Skip to main content

Advertisement

SpringerLink
Log in

Differential Effects of D-Hormone Analogs and Native Vitamin D on the Risk of Falls: A Comparative Meta-Analysis

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

The aim of this meta-analysis was to compare the antifall efficacy of native vitamin D to that of its hydroxylated analogs alfacalcidol and calcitriol. Randomized clinical trials comparing oral native vitamin D and its analogs alfacalcidol and calcitriol to a placebo were included. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, a hand search of abstracts, as well as reference lists. The time range was January 1995 to May 2007. Data were abstracted and scored by two investigators. The core analysis was based on double-blind trials, while open trials were included as a robustness analysis. Relative risks (RRs) for falls while allocated to D-hormone analogs or vitamin D were calculated. Publication bias and robustness were formally tested. Fourteen trials including 21,268 subjects were included. Using double-blind data only, vitamin D-hormone analogs provided a statistically significant lower level of risk for falling compared to native vitamin D: RR = 0.79 (95% confidence interval 0.64–0.96) vs. 0.94 (0.87–1.01) (intergroup difference P = 0.049). The dropout rates observed in the two sets of trials were comparable: 0.33% per month. Publication bias investigation did not report any significant trend for selective publication favoring active treatment arms. Upon current evidence, D-hormone analogs seem to prevent falls to a greater extent than their native compound. Long-term, prospective, head-to-head, confirmatory trials are required to address the exact role of vitamin D and D-hormone analogs in the prevention of falls and fractures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Campbell AJ, Robertson MC (2006) Implementation of multifactorial interventions for fall and fracture prevention. Age Ageing 35(Suppl 2):60–64

    Google Scholar 

  2. Sanders KM, Nicholson GC, Watts JJ, Pasco JA, Henry MJ, Kotowicz MA, Seeman E (2006) Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective? Bone 38:694–700

    Article  PubMed  Google Scholar 

  3. Moreland JD, Richardson JA, Goldsmith CH, Clase CM (2004) Muscle weakness and falls in older adults: a systematic review and meta-analysis. J Am Geriatr Soc 52:1121–1129

    Article  PubMed  Google Scholar 

  4. Gallagher JC (2004) The effects of calcitriol on falls and fractures and physical performance tests. J Steroid Biochem Mol Biol 89–90:497–501

    Article  PubMed  Google Scholar 

  5. Dukas L, Staehelin HB, Schacht E, Bischoff HA (2005) Better functional mobility in community-dwelling elderly is related to D-hormone serum levels and to daily calcium intake. J Nutr Health Aging 9:347–351

    PubMed  CAS  Google Scholar 

  6. Bischoff-Ferrari HA, Borchers M, Gudat F, Dürmüller U, Stähelin HB, Dick W (2004) Vitamin D receptor expression in human muscle tissue decreases with age. J Bone Miner Res 19:265–269

    Article  PubMed  CAS  Google Scholar 

  7. Faulkner KA, Cauley JA, Zmuda JM, Landsittel DP, Newman AB, Studenski SA, Redfern MS, Ensrud KE, Fink HA, Lane NE, Nevitt MC (2006) Higher 1,25-dihydroxyvitamin D3 concentrations associated with lower fall rates in older community-dwelling women. Osteoporos Int 17:1318–1328

    Article  PubMed  CAS  Google Scholar 

  8. Gallagher JC, Rapuri PB, Smith LM (2007) An age related decrease in creatinine clearance is associated with an increase in number of falls in untreated women but not in women receiving calcitriol. J Clin Endocrinol Metab 92:51–58

    Article  PubMed  CAS  Google Scholar 

  9. Strugnell SA, Deluca HF (1997) The vitamin D receptor—structure and transcriptional activation. In: Proceedings of the Society for Experimental Biology and Medicine, vol 215. Society for Experimental Biology and Medicine, New York, pp. 223–228

  10. Bischoff HA, Stahelin HB, Tyndall A, Theiler R (2000) Relationship between muscle strength and vitamin D metabolites: are there therapeutic possibilities in the elderly? Z Rheumatol 59(Suppl 1):39–41

