Previous research suggests that aspirin may reduce the risk of fragility fractures by delaying bone loss, but the direct effects of aspirin on bone microarchitecture and the association between aspirin use and fracture risk in humans has not been explored, corresponding author Anna L. Barker, PhD, and colleagues wrote in their paper published in JAMA Internal Medicine.
Dr. Barker, who is executive director of research and innovation for Silverchain (a senior care program), said, in an interview, that she and her coauthors hypothesized “that aspirin could reduce both falls and fractures by reducing cardiovascular-associated physical and cognitive impairments and the anti-inflammatory properties mediating bone remodeling.”
Study methods and results
In the ASPREE-FRACTURE substudy, the authors examined the impact of daily low-dose aspirin (100 mg) on incidence of any fracture in more than 16,000 community-dwelling adults aged 70 years and older. A secondary endpoint was the incidence of serious falls, defined as falls requiring a hospital visit. Individuals with chronic illness and cardiovascular or cerebrovascular disease were excluded, as were those with dementia or other cognitive impairment, or a physical disability.
The study population included 16,703 participants enrolled in the larger Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial between 2010 and 2014. Of these, 8,322 were randomized to aspirin and 8,381 to a placebo. The median age was 74 years, and 55% of the participants were women.
Over a median follow-up of 4.6 years (76,219 total person-years), the risk of first fracture was similar between the aspirin and placebo groups (hazard ratio, 0.97), but the risk of serious falls was significantly higher in the aspirin group (884 falls vs. 804 falls, P = .01).
The incidence of first fracture was similar between the aspirin and placebo groups (813 vs. 718), as was the incidence of all fractures (1,394 and 1,471, respectively).
The results for both fractures and falls were essentially unchanged in a multivariate analysis controlling for variables known to affect fracture and fall risk and remained similar for different types of fractures (hip, trauma-related, nonpathological) as well, the researchers noted.
In their discussion, the researchers wrote that the clinical significance of the study is the inability of aspirin to reduce the risk of fractures in otherwise healthy older adults. They expressed surprise at the increase in serious falls, citing their hypothesis that the antiplatelet effects of aspirin may reduce cardiovascular and cerebrovascular events, thereby slowing physical decline and decreasing fall risk.
The increased risk of serious falls was not accompanied by an increase in fractures, and the increased fall risk was similar across subgroups of aspirin users, the researchers said.
Low-dose aspirin’s failure to reduce the risk of fractures but increasing the risk of serious falls adds to evidence that this agent provides little favorable benefit in a healthy, White older adult population.
The study findings were limited by several factors including the relatively homogeneous older and healthy population, and possible insufficient study duration to allow for changes in fracture and fall risk, the researchers noted. Other potential limitations include that the dose of aspirin used in the study was too low to affect bone remodeling and the lack of data on bone density, rheumatoid arthritis, and osteoporosis, they said.
However, the results were strengthened by the large sample size and high participant retention rate, and represent the first known examination of data from a randomized, controlled trial of the effect of aspirin on fractures, they added.