Higher HDL cholesterol associated with increased fracture risk

27th January 2023

A higher HDL cholesterol level has been found to be linked with a greater risk of all types of fracture in those aged 70 years and older

Greater high-density lipoprotein cholesterol (HDL) levels in older people are associated with an increased risk of fractures according to a post hoc analysis of data collected as part of the Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial and the ASPREE fracture substudy by Australian researchers.

Fractures are a common problem with one study estimating that one in 3 women and one in 5 men would be expected to have a minimal trauma fracture after the age of 50. Interestingly, a recent meta-analysis of 12 studies with over 12,000 patients found that HDL cholesterol levels were higher among those with osteoporosis. While HDL cholesterol as a recognised protective role in cardiovascular disease, more recently, it has been found that the lipid also has a role in the pathogenesis of degenerative and metabolic bone diseases in experimental mouse models. Nevertheless, the evidence from human studies is mixed, with one study in over 2000 women finding no association between fracture risk and higher HDL cholesterol, whereas in another, higher HDL particle size was linked to a higher fracture risk.

With an element of uncertainty surrounding the role of lipids and fracture risk, in the current study, the Australian team sought to clarify this connection. They turned to data from the two ASPREE studies and examined the association between plasma HDL cholesterol levels, which were categorised into quintiles, and incident fractures. The researchers used regression analysis, adjusting for various factors including age, gender, physical activity and measures of fragility.

Higher HDL levels and incident fracture risk

A total of 16,264 individuals with a mean age of 75 years (55% female) were included in the analysis and followed for a median of 4 years. During follow-up, 10.2% of the cohort experienced at least one fracture, 4% defined as minimal trauma (i.e., falls from standing height) and the remainder trauma (i.e., falling on stairs, ladders etc).

In fully adjusted models, among those with the highest quintile HDL cholesterol, there was a 33% higher risk of fracture, compared to the lowest quintile (hazard ratio, HR = 1.33, 95% CI 1.14 – 1.54). When stratified by gender, there was still an elevated risk for both men (HR = 1.45) and women (HR = 1.29) with higher HDL levels. There were no important associations between other plasma lipids and fracture risk.

The authors concluded that a higher HDL cholesterol level was associated with an increased fracture risk in older adults, independently of common fracture risk factors.

Citation
Hussain SM et al. Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults. JAMA Cardiol 2023.

Low-dose aspirin use linked to increased risk of serious falls in elderly

18th November 2022

An RCT has found that low-dose aspirin use failed to reduce fracture risk but was associated with higher risk of serious falls in the elderly

Daily low-dose aspirin (100 mg) given to healthy elderly patients failed to reduce the risk of fractures but did increase the risk of a serious fall according to the findings of a randomised, placebo-controlled trial by Australian researchers.

In a 2017 study it was found that, globally, falls resulted in 695,771 deaths and more than 95% of hip fractures are caused by falling. Low-dose aspirin is often taken by elderly patients with cardiovascular disease although interestingly, there is some evidence to suggest that aspirin inhibits osteoclastogenesis by suppressing the activation of NF‑κB and therefore may possess therapeutic potential for use in the prevention and treatment of osteoporosis.

By inhibiting osteoclasts, aspirin may increase bone mineral density and therefore reduce the risk of fractures. In fact, a systematic review of 12 observational studies found that aspirin use was associated with 17% lower odds for any fracture. Nevertheless, to date, no randomised, placebo-controlled trials have examined the potential role of low-dose aspirin as an approach to reduce fracture risk among older adults.

In the present study, the Australian researchers created the ASPREE-FRACTURE study which was actually a sub-study of the Aspirin in Reducing Events in the Elderly trial designed to examine if daily low-dose aspirin use outweigh the risks in older healthy individuals. Participants in the trial received low-dose aspirin (100 mg daily) or matching placebo and the primary outcome was the occurrence of any fracture whereas the secondary outcome was set as a serious fall that resulted in hospital presentation. All participants were free of cardiovascular disease, dementia or physical disability at the start of the study.

Low-dose aspirin and fracture outcomes

A total of 16,703 individuals with a median age of 74 years (55% female) were recruited and randomised to either aspirin (8,322) or placebo and followed-up for a median of 4.6 years.

During follow-up there was no difference in the risk of first (hazard ratio, HR = 0.96, 95% CI -087 – 1.06, p = 0.50) or recurrent (HR = 0.96, 95% CI 0.87 – 1.06, p = 0.40) fracture events. In subgroup analysis based on several factors such as gender, body mass index or frailty, there were no significant differences in the risk of a first fracture event.

However, when researchers looked at the secondary out, 9% of those receiving aspirin compared to 8.2% in the placebo arm, experienced a serious fall, indicating that use of low-dose aspirin used was associated with a significant increase in the risk of such falls (HR = 1.17, 95% CI 1.03 – 1.33, p = 0.01).

The authors concluded that the use of low-dose aspirin provides little favourable benefit in a healthy, older adult population.

Citation
Barker AL et al. Daily Low-Dose Aspirin and Risk of Serious Falls and Fractures in Healthy Older People: A Substudy of the ASPREE Randomized Clinical Trial. JAMA Intern Med 2022.