Skip to main content

Advertisement

SpringerLink
Log in

Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

Inconsistent findings in regard to association between thiazide diuretic use and the risk of fracture have been reported during the past decade. This updated meta-analysis, which pooled data from 11 qualified prospective designed studies, found that thiazides have a significant protective effect on fracture risk.

Introduction

An updated comprehensive meta-analysis examine the association between thiazide diuretic use and therisk of fracture is needed.

Methods

Cohort studies regarding thiazide diuretic exposure and the risk of fracture, published from inception to May 1 2017, were identified through MEDLINE, EMBASE, SCOPUS, and the Cochrane Database of Systematic Reviews. The literature search, study selection, study appraisal, and data extraction were pre-defined in the protocol and were independently conducted by two investigators. Due to the heterogeneity of the original studies, a random effects model was used to pool the confounder-adjusted relative risk (RR).

Results

Eleven eligible cohort studies involving 2,193,160 participants were included for analysis. Overall, thiazide diuretic users, as compared with non-users, had a significant 14% reduction in the risk of all fractures (relative risk [RR], 0.86; 95% confidence interval [CI], 0.80–0.93; p = 0.009) and an 18% reduction in the risk of hip fracture (RR, 0.82; 95%CI, 0.80–0.93; p = 0.009). However, the effect size associated with thiazide use became slightly weaker when the analysis was limited to only high-quality original studies (quality score > 8) (RR, 0.89; 95%CI, 0.80–0.99; p = 0.005), studies with a larger sample size (> 10,000) (RR, 0.90; 95%CI, 0.80–1.00; p = 0.002), and studies published after 2007 (RR, 0.92; 95%CI, 0.82–1.02; p = 0.001).

Conclusion

Our findings indicate that thiazide diuretic use may convey a decreased risk of fracture and as such, the protective effect of this class of medicine should be considered when prescribing thiazide diuretics in clinical practice.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jose LP-C, Isabel J, Alberto S-C, Carol P, Gonzalo H, Antonio D (2005) Effect of the antihypertensive treatment on the bone mineral density and osteoporotic fracture. Curr Hypertens Rev 1:61–66

    Article  Google Scholar 

  2. Cauley JA (2013) Public health impact of osteoporosis. J Gerontology Ser A 68:1243–1251

    Article  Google Scholar 

  3. Colón-Emeric CS, Saag KG (2006) Osteoporotic fractures in older adults. Best Pract Res Clin Rheumatol 20:695–706

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wright NC, Looker AC, Saag KG, Curtis JR, Delzell ES, Randall S, Dawson-Hughes B (2014) The recent prevalence of osteoporosis and low bone mass in the United States based on bone mineral density at the femoral neck or lumbar spine. J Bone Miner Res : Off J Am Soc Bone Miner Res 29:2520–2526

    Article  Google Scholar 

  5. Burge R, Dawson-Hughes B, Solomon DH, Wong JB, King A, Tosteson A (2007) Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025. J Bone Miner Res : Off J Am Soc Bone Miner Res 22:465–475

    Article  Google Scholar 

  6. Ilic K, Obradovic N, Vujasinovic-Stupar N (2013) The relationship among hypertension, antihypertensive medications, and osteoporosis: a narrative review. Calcif Tissue Int 92:217–227

    Article  PubMed  CAS  Google Scholar 

  7. Prevention, T. C. f. D. C. a. (2014) Health, United States, 2016, table 5s3

  8. Moser M, Feig PU (2009) Fifty years of thiazide diuretic therapy for hypertension. Arch Intern Med 169:1851–1856

    Article  PubMed  CAS  Google Scholar 

  9. Grossman E, Verdecchia P, Shamiss A, Angeli F, Reboldi G (2011) Diuretic treatment of hypertension. Diabetes Care 34:S313–S319

    Article  PubMed  PubMed Central  Google Scholar 

  10. Ellison DH, Loffing J (2009) Thiazide effects and side effects: insights from molecular genetics. Hypertension 54:196–202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Pérez-Castrillón, J., Justo, I., Sanz-Cantalapiedra, A., Pueyo, C., Hernandez, G. & Duenas, A. (2005) Effect of the antihypertensive treatment on the bone mineral density and osteoporotic fracture

