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

Abstract

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. Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults. 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. 5019U.S. adults aged ≥65years. Plasma TMAO. Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n=1400). Six hundred sixty-six incident hip fractures occurred during up to 26years 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 0.42g/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. 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.