Research Paper Volume 12, Issue 11 pp 10633—10641

Gut microbiota–dependent Trimethylamine N-Oxide are related with hip fracture in postmenopausal women: a matched case-control study

Yakun Liu1, *, , Yan-Long Guo2, *, , Shan Meng3, , Hua Gao1, , Li-Juan Sui2, , Shaobin Jin1, , Yang Li1, , Shao-Guang Fan2, ,

  • 1 Department of Pediatric Surgery, Qilu Hospital of Shandong University, Jinan, China
  • 2 Institute of Traumatic Orthopedics, The 80th Army Hospital of the Chinese People's Liberation Army, Weifang, Shandong Province, China
  • 3 Department of Rheumatology, Affiliated Hospital of Weifang Medical College, Weifang, Shandong Province, China
* Equal contribution

Received: September 27, 2019       Accepted: April 27, 2020       Published: June 1, 2020
How to Cite

Copyright © 2020 Liu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


The study evaluates the serum levels of Trimethylamine N-Oxide (TMAO), a gut microbial metabolite, in 286 postmenopausal women with hip fracture. From January 1, 2018 to December 31, 2018, eligible patients were included. Same women without fracture mated age were enrolled. TMAO serum levels were tested by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The serum levels of TMAO were significantly higher in patients with hip fracture than in those controls (P<0.001). The serum levels of TMAO were also higher in patients with hip fracture only than in those who also had upper limb fracture (P=0.001). High level of TMAO was proved a predictor of both hip fracture and had upper limb fracture combined hip fracture, after the adjustment of other existing risk factors [e.g., for each 1 uM increase of TMAO, odd ratio 1.16 (95% CI, 1.07–1.25), P < 0.001; and 1.12 (95% CI, 1.03–1.26), P=0.008, respectively]. In summary, increased TMAO serum levels associated with high risk of hip fracture, suggesting that increase TMAO may contribute to osteoporosis and fracture in postmenopausal women.


TMAO: Trimethylamine-N-oxide; BMI: Body mass index; Hs-CRP: High-sensitivity C-reactive protein; ALP: Alkaline phosphatase; CV: Coefficients of variation; IQR: Interquartile range; OR: Odds ratios; CI: Confidence intervals; ROC: Receiver operating characteristic; AUC: Area under the ROC curve; BMD: Bone mineral density.