Skip to main content

Advertisement

Log in

Nutritional Supplements and Skeletal Health

  • Therapeutics and Medical Management (S Jan De Beur and B Clarke, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available.

Recent Findings

Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited.

Summary

The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. Johnell O, Kanis J. Epidemiology of osteoporotic fractures. Osteoporos Int. 2005;16(Suppl 2):S3–7.

    Article  PubMed  Google Scholar 

  2. Carlberg C. Endocrine functions of vitamin D. Mol Cell Endocrinol. 2017;453:1–2.

    Article  CAS  PubMed  Google Scholar 

  3. Bailey RL, Dodd KW, Goldman JA, Gahche JJ, Dwyer JT, Moshfegh AJ, et al. Estimation of total usual calcium and vitamin D intakes in the United States. J Nutr. 2010;140:817–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Institute of Medicine (US). Dietary Reference Intakes for Calcium and Vitamin D. Washington DC: The National Academies Press; 2011.

    Google Scholar 

  5. Parva NR, et al. Prevalence of vitamin D deficiency and associated risk factors in the US population (2011-2012). Cureus. 2018;10:e2741.

    PubMed  PubMed Central  Google Scholar 

  6. Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012;3:118–26.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Lips P, Cashman KD, Lamberg-Allardt C, Bischoff-Ferrari HA, Obermayer-Pietsch B, Bianchi ML, et al. Current vitamin D status in European and Middle East countries and strategies to prevent vitamin D deficiency: a position statement of the European Calcified Tissue Society. Eur J Endocrinol. 2019;180:P23–54.

    Article  CAS  PubMed  Google Scholar 

  8. Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016;27:1281–386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chung M, Lee J, Terasawa T, Lau J, Trikalinos TA. Vitamin D with or without calcium supplementation for prevention of cancer and fractures: an updated meta-analysis for the U.S. Preventive Services Task Force. Ann Intern Med. 2011;155:827–38.

    Article  PubMed  Google Scholar 

  10. Tang BM, Eslick GD, Nowson C, Smith C, Bensoussan A. 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. 2007;370:657–66.

    Article  CAS  PubMed  Google Scholar 

  11. Eleni A, Panagiotis P. A systematic review and meta-analysis of vitamin D and calcium in preventing osteoporotic fractures. Clin Rheumatol. 2020;39:3571–9.

    Article  PubMed  Google Scholar 

  12. Yao P, Bennett D, Mafham M, Lin X, Chen Z, Armitage J, et al. Vitamin D and calcium for the prevention of fracture: a systematic review and meta-analysis. JAMA Netw Open. 2019;2:e1917789.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Chakhtoura M, Chamoun N, Rahme M, Fuleihan GE. Impact of vitamin D supplementation on falls and fractures-a critical appraisal of the quality of the evidence and an overview of the available guidelines. Bone. 2020;131:115112.

    Article  CAS  PubMed  Google Scholar 

  14. DIPART (Vitamin D Individual Patient Analysis of Randomized Trials) Group. Patient level pooled analysis of 68 500 patients from seven major vitamin D fracture trials in US and Europe. BMJ. 2010;340:b5463.

    Article  Google Scholar 

  15. Bolland MJ, et al. Calcium intake and risk of fracture: systematic review. BMJ. 2015;351:h4580.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Avenell A, Mak JC, O'Connell D. Vitamin D and vitamin D analogues for preventing fractures in post-menopausal women and older men. Cochrane Database Syst Rev. 2014;4:CD000227.

    Google Scholar 

  17. Weaver CM, Alexander DD, Boushey CJ, Dawson-Hughes B, Lappe JM, LeBoff MS, et al. Calcium plus vitamin D supplementation and risk of fractures: an updated meta-analysis from the National Osteoporosis Foundation. Osteoporos Int. 2016;27:367–76.

    Article  CAS  PubMed  Google Scholar 

  18. Zhao JG, Zeng XT, Wang J, Liu L. Association between calcium or Vitamin D supplementation and fracture incidence in community-dwelling older adults: a systematic review and meta-analysis. JAMA. 2017;318:2466–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. US Preventive Services Task Force, et al. Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: US Preventive Services Task Force Recommendation Statement. JAMA. 2018;319:1592–9.

