European Journal of Nutrition

, Volume 50, Issue 5, pp 341–349 | Cite as

Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study

  • Roxane Tenta
  • George Moschonis
  • Michael Koutsilieris
  • Yannis ManiosEmail author
Original Contribution



To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women.


Forty postmenopausal women (55–65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D3 for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA.


A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (−0.08; −0.12 to −0.03) and 12 (−0.03; −0.08 to −0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001).


Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.


Calcium and vitamin D RANKL Bone metabolism Postmenopausal women Physiology 



The present study was supported with a research grant by Friesland Foods Hellas. The authors would like to thank Eva Grammatikaki, Ioanna Katsaroli, and Paraskevi Kannelou, dietitians, as well as Sofia Tanagra, technician, for their valuable contribution in data collection and processing.

Conflict of interest

YM also works as a science and nutrition consultant for FrieslandCampina Hellas. The study sponsor had no role in the study design; the collection, analysis, or interpretation of the data; the writing of the manuscript; the submission and revision of the paper. None of the other authors had any potential conflict of interest.


  1. 1.
    Heaney RP, McCarron DA, Dawson-Hughes B, Oparil S, Berga SL, Stern JS, Barr SI, Rosen CJ (1999) Dietary changes favorably affect bone remodeling in older adults. J Am Diet Assoc 99(10):1228–1233CrossRefGoogle Scholar
  2. 2.
    Bonde M, Qvist P, Fledelius C, Riis BJ, Christiansen C (1994) Immunoassay for quantifying type I collagen degradation products in urine evaluated. Clin Chem 40(11 Pt 1):2022–2025Google Scholar
  3. 3.
    Wittrant Y, Theoleyre S, Chipoy C, Padrines M, Blanchard F, Heymann D, Redini F (2004) Rankl/rank/opg: new therapeutic targets in bone tumours and associated osteolysis. Biochim Biophys Acta 1704(2):49–57. doi: 10.1016/j.bbcan.2004.05.002S0304419X04000320[pii] Google Scholar
  4. 4.
    Hadjidakis DJ, Androulakis II (2006) Bone remodeling. Ann N Y Acad Sci 1092:385–396CrossRefGoogle Scholar
  5. 5.
    Mathers CD, Iburg KM, Salomon JA, Tandon A, Chatterji S, Ustun B, Murray CJ (2004) Global patterns of healthy life expectancy in the year 2002. BMC Public Health 4(1):66CrossRefGoogle Scholar
  6. 6.
    Hodgson SF, Watts NB, Bilezikian JP, Clarke BL, Gray TK, Harris DW, Johnston CC Jr, Kleerekoper M, Lindsay R, Luckey MM, McClung MR, Petak SM, Recker RR, Anderson RJ, Bergman DA, Bloomgarden ZT, Dickey RA, Palumbo PJ, Peters AL, Rettinger HI, Rodbard HW, Rubenstein HA (2003) American association of clinical endocrinologists medical guidelines for clinical practice for the prevention and treatment of postmenopausal osteoporosis: 2001 edition, with selected updates for 2003. Endocr Pract 9(6):544–564Google Scholar
  7. 7.
    Nieves JW (2005) Osteoporosis: the role of micronutrients. Am J Clin Nutr 81(5):1232S–1239SGoogle Scholar
  8. 8.
    Weisman SM, Matkovic V (2005) Potential use of biochemical markers of bone turnover for assessing the effect of calcium supplementation and predicting fracture risk. Clin Ther 27(3):299–308CrossRefGoogle Scholar
  9. 9.
    Baeksgaard L, Andersen KP, Hyldstrup L (1998) Calcium and vitamin d supplementation increases spinal BMD in healthy, postmenopausal women. Osteoporos Int 8(3):255–260CrossRefGoogle Scholar
  10. 10.
    Dawson-Hughes B, Dallal GE, Krall EA, Sadowski L, Sahyoun N, Tannenbaum S (1990) A controlled trial of the effect of calcium supplementation on bone density in postmenopausal women. N Engl J Med 323(13):878–883CrossRefGoogle Scholar
  11. 11.
    Reid IR, Ames RW, Evans MC, Gamble GD, Sharpe SJ (1995) Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 98(4):331–335CrossRefGoogle Scholar
  12. 12.
    Vieth R, Chan PC, MacFarlane GD (2001) Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 73(2):288–294Google Scholar
  13. 13.
    Storm D, Eslin R, Porter ES, Musgrave K, Vereault D, Patton C, Kessenich C, Mohan S, Chen T, Holick MF, Rosen CJ (1998) Calcium supplementation prevents seasonal bone loss and changes in biochemical markers of bone turnover in elderly New England women: a randomized placebo-controlled trial. J Clin Endocrinol Metab 83(11):3817–3825CrossRefGoogle Scholar
  14. 14.
    Chee WS, Suriah AR, Chan SP, Zaitun Y, Chan YM (2003) The effect of milk supplementation on bone mineral density in postmenopausal Chinese women in Malaysia. Osteoporos Int 14(10):828–834CrossRefGoogle Scholar
  15. 15.
    Manios Y, Moschonis G, Trovas G, Lyritis GP (2007) Changes in biochemical indexes of bone metabolism and bone mineral density after a 12-mo dietary intervention program: the postmenopausal health study. Am J Clin Nutr 86(3):781–789Google Scholar