    Article  PubMed  Google Scholar 

  11. Janssen HC, Samson MM, Verhaar HJ (2002) Vitamin D deficiency, muscle function, and falls in elderly people. Am J Clin Nutr 75:611–615

    PubMed  CAS  Google Scholar 

  12. Nordin BEC, Need AG, Morris HA, Horowitz M (1999) The special role of “hormonal” forms of vitamin D in the treatment of osteoporosis. Calcif Tissue Int 65:307–310

    Article  PubMed  CAS  Google Scholar 

  13. Lau KHW, Baylink DJ (1999) Vitamin D therapy of osteoporosis: plain vitamin D therapy vs. active vitamin D analog (D-hormone) therapy. Calcif Tissue Int 65:295–306

    Article  PubMed  CAS  Google Scholar 

  14. Richy F, Deroisy R, Lecart MP, Hanssens L, Mawet A, Reginster JY (2005) D-hormone analog alfacalcidol: an update on its role in post-menopausal osteoporosis and rheumatoid arthritis. Aging Clin Exp Res 17:133–142

    PubMed  CAS  Google Scholar 

  15. Wiese RJ, Uhland-Smith A, Ross TK, Prahl JM, DeLuca HF (1992) Up-regulation of the vitamin D receptor in response to 1,25-dihydroxyitamin D3 results from ligand-induced stabilization. J Biol Chem 267:20082–20086

    PubMed  CAS  Google Scholar 

  16. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, Staehelin HB, Bazemore MG, Zee RY, Wong JB (2004) Effect of vitamin D on falls: a meta-analysis. JAMA 291:1999–2006

    Article  PubMed  CAS  Google Scholar 

  17. 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

    Article  PubMed  CAS  Google Scholar 

  18. Grant AM, Avenell A, Campbell MK, McDonald AM, MacLennan GS, McPherson GC, Anderson FH, Cooper C, Francis RM, Donaldson C, Gillespie WJ, Robinson CM, Torgerson DJ, Wallace WA; on behalf of 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 5:63013–63019

    Google Scholar 

  19. Egger M, Davey Smith G, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    PubMed  CAS  Google Scholar 

  20. Sterne JA, Gavaghan D, Egger M (2000) Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 53:1119–1129

    Article  PubMed  CAS  Google Scholar 

  21. Dukas L, Bischoff HA, Lindpaintner LS, Schacht E, Birkner-Binder D, Damm TN, Thalmann B, Stahelin HB (2004) Alfacalcidol reduces the number of fallers in a community-dwelling elderly population with a minimum calcium intake of more than 500 mg daily. J Am Geriatr Soc 52:230–236

    Article  PubMed  Google Scholar 

  22. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, Nebiker M, Theiler R, Pfeifer M, Begerow B, Lew RA, Conzelmann M (2003) Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res 18:343–351

    Article  PubMed  CAS  Google Scholar 

  23. Broe KE, Chen TC, Weinberg J, Bischoff-Ferrari HA, Holick MF, Kiel DP (2007) A higher dose of vitamin D reduces the risk of falls in nursing home residents: a randomized, multiple-dose study. J Am Geriatr Soc 55:234–239

    Article  PubMed  Google Scholar 

  24. Chapuy MC, Pamphile R, Paris E, Kempf C, Schlichting M, Arnaud S, Garnero P, Meunier PJ (2002) Combined calcium and vitamin D3 supplementation in elderly women: confirmation of reversal of secondary hyperparathyroidism and hip fracture risk: the Decalyos II study. Osteoporos Int 13:257–264

    Article  PubMed  CAS  Google Scholar 

  25. Flicker L, MacInnis RJ, Stein MS, Scherer SC, Mead KE, Nowson CA, Thomas J, Lowndes C, Hopper JL, Wark JD (2005) Should older people in residential care receive vitamin D to prevent falls? Results of a randomized trial. J Am Geriatr Soc 53:1881–1888

    Article  PubMed  Google Scholar 

  26. Gallagher JC, Fowler SE, Detter JR, Sherman SS (2001) Combination treatment with estrogen and calcitriol in the prevention of age-related bone loss. J Clin Endocrinol Metab 86:3618–3628

