Metabolic and osteogenic susceptibility in DISH: A prognostic index from propensity score modelling.

Abstract

Diffuse idiopathic skeletal hyperostosis (DISH) is increasingly recognised as a systemic condition associated with trabecular deterioration, and metabolic or vascular disruption. Within this spectrum, a phenotype characterised by accelerated skeletal progression has been described (Fast Ossifier, FO). We aimed to develop sex-specific prognostic indices derived from propensity score (PS) covariates-FOSSI-F (women) and FOSSI-M (men)-to stratify the risk of FO status within a population-based cohort. Using longitudinal data from the Camargo Cohort, sex-stratified logistic models were constructed based on PS-derived upstream variables. Internal validation (bootstrap), discriminative performance (ROC/AUC) and exploratory analyses (non-linear models, clustering, Shapley-R² decomposition) were performed. We analysed 178 individuals (61 with FO; 64% women; mean age = 61 ± 7 years). FOSSI-F included visceral adiposity and hypertension, FOSSI-M included waist circumference, and both incorporated age, body mass index and cardiometabolic index. They showed high discriminatory capacity (AUC = 0.875 in women and 0.836 in men). Non-linear modelling revealed a broad sigmoid transition zone in women (approximately 5.8-9.6) and a sharp threshold-like pattern in men (0.45-0.71). In high FOSSI values, clustering analyses identified insulin resistance predominating in women and endocrine-inflammatory signals in men. Shapley analysis revealed TyG as the most influential factor in FOSSI-F variance (79.8%), while iPTH was in FOSSI-M (59.5%). Both indices correlated inversely with trabecular bone score (p < 0.0001). FOSSI-F and FOSSI-M are sex-specific, PS-derived prognostic indices that capture latent metabolic-osteogenic susceptibility associated with FO status. Their strong internal discrimination supports their use for risk stratification and research-oriented interpretation.