    Article  Google Scholar 

  20. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257–64.

    Article  CAS  PubMed  Google Scholar 

  21. Bischoff-Ferrari HA, Orav EJ, Abderhalden L, Dawson-Hughes B, Willett WC. Vitamin D supplementation and musculoskeletal health. Lancet Diabetes Endocrinol. 2019;7:85–8587(18)30347.

    Article  Google Scholar 

  22. Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JP. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348:g2035.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, et al. Annual high-dose oral vitamin D and falls and fractures in older women: a randomized controlled trial. JAMA. 2010;303:1815–22.

    Article  CAS  PubMed  Google Scholar 

  24. Bischoff-Ferrari HA, Dawson-Hughes B, Orav EJ, Staehelin HB, Meyer OW, Theiler R, et al. Monthly high-dose vitamin D treatment for the prevention of functional decline: a randomized clinical trial. JAMA Intern Med. 2016;176:175–83.

    Article  PubMed  Google Scholar 

  25. Weaver CM, Heaney RP. Calcium in human health. In: Weaver CM, Heaney RP, editors. Nutrition and Health: Humana Press; 2006.

  26. Recker RR. Calcium absorption and achlorhydria. N Engl J Med. 1985;313:70–3.

    Article  CAS  PubMed  Google Scholar 

  27. Keller JL, Lanou A, Barnard ND. The consumer cost of calcium from food and supplements. J Am Diet Assoc. 2002;102:1669–71.

    Article  PubMed  Google Scholar 

  28. Ramsubeik K, Keuler NS, Davis LA, Hansen KE. Factors associated with calcium absorption in postmenopausal women: a post hoc analysis of dual-isotope studies. J Acad Nutr Diet. 2014;114:761–7.

    Article  PubMed  Google Scholar 

  29. Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Ziegler TE, Penniston KL, et al. Do proton pump inhibitors decrease calcium absorption? J Bone Miner Res. 2010;25:2786–95.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Wright MJ, Sullivan RR, Gaffney-Stomberg E, Caseria DM, O'Brien KO, Proctor DD, et al. Inhibiting gastric acid production does not affect intestinal calcium absorption in young, healthy individuals: a randomized, crossover, controlled clinical trial. J Bone Miner Res. 2010;25:2205–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies). Dietary reference values for vitamin D. EFSA J. 2016;14:4547.

    Google Scholar 

  32. UK Scientific Advisory Committee on Nutrition. Vitamin D and health. 2016. https://www.gov.uk/government/publications/sacn-vitamin-d-and-health-report.

  33. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011;96:1911–30.

    Article  CAS  PubMed  Google Scholar 

  34. Dawson-Hughes B, Mithal A, Bonjour JP, Boonen S, Burckhardt P, Fuleihan GEH, et al. IOF position statement: vitamin D recommendations for older adults. Osteoporos Int. 2010;21:1151–4.

    Article  CAS  PubMed  Google Scholar 

  35. Camacho PM, Petak SM, Binkley N, Diab DL, Eldeiry LS, Farooki A, et al. American Association of Clinical Endocrinologists/American College of Endocrinology Clinical Practice Guidelines for the diagnosis and treatment of postmenopausal osteoporosis- 2020 update executive summary. Endocr Pract. 2020;26:564–70.

    Article  PubMed  Google Scholar 

  36. Macdonald HM, Reid IR, Gamble GD, Fraser WD, Tang JC, Wood AD. 25-Hydroxyvitamin D threshold for the effects of vitamin D supplements on bone density: secondary analysis of a randomized controlled trial. J Bone Miner Res. 2018;33:1464–9.

