'Fast Ossifier' stratification index in DISH: FOSSI on-line calculator and Methodological Guide

'Fast Ossifier' phenotype

Diffuse idiopathic skeletal hyperostosis (DISH) is a common yet under-recognised condition characterised by abnormal ossification of spinal and extraspinal entheses. Traditionally regarded as a slowly progressive and relatively homogeneous disorder of older adults, DISH in fact exhibits marked clinical heterogeneity.

Recent work from the Camargo Cohort has identified the Fast Ossifier (FO) phenotype, a distinct subset of individuals who experience accelerated structural ossification together with early trabecular bone deterioration. This finding challenges the conventional view of DISH as a uniformly indolent condition and supports a more dynamic, trajectory-based model of disease evolution. Importantly, the FO phenotype is associated with an unfavourable metabolic and biological profile, suggesting that accelerated ossification may reflect a broader systemic dysregulation rather than a purely mechanical or age-related process.

Within this framework, the ability to identify individuals at increased risk of an aggressive ossification trajectory before extensive skeletal damage—and potentially metabolic or vascular complications—has occurred becomes a critical unmet need.

FOSSI, a sex-specific prognostic tool linking upstream susceptibility and downstream activation

While the FO phenotype provides a robust biological and conceptual framework, its early recognition posed substantial challenges. Conventional imaging criteria lack sensitivity in the initial phases of disease, and no single biomarker has proven capable of anticipating the FO trajectory.

To address this gap, we developed the Fast Ossifier Stratification Index (FOSSI), a pair of sex-specific indices—FOSSI-F for women and FOSSI-M for men—derived from a propensity score–based modelling approach. FOSSI translates latent, multidimensional epidemiological information into interpretable risk strata, enabling early susceptibility assessment.

FOSSI is not a diagnostic tool and not intended for individual-level clinical prediction. It is a susceptibility stratification index, developed for clinical and epidemiological research, comparative group analyses, pathophysiological interpretation of DISH-related ossification trajectories.

FOSSI captures sex-specific biological pathways underlying accelerated ossification, with insulin resistance–related mechanisms predominating in women and inflammatory–endocrine drivers more prominent in men. Validated cut-off points allow stratification into low, intermediate, and high susceptibility categories, providing a practical framework for risk differentiation.

In this sense, FOSSI bridges epidemiological modelling and clinical reasoning, addressing a long-standing gap in DISH research: the lack of tools capable of identifying individuals at higher risk of rapid disease progression at a stage when preventive or monitoring strategies may still be feasible.

With regard to the target population, FOSSI was developed and validated in middle-aged and older adults from a population-based cohort with and without radiographic DISH. It is intended for use in research settings involving comparable populations. Its applicability to other populations, ethnicities or clinical contexts has yet to be determined.

The development of FOSSI also aligns with emerging trends in the propensity score literature, where increasing emphasis has been placed on leveraging the rich covariate structure embedded in propensity models not only for confounding control, but also for risk stratification and susceptibility profiling. The rationale, development, and internal validation of FOSSI are fully described in the published methodological report.

The framework, rationale, variable selection, and discriminative performance of these indices are described in :

Pariente E, Martín-Millán M, Maamar M, et al.
Metabolic and osteogenic susceptibility in DISH: A prognostic index from propensity score modelling.
Bone. 2026;117819. https://doi.org/10.1016/j.bone.2026.117819

FOSSI on-line calculator

To facilitate the application of FOSSI, promote transparency, and encourage external validation, we released the free and publicly accessible FOSSI Online Calculator. By entering routinely available clinical variables, the calculator computes the corresponding FOSSI-F or FOSSI-M value and assigns the individual to a predefined susceptibility category. To enhance interpretability, the FOSSI on-line Calculator generates a probability curve plot linking FOSSI values to the estimated probability of belonging to the FO group. The plot displays the logistic relationship derived from the underlying models, with reference cut-off points informed by ROC analysis

The calculator is intended for research and clinical-contextual use, offering a practical means to operationalise the FOSSI framework. It enables researchers and clinicians to recognise individuals with increased susceptibility to accelerated ossification, supporting closer follow-up, hypothesis generation, and comparative analyses across cohorts.

A Methodological Guide is provided to facilitate interpretation and standardise concepts. 

Individual clinical interpretation must be performed within the context of a comprehensive medical assessment, and FOSSI Calc outputs should not be used in isolation for clinical decision-making