  12. Wasnich RD, Benfante RJ, Yano K, Heilbrun L, Vogel JM (1983) Thiazide effect on the mineral content of bone. N Engl J Med 309:344–347

    Article  PubMed  CAS  Google Scholar 

  13. Vestergaard P, Rejnmark L, Mosekilde L (2009) Hypertension is a risk factor for fractures. Calcif Tissue Int 84:103–111

    Article  PubMed  CAS  Google Scholar 

  14. Gribbin J, Hubbard R, Gladman JR, Smith C, Lewis S (2010) Risk of falls associated with antihypertensive medication: population-based case-control study. Age Ageing 39:592–597

    Article  PubMed  Google Scholar 

  15. Järvinen TLN, Sievänen H, Khan KM, Heinonen A, Kannus P (2008) Shifting the focus in fracture prevention from osteoporosis to falls. BMJ 336:124–126

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jones G, Nguyen T, Sambrook PN, Eisman JA (1995) Thiazide diuretics and fractures: can meta-analysis help? J Bone Miner Res : Off J Am Soc Bone Miner Res 10:106–111

    CAS  Google Scholar 

  17. Wiens M, Etminan M, Gill SS, Takkouche B (2006) Effects of antihypertensive drug treatments on fracture outcomes: a meta-analysis of observational studies. J Intern Med 260:350–362

    Article  PubMed  CAS  Google Scholar 

  18. Aung K. & Htay T. (2011) Thiazide diuretics and the risk of hip fracture, The Cochrane database of systematic reviews, Cd005185

  19. Covidence systematic review software in, Melbourne, Australia, Veritas Health Innovation

  20. Wells G, Shea B, O'Connell D, Peterson j, Welch V, Losos M & Tugwell P (2000) The Newcastle–Ottawa Scale (NOS) for assessing the quality of non-randomized studies in meta-analysis

  21. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis of Observational Studies in Epidemiology (MOOSE) group. JAMA 283:2008–2012

    Article  PubMed  CAS  Google Scholar 

  22. Lau J, Schmid CH, Chalmers TC (1995) Cumulative meta-analysis of clinical trials builds evidence for exemplary medical care. J Clin Epidemiol 48:45–57 discussion 59-60

    Article  PubMed  CAS  Google Scholar 

  23. Cumming RG, Klineberg RJ (1993) Psychotropics, thiazide diuretics and hip fractures in the elderly. Med J Aust 158:414–417

    PubMed  CAS  Google Scholar 

  24. Cauley JA, Cummings SR, Seeley DG, Black D, Browner W, Kuller LH, Nevitt MC (1993) Effects of thiazide diuretic therapy on bone mass, fractures, and falls. The Study of Osteoporotic Fractures Research Group. Ann Intern Med 118:666–673

    Article  PubMed  CAS  Google Scholar 

  25. Nguyen TV, Eisman JA, Kelly PJ, Sambrook PN (1996) Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 144:255–263

    Article  PubMed  CAS  Google Scholar 

  26. Yang S, Nguyen N, Center J, Eisman J, Nguyen T (2009) Effect of beta-blocker and thiazide use on fracture risk. Bone 44:S93

    Article  CAS  Google Scholar 

  27. Bokrantz T, Ljungman C, Kahan T, Bostrom KB, Hasselstrom J, Hjerpe P, Mellstrom D, Schioler L, Manhem K (2017) Thiazide diuretics and the risk of osteoporotic fractures in hypertensive patients. Results from the Swedish Primary Care Cardiovascular Database. J Hypertens 35:188–197

    Article  PubMed  CAS  Google Scholar 

  28. Chen H-Y, Ma K-Y, Hsieh P-L, Liou Y-S, Jong G-P (2016) Long-term effects of antihypertensive drug use and new-onset osteoporotic fracture in elderly patients: a population-based longitudinal cohort study. Chin Med J 129:2907–2912

    Article  PubMed  PubMed Central  Google Scholar 

  29. Feskanich D, Willett WC, Stampfer MJ, Colditz GA (1997) A prospective study of thiazide use and fractures in women. Osteoporos Int : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 7:79–84

    Article  CAS  Google Scholar 

  30. Guo Z, Wills P, Viitanen M, Fastbom J, Winblad B (1998) Cognitive impairment, drug use, and the risk of hip fracture in persons over 75 years old: a community-based prospective study. Am J Epidemiol 148:887–892

