Aging Clinical and Experimental Research

, Volume 19, Issue 6, pp 472–477 | Cite as

Long-term 1,25(OH)2 vitamin D therapy increases bone mineral density in osteopenic women. Comparison with the effect of plain vitamin D

  • Ivana Zofkova
  • Martin Hill
Original Articles


Backgroud and aims: Although the bone protective effect of vitamin D has been studied intensively, the usefulness of 1,25(OH)2D3 in treating osteoporosis is still questionable. The aim of the present prospective study was to evaluate the effect of a standard pharmacological dose of 1,25(OH)2D3 in post-menopausal unsubstituted women. Methods: Our study group comprised 52 post-menopausal women with low normal or osteopenic values of bone mineral density (BMD). Thirty-two of them were treated with 1,25(OH)2D3 for 3 years. In parallel, another group of women was treated with cholecalciferol (n=20). Vitamin D adequacy before administration of 1,25(OH)2D3 and compliance with treatment were checked by serum PTH levels, which were assessed at the start and three times in the course of treatment. Results: Increase in BMD at the spine at the end of the 1st, 2nd and 3rd years of treatment with 1,25(OH)2D3 (expressed as a percentage of the value before treatment) was higher, but did not significantly differ from the effect of plain vitamin D. A significant increase in BMD at the hip at the end of the 3rd (but not the 1st and 2nd) year of treatment with 1,25(OH)2D3 was found (p<0.05, compared with the effect of plain vitamin D). The protective effect of cholecalciferol was found only on spine but not hip BMD. Conclusion: The study supports the hypothesis that long-term administration of 1,25(OH)2D3 is effective in treating low bone mass in post-menopausal women.


