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Original Investigation
November 7, 2022

Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial

Author Affiliations
  • 1School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
  • 2Silverchain Group, Melbourne, Victoria, Australia
  • 3Department of Endocrinology and Medicine, Austin Health, University of Melbourne, Melbourne, Victoria, Australia
  • 4Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia
  • 5Department of Medicine, Western Health, University of Melbourne, St Albans, Victoria, Australia
  • 6School of Public Health, University of Sydney, Sydney, New South Wales, Australia
  • 7Deakin University, Institute for Mental and Physical Health and Clinical Translation (IMPACT), Barwon Health, Geelong, Victoria, Australia
  • 8Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia
  • 9Endocrine Research Unit, College of Medicine, Mayo Clinic, Rochester, Minnesota
  • 10Department of Medical Education, Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
  • 11Center for Aging and Population Health, School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
  • 12Sticht Center on Aging and Alzheimer’s Prevention, Section on Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina
JAMA Intern Med. 2022;182(12):1289-1297. doi:10.1001/jamainternmed.2022.5028
Key Points

Question  Does daily low-dose aspirin reduce fractures and serious falls in healthy older people?

Findings  In this substudy of a randomized placebo-controlled trial, the risk of first fracture was similar in the aspirin and placebo groups, but the risk of serious fall was statistically significantly greater in the aspirin group (total falls 884 vs 804).

Meaning  The findings indicate a potential additional risk for the use of low-dose aspirin in older people.


Importance  Falls and fractures are frequent and deleterious to the health of older people. Aspirin has been reported to reduce bone fragility and slow bone loss.

Objective  To determine if daily low-dose aspirin (100 mg) reduces the risk of fractures or serious falls (fall-related hospital presentations) in healthy older men and women.

Design, Setting, and Participants  This substudy of a double-blind, randomized, placebo-controlled trial studied older adult men and women in 16 major sites across southeastern Australia. The ASPREE-FRACTURE substudy was conducted as part of the Australian component of the ASPREE trial. Between 2010 and 2014 healthy (free of cardiovascular disease, dementia or physical disability), community-dwelling volunteers aged 70 years or older were recruited to participate in the ASPREE trial. Potentially eligible participants were identified by medical practitioners and trial personnel and were then sent a letter of invitation to participate. Interested participants were screened for suitability. Eligible participants with medical practitioner authorization and adherent to a 4-week run-in medication trial were randomized. Data were analyzed from October 17, 2019, to August 31, 2022.

Interventions  Participants in the intervention group received a daily dose of oral 100 mg enteric-coated (low-dose) aspirin. The control group received a daily identical enteric-coated placebo tablet.

Main Outcomes and Measures  The primary outcome of ASPREE-FRACTURE was the occurrence of any fracture. The secondary outcome was serious fall resulting in hospital presentation.

Results  In total, 16 703 people with a median (IQR) age of 74 (72-78) years were recruited, and 9179 (55.0%) were women. There were 8322 intervention participants and 8381 control participants included in the primary and secondary outcome analysis of 2865 fractures and 1688 serious falls over the median follow-up of 4.6 years. While there was no difference in the risk of first fracture between the intervention and control participants (hazard ratio, 0.97; 95% CI, 0.87-1.06; P = .50), aspirin was associated with a higher risk of serious falls (total falls 884 vs 804; incidence rate ratio, 1.17; 95% CI, 1.03-1.33; P = .01). Results remained unchanged in analyses that adjusted for covariates known to influence fracture and fall risk.

Conclusions and Relevance  In this substudy of a randomized clinical trial, the failure of low-dose aspirin to reduce the risk of fractures while increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.

Trial Registration  This substudy is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000347561).

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1 Comment for this article
Comments about the low-dose aspirin and the risk of serious falls and fractures
David Karpf, MD | Stanford University School of Medicine
I have several comments about this study.

First, studies using enteric aspirin at the 81 mg dose show little-or-no absorption based on thomboxane B2 inhibition, attributed to the enteric coating preventing aspirin absorption in the stomach (Cox D, et al. Effect of Enteric Coating on Antiplatelet Activity of Low-Dose Aspirin in Healthy Volunteers. Stroke, 2006;37:2153-2158). So the biological plausibility of a daily dose of 100 mg of enteric coated aspirin is questionable.

Second, the study does not report that any correction by spend of alpha was made for multiple comparisons. So after analyzing all fractures, osteoporotic
fractures, hip fractures, vertebral fractures, and non-vertebral fractures, the authors found a statistically significant increase in the risk of serious falls. This finding maybe real, but also could be the result of rolling the dice multiple times.

I, for one, remain to be convinced that 100 mg of enteric coated aspirin does much of anything (other than probably increasing the risk of UGI bleeds), including that it increases the risk of falls.

David B. Karpf, MD
Adj. Clinical Professor of Endocrinology
Stanford University School of Medicine