Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition

Dongsheng Di; Haolong Zhou; Zhangbo Cui; Jianli Zhang; Qian Liu; Tingting Yuan; Tingting Zhou; Xiao Luo; Danyang Ling; Qi Wang

doi:10.1016/j.jare.2024.02.021

Early-life tobacco smoke elevating later-life osteoporosis risk: Mediated by telomere length and interplayed with genetic predisposition

J Adv Res. 2024 Mar 1:S2090-1232(24)00083-3. doi: 10.1016/j.jare.2024.02.021. Online ahead of print.

Authors

Dongsheng Di¹, Haolong Zhou², Zhangbo Cui³, Jianli Zhang⁴, Qian Liu⁵, Tingting Yuan⁶, Tingting Zhou⁷, Xiao Luo⁸, Danyang Ling⁹, Qi Wang¹⁰

Affiliations

¹ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: dids666@163.com.
² Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 120785904@qq.com.
³ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: 844255261@qq.com.
⁴ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhangjjjianli@163.com.
⁵ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: liuqian971215@163.com.
⁶ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: yuantingtinghappy@163.com.
⁷ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhoutingting3333@163.com.
⁸ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: luoxiao199905@163.com.
⁹ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: ldany9@163.com.
¹⁰ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wangqi_tj@hust.edu.cn.

PMID: 38431123
DOI: 10.1016/j.jare.2024.02.021

Abstract

Introduction: The growing prevalence of osteoporosis (OP) in an aging global population presents a significant public health concern. Tobacco smoke negatively affects bone turnover, leading to reduced bone mass and heightened OP and fracture risk. However, the impact of early-life tobacco smoke exposure on later-life OP risk remains unclear.

Objectives: This study was to explore the effects of early-life tobacco smoke exposure on incident OP risk in later life. The mediating role of telomere length (TL) and the interaction with genetic predisposition were also studied.

Methods: Data on in utero tobacco smoke exposure (IUTSE) status and age of tobacco use initiation from the UK Biobank were used to estimate early-life tobacco smoke exposure. Incident OP cases were identified according to health-related records. Linear, Cox, and Laplace regression models were mainly used for data analysis.

Results: Individuals with IUTSE showed a higher OP risk [hazard ratio (HR): 1.06, 95 % confidence interval (CI): 1.01, 1.11] and experienced earlier OP onset by 0.30 years [50th percentile difference = -0.30, 95 % CI: -0.51, -0.09] compared to those without. Participants initiating tobacco smoke in childhood, adolescence, and adulthood had 1.41 times (95 % CI: 1.23, 1.61), 1.17 times (95 % CI:1.10, 1.24), and 1.14 times (95 % CI: 1.07, 1.20) the risk of OP, respectively, compared to never smokers. They also experienced earlier OP onset by 2.16, 0.95, and 0.71 years, sequentially. The TL significantly mediated the early-life tobacco exposure and OP association. Significant joint and interactive effects were detected between early-life tobacco smoke exposure and genetic elements.

Conclusions: Our findings implicate that early-life tobacco smoke exposure elevates the later-life OP risk, mediated by telomere length and interplayed with genetic predisposition. These findings highlight the importance of early-life intervention against tobacco smoke exposure and ageing status for precise OP prevention, especially in individuals with a high genetic risk.

Keywords: Age of tobacco use initiation; Genetic susceptibility; In utero tobacco smoke exposure; Osteoporosis; Telomere length.