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Anticholinergic Medication Use and Fractures in Postmenopausal Women: Findings from the Women’s Health Initiative

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Abstract

Background

Anticholinergic medication use has been associated with several negative health outcomes in older adults, but little is known about its risk for fractures.

Objective

To examine the association between anticholinergic medication use and fracture outcomes in community-dwelling postmenopausal women.

Methods

Utilizing a prospective cohort design, we examined data collected from 137,408 women aged 50–79 years from the Women’s Health Initiative observational study and clinical trials not reporting hip fracture at baseline. Medications with moderate or strong anticholinergic effects were identified directly from drug containers during in-person interviews. The main outcome was fractures (hip, lower arm/wrist and total fractures). We performed multivariable Cox proportional hazard survival modelling to assess the association between anticholinergic use and the risk of fractures.

Results

At baseline, 10.6 % of the women were using an anticholinergic medication, of which antihistamines were the most common medication class (48.4 %). The multivariable-adjusted hazard ratios for anticholinergic medication use were 1.08 (95 % confidence interval [CI] 0.89–1.30) for hip fracture, 1.01 (95 % CI 0.91–1.13) for lower arm/wrist fracture and 1.03 (95 % CI 0.98–1.09) for total fractures. We observed no association according to subclass or count of anticholinergic medications, or trends between the duration of anticholinergic use and any of the fracture outcomes.

Conclusion

Anticholinergic medication use was not associated with an increased risk of fractures among community-dwelling women. Future research should make efforts to capture over-the-counter medication use and the cumulative anticholinergic burden in relation to important health outcomes for older adults.

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References

  1. Ness J, Hoth A, Barnett MJ, et al. Anticholinergic medications in community-dwelling older veterans: prevalence of anticholinergic symptoms, symptom burden, and adverse drug events. Am J Geriatr Pharmacother. 2006;4:42–51.

    Article  CAS  PubMed  Google Scholar 

  2. Hilmer SN, Mager DE, Simonsick EM, et al. A drug burden index to define the functional burden of medications in older people. Arch Intern Med. 2007;167:781–7.

    Article  PubMed  Google Scholar 

  3. Boudreau RM, Hanlon JT, Roumani YF, et al. Central nervous system medication use and incident mobility limitation in community elders: the Health, Aging, and Body Composition Study. Pharmacoepidemiol Drug Saf. 2009;18:916–22.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Sumukadas D, McMurdo MET, Mangoni AA, et al. Temporal trends in anticholinergic medication prescription in older people: repeated cross-sectional analysis of population prescribing data. Age Ageing. 2014;43:515–21.

    Article  PubMed  Google Scholar 

  5. American Geriatrics Society updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc 2012;60:616–631.

  6. Myint PK, Fox C, Kwok CS, et al. Total anticholinergic burden and risk of mortality and cardiovascular disease over 10 years in 21,636 middle-aged and older men and women of EPIC-Norfolk prospective population study. Age Ageing. 2014;0:1–6.

    Google Scholar 

  7. Woolcott JC, Richardson KJ, Wiens MO, et al. Meta-analysis of the impact of 9 medication classes on falls in elderly persons. Arch Intern Med. 2009;169:1952–60.

    Article  PubMed  Google Scholar 

  8. Aizenberg D, Sigler M, Weizman A, et al. Anticholinergic burden and the risk of falls among elderly psychiatric inpatients: a 4-year case–control study. Int Psychogeriatr. 2002;14:307–10.

    Article  PubMed  Google Scholar 

  9. Berdot S, Bertrand M, Dartigues JF, et al. Inappropriate medication use and risk of falls—a prospective study in a large community-dwelling elderly cohort. BMC Geriatr. 2009;9:30.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Richardson K, Bennett K, Maidment ID, et al. Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults. J Am Geriatr Soc. 2015;63(8):1561–9.

    Article  PubMed  Google Scholar 

  11. Nurminen J, Puustinen J, Piirtola M, et al. Opioids, antiepileptic and anticholinergic drugs and the risk of fractures in patients 65 years of age and older: a prospective population-based study. Age Ageing. 2013;42:318–24.

    Article  PubMed  Google Scholar 

  12. Fraser LA, Adachi JD, Leslie WD, et al. The effect of anticholinergic medications on falls, fracture risk, and bone mineral density over a 10-year period. Ann Pharmacother. 2014;48:954–61.

    Article  PubMed  Google Scholar 

  13. Moga DC, Carnahan RM, Lund BC, et al. Risks and benefits of bladder antimuscarinics among elderly residents of Veterans Affairs Community Living Centers. J Am Med Dir Assoc. 2013;14:749–60.

    Article  PubMed  Google Scholar 

  14. Women’s Health Initiative Study Group. Design of the Women’s Health Initiative clinical trial and observational study. Control Clin Trials. 1998;19:61–109.

    Article  Google Scholar 

  15. Langer RD, White E, Lewis CE, et al. The Women’s Health Initiative observational study: baseline characteristics of participants and reliability of baseline measures. Ann Epidemiol. 2003;13:S107–21.

