Zhang Gongzi, Zheng Juan, Zhou Ying, Zhou Ming, Zhang Jiali, Liu Yangxiaoxue, Geng Yuhan, Wang Wenxin, Xin Min, Yang Bo, Zhang Lihai, Huang Liping
Department of Rehabilitation, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
Department of Orthopedics, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, 100853, People's Republic of China.
BMC Oral Health. 2025 Mar 5;25(1):340. doi: 10.1186/s12903-025-05735-7.
Evidence from observational studies suggested oral diseases (periodontitis (PD) and dental caries) may increase susceptibility to bone loss. However, inherent confounding of observational studies limits causal interpretation. We aimed to conduct Mendelian randomization (MR) analysis to estimate the causal effect of oral diseases on osteoporosis (OP), bone mineral density (BMD) and fracture risk.
We used summary-level GWAS meta-analysis data from the GLIDE consortium to identify 7 and 17 single-nucleotide polymorphisms (SNPs) for periodontitis and DMFS (the sum of Decayed, Missing, and Filled tooth Surfaces) as the instrumental variables. MR analyses of these instruments were performed on European individuals for the association with BMD of forearm, femoral neck and lumbar spine; and individuals from FinnGen consortium for OP, OP with pathological fracture, postmenopausal OP with pathological fracture, and site-specific fractures. We performed single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess independent causal effects of PD and DMFS on different outcomes. The estimates were primarily derived using inverse variance weighted (IVW) methods. Sensitivity analyses included weighted median, MR-egger, and Leave-one-out test.
In MVMR, after adjusting for PD, DMFS has a positive causal effect osteoporosis (OR = 1.165, [95% CI 1.020 to 1.331, P = 0.025]) and postmenopausal OP with pathological fracture (OR = 1.422, [95% CI 1.027 to 1.969, P = 0.034]). However, these causal relationships were not observed in the single-variable Mendelian randomization (SVMR) analysis. The causal associations were robust in various sensitivity analyses.
In conclusion, dental caries causally increases the risk of OP and postmenopausal OP with pathological fracture, suggesting the existence of teeth-bone axis. Proactive osteoporosis screening in patients with severe dental caries may be warranted for clinical consideration.
观察性研究的证据表明，口腔疾病（牙周炎（PD）和龋齿）可能会增加骨质流失的易感性。然而，观察性研究固有的混杂因素限制了因果关系的解释。我们旨在进行孟德尔随机化（MR）分析，以估计口腔疾病对骨质疏松症（OP）、骨矿物质密度（BMD）和骨折风险的因果效应。
我们使用了来自GLIDE联盟的汇总水平全基因组关联研究（GWAS）荟萃分析数据，以确定7个和17个单核苷酸多态性（SNP），分别作为牙周炎和DMFS（龋失补牙面总数）的工具变量。对这些工具变量进行MR分析，针对欧洲个体研究其与前臂、股骨颈和腰椎骨密度的关联；针对来自芬兰基因联盟的个体研究其与骨质疏松症、病理性骨折的骨质疏松症、绝经后病理性骨折的骨质疏松症以及特定部位骨折的关联。我们进行了单变量孟德尔随机化（SVMR）和多变量孟德尔随机化（MVMR），以同时评估牙周炎和DMFS对不同结局的独立因果效应。估计值主要使用逆方差加权（IVW）方法得出。敏感性分析包括加权中位数、MR-egger和留一法检验。
在多变量孟德尔随机化（MVMR）中，在调整牙周炎后，DMFS对骨质疏松症具有正向因果效应（比值比（OR）=1.165，[95%置信区间（CI）1.020至1.331，P = 0.025]）以及对绝经后病理性骨折的骨质疏松症具有正向因果效应（OR = 1.422，[95% CI 1.027至1.969，P = 0.034]）。然而，在单变量孟德尔随机化（SVMR）分析中未观察到这些因果关系。在各种敏感性分析中，因果关联具有稳健性。
总之，龋齿会因果性地增加骨质疏松症以及绝经后病理性骨折的骨质疏松症的风险，提示存在牙-骨轴。对于患有严重龋齿的患者，积极进行骨质疏松症筛查可能值得临床考虑。
