Spine age estimation using deep learning in lateral spine radiographs and DXA VFA to predict incident fracture and mortality

Background

Spine age estimated from lateral spine radiographs and DXA vertebral fracture assessments (VFAs) could be associated with fracture and mortality risk.

Methods

In the VERTE-X cohort (n=10,341, age 40 or older; derivation set) and KURE cohort (n=3,517; age 65 or older; external test set), predicted age difference was defined as estimated spine age minus chronological age. The primary outcome was incident fracture. Secondary outcomes included morphologic vertebral fracture, osteoporosis, and incident mortality.

Results

Incidence of overall fracture was 20.5/1000 and 21.0/1000 person-years (median follow-up 5.4 and 6.6 years) in VERTE-X and KURE, respectively. Spine age discriminated prevalent vertebral fractures and osteoporosis better than chronological age. Higher predicted age difference (PAD) was associated with greater risk of overall (VERTE-x: adjusted HR [aHR] 1.71; KURE: aHR 1.22 per 1 standard deviation [SD] increment), vertebral (aHR 1.55 and 1.34), and non-vertebral fractures (aHR 1.89 and 1.15, p<0.05 for all), independent of chronological age and prevalent vertebral fracture. FRAX hip fracture probabilities based on spine age improved discrimination for incident hip fracture over chronological age (AUROC 0.83 vs. 0.78, p=0.027). Shorter height, lower femoral neck BMD, diabetes, vertebral fractures, and surgical prosthesis were associated with higher predicted age difference, explaining 40% of variance. In the external test set, higher predicted age difference was associated with greater risk of mortality (aHR 1.31 per 1 SD increment, p=0.001), independent of covariates.

Conclusion

Spine age estimated from lateral spine radiographs and DXA VFA enhanced fracture risk assessment and mortality prediction in adults.

Key Points

• Spine age estimated from lateral spine radiographs and DXA VFA using deep learning outperformed chronological age in discriminating morphologic vertebral fracture and osteoporosis.

• Higher predicted age difference (predicted spine age minus chronological age) was associated with greater risk of overall, vertebral, and non-vertebral incident fracture, independent of covariates.

• Male sex, lower height, lower femoral neck BMD, diabetes mellitus, morphologic vertebral fractures, and surgical prosthesis were correlated with higher predicted age difference, explaining up to 40% variance.

• Higher predicted age difference was associated with greater risk of mortality, independent of chronological age, sex, prevalent morphologic vertebral, fracture, and clinical biomarkers related to mortality including serum albumin, hemoglobin, and creatinine.