Abstract: Objective: Diffuse idiopathic skeletal hyperostosis (DISH) has been associated with an increased risk of vertebral fracture. To date, no studies have investigated the relationship between DISH and bone microstructure assessed by the trabecular bone score (TBS). Methods: Cross-sectional study, nested in a prospective population-based cohort. All men (968) aged?50 years were included. Clinical covariates, DISH, TBS, serum bone turnover markers and bone mineral density (BMD) were analyzed. Results: Mean age of participants was 65 ± 9 years. 207 (21.6%) had DISH. DISH subjects were older, had higher body mass index (BMI) and abdominal perimeter, lower glomerular filtration rate (GFR), and higher prevalence of metabolic syndrome (MetS) than non-DISH (NDISH) subjects. Bone mineral density at the lumbar spine (LS-BMD) was significantly higher in the DISH group. TBS values were 1.317 [1.303-1.331] for DISH and 1.334 [1.327-1.341] for NDISH subjects, after adjusting by age, BMI, abdominal perimeter, arterial hypertension, diabetes mellitus, MetS, GFR, serum alkaline phosphatase (ALP), LS and femoral neck BMD (p = 0.03). Serum ALP levels were higher in DISH subjects, showing an inverse correlation with TBS that remained significant after adjusting by age and BMI. Conclusions: TBS values were significantly lower in men with DISH irrespective of age, BMI and BMD, suggesting that the presence of DISH might be related to a worse trabecular microstructure

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