    Article  CAS  PubMed  Google Scholar 

  37. Durazo-Arvizu RA, et al. Three-phase model harmonizes estimates of the maximal suppression of parathyroid hormone by 25-hydroxyvitamin D in persons 65 years of age and older. J Nutr. 2010;140:595–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Kincse G, Varga J, Somogyi P, Szodoray P, Surányi P, Gaál J. The impact of secondary hyperparathyroidism on the efficacy of antiresorptive therapy. BMC Musculoskelet Disord. 2012;13:244–2474.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Cellini M, Piccini S, Ferrante G, Carrone F, Olivetti R, Cicorella N, et al. Secondary hyperparathyroidism and thoracic vertebral fractures in heart failure middle-aged patients: a 3-year prospective study. J Endocrinol Investig. 2020;43:1561–9.

    Article  CAS  Google Scholar 

  40. Dadra A, Aggarwal S, Kumar P, Kumar V, Dibar DP, Bhadada SK. High prevalence of vitamin D deficiency and osteoporosis in patients with fragility fractures of hip: a pilot study. J Clin Orthop Trauma. 2019;10:1097–100.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Gomez-Alonso C, et al. Vitamin D status and secondary hyperparathyroidism: the importance of 25-hydroxyvitamin D cut-off levels. Kidney Int Suppl. 2003;85:S44–8.

    Article  CAS  Google Scholar 

  42. Berger C, Almohareb O, Langsetmo L, Hanley DA, Kovacs CS, Josse RG, et al. Characteristics of hyperparathyroid states in the Canadian multicentre osteoporosis study (CaMos) and relationship to skeletal markers. Clin Endocrinol. 2015;82(359–368):359–68.

    Article  CAS  Google Scholar 

  43. Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22:142–6.

    Article  CAS  PubMed  Google Scholar 

  44. Aloia JF, Dhaliwal R, Shieh A, Mikhail M, Fazzari M, Ragolia L, et al. Vitamin D supplementation increases calcium absorption without a threshold effect. Am J Clin Nutr. 2014;99:624–31.

    Article  CAS  PubMed  Google Scholar 

  45. Schild A, Herter-Aeberli I, Fattinger K, Anderegg S, Schulze-König T, Vockenhuber C, et al. Oral vitamin D supplements increase serum 25-Hydroxyvitamin D in postmenopausal women and reduce bone calcium flux measured by 41Ca skeletal labeling. J Nutr. 2015;145:2333–40.

    Article  CAS  PubMed  Google Scholar 

  46. Priemel M, von Domarus C, Klatte TO, Kessler S, Schlie J, Meier S, et al. Bone mineralization defects and vitamin D deficiency: histomorphometric analysis of iliac crest bone biopsies and circulating 25-hydroxyvitamin D in 675 patients. J Bone Miner Res. 2010;25:305–12.

    Article  CAS  PubMed  Google Scholar 

  47. Reid I, Vitamin R. D effect on bone mineral density and fractures. Endocrinol Metab Clin N Am. 2017;46:935–45.

    Article  Google Scholar 

  48. Harvey NC, Biver E, Kaufman JM, Bauer J, Branco J, Brandi ML, et al. The role of calcium supplementation in healthy musculoskeletal ageing : an expert consensus meeting of the European Society for Clinical and Economic Aspects of osteoporosis, osteoarthritis and musculoskeletal diseases (ESCEO) and the International Foundation for Osteoporosis (IOF). Osteoporos Int. 2017;28:447–62.

    Article  CAS  PubMed  Google Scholar 

  49. Bauer DC. Clinical practice. Calcium supplements and fracture prevention. N Engl J Med. 2013;369:1537–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Wallace RB, Wactawski-Wende J, O’Sullivan MJ, Larson JC, Cochrane B, Gass M, et al. Urinary tract stone occurrence in the Women’s Health Initiative (WHI) randomized clinical trial of calcium and vitamin D supplements. Am J Clin Nutr. 2011;94:270–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Reid IR, Avenell A, Grey A, Bolland MJ. Calcium intake and cardiovascular disease risk. Ann Intern Med. 2017;166:684–5.

    Article  PubMed  Google Scholar 

  52. Melamed ML, Michos ED, Post W, Astor B. 25-hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med. 2008;168:1629–37.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Ginde AA, Scragg R, Schwartz RS, Camargo CA. Prospective study of serum 25-hydroxyvitamin D level, cardiovascular disease mortality, and all-cause mortality in older U.S. adults. J Am Geriatr Soc. 2009;57:1595–603.

