@article {9089, title = {Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study.}, journal = {Bone}, volume = {161}, year = {2022}, month = {2022 08}, pages = {116431}, 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/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.

}, keywords = {Absorptiometry, Photon, Aged, Bone Density, Female, Hip Fractures, Humans, Male, Methylamines, Risk Factors}, issn = {1873-2763}, doi = {10.1016/j.bone.2022.116431}, author = {Elam, Rachel E and B{\r u}zkov{\'a}, Petra and Barzilay, Joshua I and Wang, Zeneng and Nemet, Ina and Budoff, Matthew J and Cauley, Jane A and Fink, Howard A and Lee, Yujin and Robbins, John A and Wang, Meng and Hazen, Stanley L and Mozaffarian, Dariush and Carbone, Laura D} }