Abstract: Background: Diffuse idiopathic skeletal hyperostosis (DISH) is considered a slowly progressive condition, typically requiring a decade to achieve full radiographic development. However, some individuals exhibit accelerated ossification. This study aimed to characterise the clinical profile of these patients, referred to as Fast Ossifiers (FO). Methods: Study nested within the Camargo Cohort, integrating cross-sectional and longitudinal data (baseline (E0), 5 year (E1) and 10 year assessments (E2)). Propensity Score matching was applied. FO was defined as progression of ?2 grades in Schlapbach's Scale between consecutive assessments. We evaluated inflammation, insulin resistance (via Triglyceride-Glucose Index (TyG)), Visceral Adiposity Index (VAI), intact parathormone (iPTH), bone turnover markers and Trabecular Bone Score (TBS). Results: We analysed 455 DISH cases and 455 matched controls. During follow-up, 61 individuals fulfilled FO criteria (18%<60 years; 49% female; 65.6% obese; 72.1% hypertensive). Compared with controls, FO subjects had higher TyG (8.65±0.9 vs 8.39±0.4; p=0.002), FO-females showed higher visceral adiposity (VAI 2.30±2 vs 1.44±0.1; p=0.024), and both sexes presented elevated iPTH at E2. In multivariable models, FO was associated with high TyG (adjusted OR=9.31; 95% CI: 1.04 to 36; p=0.046), low TBS (adjusted OR=0.002; 95% CI: 0.001 to 0.61) and higher alkaline phosphatase levels (79 vs 69 (U/L); p=0.043). Conclusions: FO represents an active variant that challenges the view of DISH as a quiescent disease affecting older men. Rather than a single entity, FO emerges as a convergent phenotype driven by diverse metabolic pathways and linked to accelerated skeletal changes, including ossification and early trabecular impairment.

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