Skip to main content

Advertisement

SpringerLink
Log in

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry.

Introduction

Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance.

Methods

This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined.

Results

Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (−3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by −1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05).

Conclusion

The decline in Ct thickness was prevented with higher vitamin D3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. DeLuca HF (2008) The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J 2:224–36

    Google Scholar 

  2. Reichel H, Norman AW (1989) Systemic effects of vitamin D. Annu Rev Med 40:71–8

    Article  CAS  PubMed  Google Scholar 

  3. Reid IR, Bolland MJ, Grey A (2014) Effects of vitamin D supplements on bone mineral density: a systematic review and meta-analysis. Lancet 383:146–55

    Article  CAS  PubMed  Google Scholar 

  4. Lappe JM, Heaney RP (2012) Why randomized controlled trials of calcium and vitamin D sometimes fail. Dermatoendocrinol 4:95–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Jorde R, Grimnes G (2015) Vitamin D and health: the need for more randomized controlled trials. J Steroid Biochem Mol Biol 148:269–74

    Article  CAS  PubMed  Google Scholar 

  6. Powe CE, Ricciardi C, Berg AH et al (2011) Vitamin D-binding protein modifies the vitamin D-bone mineral density relationship. J Bone Miner Res 26:1609–16

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Chun RF, Peercy BE, Orwoll ES, Nielson CM, Adams JS, Hewison M (2014) Vitamin D and DBP: the free hormone hypothesis revisited. J Steroid Biochem Mol Biol 144(Pt A):132–7

    Article  CAS  PubMed  Google Scholar 

  8. Liel Y, Ulmer E, Shary J, Hollis BW, Bell NH (1988) Low circulating vitamin D in obesity. Calcif Tissue Int 43:199–201

    Article  CAS  PubMed  Google Scholar 

  9. Parikh SJ, Edelman M, Uwaifo GI, Freedman RJ, Semega-Janneh M, Reynolds J, Yanovski JA (2004) The relationship between obesity and serum 1,25-dihydroxy vitamin D concentrations in healthy adults. J Clin Endocrinol Metab 89:1196–9

    Article  CAS  PubMed  Google Scholar 

  10. Jungert A, Roth HJ, Neuhäuser-Berthold M (2012) Serum 25-hydroxyvitamin D3 and body composition in an elderly cohort from Germany: a cross-sectional study. Nutr Metab (Lond) 9:42

    Article  CAS  Google Scholar 

  11. Wortsman J, Matsuoka LY, Chen TC, Lu Z, Holick MF (2000) Decreased bioavailability of vitamin D in obesity. Am J Clin Nutr 72:690–3

    CAS  PubMed  Google Scholar 

  12. Drincic AT, Armas LA, Van Diest EE, Heaney RP (2012) Volumetric dilution, rather than sequestration best explains the low vitamin D status of obesity. Obesity (Silver Spring) 20:1444–8

    Article  CAS  Google Scholar 

  13. Gallagher JC, Yalamanchili V, Smith LM (2013) The effect of vitamin D supplementation on serum 25(OH)D in thin and obese women. J Steroid Biochem Mol Biol 136:195–200

    Article  CAS  PubMed  Google Scholar 

  14. Zittermann A, Ernst JB, Gummert JF, Börgermann J (2014) Vitamin D supplementation, body weight and human serum 25-hydroxyvitamin D response: a systematic review. Eur J Nutr 53:367–74

    Article  CAS  PubMed  Google Scholar 

  15. Andreopoulou P, Bockman RS (2015) Management of postmenopausal osteoporosis. Annu Rev Med 66:329–42

    Article  CAS  PubMed  Google Scholar 

  16. Shapses SA, Sukumar D (2012) Bone metabolism in obesity and weight loss. Annu Rev Nutr 32:287–309

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Salamone LM, Cauley JA, Black DM et al (1999) Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr 70:97–103

