Osteoporosis International

, Volume 20, Issue 2, pp 239–244

Vitamin D status and response to treatment in post-menopausal osteoporosis

  • S. Adami
  • S. Giannini
  • G. Bianchi
  • L. Sinigaglia
  • O. Di Munno
  • C. E. Fiore
  • S. Minisola
  • M. Rossini
Original Article



Treatment with anti-resorptive agents over 13 months was associated with for three to fivefold lower bone mineral density changes and 1.5-fold increased risk of incidence fracture in vitamin D insufficient as compared to vitamin D repleted postmenopausal osteoporotic women.


Several drugs were registered for the treatment of osteoporosis on the basis of clinical trials in which vitamin D repletion was a pre-requisite inclusion criteria and vitamin D supplements were used as adjunctive therapy. However, in routine clinical practice these supplements are not consistently recommended.


We studied 1515 women with postmenopausal osteoporosis under treatment with anti-resorbing agents (alendronate, risedronate, raloxifene) for 13.1 months with an adherence > 75%. The patients were classified as vitamin D deficient (N = 514) or vitamin D repleted (N = 1001) according to risk factors (N = 1062) or the level of 25(OH) vitamin D [25(OH)D] above or below 50 nmol/l (N = 453).


Vitamin D deficient and vitamin D repleted subjects differed significantly for annualized spine and hip bone mineral density (BMD) changes adjusted for all available confounding factors (type of treatment, age, global calcium intake, baseline BMD values). One hundred fifty one patients suffered from a new incident clinical fracture. The adjusted odds ratio for incident fractures in vitamin D deficient as compared to vitamin D repleted women was 1.77 (1.20 – 2.59, 95% CI; p = 0.004).


Optimal vitamin D repletion seems to be necessary to maximize the response to anti-resorbers in terms of both BMD changes and anti-fracture efficacy.


Alendronate BMD changes Fracture risk Osteoporosis treatment Risedronate Vitamin D deficiency 


