubMedCrossRef

172.

Bischoff-Ferrari HA, Zhang Y, Kiel DP, Felson DT (2005) Positive association between serum 25-hydroxyvitamin D level and bone density in osteoarthritis. Arthritis Rheum 53:821–826PubMedCrossRef

173.

Bischoff-Ferrari HA, Dietrich T, Orav EJ, Hu FB, Zhang Y, Karlson EW, Dawson-Hughes B (2004) Higher 25-hydroxyvitamin D concentrations are associated with better lower-extremity function in both active and inactive persons aged > or =60 y. Am J Clin Nutr 80:752–758PubMed

174.

Boonen S, Lips P, Bouillon R, Bischoff-Ferrari HA, Vanderschueren D, Haentjens P (2007) Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J Clin Endocrinol Metab 92:1415–1423PubMedCrossRef

175.

Avenell A, Gillespie WJ, Gillespie LD, O’Connell D (2009) Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev CD000227

176.

The DIPART, B Abrahamsen (2010) Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ 340:b5463

Title: Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D
Author: J. W. Nieves
Publication date: 01-03-2013
Publisher: Springer-Verlag
Published in: Osteoporosis International / Issue 3/2013
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-012-2214-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Skeletal effects of nutrients and nutraceuticals, beyond calcium and vitamin D

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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