    CAS  PubMed  Google Scholar 

  18. Uusi-Rasi K, Sievänen H, Pasanen M, Oja P, Vuori I (2001) Maintenance of body weight, physical activity and calcium intake helps preserve bone mass in elderly women. Osteoporos Int 12:373–9

    Article  CAS  PubMed  Google Scholar 

  19. Inst. Med (2011) Dietary reference intakes for calcium and vitamin D. Washington, DC: Natl. Acad. Press

  20. Ainsworth BE, Haskell WL, Herrmann SD et al (1998) Compendium of Physical Activities: a second update of codes and MET values. Med Sci Sports Exerc 43:1575–81

    Article  Google Scholar 

  21. Takiwaki H (1998) Measurement of skin color: practical application and theoretical considerations. J Med Invest 44:121–6

    CAS  PubMed  Google Scholar 

  22. Wong AK, Beattie KA, Min KK, Webber CE, Gordon CL, Papaioannou A et al (2014) A trimodality comparison of volumetric bone imaging technologies. Part I: short-term precision and validity. J Clin Densitom 18:124–35

    Article  PubMed  PubMed Central  Google Scholar 

  23. Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84:3666–3672

    Article  CAS  PubMed  Google Scholar 

  24. Riedt CS, Cifuentes M, Stahl T, Chowdhury HA, Schlussel Y, Shapses SA (2005) Overweight postmenopausal women lose bone with moderate weight reduction and 1 g/day calcium intake. J Bone Miner Res 20:455–63

    Article  CAS  PubMed  Google Scholar 

  25. Villareal DT, Fontana L, Weiss EP et al (2006) Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 166:2502–10

    Article  PubMed  Google Scholar 

  26. Uusi-Rasi K, Sievanen H, Kannus P, Pasanen M, Kukkonen-Harjula K, Fogelholm M (2009) Influence of weight reduction on muscle performance and bone mass, structure and metabolism in obese premenopausal women. J Musculoskelet Neuronal Interact 9:72–80

    CAS  PubMed  Google Scholar 

  27. Jensen LB, Kollerup G, Quaade F, Sorensen OH (2001) Bone minerals changes in obese women during a moderate weight loss with and without calcium supplementation. J Bone Miner Res 16:141–147

    Article  CAS  PubMed  Google Scholar 

  28. Ricci TA, Heymsfield SB, Pierson RN Jr, Stahl T, Chowdhury HA, Shapses SA (2001) Moderate energy restriction increases bone resorption in obese postmenopausal women. Am J Clin Nutr 73:347–352

    CAS  PubMed  Google Scholar 

  29. Cifuentes M, Riedt CS, Brolin RE, Field MP, Sherrell RM, Shapses SA (2004) Weight loss and calcium intake influence calcium absorption in overweight postmenopausal women. Am J Clin Nutr 80:123–30

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Shapses SA, Sukumar D, Schneider SH, Schlussel Y, Sherrell RM, Field MP, Ambia-Sobhan H (2013) Vitamin D supplementation and calcium absorption during caloric restriction: a randomized double-blind trial. Am J Clin Nutr 97:637–45

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Chapuy MC, Arlot ME, Duboeuf F, Brun J, Crouzet B, Arnaud S, Delmas PD, Meunier PJ (1992) Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med 327:1637–42

    Article  CAS  PubMed  Google Scholar 

  32. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE, Falconer G, Green CL (1995) Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 61:1140–5

    CAS  PubMed  Google Scholar 

  33. Ooms ME, Roos JC, Bezemer PD, Vandervijgh WJF, Bouter LM, Lips P (1995) Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 80:1052–58

    CAS  PubMed  Google Scholar 

  34. Cooper L, Clifton-Bligh PB, Nery ML et al (2003) Vitamin D supplementation and bone mineral density in early postmenopausal women. Am J Clin Nutr 77:1324–29

    CAS  PubMed  Google Scholar 

  35. Meier C, Woitge HW, Witte K, Lemmer B, Seibel MJ (2004) Supplementation with oral vitamin D3 and calcium during winter prevents seasonal bone loss: a randomized controlled open-label prospective trial. J Bone Miner Res 19:1221–30

