Skip to main content

Advertisement

SpringerLink
Log in

Reduced Fracture Risk in Users of Thiazide Diuretics

  • Published:
Calcified Tissue International Aims and scope Submit manuscript

Abstract

Thiazide diuretics (TD) reduce renal calcium excretion and may increase bone mineral density. A reduced fracture risk has been reported in some but not all studies. The aim of this study was to assess fracture risk in users of TD. The study design was nationwide population-based pharmacoepidemiological case-control study with fracture in year 2000 as outcome and use of TD during the previous 5 years as the exposure variable. Individual use of TD was derived from the Danish National Pharmacological Database and related to fracture data from the National Hospital Discharge Register. These data were combined with information on use of other drugs, social status, working status, income, educational status, contacts with general practitioners and practicing specialists, and comorbidity. A total of 64,699 patients (age = 40 years) who sustained a fracture during the year 2000 were compared to 194,111 age- and gender-matched controls. After adjustment for potential confounders, current use of TD was associated with a 10% (95% confidence interval [CI], 7% to 12%) reduced risk of any fracture and a 17% (95% CI 11% to 23%) reduced risk of forearm fractures. In former TD users, the risk reduction was slightly less pronounced. Similar results were found in men and women, and in subjects younger or ≥ 65 years of age. Dose-effect analysis revealed a decreased risk of any fracture and fractures at the forearm and hip with an increased number of redeemed defined daily dosages (DDDs) of TD. Therefore, use of more than 2000 DDD was associated with a 19% (95% CI 10% to 27%) decreased hip fracture risk. We conclude that use of TD is associated with a significantly reduced fracture risk.

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

Similar content being viewed by others

References

  1. L Rejnmark P Vestergaard AR Pedersen L Heickendorff F Andreasen L Mosekilde (2003) ArticleTitleDose-effect relations of loop- and thiazide-diuretics on calcium homeostasis: a randomized, double-blinded Latin-square multiple cross-over study in postmenopausal osteopenic women Eur J Clin Invest 33 41–50 Occurrence Handle10.1046/j.1365-2362.2003.01103.x Occurrence Handle1:CAS:528:DC%2BD3sXht1Wqurw%3D Occurrence Handle12492451

    Article  CAS  PubMed  Google Scholar 

  2. T Steiniche L Mosekilde MS Christensen F Melsen (1989) ArticleTitleHistomorphometric analysis of bone in idiopathic hypercalciuria before and after treatment with thiazide APMIS 97 302–308 Occurrence Handle1:STN:280:BiaB2cjhtFQ%3D Occurrence Handle2719851

    CAS  PubMed  Google Scholar 

  3. B Dawson Hughes S Harris (1993) ArticleTitleThiazides and seasonal bone change in healthy postmenopausal women Bone Miner 21 41–51 Occurrence Handle1:CAS:528:DyaK3sXlvFGgt78%3D Occurrence Handle8324419

    CAS  PubMed  Google Scholar 

  4. DJ Morton EL Barrett Connor SL Edelstein (1994) ArticleTitleThiazides and bone mineral density in elderly men and women Am J Epidemiol. 139 1107–1115 Occurrence Handle1:STN:280:ByuB2cbmslU%3D Occurrence Handle8192143

    CAS  PubMed  Google Scholar 

  5. RD Wasnich PD Ross LK Heilbrun JM Vogel K Yano RJ Benfante (1986) ArticleTitleDifferential effects of thiazide and estrogen upon bone mineral content and fracture prevalence Obstet Gynecol 67 457–462 Occurrence Handle1:STN:280:BimC2srovVE%3D Occurrence Handle3960416

    CAS  PubMed  Google Scholar 

  6. AZ LaCroix SM Ott L Ichikawa D Scholes WE Barlow (2000) ArticleTitleLow-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial Ann Intern Med 133 516–526 Occurrence Handle1:CAS:528:DC%2BD3cXnt1Ort7o%3D Occurrence Handle11015164

    CAS  PubMed  Google Scholar 

  7. IR Reid RW Ames BJ Orr-Walker JM Clearwater AM Horne MC Evans MA Murray AR McNeil GD Gamble (2000) ArticleTitleHydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial Am J Med 109 362–370 Occurrence Handle10.1016/S0002-9343(00)00510-6 Occurrence Handle1:CAS:528:DC%2BD3cXntVWgsr4%3D Occurrence Handle11020392

