Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter November 21, 2012

One year B and D vitamins supplementation improves metabolic bone markers

  • Wolfgang Herrmann EMAIL logo , Susanne H. Kirsch , Vera Kruse , Rudolf Eckert , Stefan Gräber , Jürgen Geisel and Rima Obeid


Background: Vitamin D and vitamin B deficiency are common in elderly subjects and are important risk factors for osteoporosis and age-related diseases. Supplementation with these vitamins is a promising preventative strategy. The objective of this study was to evaluate the effects of vitamins D3 and B supplementation on bone turnover and metabolism in elderly people.

Methods: Healthy subjects (n=93; >54 years) were randomly assigned to receive either daily vitamin D3 (1200 IU), folic acid (0.5 mg), vitamin B12 (0.5 mg), vitamin B6 (50 mg), and calcium carbonate (456 mg) (group A) or only vitamin D3 plus calcium carbonate (group B) in a double blind trial. We measured at baseline and after 6 and 12 months of supplementation vitamins, metabolites, and bone turnover markers.

Results: At baseline mean plasma 25-hydroxy vitamin D [25(OH)D] was low (40 or 30 nmol/L) and parathormone was high (63.7 or 77.9 pg/mL). 25(OH)D and parathormone correlated inversely. S-Adenosyl homocysteine and S-adenosyl methionine correlated with bone alkaline phosphatase, sclerostin, and parathormone. One year vitamin D3 or D3 and B supplementation increased plasma 25(OH)D by median 87.6% (group A) and 133.3% (group B). Parathormone was lowered by median 28.3% (A) and 41.2% (B), bone alkaline phosphatase decreased by 2.8% (A) and 16.2% (B), osteocalin by 37.5% (A) and 49.4% (B), and tartrate-resistant-acid-phosphatase 5b by 6.1% (A) and 36.0% (B). Median total homocysteine (tHcy) was high at baseline (group A: 12.6, group B: 12.3 µmol/L) and decreased by B vitamins (group A) to 8.9 µmol/L (29.4%). tHcy lowering had no additional effect on bone turnover.

Conclusions: One year vitamin D3 supplementation with or without B vitamins decreased the bone turnover significantly. Vitamin D3 lowered parathormone. The additional application of B vitamins did not further improve bone turnover. The marked tHcy lowering by B vitamins may modulate the osteoporotic risk.

Corresponding author: Prof. Dr. Wolfgang Herrmann, Department of Clinical Chemistry and Laboratory Medicine, Saarland University Hospital, Building 57, 66421 Homburg/Saar, Germany, Phone: +49 68411630701, Fax: +49 68411630703


1. Herrmann M, Duque G. Vitamin D and bone health. In: Herrmann W, Obeid R, editors. Vitamins in the prevention of human diseases, 1st ed. Berlin/New York: Walter de Gruyter, 2011: 429–55.Search in Google Scholar

2. Cummings SR, Melton LJ. Epidemiology and outcomes of osteoporotic fractures. Lancet 2002;359:1761–7.10.1016/S0140-6736(02)08657-9Search in Google Scholar

3. Suda T, Ueno Y, Fujii K, Shinki T. Vitamin D and bone. J Cell Biochem 2003;88:259–66.10.1002/jcb.10331Search in Google Scholar PubMed

4. Barnes MS, Robson PJ, Bonham MP, Strain JJ, Wallace JM. Effect of vitamin D supplementation on vitamin D status and bone turnover markers in young adults. Eur J Clin Nutr 2006;60: 727–33.10.1038/sj.ejcn.1602374Search in Google Scholar PubMed

5. Hutchison FN, Bell NH. Osteomalacia and rickets. Semin Nephrol 1992;12:127–45.Search in Google Scholar

6. Grant WB. Solar ultraviolet irradiance and cancer incidence and mortality. Adv Exp Med Biol 2008;624:16–30.10.1007/978-0-387-77574-6_2Search in Google Scholar PubMed

7. Reichrath J. Using vitamin D for management of human diseases. In: Herrmann W, Obeid R, editors. Vitamins in the prevention of human diseases, 1st ed. Berlin/New York: Walter de Gruyter, 2011:399–409.Search in Google Scholar

