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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

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Abstract

Summary

Vitamin D is widely used in osteoporosis treatment, although the optimal dose is not known. This 1-year clinical study among 297 women aged 50–80 years old showed that a vitamin D3 dose of 6,500 IU/day was not better than the standard dose of 800 IU/day in improving bone mineral density (BMD) in the hip and spine.

Introduction

The purpose of this study was to determine whether a high dose of vitamin D3 was better than the standard dose in improving BMD and reducing bone turnover in postmenopausal women with reduced bone mass.

Methods

The study was a 1-year randomized double-blind controlled trial comparing high-dose vitamin D3 with the standard dose. Postmenopausal women (n = 297) with a BMD T-score ≤ −2.0 in either lumbar spine (L2–4) or total hip were included and randomized to 6,500 IU vitamin D3/day (20,000 IU twice per week + 800 IU/day) or 800 IU vitamin D3/day (placebo twice per week + 800 IU/day). Both groups were given 1,000 mg elemental calcium/day. The primary endpoint was a change in BMD in total hip and lumbar spine (L2–4).

Results

After 1 year, serum 25-hydroxyvitamin D (25(OH)D) increased [mean (SD)] from 71 (23) to 185 (34) nmol/l and from 71 (22) to 89 (17) nmol/l in the high- and standard-dose vitamin D groups, respectively. BMD at all measurement sites was unchanged or slightly improved with no significant differences between the groups. Although bone turnover was reduced in both groups, the more pronounced reduction in serum levels of the bone formation marker P1NP in the standard-dose group may indicate that this treatment was more efficient. Adverse events did not differ between the groups.

Conclusions

One year treatment with 6,500 IU vitamin D3/day was not better than 800 IU/day regarding BMD in vitamin D-replete postmenopausal women with reduced bone mass and was less efficient in reducing bone turnover.

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References

  1. Need AG, Nordin BE (2008) Misconceptions—vitamin D insufficiency causes malabsorption of calcium. Bone 42:1021–1024

    Article  PubMed  CAS  Google Scholar 

  2. Anderson PH, Atkins GJ (2008) The skeleton as an intracrine organ for vitamin D metabolism. Mol Aspects Med 29:397–406

    Article  PubMed  CAS  Google Scholar 

  3. Kogawa M, Findlay DM, Anderson PH, Ormsby R, Vincent C, Morris HA, Atkins GJ (2010) Osteoclastic metabolism of 25(OH)-vitamin D3: a potential mechanism for optimization of bone resorption. Endocrinology 151:4613–4625

    Article  PubMed  CAS  Google Scholar 

  4. Geng S, Zhou S, Glowacki J (2010) Effects of 25-hydroxyvitamin D3 on proliferation and osteoblast differentiation of human marrow stromal cells require CYP27B1/1-α-hydroxylase. J Bone Miner Res doi:10.1002/JBMR.298

  5. Baldock PA, Thomas GP, Hodge JM, Baker SU, Dressel U, O’Loughlin PD, Nicholson GC, Briffa KH, Eisman JA, Gardiner EM (2006) Vitamin D action and regulation of bone remodeling: suppression of osteoclastogenesis by the mature osteoblast. J Bone Miner Res 21:1618–1626

    Article  PubMed  CAS  Google Scholar 

  6. Bischoff-Ferrari HA (2007) How to select the doses of vitamin D in the management of osteoporosis. Osteoporos Int 18:401–407

    Article  PubMed  CAS  Google Scholar 

  7. Bischoff-Ferrari HA, Willett WC, Wong JB, Stuck AE, Staehelin HB, Orav J, Thoma A, Kiel DP, Henschkowski J (2009) Prevention of nonvertebral fractures with oral vitamin D and dose dependency. Arch Intern Med 169:551–561

    Article  PubMed  CAS  Google Scholar 

  8. Vieth R (2006) Critique of the considerations for establishing the tolerable upper intake level for vitamin D: critical need for revision upwards. J Nutr 136:1117–1122

    PubMed  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Borud EK, Alraek T, White A, Fonnebo V, Eggen AE, Hammar M, Åstrand LL, Theodorsson E, Grimsgaard S (2009) The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial. Menopause 16:484–493

    Article  PubMed  Google Scholar 

  11. Borrelli F, Ernst E (2010) Alternative and complementary therapies for the menopause. Maturitas 66:333–343

    Article  PubMed  Google Scholar 

  12. Engelsen O, Brustad M, Aksnes L, Lund E (2005) Daily duration of vitamin D synthesis in human skin with relation to latitude, total ozone, altitude, ground cover, aerosols and cloud thickness. Photochem Photobiol 81:1287–1290

    Article  PubMed  CAS  Google Scholar 

  13. Andersen LF, Solvoll K, Johansson LR, Salminen I, Aro A, Drevon CA (1999) Evaluation of a food frequency questionnaire with weighed records, fatty acids, and alpha-tocopherol in adipose tissue and serum. Am J Epidemiol 150:75–87

    PubMed  CAS  Google Scholar 

  14. Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P (2003) International Physical Activity Questionnaire: 12-country reliability and validity. Med Sci Sports Exerc 35:1381–1395

    Article  PubMed  Google Scholar 

  15. Grimnes G, Almaas B, Eggen AE, Emaus N, Figenschau Y, Hopstock LA, Hutchinson MS, Methlie P, Mihailova A, Sneve M, Torjesen P, Wilsgaard T, Jorde R (2010) Effect of smoking on the serum levels of 25-hydroxyvitamin D depends on the assay employed. Eur J Endocrinol 163:339–348

    Article  PubMed  CAS  Google Scholar 

  16. Aloia JF, Patel M, DiMaano R, Li-Ng M, Talwar SA, Mikhail M, Pollack S, Yeh JK (2008) Vitamin D intake to attain a desired serum 25-hydroxyvitamin D concentration. Am J Clin Nutr 87:1952–1958