    Article  PubMed  Google Scholar 

  54. • Kopecky SL, et al. Lack of evidence linking calcium with or without vitamin D supplementation to cardiovascular disease in generally healthy adults: a clinical guideline from the National Osteoporosis Foundation and the American Society for Preventive Cardiology. Ann Intern Med. 2016;165:867–8. Joint organization data review concluding no relationship between calcium and/or vitamin D supplements and vascular disease.

  55. Bjelakovic G, et al. Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev. 2014;1:CD007470.

    Google Scholar 

  56. Moe SM. Rationale to reduce calcium intake in adult patients with chronic kidney disease. Curr Opin Nephrol Hypertens. 2018;27:251–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Tzaphlidou M. Bone architecture: collagen structure and calcium/phosphorus maps. J Biol Phys. 2008;34:39–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Institute of Medicine (US). in Dietary Reference Intakes for Energy. Carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. Washington, DC: The National Academies Press; 2005.

    Google Scholar 

  59. Lonnie M, et al. Protein for life: review of optimal protein intake, sustainable dietary sources and the effect on appetite in ageing adults. Nutrients. 2018;10. https://doi.org/10.3390/nu10030360.

  60. Wolfe RR, Cifelli AM, Kostas G, Kim IY. Optimizing protein intake in adults: interpretation and application of the recommended dietary allowance compared with the acceptable macronutrient distribution range. Adv Nutr. 2017;8:266–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Koutsofta I, Mamais I, Chrysostomou S. The effect of protein diets in postmenopausal women with osteoporosis: systematic review of randomized controlled trials. J Women Aging. 2019;31:117–39.

    Article  PubMed  Google Scholar 

  62. Darling AL, Manders RJF, Sahni S, Zhu K, Hewitt CE, Prince RL, et al. Dietary protein and bone health across the life-course: an updated systematic review and meta-analysis over 40 years. Osteoporos Int. 2019;30:741–61.

    Article  CAS  PubMed  Google Scholar 

  63. Shams-White MM, Chung M, du M, Fu Z, Insogna KL, Karlsen MC, et al. Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. Am J Clin Nutr. 2017;105:1528–43.

    CAS  PubMed  Google Scholar 

  64. Rizzoli R, Biver E, Bonjour JP, Coxam V, Goltzman D, Kanis JA, et al. Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical Aspects of osteoporosis, osteoarthritis, and musculoskeletal diseases and by the International Osteoporosis Foundation. Osteoporos Int. 2018;29:1933–48.

    Article  CAS  PubMed  Google Scholar 

  65. Wallace TC, Frankenfeld CL. Dietary protein intake above the current RDA and bone health: a systematic review and meta-analysis. J Am Coll Nutr. 2017;36:481–96.

    Article  CAS  PubMed  Google Scholar 

  66. Shams-White MM, Chung M, Fu Z, Insogna KL, Karlsen MC, LeBoff MS, et al. Animal versus plant protein and adult bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. PLoS One. 2018;13:e0192459.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Frassetto L, Banerjee T, Powe N, Sebastian A. Acid balance, dietary acid load, and bone effects-a controversial subject. Nutrients. 2018;10. https://doi.org/10.3390/nu10040517.

  68. Tabatabai LS, Cummings SR, Tylavsky FA, Bauer DC, Cauley JA, Kritchevsky SB, et al. Arterialized venous bicarbonate is associated with lower bone mineral density and an increased rate of bone loss in older men and women. J Clin Endocrinol Metab. 2015;100:1343–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Chen W, Melamed ML, Abramowitz MK. Serum bicarbonate and bone mineral density in US adults. Am J Kidney Dis. 2015;65:240–8.