    Article  PubMed  Google Scholar 

  16. Chen Z, Kooperberg C, Pettinger MB, et al. Validity of self-report for fractures among a multiethnic cohort of postmenopausal women: results from the Women’s Health Initiative observational study and clinical trials. Menopause. 2004;11:264–74.

    Article  PubMed  Google Scholar 

  17. Carnahan RM, Lund BC, Perry PJ, et al. The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity. J Clin Pharmacol. 2006;46:1481–6.

    Article  CAS  PubMed  Google Scholar 

  18. Chew ML, Mulsant BH, Pollock BG, et al. Anticholinergic activity of 107 medications commonly used by older adults. J Am Geriatr Soc. 2008;56:1333–41.

    Article  PubMed  Google Scholar 

  19. Boustani M, Campbell N, Munger S, et al. Impact of anticholinergics on the aging brain: a review and practical application. Aging Health. 2008;4:311–20.

    Article  CAS  Google Scholar 

  20. Rudolph JL, Salow MJ, Angelini MC, et al. The anticholinergic risk scale and anticholinergic adverse effects in older persons. Arch Intern Med. 2008;168:508–13.

    Article  PubMed  Google Scholar 

  21. Ware JE Jr, Sherbourne CD. The MOS 36-Item Short-Form Health Survey (SF-36): I. Conceptual framework and item selection. Med Care. 1992;30:473–83.

    Article  PubMed  Google Scholar 

  22. Burnam MA, Wells KB, Leake B, et al. Development of a brief screening instrument for detecting depressive disorders. Med Care. 1988;26:775–89.

    Article  CAS  PubMed  Google Scholar 

  23. Tuunainen A, Langer RD, Klauber MR, et al. Short version of the CES-D (Burnam Screen) for depression in reference to the structured psychiatric interview. Psychiatry Res. 2001;103:261–70.

    Article  CAS  PubMed  Google Scholar 

  24. Kristal AR, Feng Z, Coates RJ, et al. Associations of race/ethnicity, education, and dietary intervention with the validity and reliability of a food frequency questionnaire: the Women’s Health Trial Feasibility Study in Minority Populations. Am J Epidemiol. 1997;146:856–69.

    Article  CAS  PubMed  Google Scholar 

  25. Rudd KM, Raehl CL, Bond CA, et al. Methods for assessing drug-related anticholinergic activity. Pharmacotherapy. 2005;25:1592–601.

    Article  CAS  PubMed  Google Scholar 

  26. Molchan SE, Martinez RA, Hill JL, et al. Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model. Brain Res Brain Rev. 1992;17:215–26.

    Article  CAS  Google Scholar 

  27. Sunderland T, Tariot PN, Cohen RM, et al. Anticholinergic sensitivity in patients with dementia of the Alzheimer type and age-matched controls: a dose–response study. Arch Gen Psychiatry. 1987;44:418–26.

    Article  CAS  PubMed  Google Scholar 

  28. Tinetti ME, Doucette J, Claus E, et al. Risk factors for serious injury during falls by older persons in the community. J Am Geriatr Soc. 1995;43:1214–21.

    Article  CAS  PubMed  Google Scholar 

  29. Naples JG, Marcum ZA, Perera S, et al. Concordance among anticholinergic burden scales. J Am Geriatr Soc 2015 (in press).

  30. Gray SL, Anderson ML, Dublin S, et al. Cumulative use of strong anticholinergics and incident dementia: a prospective cohort study. JAMA Intern Med. 2015;175(3):401–7.

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank the WHI investigators and staff for their dedication, and the study participants for making the programme possible. A full listing of WHI investigators can be found online at https://cleo.whi.org/researchers/Documents%20%20Write%20a%20Paper/WHI%20Investigator%20Short%20List.pdf.

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Corresponding author

Correspondence to Zachary A. Marcum.

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Funding

The WHI programme is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, US Department of Health and Human Services, through contract nos. HHSN268201100046C, HHSN268201100001C, HHSN268201100002C, HHSN268201100003C, HHSN268201100004C and HHSN271201100004C.

Conflict of interest

Heidi Wirtz owns stock in Teva Pharmaceuticals. During the past 3 years, Andrea LaCroix served on the Scientific Methodology Advisory Panel for monitoring the safety of Prolia for Amgen. She also served on the Scientific Advisory Board for the Global Longitudinal Study of Osteoporosis in Women (GLOW), funded by Sanofi-Aventis and Proctor & Gamble (the Alliance for Better Bone Health) through an unrestricted research grant from the University of Massachusetts, Center for Outcomes Research. Zachary Marcum, Mary Pettinger, Ryan Carnahan, Jane Cauley, Jennifer Bea and Shelly Gray declare that they have no conflicts of interest, including financial interests, activities, relationships or affiliations, that are relevant to this study.

Ethical approval

All procedures performed in this study were approved by the respective institutional review boards at the participating institutions and were in accordance with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Marcum, Z.A., Wirtz, H.S., Pettinger, M. et al. Anticholinergic Medication Use and Fractures in Postmenopausal Women: Findings from the Women’s Health Initiative. Drugs Aging 32, 755–763 (2015). https://doi.org/10.1007/s40266-015-0298-1

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  • DOI: https://doi.org/10.1007/s40266-015-0298-1

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