    Article  PubMed  CAS  Google Scholar 

  31. LaCroix AZ, Wienpahl J, White LR, Wallace RB, Scherr PA, George LK, Cornoni-Huntley J, Ostfeld AM (1990) Thiazide diuretic agents and the incidence of hip fracture. N Engl J Med 322:286–290

    Article  PubMed  CAS  Google Scholar 

  32. Paik JM, Rosen HN, Gordon CM, Curhan GC (2016) Diuretic use and risk of vertebral fracture in women. Am J Med 129:1299–1306

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Schoofs MW, van der Klift M, Hofman A, de Laet CE, Herings RM, Stijnen T, Pols HA, Stricker BH (2003) Thiazide diuretics and the risk for hip fracture. Ann Intern Med 139:476–482

    Article  PubMed  Google Scholar 

  34. Torstensson M, Hansen AH, Leth-Møller K, Jørgensen TSH, Sahlberg M, Andersson C, Kristensen KE, Ryg J, Weeke P, Torp-Pedersen C, Gislason G, Holm E (2015) Danish register-based study on the association between specific cardiovascular drugs and fragility fractures. BMJ Open 5:e009522

    Article  PubMed  PubMed Central  Google Scholar 

  35. Solomon DH, Mogun H, Garneau K, Fischer MA (2011) Risk of fractures in older adults using antihypertensive medications. J Bone Miner Res 26:1561–1567

    Article  PubMed  CAS  Google Scholar 

  36. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773

    Article  PubMed  CAS  Google Scholar 

  37. Abrahamsen B, Stilgren LS, Hermann AP, Tofteng CL, Barenholdt O, Vestergaard P, Brot C, Nielsen SP (2001) Discordance between changes in bone mineral density measured at different skeletal sites in perimenopausal women--implications for assessment of bone loss and response to therapy: the Danish Osteoporosis Prevention Study. J Bone Miner Res : Off J Am Soc Bone Miner Res 16:1212–1219

    Article  CAS  Google Scholar 

  38. Etikan I (2016) Meta-analysis of using both cohort and case control study. Biometrics Biostat Int J 3:00068

    Google Scholar 

  39. Wasnich RD, Ross PD, Heilbrun LK, Vogel JM, Yano K, Benfante RJ (1986) Differential effects of thiazide and estrogen upon bone mineral content and fracture prevalence. Obstet Gynecol 67:457–462

    PubMed  CAS  Google Scholar 

  40. Morton DJ, Barrett-Connor EL, Edelstein SL (1994) Thiazides and bone mineral density in elderly men and women. Am J Epidemiol 139:1107–1115

    Article  PubMed  CAS  Google Scholar 

  41. Reid IR, Ames RW, Orr-Walker BJ, Clearwater JM, Horne AM, Evans MC, Murray MA, McNeil AR, Gamble GD (2000) Hydrochlorothiazide reduces loss of cortical bone in normal postmenopausal women: a randomized controlled trial. Am J Med 109:362–370

    Article  PubMed  CAS  Google Scholar 

  42. Sakhaee K, Nicar MJ, Glass K, Zerwekh JE, Pak CY (1984) Reduction in intestinal calcium absorption by hydrochlorothiazide in postmenopausal osteoporosis. J Clin Endocrinol Metab 59:1037–1043

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nevada Institute of Personalized Medicine, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV, 89154-4009, USA

    X. Xiao, Y. Xu & Q. Wu

  2. Department of Environmental and Occupational Health, School of Community Health Sciences, University of Nevada Las Vegas, 4505 Maryland Parkway, Las Vegas, NV, 89154-4009, USA

    X. Xiao, Y. Xu & Q. Wu

Authors
  1. X. Xiao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Q. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Q. Wu.

Ethics declarations

Conflicts of interest

None.

Electronic supplementary material

ESM 1

(DOCX 153 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Xiao, X., Xu, Y. & Wu, Q. Thiazide diuretic usage and risk of fracture: a meta-analysis of cohort studies. Osteoporos Int 29, 1515–1524 (2018). https://doi.org/10.1007/s00198-018-4486-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-018-4486-9

Keywords

Search

Navigation