    Article  CAS  PubMed  Google Scholar 

  70. Moseley KF, Weaver CM, Appel L, Sebastian A, Sellmeyer DE. Potassium citrate supplementation results in sustained improvement in calcium balance in older men and women. J Bone Miner Res. 2013;28:497–504.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Dawson-Hughes B, Harris SS, Palermo NJ, Gilhooly CH, Shea MK, Fielding RA, et al. Potassium bicarbonate supplementation lowers bone turnover and calcium excretion in older men and women: a randomized dose-finding trial. J Bone Miner Res. 2015;30:2103–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Jehle S, Zanetti A, Muser J, Hulter HN, Krapf R. Partial neutralization of the acidogenic Western diet with potassium citrate increases bone mass in postmenopausal women with osteopenia. J Am Soc Nephrol. 2006;17:3213–22.

    Article  CAS  PubMed  Google Scholar 

  73. Macdonald HM, Black AJ, Aucott L, Duthie G, Duthie S, Sandison R, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  74. Jehle S, Hulter HN, Krapf R. Effect of potassium citrate on bone density, microarchitecture, and fracture risk in healthy older adults without osteoporosis: a randomized controlled trial. J Clin Endocrinol Metab. 2013;98:207–17.

    Article  CAS  PubMed  Google Scholar 

  75. Park CY, Weaver CM. Vitamin D interactions with soy isoflavones on bone after menopause: a review. Nutrients. 2012;4:1610–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Weaver CM, Cheong JM. Soy isoflavones and bone health: the relationship is still unclear. J Nutr. 2005;135:1243–7.

    Article  CAS  PubMed  Google Scholar 

  77. Pawlowski JW, Martin BR, McCabe GP, McCabe L, Jackson GS, Peacock M, et al. Impact of equol-producing capacity and soy-isoflavone profiles of supplements on bone calcium retention in postmenopausal women: a randomized crossover trial. Am J Clin Nutr. 2015;102:695–703.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Taku K, Melby MK, Takebayashi J, Mizuno S, Ishimi Y, Omori T, et al. Effect of soy isoflavone extract supplements on bone mineral density in menopausal women: meta-analysis of randomized controlled trials. Asia Pac J Clin Nutr. 2010;19:33–42.

    CAS  PubMed  Google Scholar 

  79. Ricci E, Cipriani S, Chiaffarino F, Malvezzi M, Parazzini F. Soy isoflavones and bone mineral density in perimenopausal and postmenopausal Western women: a systematic review and meta-analysis of randomized controlled trials. J Women's Health (Larchmt). 2010;19(1609–1617):1609–17.

    Article  Google Scholar 

  80. Lambert MNT, Hu LM, Jeppesen PB. A systematic review and meta-analysis of the effects of isoflavone formulations against estrogen-deficient bone resorption in peri- and postmenopausal women. Am J Clin Nutr. 2017;106:801–11.

    CAS  PubMed  Google Scholar 

  81. • Sansai K, et al. Effects of isoflavone interventions on bone mineral density in postmenopausal women: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2020. Updated meta-analysis demonstrating growing evidence that soy, in some forms, may have a beneficial effect on skeletal health.

  82. Alexandersen P, et al. Ipriflavone in the treatment of postmenopausal osteoporosis: a randomized controlled trial. JAMA. 2001;285:1482–8.

    Article  CAS  PubMed  Google Scholar 

  83. Dostal AM, Arikawa A, Espejo L, Kurzer MS. Long-term supplementation of green tea extract does not modify adiposity or bone mineral density in a randomized trial of overweight and obese postmenopausal women. J Nutr. 2016;146:256–64.

    Article  CAS  PubMed  Google Scholar 

  84. Shen CL, Chyu MC, Yeh JK, Zhang Y, Pence BC, Felton CK, et al. Effect of green tea and Tai Chi on bone health in postmenopausal osteopenic women: a 6-month randomized placebo-controlled trial. Osteoporos Int. 2012;23:1541–52.

    Article  CAS  PubMed  Google Scholar 

  85. Martin BR, McCabe GP, McCabe L, Jackson GS, Horcajada MN, Offord-Cavin E, et al. Effect of hesperidin with and without a calcium (calcilock) supplement on bone health in postmenopausal women. J Clin Endocrinol Metab. 2016;101:923–7.

