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Low-dose aspirin did not reduce risks of fracture in healthy older adults, but was associated with an increased risk of serious falls, a substudy of the randomized ASPREE trial showed.

Over a median follow-up of 4.6 years, there was no difference in the risk of first fracture between participants who were taking aspirin 100 mg daily and those taking placebo (HR 0.97, 95% CI 0.87-1.06, P=0.50), but aspirin was linked with a higher risk of serious falls (incidence rate ratio 1.17, 95% CI 1.03-1.33, P=0.01), reported Anna L. Barker, PhD, of Monash University in Melbourne, Australia, and co-authors.

Results did not change after adjusting for covariates known to influence fracture and fall risk, they noted in .

"This finding adds to evidence from the ASPREE principal trial which showed that, among these participants, the use of low-dose aspirin did not confer any advantage in terms of disability-free survival (a composite that integrated the risks and benefits of aspirin)," they wrote.

"The increase in serious falls observed among those randomized to aspirin was not anticipated and might have resulted from either an increased tendency to fall or more substantial nonfracture injuries sustained as a consequence of falling," they noted. "It was originally hypothesized that aspirin may decrease falls by slowing physical decline by reducing cardiovascular and cerebrovascular events through antiplatelet effects and/or reducing cognitive decline by protecting against Alzheimer disease and/or vascular dementia -- well-known fall risk factors."

Falls account for 95% of and about 80% of -related hospital presentations and deaths in older adults, Barker and co-authors said, adding that "the burden of both falls and fractures is likely to escalate with population aging as the risks of both falls and fractures increase exponentially with age."

One reason for the lack of reduction in fall risks seen in the treatment group may relate to aspirin's similar lack of protective effect against cognitive deterioration, they suggested, pointing to recent findings from another analysis of ASPREE, which showed that daily low-dose aspirin did not reduce the risks of dementia, mild cognitive impairment, or cognitive decline.

For the ASPREE-FRACTURE substudy, Barker's group recruited 16,703 community-dwelling older adults free of cardiovascular disease, dementia, and physical disability from 2010 to 2014. Median age was 74, and 55% were women.

Of these participants, 8,322 were randomized to aspirin and 8,381 to placebo. Over follow-up, 2,865 fractures were recorded, as were 1,688 serious falls (884 in the aspirin arm vs 804 in the placebo arm).

To expand the substudy's generalizability and avoid fracture misclassification, Barker and colleagues included non-osteoporotic fractures in this analysis. While aspirin use is thought to help reduce bone fragility and falls by delaying bone loss, the authors pointed to a literature review suggesting that a 17% reduction in odds of fracture observed with aspirin use was only marginally associated with bone mineral density. Additionally, most fractures occur in people without significant , they noted.

Study limitations included the inability to generalize the findings to less healthy, higher-risk populations, the authors said, as well as the fact that the treatment duration and dosage may have been insufficient to allow for a full effect.

Nevertheless, the results are clinically relevant "to the large percentage of the older population who are both at risk of fracture and are taking aspirin for the prevention of cardiovascular and cerebrovascular disease," they concluded. "The lack of an effect of low-dose aspirin on the risk of fractures while increasing the risk of serious falls adds to the body of evidence that this agent provides little favorable benefit in a healthy, white older adult population."

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