  1. 1.
    Wielen van der RPJ, Lowik MRH, Berg van den H, Groot de LCPGM, Haller J, Moreiras O, Staveren van WA (1995) Serum vitamin D concentrations among elderly people in Europe. Lancet 346:207–210CrossRefGoogle Scholar
  2. 2.
    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 86:1212–1221PubMedCrossRefGoogle Scholar
  3. 3.
    Isaia G, Giorgino R, Rini GB, Bevilacqua M, Maugeri D, Adami S (2003) Prevalence of hypovitaminosis D in elderly women in Italy: clinical consequences and risk factors. Oteoporos Int 14:577–582CrossRefGoogle Scholar
  4. 4.
    Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R (2005) Estimates of optimal vitamin D status. Osteoporos Int 16(7):713–716PubMedCrossRefGoogle Scholar
  5. 5.
    Bischoff-Ferrari HA, Giovannucci E, Willett WC, Dietrich T, Dawson-Hughes B (2006) Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 84:18–28PubMedGoogle Scholar
  6. 6.
    The RECORD trial Group (2005) Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial. Lancet 365:1621–1628CrossRefGoogle Scholar
  7. 7.
    Porthouse J, Cockayne S, King C, Saxon L, Steele E, Aspray T, Baverstock M, Birks Y, Dumville J, Francis R, Iglesias C, Puffer S, Sutcliffe A, Watt I, Torgerson DJ (2005) Randomised controlled trial of calcium and supplementation with cholecalciferol (vitamin D3) for prevention of fractures in primary care. BMJ 330:1003–1006PubMedCrossRefGoogle Scholar
  8. 8.
    Bischoff-Ferrari HA (2007) How to select the doses of vitamin D in the management of osteoporosis. Osteoporos Int 18:401–407PubMedCrossRefGoogle Scholar
  9. 9.
    Stevenson M, Lloyd Jones M, Davis S, Beverley C (2005) Extract from DSU report by Scharr. Available at: http://www.nice.org.uk/pdf/Osteo_Clinical_Effectiveness_DSU_report.pdf; Accessed Sept 2007
  10. 10.
    Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE (2005) Prevalence of vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab 90:3215–3224PubMedCrossRefGoogle Scholar
  11. 11.
    Rossini M, Bianchi G, Di Munno O et al (2006) Treatment of Osteoporosis in clinical Practice (TOP) Study Group. Determinants of adherence to osteoporosis treatment in clinical practice. Osteoporos Int 17:914–921PubMedCrossRefGoogle Scholar
  12. 12.
    LaPlante MP, Rice DP,Wenger BL (1995) Medical Care Use, Health Insurance in the United States. Disability Statistics Abstract, Number 8. Disability Statistics Rehabilitation Research and Training Center, University of California, San Francisco. U.S. Department of Education, National Institute on Disability and Rehabilitation Research, May, pp 1–4Google Scholar
  13. 13.
    Lu Y, Fuerst T, Hui S, Genant HK (2001) Standardization of bone mineral density at femoral neck, trochanter and Ward’s triangle. Osteoporos Int 12:438–444PubMedCrossRefGoogle Scholar
  14. 14.
    Adami S, Isaia G, Luisetto G, Minisola S, Sinigaglia L, Gentilella R, Agnusdei D, Iori N, Nuti R, ICARO Study Group (2006) Fracture incidence and characterization in patients on osteoporosis treatment:the ICARO study. J Bone Miner Res 21:1565–1570PubMedCrossRefGoogle Scholar
  15. 15.
    Antoniucci DM, Vittinghoff E, Blackwell T, Black DM, Sellmeyer DE (2005) Vitamin D insufficiency does not affect bone mineral density response to raloxifene. J Clin Endocrinol Metab 90:4566–4572PubMedCrossRefGoogle Scholar
  16. 16.
    Deane A, Constancio L, Fogelman I, Hampson G (2007) The impact of vitamin D status on changes in bone mineral density during treatment with bisphosphonates and after discontinuation following long-term use in post-menopausal osteoporosis. BMC Musculoskeletal Disorders 8:3PubMedCrossRefGoogle Scholar
  17. 17.
    Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG, Iowa Women’s Health Study (2004) Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 50:72–77PubMedCrossRefGoogle Scholar
  18. 18.
    McAlindon TE, Felson DT, Zhang Y, Hannan MT, Aliabadi P, Weissman B, Rush D, Wilson PW, Jacques P (1996) Relation of dietary intake and serum levels of vitamin D to progression of osteoarthritis of the knee among participants in the Framingham Study. Ann Intern Med 125:353–359PubMedGoogle Scholar
  19. 19.
    Binkley N, Novotny R, Krueger D, Kawahara T, Daida YG, Lensmeyer G, Hollis BW, Drezner MK (2007) Low vitamin D status despite abundant sun exposure. J Clin Endocrinol Metab 92:2130–2135PubMedCrossRefGoogle Scholar
  20. 20.
    Adami S, Viapiana O, Gatti D, Idolazzi L, Rossini M (2008) Relationship between serum parathyroid hormone vitamin D sufficiency, age and calcium intake. Bone 42:267–270PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2008

Authors and Affiliations

  • S. Adami
    • 1
  • S. Giannini
    • 2
  • G. Bianchi
    • 3
  • L. Sinigaglia
    • 4
  • O. Di Munno
    • 5
  • C. E. Fiore
    • 6
  • S. Minisola
    • 7
  • M. Rossini
    • 1
  1. 1.Rheumatology UnitOspedale di ValeggioVeronaItaly
  2. 2.Internal MedicineUniversity of PaduaPaduaItaly
  3. 3.Rheumatology Unit, ASL3GenoaItaly
  4. 4.Rheumatology UnitOspedale G PiniMilanItaly
  5. 5.Rheumatology UnitUniversity of PisaPisaItaly
  6. 6.Internal MedicineUniversity of CataniaCataniaItaly
  7. 7.Internal MedicineUniversity of RomeRomeItaly

Personalised recommendations