Title | Trimethylamine N-oxide and hip fracture and bone mineral density in older adults: The cardiovascular health study. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Elam, RE, Bůzková, P, Barzilay, JI, Wang, Z, Nemet, I, Budoff, MJ, Cauley, JA, Fink, HA, Lee, Y, Robbins, JA, Wang, M, Hazen, SL, Mozaffarian, D, Carbone, LD |
Journal | Bone |
Volume | 161 |
Pagination | 116431 |
Date Published | 2022 08 |
ISSN | 1873-2763 |
Keywords | Absorptiometry, Photon, Aged, Bone Density, Female, Hip Fractures, Humans, Male, Methylamines, Risk Factors |
Abstract | <p><b>CONTEXT: </b>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.</p><p><b>OBJECTIVE: </b>Determine the associations of plasma TMAO with hip fracture and bone mineral density (BMD) in older adults.</p><p><b>DESIGN AND SETTING: </b>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.</p><p><b>PARTICIPANTS: </b>5019 U.S. adults aged ≥65 years.</p><p><b>EXPOSURE: </b>Plasma TMAO.</p><p><b>MAIN OUTCOME MEASURES: </b>Incident hip fractures; total hip BMD dual x-ray absorptiometry in a subset (n = 1400).</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
DOI | 10.1016/j.bone.2022.116431 |
Alternate Journal | Bone |
PubMed ID | 35577327 |
Grant List | R01 HL135920 / HL / NHLBI NIH HHS / United States HHSN268201800001C / HL / NHLBI NIH HHS / United States HHSN268200800007C / HL / NHLBI NIH HHS / United States HHSN268201200036C / HL / NHLBI NIH HHS / United States N01HC85081 / HL / NHLBI NIH HHS / United States N01HC85080 / HL / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States 75N92021D00006 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01HC85083 / HL / NHLBI NIH HHS / United States N01HC85082 / HL / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States U01 HL130114 / HL / NHLBI NIH HHS / United States R01 AG023629 / AG / NIA NIH HHS / United States |