8. Zittermann A. Potential health effects of vitamin D. In: Herrmann W, Obeid R, editors. Vitamins in the prevention of human diseases, 1st ed. Berlin/New York: Walter de Gruyter, 2011: 380–95.Search in Google Scholar

9. Holick MF. Vitamin D deficiency. N Engl J Med 2007;357:266–81.10.1056/NEJMra070553Search in Google Scholar PubMed

10. Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med 2004;158:531–7.10.1001/archpedi.158.6.531Search in Google Scholar PubMed

11. Sullivan SS, Kushida CA. Multiple sleep latency test and maintenance of wakefulness test. Chest 2008;134:854–61.10.1378/chest.08-0822Search in Google Scholar PubMed

12. Herrmann M, Peter SJ, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T, et al. The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med 2007;45:1621–32.10.1515/CCLM.2007.362Search in Google Scholar PubMed

13. Herrmann W. The importance of hyperhomocysteinemia as a risk factor for diseases: an overview. Clin Chem Lab Med 2001;39:666–74.10.1515/CCLM.2001.110Search in Google Scholar PubMed

14. Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999;69:842–56.10.1093/ajcn/69.5.842Search in Google Scholar PubMed

15. Lips P, Wiersinga A, van Ginkel FC, Jongen MJ, Netelenbos JC, Hackeng WH, et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab 1988;67:644–50.10.1210/jcem-67-4-644Search in Google Scholar PubMed

16. Bates CJ, Carter GD, Mishra GD, O’Shea D, Jones J, Prentice A. In a population study, can parathyroid hormone aid the definition of adequate vitamin D status? A study of people aged 65 years and over from the British National Diet and Nutrition Survey. Osteoporos Int 2003;14:152–9.10.1007/s00198-002-1338-3Search in Google Scholar PubMed

17. Bischoff-Ferrari HA, Dietrich T, Orav EJ, Dawson-Hughes B. Positive association between 25-hydroxy vitamin D levels and bone mineral density: a population-based study of younger and older adults. Am J Med 2004;116:634–9.10.1016/j.amjmed.2003.12.029Search in Google Scholar PubMed

18. Cauley JA, Lacroix AZ, Wu L, Horwitz M, Danielson ME, Bauer DC, et al. Serum 25-hydroxyvitamin D concentrations and risk for hip fractures. Ann Intern Med 2008;149:242–50.10.7326/0003-4819-149-4-200808190-00005Search in Google Scholar PubMed PubMed Central

19. Looker AC, Mussolino ME. Serum 25-hydroxyvitamin D and hip fracture risk in older U.S. white adults. J Bone Miner Res 2008;23:143–50.10.1359/jbmr.071003Search in Google Scholar PubMed

20. Lips P. Vitamin D deficiency and secondary hyperparathyroidism in the elderly: consequences for bone loss and fractures and therapeutic implications. Endocr Rev 2001;22:477–501.10.1210/edrv.22.4.0437Search in Google Scholar PubMed

21. Bjorkman M, Sorva A, Risteli J, Tilvis R. Vitamin D supplementation has minor effects on parathyroid hormone and bone turnover markers in vitamin D-deficient bedridden older patients. Age Ageing 2008;37:25–31.10.1093/ageing/afm141Search in Google Scholar PubMed

22. Dhonukshe-Rutten RA, Pluijm SM, de Groot LC, Lips P, Smit JH, van Staveren WA. Homocysteine and vitamin B12 status relate to bone turnover markers, broadband ultrasound attenuation, and fractures in healthy elderly people. J Bone Miner Res 2005;20:921–9.10.1359/JBMR.050202Search in Google Scholar PubMed

23. McLean RR, Jacques PF, Selhub J, Tucker KL, Samelson EJ, Broe KE, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 2004;350:2042–9.10.1056/NEJMoa032739Search in Google Scholar PubMed

24. Herrmann M, Kraenzlin M, Pape G, Sand-Hill M, Herrmann W. Relation between homocysteine and biochemical bone turnover markers and bone mineral density in peri- and post-menopausal women. Clin Chem Lab Med 2005;43:1118–23.10.1515/CCLM.2005.195Search in Google Scholar PubMed

