Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study

Rachel E. Elam, Petra Bůžková, Joshua I. Barzilay, Zeneng Wang, Ina Nemet, Matthew J. Budoff, Jane A. Cauley, Howard A. Fink, Yujin Lee, John A. Robbins, Meng Wang, Stanley L. Hazen, Dariush Mozaffarian, Laura D. Carbone

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) may adversely affect bone by inducing oxidative stress. Whether this translates into increased fracture risk in older adults is uncertain. Objective: Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. Design and setting: Cox hazard models and linear regression stratified by sex examined the associations of TMAO with hip fracture and BMD in the longitudinal cohort of the Cardiovascular Health Study. Participants: 5019 U.S. adults aged ≥65 years. Exposure: Plasma TMAO. Main Outcome Measures: Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400). Results: Six hundred sixty-six incident hip fractures occurred during up to 26 years of follow-up (67,574 person-years). After multivariable adjustment, TMAO was not significantly associated with hip fracture (women: hazard ratio (HR) [95% confidence interval (CI)] of 1.00[0.92,1.09] per TMAO doubling; men: 1.12[0.95,1.33]). TMAO was also not associated with total hip BMD (women: BMD difference [95% CI] of 0.42 g/cm2*100 [−0.34,1.17] per TMAO doubling; men: 0.19[−1.04,1.42]). In exploratory analyses, we found an interaction between body mass index (BMI) and the association of TMAO with hip fracture (P < 0.01). Higher TMAO was significantly associated with risk of hip fracture in adults with overweight or obesity (BMI ≥ 25) (HR [95% CI]:1.17[1.05,1.31]), but not normal or underweight. Conclusions: Among older US men and women, TMAO was not significantly associated with risk of hip fracture or BMD overall. Exploratory analyses suggested a significant association between higher TMAO and hip fracture when BMI was elevated, which merits further study.

Original languageEnglish (US)
Article number116431
JournalBone
Volume161
DOIs
StatePublished - Aug 2022
Externally publishedYes

Bibliographical note

Funding Information:
This work was supported by grant RO1HL135920 from the National Heart, Lung, and Blood Institute (NHLBI) and contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, 75N92021D00006, and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

Funding Information:
This work was supported by grant RO1HL135920 from the National Heart, Lung, and Blood Institute (NHLBI) and contracts HHSN268201200036C , HHSN268200800007C , HHSN268201800001C , N01HC55222 , N01HC85079 , N01HC85080 , N01HC85081 , N01HC85082 , N01HC85083 , N01HC85086 , 75N92021D00006 , and grants U01HL080295 and U01HL130114 from the National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

  • Animal food
  • Bone mineral density
  • Gut microbiome
  • Hip fracture
  • Osteoporosis
  • Trimethylamine N-oxide

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural

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