    PubMed  CAS  Google Scholar 

  17. Altmann DG (1991) Practical statistics for medical research. Chapman & Hall, Boca Raton

    Google Scholar 

  18. Young R, May H, Murphy S, Grey C, Compston JE (1996) Rates of bone loss in peri- and postmenopausal women: a 4 year, prospective, population-based study. Clin Sci 91:307–312

    PubMed  CAS  Google Scholar 

  19. Guthrie JR, Ebeling PR, Hopper JL, Barrett-Connor E, Dennerstein L, Dudley EC, Burger HG, Wark JD (1998) A prospective study of bone loss in menopausal Australian-born women. Osteoporos Int 8:282–290

    Article  PubMed  CAS  Google Scholar 

  20. Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D’Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F (2007) Effects of phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women. Ann Intern Med 146:839–847

    PubMed  Google Scholar 

  21. Rabenda V, Bruyére O, Reginster JY (2011) Relationship between bone mineral density changes and risk of fractures among patients receiving calcium with or without vitamin D supplementation: a meta-regression. Osteoporos Int 22:893–901

    Article  PubMed  CAS  Google Scholar 

  22. Jorde R, Sneve M, Hutchinson M, Emaus N, Figenschau Y, Grimnes G (2010) Tracking of serum 25-hydroxyvitamin D levels during 14 years in a population-based study and during 12 months in an intervention study. Am J Epidemiol 171:903–908

    Article  PubMed  Google Scholar 

  23. Christensen MH, Lien EA, Hustad S, Almås B (2010) Seasonal and age-related differences in serum 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone in patients from Western Norway. Scand J Clin Lab Invest 70:281–286

    Article  PubMed  CAS  Google Scholar 

  24. Lips P, Duong T, Oleksik A, Black D, Cummings S, Cox D, Nickelsen T (2001) A global study of vitamin D status and parathyroid function in postmenopausal women with osteoporosis: baseline data from the multiple outcomes of raloxifene evaluation clinical trial. J Clin Endocrinol Metab 86:1212–1221

    Article  PubMed  CAS  Google Scholar 

  25. 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 mcg (5000 IU) vitamin D3 per daily serving. Am J Clin Nutr 89:1132–1137

    Article  PubMed  CAS  Google Scholar 

  26. Von Hurst PR, Stonehouse W, Kruger MC, Coad J (2010) Vitamin D supplementation suppresses age-induced bone turnover in older women who are vitamin D deficient. J Steroid Biochem Mol Biol 121:293–296

    Article  Google Scholar 

  27. Ueno Y, Shinki T, Nagai Y, Murayama H, Fujii K, Suda T (2003) In vivo administration of 1,25-dihydroxyvitamin D3 suppresses the expression of RANKL mRNA in bone of thyroparathyroidectomized rats constantly infused with PTH. J Cell Biochem 90:267–277

    Article  PubMed  CAS  Google Scholar 

  28. Anderson PA, Iida S, Tyson JH, Turner AG, Morris HA (2010) Bone CYP27B1 gene expression is increased with high dietary calcium and in mineralising osteoblasts. J Steroid Biochem Mol Biol 121:71–75

    Article  PubMed  CAS  Google Scholar 

  29. Jackson RD, LaCroix AZ, Gass M et al (2006) Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683

    Article  PubMed  CAS  Google Scholar 

  30. Jones G (2008) Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 88:582S–586S

    PubMed  CAS  Google Scholar 

  31. Heaney RP (2008) Vitamin D—criteria for safety and efficacy. Nutr Rev 66:S178–S181

    Article  PubMed  Google Scholar 

  32. Sanders KM, Stuart AL, Williamson EJ, Simpson JA, Kotowicz MA, Young D, Nicholson GC (2010) Annual high-dose oral vitamin D and falls and fractures in older women. JAMA 303:1815–1822

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The study was funded by a grant from The Norwegians Women Public Health Association in Troms. The superb assistance by the staff at the Research Unit, from Marian Remijn and Line Wilsgaard at the DEXA laboratory, Inger Myrnes and Astrid Lindvall at the Department of Medical Biochemistry at the University Hospital of North Norway, Otto Bårholm at the Hormone Laboratory, Haukeland University Hospital, and Anikken Kristiansen and Nina Norstrand at the Hormone Laboratory, Oslo University Hospital is greatly appreciated. We are grateful for the generous supply of Calcigran Forte from Nycomed Norway.

Conflicts of interest

None.

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Authors and Affiliations

  1. Tromsø Endocrine Research Group, Department of Clinical Medicine, University of Tromsø, 9037, Tromsø, Norway

    G. Grimnes, R. Joakimsen & R. Jorde

  2. Division of Internal Medicine, University Hospital of North Norway, 9038, Tromsø, Norway

    G. Grimnes, R. Joakimsen & R. Jorde

  3. Department of Medical Biology, University of Tromsø, 9037, Tromsø, Norway

    Y. Figenschau

  4. Department of Medical Biochemistry, University Hospital of North Norway, 9038, Tromsø, Norway

    Y. Figenschau

  5. Hormone Laboratory, Department of Endocrinology, Oslo University Hospital, Aker, 0424, Oslo, Norway

    P. A. Torjesen

  6. Hormone Laboratory, Haukeland University Hospital, 5021, Bergen, Norway

    B. Almås

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  1. G. Grimnes
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  2. R. Joakimsen
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Correspondence to G. Grimnes.

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Grimnes, G., Joakimsen, R., Figenschau, Y. et al. 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, 201–211 (2012). https://doi.org/10.1007/s00198-011-1752-5

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