Higher HDL cholesterol levels may increase fracture risk in elderly: JAMA

The study is a post hoc analysis of data from the ASPREE (Aspirin in Reducing Events in the Elderly) clinical trial and the ASPREE-Fracture substudy.

Preclinical studies have revealed that HDL-C reduces BMD (bone mineral density) by reducing the number and function of osteoblast. Increased HDL-C levels have been associated with osteoporosis. However, there needs to be more clarity on the clinical significance of these findings. To clarify the same, Sultana Monira Hussain from Monash University in Melbourne, Australia, and colleagues aimed to determine whether higher HDL-C levels predict increased fracture risk in healthy older adults.

ASPREE was a randomized, double-blind, placebo-controlled primary prevention trial of aspirin. The trial recruited participants between 2010 and 2014, comprising community-based older adults (2411 US participants ≥65 years, 16 703 Australians aged ≥70 years) without evident dementia, cardiovascular disease, life-limiting chronic illness, and physical disability. The ASPREE-Fracture substudy collected data on fractures reported post-randomization from Australian participants.

The fractures were confirmed by medical imaging and included both minimal trauma and traumatic fractures. An expert review panel adjudicated fractures.

The study revealed the following findings:

• Of the 16 262 participants with a plasma HDL-C measurement at baseline (8945 female participants and 7319 male), 1659 experienced at least one fracture over a median (IQR) of 4.0 years.
• In a fully adjusted model, each 1-SD increment in HDL-C level was associated with a 14% higher risk of fractures (HR, 1.14). The results remained similar when these analyses were stratified by sex.
• Sensitivity and stratified analyses demonstrated that these associations persisted when the analyses were repeated to include only (1) minimal trauma fractures, (2) participants not taking osteoporosis medications, (3) participants who were never smokers and reported that they did not drink alcohol, and (4) participants who walked outside for less than 30 minutes per day and reported no participation in moderate/vigorous physical activity and to examine only (5) statin use.
• No association was observed between non–HDL-C levels and fractures.

The researchers found that higher HDL-C at baseline was tied to increased fracture risk, independent of other risk factors.

"Given the well-known inverse associations between HDL-C and heart disease, these findings suggest inconsistencies in the HDL-C's epidemiology and suggest the provocative question of whether high HDL-C could be a useful biomarker for identifying those at fracture risk," John Wilkins and Anand Rohatgi wrote in an accompanying editorial.

Reference:

Hussain SM, Ebeling PR, Barker AL, Beilin LJ, Tonkin AM, McNeil JJ. Association of Plasma High-Density Lipoprotein Cholesterol Level With Risk of Fractures in Healthy Older Adults. JAMA Cardiol. Published online January 18, 2023. doi:10.1001/jamacardio.2022.5124