Bone density 1,25-dihydroxyvitamin D3 cholecalciferol 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Lee CJ, Lawler GS, Johnson GH. Effect of supplementation of the diets with calcium and calcium-rich foods on bone density of elderly females with osteoporosis. Am J Clin Nutr 1981; 34: 819–23.PubMedGoogle Scholar
  2. 2.
    Smith EL Jr. Reddan W, Smith PE. Physical activity and calcium modalities for bone mineral increase in aged women. Med Sci Sports Exerc 1981; 13: 60–4.PubMedGoogle Scholar
  3. 3.
    McKenna MJ, Freaney R, Meade A, Muldowney FP. Hypovitaminosis D and elevated serum alkaline phosphatase in elderly Irish people. Am J Clin Nutr 1985; 41: 101–9.PubMedGoogle Scholar
  4. 4.
    Lips P, Wiersunga A, van Ginkel FC, 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.PubMedCrossRefGoogle Scholar
  5. 5.
    Himmelstein S, Clemens TL, Rubin A, Lindsay R. Vitamin D supplementation in elderly nursing home residents increases 25(OH)D but not 1,25(OH)2D. Am J Clin Nutr 1990; 52: 701–6.PubMedGoogle Scholar
  6. 6.
    Francis RM, Boyle IT, Moniz C, et al. A comparison of the effects of alfacalcidiol treatment and vitamin D2 supplementation on calcium absorption in elderly women with vertebral fractures. Osteoporos Int 1996; 6: 284–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Eastel R, Riggs BL. Vitamin D and osteoporosis. In: Feldman D, Glorieux FH. Pike JW. eds. Vitamin D. San Diego: Academic Press, 1997: 695–711.Google Scholar
  8. 8.
    Nishi Y. Rationale for active vitamin D and analogs in the treatment of osteoporosis. J Cell Biochem 2003; 88: 381–6.CrossRefGoogle Scholar
  9. 9.
    Suda T. Ueno Y. Fujii K. Shinki T. Vitamin D and bone. J Cell Biochem 2003; 88: 259–66.CrossRefGoogle Scholar
  10. 10.
    Takashu H, Sugita A, Uchiyama Y, et al. c-Fos protein as a target of anti-osteoclastogenic action of vitamin D, and synthesis of new analogs. J Clin Invest 2006; 116: 528–35.CrossRefGoogle Scholar
  11. 11.
    Inanir A, Ozoran K, Tutkak H, Mermerci B. The effects of calcitriol therapy on serum interleukin-1, interleukin-6 and tumor necrosis factor-alpha concentrations in post-menopausal patients with osteoporosis. J Int Med Res 2004; 32: 570–82.PubMedCrossRefGoogle Scholar
  12. 12.
    Iwamoto J, Seki A, Takeda T, et al. Comparative effects of risedronate and calcitriol on cancellous bone in rats with glucocorticoid-induced osteopenia. J Nutr Sci Vitaminol (Tokyo) 2006; 52: 21–7.CrossRefGoogle Scholar
  13. 13.
    Need AG, Nordin C, Horowitz M, Morris HA. Calcium and calcitiol therapy in osteoporotic postmenopausal women with impaired calcium absorption. Metabolism 1990; 39: 53–4.PubMedCrossRefGoogle Scholar
  14. 14.
    Zofkova I, Kancheva R. The effect of 1,25(OH)2 vitamin D3 on circulating insulin-like growth factor I and beta 2 microglobulin in patients with osteoporosis. Calcif Tissue Int 1997; 60: 236–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Lau KHW, Baylink DJ. Vitamin D therapy of osteoporosis: plain vitamin D therapy versus active vitamin D analog (D-hormone) therapy. Calcif Tissue Int 1999; 65: 295–306.PubMedCrossRefGoogle Scholar
  16. 16.
    Weber K, Kaschig C, Erben RG. 1 Alpha-hydroxyvitamin D-2 and 1 alpha-hydroxyvitamin D-3 have anabolic effects on cortical bone, but induce intracortical remodeling at toxic doses in ovariectomized rats. Bone 2004; 35: 704–10.PubMedCrossRefGoogle Scholar
  17. 17.
    Duque G, Macoritto M, Dion N, SteMarie LG, Kremer R. 1,25(OH)(2)D-3 acts as a bone-forming agent in the hormone-independent senescence-accelerated mouse (SAM-P/6). Am J Physiol — Endocrinol Metab 2005; 288: E723–30.PubMedCrossRefGoogle Scholar
  18. 18.
    Del Pino-Montes J, Benito GE, Fernandez Salazar MP, et al. Calcitriol improves streptozotocin-induced diabetes and recovers bone mineral density in diabetic rats. Calcif Tissue Int 2004; 75: 526–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Visser M, Deeg DJ, Lips P. Low vitamin D and high parathyroid hormone levels as determinants of loss of muscle strength and muscle mass (sarcopenia): the Longitudinal Aging Study Amsterdam. J Clin Endocrinol Metab 2003; 88: 5766–72.PubMedCrossRefGoogle Scholar
  20. 20.
    Bischoff HA, Borchers M, Gudat F, et al. In situ detection of 1,25-dihydroxyvitamin D3 receptor in human skeletal muscle tissue. Histochem J 2001; 33: 19–24.PubMedCrossRefGoogle Scholar
  21. 21.
    Aloia JF, Arunabh Talwar S, Polack S, Yeh J. A randomized controlled trial of vitamin D3 supplementation in African American women. Arch Intern Med 2005; 165: 1618–23.PubMedCrossRefGoogle Scholar
  22. 22.
    Aloia F, Vaswani A, Yeh JK, Ellis K, Yasumura S, Cohn SH. Calcitriol in the treatment of postmenopausal osteoporosis. Am J Mod 1988; 84: 401–8.CrossRefGoogle Scholar
  23. 23.
    Gallagher JC, Jerpbak CM, Jee WS, Johnson KA, DeLuca HF, Riggs BL. 1,25-dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis. Proc Natl Acad Sci USA 1982; 79: 3325–9.PubMedCrossRefGoogle Scholar
  24. 24.
    Ott SM, Chesnut CH. Calcitriol treatment is not effective in postmenopausal osteoporosis. Ann Intern Med 1989; 110: 267–74.PubMedCrossRefGoogle Scholar
  25. 25.
    Gallagher JC, Goldgar D. Treatment of postmenopausal osteoporosis with high doses of synthetic calciferol. A randomized controlled study. Ann Internal Med 1990; 113: 649–55.CrossRefGoogle Scholar
  26. 26.
    Christiansen C, Christiansen MS, Rodbro P, Hagen C, Transbol I. Effect of 1,25-dihydroxy-vitamin D3 in itself or combined with hormone treatment in preventing postmenopausal osteoporosis. Eur J Clin Invest 1981; 11: 305–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Falch IA, Odegaard OR, Finnanger AM, Matheson I. Postmenopausal osteoporosis: no effect of three years treatment with 1,25-dihydroxycholecalciferol. Acta Med Scand 1987; 221: 199–204.PubMedCrossRefGoogle Scholar
  28. 28.
    Avenell A, Gillespie WJ, Gillespie LD, O’Connell DL. Vitamin D and vitamin D analogues for preventing fractures associated with involutional and post-menopausal osteoporosis. Cochrane Database Syst Rev 2005; 3: CD000227.PubMedGoogle Scholar
  29. 29.
    Richy F, Schacht E, Bruyere O, Ethgen O, Gourlay M, Reginster JY. Vitamin D analogs versus native vitamin D in preventing bone loss and osteoporosis-related fractures: A comparative meta-analysis. Calcif Tissue Int 2005; 76: 176–86.PubMedCrossRefGoogle Scholar
  30. 30.
    Sairanen S, Kärkkäinen M, Tähtelä R, et al. Bone mass and markers of bone and calcium metabolism in postmenopausal women treated with 1,25-dihydroxyvitamin D (calcitriol) for four years. Calcif Tissue Int 2000; 67: 122–7.PubMedCrossRefGoogle Scholar
  31. 31.
    Klein B, Kaufman JH, Isaacs J. Automated simultaneous calcium and phosphorus analysis. Clin Chem 1967; 13: 1071–8.PubMedGoogle Scholar
  32. 32.
    Matsuyama T, Ishii S, Tokita A, et al. Vitamin D receptor genotypes and bone mineral density. Lancet 1995; 345: 1238–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Graafmans WC, Lips P, Ooms ME, van Leeuwen JP, Pols HA, Uitterlinden AG. The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype. J Bone Miner Res 1997; 12: 1241–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Kobayashi N, Fujino T, Shirogane T, et al. Estrogen receptor alpha polymorphism as a genetic marker for bone loss, vertebral fractures and susceptibility to estrogen. Maturitas 2002; 41: 193–201.PubMedCrossRefGoogle Scholar
  35. 35.
    Kurabayashi T, Tomita M, Matsushita H, et al. Association of vitamin D and estrogen receptor gene polymorphism with the effect of hormone replacement therapy on bone mineral density in Japanese women. Am J Obstet Gynecol 1999; 180: 1115–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Internal Publishing Switzerland 2007

Authors and Affiliations

  1. 1.Institute of EndocrinologyPragueCzech Republic

Personalised recommendations