    Article  CAS  PubMed  Google Scholar 

  8. RD Wasnich RJ Benfante K Yano L Heilbrun JM .Vogel (1983) ArticleTitleThiazide effect on the mineral content of bone N Engl J Med. 309 344–347 Occurrence Handle1:STN:280:BiyB2cvptFc%3D Occurrence Handle6866070

    CAS  PubMed  Google Scholar 

  9. MR Sowers RB Wallace JH Lemke (1985) ArticleTitleCorrelates of mid-radius bone density among postmenopausal women: a community study Am J Clin Nutr 41 1045–1053 Occurrence Handle1:STN:280:BiqC1Mngs1c%3D Occurrence Handle3873171

    CAS  PubMed  Google Scholar 

  10. P Adland Davenport MW McKenzie M Notelovitz LC McKenzie JF Pendergast (1985) ArticleTitleThiazide diuretics and bone mineral content in postmenopausal women Am J Obstet Gynecol L 152 630–634 Occurrence Handle1:STN:280:BiqB2snktlI%3D

    CAS  Google Scholar 

  11. MW Schoofs KM van der A Hofman CE Laet Particlede RM Herings T Stijnen HA. BH Pols Stricker (2003) ArticleTitleThiazide diuretics and the risk for hip fracture Ann Intern Med 139 476–482 Occurrence Handle13679324

    PubMed  Google Scholar 

  12. G Jones T Nguyen PN Sambrook JA Eisman (1995) ArticleTitleThiazide diuretics and fractures: can meta-analysis help? J Bone Miner Res 10 106–111 Occurrence Handle1:CAS:528:DyaK2MXmvVWns7s%3D Occurrence Handle7747616

    CAS  PubMed  Google Scholar 

  13. FE Heidrich A Stergachis KM Gross (1991) ArticleTitleDiuretic drug use and the risk for hip fracture Ann Intern Med. 115 1–6 Occurrence Handle1:STN:280:By6B28vktFM%3D Occurrence Handle2048857

    CAS  PubMed  Google Scholar 

  14. L Frank (2000) ArticleTitleEpidemiology. When an entire country is a cohort Science 287 2398–2399 Occurrence Handle10.1126/science.287.5462.2398 Occurrence Handle1:CAS:528:DC%2BD3cXitlKgtbY%3D Occurrence Handle10766613

    Article  CAS  PubMed  Google Scholar 

  15. TF Andersen M Madsen J Jorgensen L Mellemkjoer JH Olsen (1999) ArticleTitleThe Danish National Hospital Register. A valuable source of data for modern health sciences Dan Med Bull 46 263–268 Occurrence Handle1:STN:280:DyaK1MzltVyrtw%3D%3D Occurrence Handle10421985

    CAS  PubMed  Google Scholar 

  16. P Vestergaard L Mosekilde (2002) ArticleTitleFracture risk in patients with celiac Disease, Crohn’s disease, and ulcerative colitis: a nationwide follow-up study of 16,416 patients in Denmark Am J Epidemiol 156 1–10 Occurrence Handle10.1093/aje/kwf007 Occurrence Handle12076883

    Article  PubMed  Google Scholar 

  17. S Wacholder JK McLaughlin DT Silverman JS Mandel (1992) ArticleTitleSelection of controls in case-control studies. I. Principles Am J Epidemiol 135 1019–1028 Occurrence Handle1:STN:280:By2B1c%2FnvFM%3D Occurrence Handle1595688

    CAS  PubMed  Google Scholar 

  18. GL Nielsen HT Sorensen W Zhou FH Steffensen J Olsen (1997) ArticleTitleThe pharmacoepidemiologic prescription database of North Jutlanda-a valid tool in pharmacoepidemiological research Int J Risk Safety Med 10 203–205

    Google Scholar 

  19. D Capella (1993) Descriptive tools and analysis MNG Dukes (Eds) Drug utilization studies: methods and uses WHO Regional Publications Copenhagen 55–58

    Google Scholar 

  20. ME Charlson P Pompei KL Ales CR MacKenzie (1987) ArticleTitleA new method of classifying prognostic comorbidity in longitudinal studies: development and validation J Chronic Dis 40 373–383 Occurrence Handle10.1016/0021-9681(87)90171-8 Occurrence Handle1:STN:280:BiiC28nlsVc%3D Occurrence Handle3558716