    Article  CAS  PubMed  Google Scholar 

  86. Hooshmand S, Chai SC, Saadat RL, Payton ME, Brummel-Smith K, Arjmandi BH. Comparative effects of dried plum and dried apple on bone in postmenopausal women. Br J Nutr. 2011;106:923–30.

    Article  CAS  PubMed  Google Scholar 

  87. Simonavice E, Liu PY, Ilich JZ, Kim JS, Arjmandi B, Panton LB. The effects of a 6-month resistance training and dried plum consumption intervention on strength, body composition, blood markers of bone turnover, and inflammation in breast cancer survivors. Appl Physiol Nutr Metab. 2014;39:730–9.

    Article  CAS  PubMed  Google Scholar 

  88. Hooshmand S, Kern M, Metti D, Shamloufard P, Chai SC, Johnson SA, et al. The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial. Osteoporos Int. 2016;27:2271–9.

    Article  CAS  PubMed  Google Scholar 

  89. Asis M, Hemmati N, Moradi S, Nagulapalli Venkata KC, Mohammadi E, Farzaei MH, et al. Effects of resveratrol supplementation on bone biomarkers: a systematic review and meta-analysis. Ann N Y Acad Sci. 2019;1457:92–103.

    Article  CAS  PubMed  Google Scholar 

  90. Ornstrup MJ, Harslof T, Kjaer TN, Langdahl BL, Pedersen SB. Resveratrol increases bone mineral density and bone alkaline phosphatase in obese men: a randomized placebo-controlled trial. J Clin Endocrinol Metab. 2014;99:4720–9.

    Article  CAS  PubMed  Google Scholar 

  91. Wong R, Zaw J, Xian C, Howe P. Regular supplementation with resveratrol improves bone mineral density in postmenopausal women: a randomized, placebo-controlled trial. J Bone Miner Res Online. 2020. https://doi.org/10.1002/jbmr.4115.

  92. Bo S, et al. Effects of resveratrol on bone health in type 2 diabetic patients. A double-blind randomized-controlled trial. Nutr Diabetes. 2018;8:51–018.

    Article  PubMed  PubMed Central  Google Scholar 

  93. Penniston KL, Tanumihardjo SA. The acute and chronic toxic effects of vitamin a. Am J Clin Nutr. 2006;83:191–201.

    Article  CAS  PubMed  Google Scholar 

  94. Tanumihardjo SA, Palacios N, Pixley KV. Provitamin a carotenoid bioavailability: what really matters? Int J Vitam Nutr Res. 2010;80:336–50.

    Article  CAS  PubMed  Google Scholar 

  95. Hayhoe RPG, Lentjes MAH, Mulligan AA, Luben RN, Khaw KT, Welch AA. Carotenoid dietary intakes and plasma concentrations are associated with heel bone ultrasound attenuation and osteoporotic fracture risk in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohort. Br J Nutr. 2017;117:1439–53.

    Article  CAS  PubMed  Google Scholar 

  96. Regu GM, et al. Association between dietary carotenoid intake and bone mineral density in Korean adults aged 30–75 years using data from the fourth and fifth Korean National Health and Nutrition Examination Surveys (2008-2011). Nutrients. 2017;9. https://doi.org/10.3390/nu9091025.

  97. Sun LL, Li BL, Xie HL, Fan F, Yu WZ, Wu BH, et al. Associations between the dietary intake of antioxidant nutrients and the risk of hip fracture in elderly Chinese: a case-control study. Br J Nutr. 2014;112:1706–14.

    Article  CAS  PubMed  Google Scholar 

  98. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Yano M. High serum carotenoids associated with lower risk for bone loss and osteoporosis in post-menopausal Japanese female subjects: prospective cohort study. PLoS One. 2012;7:e52643.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Sugiura M, Nakamura M, Ogawa K, Ikoma Y, Ando F, Yano M. Bone mineral density in post-menopausal female subjects is associated with serum antioxidant carotenoids. Osteoporos Int. 2008;19:211–9.