    Article  CAS  PubMed  Google Scholar 

  36. Aloia JF, Talwar SA, Pollack S, Yeh J (2005) A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med 165:1618–23

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Jorde R, Sneve M, Torjesen PA, Figenschau Y, Hansen JB, Grimnes G (2010) No significant effect on bone mineral density by high doses of vitamin D3 given to overweight subjects for one year. Nutr J 9:1

    Article  PubMed  PubMed Central  Google Scholar 

  38. Grimnes G, Joakimsen R, Figenschau Y, Torjesen PA, Almås B, Jorde R (2012) The effect of high-dose vitamin D on bone mineral density and bone turnover markers in postmenopausal women with low bone mass—a randomized controlled 1-year trial. Osteoporos Int 23:201–11

    Article  CAS  PubMed  Google Scholar 

  39. Mocanu V, Stitt PA, Costan AR, Voroniuc O, Zbranca E, Luca V, Vieth R (2009) Long-term effects of giving nursing home residents bread fortified with 125 μg [5000 IU] vitamin D3 per daily serving. Am J Clin Nutr 89:1132–1137

    Article  CAS  PubMed  Google Scholar 

  40. Kanis JA, Johnell O, Oden A, Johansson H, McCloskey E (2008) FRAX and the assessment of fracture probability in men and women from the UK. Osteoporos Int 19:385–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Griffith JF, Genant HK (2008) Bone mass and architecture determination: state of the art. Best Pract Res Clin Endocrinol Metab 22:737–64

    Article  PubMed  Google Scholar 

  42. Barbour KE, Zmuda JM, Horwitz MJ, Strotmeyer ES, Boudreau R, Evans RW, Ensrud KE, Gordon CL, Petit MA, Patrick AL, Cauley JA (2011) Osteoporotic Fractures in Men (MrOS) Research Group. The association of serum 25-hydroxyvitamin D with indicators of bone quality in men of Caucasian and African ancestry. Osteoporos Int 22:2475–85

    Article  CAS  PubMed  Google Scholar 

  43. Charopoulos I, Tournis S, Trovas G, Raptou P, Kaldrymides P, Skarandavos G, Katsalira K, Lyritis GP (2006) Effect of primary hyperparathyroidism on volumetric bone mineral density and bone geometry assessed by peripheral quantitative computed tomography in postmenopausal women. J Clin Endocrinol Metab 91:1748–53

    Article  CAS  PubMed  Google Scholar 

  44. Duan Y, De Luca V, Seeman E (1999) Parathyroid hormone deficiency and excess: similar effects on trabecular bone but differing effects on cortical bone. J Clin Endocrinol Metab 84:718–22

    Article  CAS  PubMed  Google Scholar 

  45. Dempster DW, Müller R, Zhou H, Kohler T, Shane E, Parisien M, Silverberg SJ, Bilezikian JP (2007) Preserved three-dimensional cancellous bone structure in mild primary hyperparathyroidism. Bone 41:19–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Lauretani F, Bandinelli S, Griswold ME, Maggio M, Semba R, Guralnik JM, Ferrucci L (2008) Longitudinal changes in BMD and bone geometry in a population-based study. J Bone Miner Res 23:400–8

    Article  PubMed  Google Scholar 

  47. Sukumar D, Ambia-Sobhan H, Zurfluh R, Schlussel Y, Stahl TJ, Gordon CL, Shapses SA (2011) Areal and volumetric bone mineral density and geometry at two levels of protein intake during caloric restriction: a randomized, controlled trial. J Bone Miner Res 26:1339–48

    Article  CAS  PubMed  Google Scholar 

  48. Hamrick MW, Ding KH, Ponnala S, Ferrari SL, Isales CM (2008) Caloric restriction decreases cortical bone mass but spares trabecular bone in the mouse skeleton: implications for the regulation of bone mass by body weight. J Bone Miner Res 23:870–8

