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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