%0 Journal Article %J Bone %D 2022 %T Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study. %A Elam, Rachel E %A Bůzková, Petra %A Barzilay, Joshua I %A Wang, Zeneng %A Nemet, Ina %A Budoff, Matthew J %A Cauley, Jane A %A Fink, Howard A %A Lee, Yujin %A Robbins, John A %A Wang, Meng %A Hazen, Stanley L %A Mozaffarian, Dariush %A Carbone, Laura D %K Absorptiometry, Photon %K Aged %K Bone Density %K Female %K Hip Fractures %K Humans %K Male %K Methylamines %K Risk Factors %X

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/cm*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.

%B Bone %V 161 %P 116431 %8 2022 08 %G eng %R 10.1016/j.bone.2022.116431