Associations of serum lipid traits with fracture and osteoporosis: A prospective cohort study from the UK Biobank

Monday, August 26, 2024

5:30 PM – 5:45 PM CEST

Location: Auditorium

Presenting Author(s)

Xi Xiong, Msc

PhD student
Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong
Hong Kong, Hong Kong

Slides

Co-Author(s)

DL

David Lui

Department of Medicine, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
Chengsheng Ju, MPharm (he/him/his)

PhD Researcher
Research Department of Practice and Policy, School of Pharmacy, University College London, United Kingdom, United Kingdom
ZZ

Ziyi Zhou

School of Health and Wellbeing, University of Glasgow, United Kingdom
CX

Chao Xu

School of Health and Wellbeing, University of Glasgow, United Kingdom
PW

Paul Welsh

School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom
NS

Naveed Sattar

School of Cardiovascular and Metabolic Health, University of Glasgow, United Kingdom
CC

Carlos Celis-Morales

School of Health and Wellbeing, University of Glasgow, United Kingdom
JP

Jill Pell

School of Health and Wellbeing, University of Glasgow, United Kingdom
IW

Ian Chi Kei Wong, PhD (he/him/his)

Professor
Centre for Safe Medication Practice and research, Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
CW

Carlos K. Wong

Department of Family Medicine and Primary Care, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong
FH

Frederick Ho

School of Health and Wellbeing, University of Glasgow, United Kingdom

Background: Previous studies have shown mixed evidence regarding the associations of serum lipid traits with the risks of fractures and osteoporosis.

Objectives: To quantify the relationships between serum lipid traits and the risks of fractures and osteoporosis, and investigate whether bone mass density (BMD) could mediate the relationships.

Methods: In this prospective cohort study, we analyzed data from 414,302 UK Biobank participants with serum lipid measurements. Serum lipids included apolipoprotein A (Apo A), apolipoprotein B (Apo B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglycerides (TG), and lipoprotein A (Lp(a)). Multivariable Cox proportional hazard models with penalized cubic splines were used to explore potential nonlinear associations of each lipid with the risks of fractures and osteoporosis. Hazard ratios (HRs) were estimated by quintile and for each standard deviation (SD) increase in serum lipid levels. Mediation analyses using the g-formula were performed to assess whether and to which extent BMD could mediate the association between serum lipids and fracture risk.

Results: Over a median follow-up period of 13.8 years, 25,918 (6.8% out of 383,530 participants without baseline fracture) individuals had incident fracture cases, and 7,591 individuals (4.1% out of 184,919 participants with primary care data and without baseline osteoporosis) were diagnosed with osteoporosis. HDL-C and TG showed nonlinear associations with fractures and osteoporosis, whereas Apo B and LDL-C had linear relationships. Apo A and TC demonstrated nonlinear associations with only the risk of fractures. Individuals in the highest quintiles for Apo A (fracture: HR 1.15 [1.09, 1.21]; osteoporosis: HR 1.14 [1.03, 1.26]) and HDL-C (fracture: HR 1.27 [1.20, 1.33]; osteoporosis: HR 1.33 [1.20, 1.49]) were associated with higher risks of fractures and osteoporosis. Conversely, those in the highest quintile for Apo B (fracture: HR 0.84 [0.80, 0.88]; osteoporosis: HR 0.85 [0.78, 0.93]), LDL-C (fracture: HR 0.88 [0.84, 0.93]; osteoporosis: HR 0.90 [0.82, 0.99]) and TG (fracture: HR 0.78 [0.74, 0.82]; osteoporosis: HR 0.74 [0.68, 0.82]) were associated with lower risks. The associations of Apo A (ratio of HR [RHR] 1.06 [1.03, 1.09]) and HDL-C (RHR 1.07 [1.03, 1.10]) with fracture risk were more pronounced in men compared to women. Except for TG and Lp(a), the associations between serum lipids and fractures appear to be partially mediated through BMD (mediation proportions: 5.70% to 40.70%), assuming causality.

Conclusions: Our study reveals a complex interplay between lipid profiles and skeletal health, partially mediated through BMD. This finding might enhance screening efficiency by focusing on the particular group intended to assist in finding fracture cases.