A three-level model of diffuse idiopathic skeletal hyperostosis (DISH): Integrating susceptibility, activation, and clinical trajectories.

Autores de IDIVAL

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  Emilio Pariente Rodrigo

  Autor

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  Victor Manuel Martínez Taboada

  Autor

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  José Luís Hernández Hernández

  Autor

Unidades

• INMUNOPATOLOGÍA

Abstract

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) exhibits marked phenotypic heterogeneity. Despite similar cardiometabolic backgrounds, individuals may develop rapid axial ossification, limited progression, or no structural disease. We aimed to identify longitudinal trajectories and to propose a hierarchical, three-level model integrating upstream-susceptibility, downstream-activation, and structural outcomes. METHODS: Longitudinal analysis within the Camargo Cohort (10-year follow-up), including clinical, metabolic, laboratory, and radiographic parameters (Schlapbach graded scale; AAC-24). Four trajectory definitions were established a priori. Analyses included Shapley-R(2) decomposition, mixed-effects models, and Spearman correlations, stratified by sex. RESULTS: Of 502 participants, 302 (60.2%) were classified into trajectories: Fast Ossifier (FO, n?=?61), Low-Load DISH (LLD, n?=?148), Vascular-Dominant DISH (VDD, n?=?48), and Persistent Non-DISH (PND, n?=?45). Downstream activation index (DAI-5) increased across susceptibility tertiles (median [IQR]: 94.5 [86-103], 98.6 [90-106], 102.2 [93-113]; p?=?0.0001). VDD showed the highest activation (median DAI-5?=?103). FO and VDD exhibited preserved associations between susceptibility and activation, whereas PND showed a flat or negative relationship, indicating upstream-downstream uncoupling despite maximal susceptibility. FO displayed efficient skeletal resolution with the greatest axial progression, while VDD combined high activation with predominant vascular involvement (AAC-24?=?12.07) and severe trabecular deterioration (TBS?=?1.220). LLD showed fragmented coupling and minimal structural progression. Waist circumference was the most consistent determinant of structural outcomes across domains in mixed-effects models. CONCLUSIONS: DISH can be understood as a system-level process in which susceptibility, activation, and trajectory-specific coupling determine tissue-level resolution of a calcific impulse. This exploratory framework could explain phenotypic divergence and may support improved skeletal and cardiovascular risk stratification.

Copyright © 2026 The Author(s). Published by Elsevier Inc. All rights reserved.

Keywords

• Alkaline phosphatase; Diffuse idiopathic skeletal hyperostosis; Fast Ossifier; Fast Ossifier stratification index; Propensity score; Sex differences