    Article  CAS  PubMed  Google Scholar 

  102. Kawahara TN, Krueger DC, Engelke JA, Harke JM, Binkley NC. Short-term vitamin A supplementation does not affect bone turnover in men. J Nutr. 2002;132:1169–72.

    Article  CAS  PubMed  Google Scholar 

  103. Ambrosini GL, Alfonso H, Reid A, Mackerras D, Bremner AP, Beilby J, et al. Plasma retinol and total carotenes and fracture risk after long-term supplementation with high doses of retinol. Nutrition. 2014;30:551–6.

    Article  CAS  PubMed  Google Scholar 

  104. Swart KM, van Schoor NM, Lips P. Vitamin B12, folic acid, and bone. Curr Osteoporos Rep. 2013;11:213–8.

    Article  PubMed  Google Scholar 

  105. Sawka AM, Ray JG, Yi Q, Josse RG, Lonn E. Randomized clinical trial of homocysteine level lowering therapy and fractures. Arch Intern Med. 2007;167:2136–9.

    Article  CAS  PubMed  Google Scholar 

  106. van Wijngaarden JP, Swart KMA, Enneman AW, Dhonukshe-Rutten RAM, van Dijk SC, Ham AC, et al. Effect of daily vitamin B-12 and folic acid supplementation on fracture incidence in elderly individuals with an elevated plasma homocysteine concentration: B-PROOF, a randomized controlled trial. Am J Clin Nutr. 2014;100:1578–86.

    Article  PubMed  Google Scholar 

  107. Stone KL, Lui LY, Christen WG, Troen AM, Bauer DC, Kado D, et al. Effect of combination folic acid, vitamin B6 , and vitamin B12 supplementation on fracture risk in women: a randomized, Controlled Trial. J Bone Miner Res. 2017;32:2331–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Gommans J, Yi Q, Eikelboom JW, Hankey GJ, Chen C, Rodgers H, et al. The effect of homocysteine-lowering with B-vitamins on osteoporotic fractures in patients with cerebrovascular disease: substudy of VITATOPS, a randomised placebo-controlled trial. BMC Geriatr. 2013;13:88–2318.

    Article  PubMed  PubMed Central  Google Scholar 

  109. Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, et al. Effects of homocysteine-lowering with folic acid plus vitamin B12 vs placebo on mortality and major morbidity in myocardial infarction survivors: a randomized trial. JAMA. 2010;303:2486–94.

    Article  Google Scholar 

  110. Wong SK, et al. The molecular mechanism of vitamin E as a bone-protecting agent: a review on current evidence. Int J Mol Sci. 2019;20. https://doi.org/10.3390/ijms20061453.

  111. Chuin A, Labonté M, Tessier D, Khalil A, Bobeuf F, Doyon CY, et al. Effect of antioxidants combined to resistance training on BMD in elderly women: a pilot study. Osteoporos Int. 2009;20:1253–8.

    Article  CAS  PubMed  Google Scholar 

  112. Shen CL, Yang S, Tomison MD, Romero AW, Felton CK, Mo H. Tocotrienol supplementation suppressed bone resorption and oxidative stress in postmenopausal osteopenic women: a 12-week randomized double-blinded placebo-controlled trial. Osteoporos Int. 2018;29:881–91.

    Article  CAS  PubMed  Google Scholar 

  113. Hamidi MS, Cheung AM. Vitamin K and musculoskeletal health in postmenopausal women. Mol Nutr Food Res. 2014;58:1647–57.

    Article  CAS  PubMed  Google Scholar 

  114. Palermo A, Tuccinardi D, D'Onofrio L, Watanabe M, Maggi D, Maurizi AR, et al. Vitamin K and osteoporosis: myth or reality? Metabolism. 2017;70:57–71.

    Article  CAS  PubMed  Google Scholar 

  115. • Mott A, et al. Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials. Osteoporos Int. 2019;30:1543–59. Recent meta-analysis showing there is limited evidence that vitamin K supplements have a beneficial effect on bone density and/or fracture.

  116. Huang ZB, Wan SL, Lu YJ, Ning L, Liu C, Fan SW. Does vitamin K2 play a role in the prevention and treatment of osteoporosis for postmenopausal women: a meta-analysis of randomized controlled trials. Osteoporos Int. 2015;26:1175–86.

