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Objectives To compare opportunistic quantitative CT (QCT) with dual energy X-ray absorptiometry (DXA) in their ability to predict incident vertebral fractures. Methods We included 84 patients aged 50 years and older, who had routine CT including the lumbar spine and DXA within a 12-month period (baseline) as well as follow-up imaging after at least 12 months or who sustained an incident vertebral fracture documented earlier. Patients with bone disorders aside from osteoporosis were excluded. Fracture status and trabecular bone mineral density (BMD) were retrospectively evaluated in baseline CT and fracture status was reassessed at follow-up. BMD QCT was assessed by opportunistic QCT with asynchronous calibration of multiple MDCT scanners. Results Sixteen patients had incident vertebral fractures showing lower mean BMD QCT than patients without fracture ( p = 0.001). For the risk of incident vertebral fractures, the hazard ratio increased per SD in BMD QCT (4.07; 95% CI, 1.98–8.38), as well as after adjusting for age, sex, and prevalent fractures (2.54; 95% CI, 1.09–5.90). For DXA, a statistically significant increase in relative hazard per SD decrease in T -score was only observed after age and sex adjustment (1.57; 95% CI, 1.04–2.38). The predictability of incident vertebral fractures was good by BMD QCT (AUC = 0.76; 95% CI, 0.64–0.89) and non-significant by T -scores. Asynchronously calibrated CT scanners showed good long-term stability (linear drift ranging from − 0.55 to − 2.29 HU per year). Conclusions Opportunistic screening of mainly neurosurgical and oncologic patients in CT performed for indications other than densitometry allows for better risk assessment of imminent vertebral fractures than dedicated DXA. Key Points • Opportunistic QCT predicts osteoporotic vertebral fractures better than DXA reference standard in mainly neurosurgical and oncologic patients. • More than every second patient (56%) with an incident vertebral fracture was misdiagnosed not having osteoporosis according to DXA. • Standard ACR QCT-cutoff values for osteoporosis (< 80 mg/cm 3 ) and osteopenia (≤ 120 mg/cm 3 ) can also be applied scanner independently in calibrated opportunistic QCT.