    Article  CAS  PubMed  Google Scholar 

  49. Mardon J, Zangarelli A, Walrand S, Davicco MJ, Lebecque P, Demigné C, Horcajada MN, Boirie Y, Coxam V (2008) Impact of energy and casein or whey protein intake on bone status in a rat model of age-related bone loss. Br J Nutr 99:764–72

    Article  CAS  PubMed  Google Scholar 

  50. Dhaliwal R, Mikhail M, Feuerman M, Aloia JF (2014) The vitamin D dose response in obesity. Endocr Pract 6:1–25

    Article  Google Scholar 

  51. Macdonald HM, Wood AD, Aucott LS et al (2013) Hip bone loss is attenuated with 1000 IU but not 400 IU daily vitamin D3: a 1-year double-blind RCT in postmenopausal women. J Bone Miner Res 28:2202–13

    Article  CAS  PubMed  Google Scholar 

  52. Ensrud KE, Palermo L, Black DM et al (1995) Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures. J Bone Miner Res 10:1778–87

    Article  CAS  PubMed  Google Scholar 

  53. Aloia JF, Arunabh-Talwar S, Pollack S, Yeh JK (2008) The remodeling transient and the calcium economy. Osteoporos Int 19:1001–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Knapp KM, Welsman JR, Hopkins SJ, Shallcross A, Fogelman I, Blake GM (2015) Obesity increases precision errors in total body dual-energy x-ray absorptiometry measurements. J Clin Densitom 18:209–16

    Article  PubMed  Google Scholar 

  55. Yu EW, Thomas BJ, Brown JK, Finkelstein JS (2012) Simulated increases in body fat and errors in bone mineral density measurements by DXA and QCT. J Bone Miner Res 27:119–24

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We thank Robert Zurfluh, RD, and the other clinical staff for their invaluable clinical assistance and Lihong Hao, PhD, for her laboratory assistance with vitamin D3 analysis of the supplements. We are also grateful for the commitment of the volunteers. This study was supported by NIH-AG12161 and Busch Biomedical Award (BBGP2010695157).

Author information

Authors and Affiliations

  1. Department of Nutritional Sciences, Rutgers University, 96 Lipman Drive, New Brunswick, NJ, 08901-8525, USA

    L. C. Pop, Y. Schlussel & S. A. Shapses

  2. Department of Nutritional Sciences, Drexel University, Philadelphia, PA, USA

    D. Sukumar

  3. Division of Endocrinology, Metabolism and Nutrition, Department of Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    S. H. Schneider & X. Wang

  4. Department of Radiology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA

    T. Stahl

  5. Department of Radiology, McMaster University, Hamilton, Ontario, Canada

    C. Gordon

  6. Department of Biomedical Engineering & Center for Cognitive Science, Rutgers University, New Brunswick, NJ, USA

    T. V. Papathomas

Authors
  1. L. C. Pop
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D. Sukumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. H. Schneider
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. Schlussel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. T. Stahl
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C. Gordon
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. X. Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. V. Papathomas
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. S. A. Shapses
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. A. Shapses.

Ethics declarations

During the first visit to the Nutrition and Bone laboratory, the subjects signed an informed consent approved by the Rutgers University Institutional Review Board. This trial was registered at clinicaltrials.gov as NCT01631292. The protocol met the ethical standards in accordance with the Helsinki Declaration.

Funding

This study is funded by NIH-AG12161, NJAES (0153866) and a Busch Biomedical Award (BBGP2010695157).

Trial number and date: NCT01631292.

Conflicts of interest

None.

Electronic supplementary material

Below is the link to the electronic supplementary material.

ESM 1

(DOCX 14 kb)

ESM 2

(DOCX 14 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pop, L.C., Sukumar, D., Schneider, S.H. et al. Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial. Osteoporos Int 28, 377–388 (2017). https://doi.org/10.1007/s00198-016-3735-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-016-3735-z

Keywords

Search

Navigation