25. van Meurs JB, Dhonukshe-Rutten RA, Pluijm SM, van der Klift M, de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med 2004;350:2033–41.10.1056/NEJMoa032546Search in Google Scholar PubMed

26. Herrmann M, Schmidt J, Umanskaya N, Colaianni G, Al-Marrawi F, Widmann T, et al. Stimulation of osteoclast activity by low B-vitamin concentrations. Bone 2007;41:584–91.10.1016/j.bone.2007.06.005Search in Google Scholar PubMed

27. Herrmann M, Umanskaya N, Wildemann B, Colaianni G, Widmann T, Zallone A, et al. Stimulation of osteoblast activity by homocysteine. J Cell Mol Med 2008;12:1205–10.10.1111/j.1582-4934.2008.00104.xSearch in Google Scholar PubMed PubMed Central

28. Ozdem S, Samanci S, Tasatargil A, Yildiz A, Sadan G, Donmez L, et al. Experimental hyperhomocysteinemia disturbs bone metabolism in rats. Scand J Clin Lab Invest 2007;67:748–56.10.1080/00365510701342088Search in Google Scholar PubMed

29. Herrmann W, Obeid R, Schorr H, Hubner U, Geisel J, Sand-Hill M, et al. Enhanced bone metabolism in vegetarians – the role of vitamin B12 deficiency. Clin Chem Lab Med 2009; 47:1381–7.10.1515/CCLM.2009.302Search in Google Scholar PubMed

30. Carmel R, Lau KH, Baylink DJ, Saxena S, Singer FR. Cobalamin and osteoblast-specific proteins. N Engl J Med 1988;319:70–5.10.1056/NEJM198807143190202Search in Google Scholar PubMed

31. Holstein JH, Herrmann M, Splett C, Herrmann W, Garcia P, Histing T, et al. High bone concentrations of homocysteine are associated with altered bone morphology in humans. Br J Nutr 2011;106:378–82.10.1017/S0007114511000304Search in Google Scholar PubMed

32. Herrmann M, Tami A, Wildemann B, Wolny M, Wagner A, Schorr H, et al. Hyperhomocysteinemia induces a tissue specific accumulation of homocysteine in bone by collagen binding and adversely affects bone. Bone 2009;44:467–75.10.1016/j.bone.2008.10.051Search in Google Scholar PubMed

33. Goerss JB, Kim CH, Atkinson EJ, Eastell R, O’Fallon WM, Melton LJ, III. Risk of fractures in patients with pernicious anemia. J Bone Miner Res 1992;7:573–9.10.1002/jbmr.5650070514Search in Google Scholar PubMed

34. Appleby P, Roddam A, Allen N, Key T. Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford. Eur J Clin Nutr 2007;61:1400–6.10.1038/sj.ejcn.1602659Search in Google Scholar PubMed

35. Dhonukshe-Rutten RA, van Dusseldorp M, Schneede J, de Groot LC, van Staveren WA. Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Eur J Nutr 2005;44:341–7.10.1007/s00394-004-0531-xSearch in Google Scholar PubMed

36. Wang YF, Chiu JS, Chuang MH, Chiu JE, Lin CL. Bone mineral density of vegetarian and non-vegetarian adults in Taiwan. Asia Pac J Clin Nutr 2008;17:101–6.Search in Google Scholar

37. Stabler SP, Lindenbaum J, Savage DG, Allen RH. Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood 1993;81:3404–13.10.1182/blood.V81.12.3404.3404Search in Google Scholar

38. Kirsch SH, Knapp JP, Geisel J, Herrmann W, Obeid R. Simultaneous quantification of S-adenosyl methionine and S-adenosyl homocysteine in human plasma by stable-isotope dilution ultra performance liquid chromatography tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009;877:3865–70.10.1016/j.jchromb.2009.09.039Search in Google Scholar PubMed

39. Kirsch SH, Knapp JP, Herrmann W, Obeid R. Quantification of key folate forms in serum using stable-isotope dilution ultra performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2010;878:68–75.10.1016/j.jchromb.2009.11.021Search in Google Scholar PubMed

40. Need AG. Bone resorption markers in vitamin D insufficiency. Clin Chim Acta 2006;368:48–52.10.1016/j.cca.2005.12.031Search in Google Scholar PubMed