  16. 16.
    University of Crete (1991) Food composition tables. Nutrition.Med.Uoc.Gr/greektablesGoogle Scholar
  17. 17.
    Trichopoulou A (2004) Composition tables of foods and Greek dishes. School of medicine: department of hygiene and epidemiology, GreeceGoogle Scholar
  18. 18.
    Groothausen J, Siemer H, Kemper HCG, Twisk J, Welten DC (1997) Influence of peak strain on lumbar bone mineral density: an analysis of 15-year physical activity in young males and females. Pediatr Exerc Sci 9(2):159–173Google Scholar
  19. 19.
    Institute of Medicine Food and Nutrition Board (2001) Dietary reference intakes: applications in dietary assessment. National Academy Press, DCGoogle Scholar
  20. 20.
    Calvo MS, Whiting SJ, Barton CN (2005) Vitamin D intake: a global perspective of current status. J Nutr 135(2):310–316Google Scholar
  21. 21.
    Souberbielle JC, Body JJ, Lappe JM, Plebani M, Shoenfeld Y, Wang TJ, Bischoff-Ferrari HA, Cavalier E, Ebeling PR, Fardellone P, Gandini S, Gruson D, Guerin AP, Heickendorff L, Hollis BW, Ish-Shalom S, Jean G, von Landenberg P, Largura A, Olsson T, Pierrot-Deseilligny C, Pilz S, Tincani A, Valcour A, Zittermann A (2010) Vitamin D and musculoskeletal health, cardiovascular disease, autoimmunity and cancer: recommendations for clinical practice. Autoimmun Rev 9(11):709–715CrossRefGoogle Scholar
  22. 22.
    Riggs BL, O’Fallon WM, Muhs J, O’Connor MK, Kumar R, Melton LJ 3rd (1998) Long-term effects of calcium supplementation on serum parathyroid hormone level, bone turnover, and bone loss in elderly women. J Bone Miner Res 13(2):168–174CrossRefGoogle Scholar
  23. 23.
    Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 128(10):801–809Google Scholar
  24. 24.
    Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ (2003) Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 77(1):204–210Google Scholar
  25. 25.
    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-hydroxy vitamin D concentration. Am J Clin Nutr 87(6):1952–1958Google Scholar
  26. 26.
    Hamdy NA (2007) Targeting the rank/rankl/opg signaling pathway: a novel approach in the management of osteoporosis. Curr Opin Investig Drugs 8(4):299–303Google Scholar
  27. 27.
    Hofbauer LC, Schoppet M (2004) Clinical implications of the osteoprotegerin/rankl/rank system for bone and vascular diseases. Jama 292(4):490–495CrossRefGoogle Scholar
  28. 28.
    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, Cancellieri F, Faraci M, Marini R, Adamo EB, Wilson S, Squadrito F (2008) Opg and srankl serum concentrations in osteopenic, postmenopausal women after 2-year genistein administration. J Bone Miner Res 23(5):715–720. doi: 10.1359/jbmr.080201 CrossRefGoogle Scholar
  29. 29.
    Stepan JJ (2000) Prediction of bone loss in postmenopausal women. Osteoporos Int 11(Suppl 6):S45–S54CrossRefGoogle Scholar
  30. 30.
    Hunter D, Major P, Arden N, Swaminathan R, Andrew T, MacGregor AJ, Keen R, Snieder H, Spector TD (2000) A randomized controlled trial of vitamin d supplementation on preventing postmenopausal bone loss and modifying bone metabolism using identical twin pairs. J Bone Miner Res 15(11):2276–2283CrossRefGoogle Scholar
  31. 31.
    Dawson-Hughes B, Harris SS, Krall EA, Dallal GE (1997) Effect of calcium and vitamin d supplementation on bone density in men and women 65 years of age or older. N Engl J Med 337(10):670–676CrossRefGoogle Scholar
  32. 32.
    Lau EM, Lynn H, Chan YH, Woo J (2002) Milk supplementation prevents bone loss in postmenopausal Chinese women over 3 years. Bone 31(4):536–540CrossRefGoogle Scholar
  33. 33.
    Moschonis G, Katsaroli I, Lyritis GP, Manios Y (2010) The effects of a 30-month dietary intervention on bone mineral density: the postmenopausal health study. Br J Nutr 104(1):100–107CrossRefGoogle Scholar
  34. 34.
    Bergman GJ, Fan T, McFetridge JT, Sen SS (2010) Efficacy of vitamin d3 supplementation in preventing fractures in elderly women: a meta-analysis. Curr Med Res Opin 26(5):1193–1201Google Scholar
  35. 35.
    Bolland MJ, Avenell A, Baron JA, Grey A, MacLennan GS, Gamble GD, Reid IR (2010) Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. Bmj 341:c3691CrossRefGoogle Scholar
  36. 36.
    Wang L, Manson JE, Song Y, Sesso HD (2010) Systematic review: vitamin d and calcium supplementation in prevention of cardiovascular events. Ann Intern Med 152(5):315–323Google Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Roxane Tenta
    • 1
  • George Moschonis
    • 1
  • Michael Koutsilieris
    • 2
  • Yannis Manios
    • 1
    Email author
  1. 1.Department of Nutrition and DieteticsHarokopio UniversityAthensGreece
  2. 2.Department of Experimental PhysiologyMedical School, University of AthensGoudi-AthensGreece

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