    Article  PubMed  CAS  Google Scholar 

  27. Graafmans WC, Ooms ME, Hofstee HM, Bezemer PD, Bouter LM, Lips P (1996) Falls in the elderly: a prospective study of risk factors and risk profiles. Am J Epidemiol 143:1129–1136

    PubMed  CAS  Google Scholar 

  28. Harwood RH, Sahota O, Gaynor K, Masud T, Hosking DJ (2004) A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: the Nottingham Neck of Femur (NONOF) study. Age Ageing 33:45–51

    Article  PubMed  Google Scholar 

  29. Larsen ER, Mosekilde L, Foldspang A (2004) Vitamin D and calcium supplementation prevents osteoporotic fractures in elderly community dwelling residents: a pragmatic population-based 3-year intervention study. J Bone Miner Res 19:370–378

    Article  PubMed  CAS  Google Scholar 

  30. Latham NK, Anderson CS, Lee A, Bennett DA, Moseley A, Cameron ID (2003) A randomized, controlled trial of quadriceps resistance exercise and vitamin D in frail older people: the Frailty Interventions Trial in Elderly Subjects (FITNESS). J Am Geriatr Soc 51:291–299

    Article  PubMed  Google Scholar 

  31. Pfeifer M, Begerow B, Minne HW, Abrams C, Nachtigall D, Hansen C (2000) Effects of a short-term vitamin D and calcium supplementation on body sway and secondary hyperparathyroidism in elderly women. J Bone Miner Res 15:1113–1138

    Article  PubMed  CAS  Google Scholar 

  32. Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469

    Article  PubMed  CAS  Google Scholar 

  33. Law M, Withers H, Morris J, Anderson F (2006) Vitamin D supplementation and the prevention of fractures and falls: results of a randomised trial in elderly people in residential accommodation. Age Ageing 35:482–486

    Article  PubMed  Google Scholar 

  34. Jackson C, Gaugris S, Sen SS, Hosking D (2007) The effect of cholecalciferol (vitamin D3) on the risk of fall and fracture: a meta-analysis. QJM 100:185–192

    Article  PubMed  CAS  Google Scholar 

  35. Richy F, Schacht E, Bruyere O, Ethgen O, Gourlay M, Reginster JY (2005) Vitamin D analogs vs. native vitamin D in preventing bone loss and osteoporosis-related fractures: a comparative meta-analysis. Calcif Tissue Int 76:176–186

    Article  PubMed  CAS  Google Scholar 

  36. Chou R, Fu R, Huffman LH, Korthuis PT (2006) Initial highly-active antiretroviral therapy with a protease inhibitor vs. a non-nucleoside reverse transcriptase inhibitor: discrepancies between direct and indirect meta-analyses. Lancet 368:1503–1515

    Article  PubMed  CAS  Google Scholar 

  37. Bucher HC, Guyatt GH, Griffith LE, Walter SD (1997) The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials. J Clin Epidemiol 50:683–691

    Article  PubMed  CAS  Google Scholar 

  38. Lumley T (2002) Network meta-analysis for indirect treatment comparisons. Stat Med 21:2313–2324

    Article  PubMed  Google Scholar 

  39. Song F, Altman DG, Glenny AM, Deeks JJ (2003) Validity of indirect comparison for estimating efficacy of competing interventions: empirical evidence from published meta-analyses. BMJ 326:472

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Public Health, Epidemiology, and Health Economics, University of Liege, CHU B23, Liege, Belgium

    Florent Richy

  2. Acute Geriatric University Clinic, Kantonsspital, Basle, Switzerland

    Laurent Dukas

  3. Zürich Osteoporosis Research Group, Zurich, Switzerland

    Erich Schacht

Authors
  1. Florent Richy
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Laurent Dukas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erich Schacht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Florent Richy.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Richy, F., Dukas, L. & Schacht, E. Differential Effects of D-Hormone Analogs and Native Vitamin D on the Risk of Falls: A Comparative Meta-Analysis. Calcif Tissue Int 82, 102–107 (2008). https://doi.org/10.1007/s00223-008-9102-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-008-9102-0

Keywords

Search

Navigation