41. Bischoff-Ferrari H, Stahelin HB, Walter P. Vitamin D effects on bone and muscle. Int J Vitam Nutr Res 2011;81:264–72.10.1024/0300-9831/a000072Search in Google Scholar PubMed

42. Moester MJ, Papapoulos SE, Lowik CW, van Bezooijen RL. Sclerostin: current knowledge and future perspectives. Calcif Tissue Int 2010;87:99–107.10.1007/s00223-010-9372-1Search in Google Scholar PubMed PubMed Central

43. Mirza FS, Padhi ID, Raisz LG, Lorenzo JA. Serum sclerostin levels negatively correlate with parathyroid hormone levels and free estrogen index in postmenopausal women. J Clin Endocrinol Metab 2010;95:1991–7.10.1210/jc.2009-2283Search in Google Scholar PubMed PubMed Central

44. Piemonte S, Romagnoli E, Bratengeier C, Woloszczuk W, Tancredi A, Pepe J, et al. Serum sclerostin levels decline in postmenopausal women with osteoporosis following treatment with intermittent PTH. J Endocrinol Invest 2012; DOI:10.3275/8522.Search in Google Scholar

45. Gatti D, Viapiana O, Fracassi E, Idolazzi L, Dartizio C, Povino MR, et al. Sclerostin and DKK1 in postmenopausal osteoporosis treated with Denosumab. J Bone Miner Res 2012;27:2259–63.10.1002/jbmr.1681Search in Google Scholar PubMed

46. Ooms ME, Roos JC, Bezemer PD, van der Vijgh WJ, Bouter LM, Lips P. Prevention of bone loss by vitamin D supplementation in elderly women: a randomized double-blind trial. J Clin Endocrinol Metab 1995;80:1052–8.Search in Google Scholar

47. Prestwood KM, Pannullo AM, Kenny AM, Pilbeam CC, Raisz LG. The effect of a short course of calcium and vitamin D on bone turnover in older women. Osteoporos Int 1996;6:314–9.10.1007/BF01623391Search in Google Scholar PubMed

48. Ambroszkiewicz J, Klemarczyk W, Gajewska J, Chelchowska M, Strucinska M, Oltarzewski M, et al. [Effect of vitamin D supplementation on serum 25-hydroxyvitamin D and bone turnover markers concentrations in vegetarian children]. Med Wieku Rozwoj 2009;13:34–9.Search in Google Scholar

49. Herrmann M, Widmann T, Colaianni G, Colucci S, Zallone A, Herrmann W. Increased osteoclast activity in the presence of increased homocysteine concentrations. Clin Chem 2005;51:2348–53.10.1373/clinchem.2005.053363Search in Google Scholar PubMed

50. Herrmann M, Wildemann B, Claes L, Klohs S, Ohnmacht M, Taban-Shomal O, et al. Experimental hyperhomocysteinemia reduces bone quality in rats. Clin Chem 2007;53:1455–61.10.1373/clinchem.2007.086272Search in Google Scholar PubMed

51. Herrmann M, Umanskaya N, Traber L, Schmidt-Gayk H, Menke W, Lanzer G, et al. The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial. Clin Chem Lab Med 2007;45:1785–92.10.1515/CCLM.2007.352Search in Google Scholar PubMed

52. Green TJ, McMahon JA, Skeaff CM, Williams SM, Whiting SJ. Lowering homocysteine with B vitamins has no effect on biomarkers of bone turnover in older persons: a 2-y randomized controlled trial. Am J Clin Nutr 2007;85:460–4.10.1093/ajcn/85.2.460Search in Google Scholar PubMed

53. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. J Am Med Assoc 2005;293:1082–8.10.1001/jama.293.9.1082Search in Google Scholar PubMed

54. Saito M, Fujii K, Marumo K. Degree of mineralization-related collagen crosslinking in the femoral neck cancellous bone in cases of hip fracture and controls. Calcif Tissue Int 2006;79:160–8.10.1007/s00223-006-0035-1Search in Google Scholar PubMed

Received: 2012-9-12
Accepted: 2012-10-4
Published Online: 2012-11-21
Published in Print: 2013-03-01

©2013 by Walter de Gruyter Berlin Boston

Downloaded on 26.2.2024 from
Scroll to top button