Frontiers in Endocrinology (Jul 2022)
HemoglobinA1c Is a Risk Factor for Changes of Bone Mineral Density: A Mendelian Randomization Study
- Xiaoxiao Ji,
- Xiaoxiao Ji,
- Xiaoxiao Ji,
- Jianqiao Hong,
- Jianqiao Hong,
- Jianqiao Hong,
- Zihao Qu,
- Zihao Qu,
- Zihao Qu,
- Weinan Yang,
- Weinan Yang,
- Weinan Yang,
- Yibo Wang,
- Yibo Wang,
- Yibo Wang,
- Jiyan Lin,
- Jiyan Lin,
- Jiyan Lin,
- Congsun Li,
- Congsun Li,
- Congsun Li,
- Jie Wang,
- Jie Wang,
- Jie Wang,
- Haochen Mou,
- Haochen Mou,
- Haochen Mou,
- Mingmin Shi,
- Mingmin Shi,
- Mingmin Shi,
- Chenhe Zhou,
- Chenhe Zhou,
- Chenhe Zhou,
- Wei Wang,
- Wei Wang,
- Wei Wang,
- Changjian Lin,
- Changjian Lin,
- Changjian Lin,
- Shigui Yan,
- Shigui Yan,
- Shigui Yan,
- Haobo Wu,
- Haobo Wu,
- Haobo Wu
Affiliations
- Xiaoxiao Ji
- Department of Orthopedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China
- Xiaoxiao Ji
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Xiaoxiao Ji
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Jianqiao Hong
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jianqiao Hong
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Jianqiao Hong
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Zihao Qu
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zihao Qu
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Zihao Qu
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Weinan Yang
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Weinan Yang
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Weinan Yang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Yibo Wang
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Yibo Wang
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Yibo Wang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Jiyan Lin
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Jiyan Lin
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Jiyan Lin
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Congsun Li
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Congsun Li
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Congsun Li
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Jie Wang
- Department of Orthopedic Surgery, The Fourth Affiliated Hospital, International Institutes of Medicine, Zhejiang University School of Medicine, Yiwu, China
- Jie Wang
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Jie Wang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Haochen Mou
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Haochen Mou
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Haochen Mou
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Mingmin Shi
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Mingmin Shi
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Mingmin Shi
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Chenhe Zhou
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Chenhe Zhou
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Chenhe Zhou
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Wei Wang
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Wei Wang
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Wei Wang
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Changjian Lin
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Changjian Lin
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Changjian Lin
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Shigui Yan
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Shigui Yan
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Shigui Yan
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- Haobo Wu
- Department of Orthopedic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Haobo Wu
- Orthopedics Research Institute of Zhejiang University, Hangzhou, China
- Haobo Wu
- Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province, Hangzhou, China
- DOI
- https://doi.org/10.3389/fendo.2022.942878
- Journal volume & issue
-
Vol. 13
Abstract
BackgroundAs a valuable blood glucose measurement, HemoglobinA1c (HbA1c) is of great clinical value for diabetes. However, in previous observational studies, studies on its effect on bone mineral density (BMD) have different results. This study aimed to use Mendelian randomization (MR) to assess the effect of HbA1c on bone mineral density and fracture risk, and try to further explore whether this association was achieved through glycemic or non-glycemic factors.MethodsTake HbA1c measurement as exposure, and BMD estimated from quantitative heel ultrasounds (eBMD) and bone fractures as outcomes. Two-Sample MR Analysis was conducted to assess the causal effect of HbA1C on heel BMD and risk fracture. Then, we performed the analysis using two subsets of these variants, one related to glycemic measurement and the other to erythrocyte indices.ResultsGenetically increased HbA1C was associated with the lower heel eBMD [odds ratio (OR) 0.91 (95% CI 0.87, 0.96) per %-unit, P = 3 × 10−4(IVW)]. Higher HbA1C was associated with lower heel eBMD when using only erythrocytic variants [OR 0.87 (0.82, 0.93), P=2× 10−5(IVW)]; However, when using only glycemic variants, this casual association does not hold. In further MR analysis, we test the association of erythrocytic traits with heel eBMD.ConclusionOur study revealed the significant causal effect of HbA1c on eBMD, and this causal link might achieve through non-glycemic pathways (erythrocytic indices).
Keywords
