Fracture prediction in a Swiss cohort.

Lehmann, Oliver; Mineeva, Olga; Dinara, Veshchezerova; Häuselmann, Hansjörg; Guyer, Laura; Reichenbach, Stephan; Lehmann, Thomas; Demler, Olga; Everts-Graber, Judith (2024). Fracture prediction in a Swiss cohort. (In Press). Journal of bone and mineral research Oxford University Press 10.1093/jbmr/zjae089

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Fracture prediction is essential in managing patients with osteoporosis, and is an integral component of many fracture prevention guidelines. We aimed to identify the most relevant clinical fracture risk factors in contemporary populations by training and validating short- and long-term fracture risk prediction models in two cohorts. We used traditional and machine learning survival models to predict risks of vertebral, hip and any fractures on the basis of clinical risk factors, T-scores and treatment history among participants in a nationwide Swiss osteoporosis registry (N = 5944 postmenopausal women, median follow-up of 4.1 years between January 2015 and October 2022; a total of 1190 fractures during follow-up). The independent validation cohort comprised 5474 postmenopausal women from the UK Biobank with 290 incident fractures during follow-up. Uno's C-index and the time-dependent area under the receiver operating characteristics curve were calculated to evaluate the performance of different machine learning models (Random survival forests and eXtreme Gradient Boosting). In the independent validation set, the C-index was 0.74 [0.58, 0.86] for vertebral fractures, 0.83 [0.7, 0.94] for hip fractures and 0.63 [0.58, 0.69] for any fractures at year 2, and these values further increased for longer estimations of up to 7 years. In comparison, the 10-year fracture probability calculated with FRAX® Switzerland was 0.60 [0.55, 0.64] for major osteoporotic fractures and 0.62 [0.49, 0.74] for hip fractures. The most important variables identified with Shapley additive explanations (SHAP) values were age, T-scores and prior fractures, while number of falls was an important predictor of hip fractures. Performances of both traditional and machine learning models showed similar C-indices. We conclude that fracture risk can be improved by including the lumbar spine T-score, trabecular bone score, numbers of falls and recent fractures, and treatment information has a significant impact on fracture prediction.

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