    Article  CAS  PubMed  Google Scholar 

  117. Su S, He N, Men P, Song C, Zhai S. The efficacy and safety of menatetrenone in the management of osteoporosis: a systematic review and meta-analysis of randomized controlled trials. Osteoporos Int. 2019;30:1175–86.

    Article  CAS  PubMed  Google Scholar 

  118. Cohen L, Laor A, Kitzes R. Magnesium malabsorption in postmenopausal osteoporosis. Magnesium. 1983;2:139–43.

    Google Scholar 

  119. Rude RK, Singer FR, Gruber HE. Skeletal and hormonal effects of magnesium deficiency. J Am Coll Nutr. 2009;28:131–41.

    Article  CAS  PubMed  Google Scholar 

  120. Aydin H, et al. Short-term oral magnesium supplementation suppresses bone turnover in postmenopausal osteoporotic women. Biol Trace Elem Res. 2010;133:136–43.

    Article  CAS  PubMed  Google Scholar 

  121. Eisinger J, Clairet D. Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a retrospective study. Magnes Res. 1993;6:247–9.

    CAS  PubMed  Google Scholar 

  122. 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.

    CAS  PubMed  Google Scholar 

  123. Rude RK, Olerich M. Magnesium deficiency: possible role in osteoporosis associated with gluten-sensitive enteropathy. Osteoporos Int. 1996;6:453–61.

    Article  CAS  PubMed  Google Scholar 

  124. Institute of Medicine (US). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. In: Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academies Press (US); 1997.

    Google Scholar 

  125. Reginster JY, Seeman E, de Vernejoul MC, Adami S, Compston J, Phenekos C, et al. Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: treatment of peripheral osteoporosis (TROPOS) study. J Clin Endocrinol Metab. 2005;90:2816–22.

    Article  CAS  PubMed  Google Scholar 

  126. Meunier PJ, Roux C, Seeman E, Ortolani S, Badurski JE, Spector TD, 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.

    Article  CAS  PubMed  Google Scholar 

  127. Maria S, et al. Melatonin-micronutrients Osteopenia Treatment Study (MOTS): a translational study assessing melatonin, strontium (citrate), vitamin D3 and vitamin K2 (MK7) on bone density, bone marker turnover and health related quality of life in postmenopausal osteopenic women following a one-year double-blind RCT and on osteoblast-oclast co-cultures. Aging (Albany NY). 2017;9:256–85.

    Article  CAS  Google Scholar 

  128. Liao J, Blake GM, McGregor AH, Patel R. The effect of bone strontium on BMD is different for different manufacturers’ DXA systems. Bone. 2010;47:882–7.

    Article  CAS  PubMed  Google Scholar 

  129. Rizzoli R. Microbiota and bone health: the gut-musculoskeletal axis. Calcif Tissue Int. 2018;102:385–6.

    Article  CAS  PubMed  Google Scholar 

  130. Rizzoli R, Biver E. Are probiotics the new calcium and vitamin D for bone health? Curr Osteoporos Rep. 2020;18(3):273–84.

  131. Weaver CM. Diet, gut microbiome, and bone health. Curr Osteoporos Rep. 2015;13:125–30.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Rizzoli R, Biver E. Effects of fermented milk products on bone. Calcif Tissue Int. 2018;102:489–500.

    Article  CAS  PubMed  Google Scholar 

  133. Whisner CM, Castillo LF. Prebiotics, bone and mineral metabolism. Calcif Tissue Int. 2018;102:443–79.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Deborah E. Sellmeyer.

Ethics declarations

Conflict of Interest

Laila S. Tabatabai, MD declares no conflict of interest. Deborah E. Sellmeyer, MD declares no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Therapeutics and Medical Management

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tabatabai, L.S., Sellmeyer, D.E. Nutritional Supplements and Skeletal Health. Curr Osteoporos Rep 19, 23–33 (2021). https://doi.org/10.1007/s11914-020-00651-x

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-020-00651-x

Keywords

Navigation