    Article  CAS  PubMed  Google Scholar 

  21. V de Groot Particlede H Beckerman GJ Lankhorst LM Bouter (2003) ArticleTitleHow to measure comorbidity. a critical review of available methods J Clin Epidemiol 56 221–229 Occurrence Handle10.1016/S0895-4356(02)00585-1 Occurrence Handle12725876

    Article  PubMed  Google Scholar 

  22. JA Cauley SR Cummings DG Seeley D Black W Browner LH Kuller MC Nevitt (1993) ArticleTitleEffects of thiazide diuretic therapy on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group Ann Intern Med. 118 666–673 Occurrence Handle1:STN:280:ByyB3MzgtVA%3D Occurrence Handle8489642

    CAS  PubMed  Google Scholar 

  23. WA Ray MR Griffin W Downey LJ Melton (1989) ArticleTitleLong-term use of thiazide diuretics and risk of hip fracture Lancet 1 687–690 Occurrence Handle10.1016/S0140-6736(89)92205-8 Occurrence Handle1:STN:280:BiaC1c%2Fkt1Q%3D Occurrence Handle2564506

    Article  CAS  PubMed  Google Scholar 

  24. DT Felson D Sloutskis JJ Anderson JM Anthony DP Kiel (1991) ArticleTitleThiazide diuretics and the risk of hip fracture. Results from the Framingham Study JAMA 265 370–373 Occurrence Handle10.1001/jama.265.3.370 Occurrence Handle1:STN:280:By6D1c%2Fis1w%3D Occurrence Handle1984536

    Article  CAS  PubMed  Google Scholar 

  25. OS Miettinen (1985) Theoretical epidemiology: principles of occurrence research in medicine Wiley & Sons New York

    Google Scholar 

  26. D Feskanich WC Willett MJ Stampfer GA Colditz (1997) ArticleTitleA prospective study of thiazide use and fractures in women Osteoporos Int. 7 79–84 Occurrence Handle1:CAS:528:DyaK2sXisVeit7w%3D Occurrence Handle9102069

    CAS  PubMed  Google Scholar 

  27. TV Nguyen JA Eisman PJ Kelly PN Sambrook (1996) ArticleTitleRisk factors for osteoporotic fractures in elderly men Am J Epidemiol 144 255–263 Occurrence Handle1:STN:280:BymA3c3hsVE%3D Occurrence Handle8686694

    CAS  PubMed  Google Scholar 

  28. A Paganini-Hill RK Ross VR Gerkins BE Henderson M Arthur TM Mack (1981) ArticleTitleMenupausal estrogen therapy and hip fractures Ann Intern Med 85 28–31

    Google Scholar 

  29. I Verhaeverbeke T Mets (1997) ArticleTitleDrug-induced orthostatic hypotension in the elderly: avoiding its onset Drug Saf 17 105–118 Occurrence Handle1:CAS:528:DyaK2sXmtVOqsrk%3D Occurrence Handle9285201

    CAS  PubMed  Google Scholar 

  30. DM Black SR Cummings DB Karpf JA Cauley DE Thompson MC Nevitt DC Bauer HK Genant WL Haskell R Marcus SM Ott JC Torner SA Quandt TF Reiss KE Ensrud (1996) ArticleTitleRandomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group [see comments] Lancet 348 1535–1541 Occurrence Handle10.1016/S0140-6736(96)07088-2 Occurrence Handle1:CAS:528:DyaK2sXisFCktQ%3D%3D Occurrence Handle8950879

    Article  CAS  PubMed  Google Scholar 

  31. S Hoidrup M Gronbaek A Gottschau JB Lauritzen M Schroll (1999) ArticleTitleAlcohol intake, beverage preference, and risk of hip fracture in men and women. Copenhagen Centre for Prospective Population Studies Am J Epidemiol 149 993–1001 Occurrence Handle1:STN:280:DyaK1M3otFGjtw%3D%3D Occurrence Handle10355374

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The National Bureau of Statistics, Denmark, is acknowledged for its help in providing data.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Aarhus University Hospital, Aarhus Sygehus, Tage Hansens Gade 2, 8000, Aarhus C, DK, Denmark

    L. Rejnmark, P. Vestergaard & L. Mosekilde

Authors
  1. L. Rejnmark
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P. Vestergaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Mosekilde
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Rejnmark.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rejnmark, L., Vestergaard, P. & Mosekilde, L. Reduced Fracture Risk in Users of Thiazide Diuretics. Calcif Tissue Int 76, 167–175 (2005). https://doi.org/10.1007/s00223-004-0084-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00223-004-0084-2

Keywords

Search

Navigation