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

• Published in: Journal of advanced research
• Main Authors: Di, Dongsheng, Zhou, Haolong, Cui, Zhangbo, Zhang, Jianli, Liu, Qian, Yuan, Tingting, Zhou, Tingting, Luo, Xiao, Ling, Danyang, Wang, Qi
• Format: Journal Article
• Language: English
• Published: Egypt Elsevier B.V 01.03.2024
• Subjects: Age of tobacco use initiation; Genetic susceptibility; In utero tobacco smoke exposure; Osteoporosis; Telomere length; Osteoporosis; Telomere length; Genetic susceptibility; In utero tobacco smoke exposure; Age of tobacco use initiation
• ISSN: 2090-1232; 2090-1224
• DOI: 10.1016/j.jare.2024.02.021

[Display omitted] •Early-life tobacco smoke exposure elevated osteoporosis (OP) in adulthood.•Early-life tobacco smoke exposure had joint effects with genetic risk on OP.•High genetic risk subjects with early-life smoke exposure had the highest OP risk.•Telomere length mediate early-life tobacco exposure and OP association.•Reducing smoking in early life might be an measure to curb the OP epidemic. 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. 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. 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. 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. 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.