Background and purposeTo investigate the image quality and accurate bone mineral density (BMD) on quantitative CT (QCT) for osteoporosis screening by deep-learning image reconstruction (DLIR) based on a multi-phantom and patient study.Materials and methodsHigh-contrast spatial resolution, low-contrast detectability, modulation function test (MTF), noise power spectrum (NPS), and image noise were evaluated for physical image quality on Caphan 500 phantom. Three calcium hydroxyapatite (HA) inserts were used for accurate BMD measurement on European Spine Phantom (ESP). CT images were reconstructed with filtered back projection (FBP), adaptive statistical iterative reconstruction-veo 50% (ASiR-V50%), and three levels of DLIR(L/M/H). Subjective evaluation of the image high-contrast spatial resolution and low-contrast detectability were compared visually by qualified radiologists, whilst the statistical difference in the objective evaluation of the image high-contrast spatial resolution and low-contrast detectability, image noise, and relative measurement error were compared using one-way analysis of variance (ANOVA). Cohen’s kappa coefficient (k) was performed to determine the interobserver agreement in qualitative evaluation between two radiologists.ResultsOverall, for three levels of DLIR, 50% MTF was about 4.50 (lp/cm), better than FBP (4.12 lp/cm) and ASiR-V50% (4.00 lp/cm); the 2 mm low-contrast object was clearly resolved at a 0.5% contrast level, while 3mm at FBP and ASiR-V50%. As the strength level decreased and radiation dose increased, DLIR at three levels showed a higher NPS peak frequency and lower noise level, leading to leftward and rightward shifts, respectively. Measured L1, L2, and L3 were slightly lower than that of nominal HA inserts (44.8, 95.9, 194.9 versus 50.2, 100.6, 199.2mg/cm3) with a relative measurement error of 9.84%, 4.08%, and 2.60%. Coefficients of variance for the L1, L2, and L3 HA inserts were 1.51%, 1.41%, and 1.18%. DLIR-M and DLIR-H scored significantly better than ASiR-V50% in image noise (4.83 ± 0.34, 4.50 ± 0.50 versus 4.17 ± 0.37), image contrast (4.67 ± 0.73, 4.50 ± 0.70 versus 3.80 ± 0.99), small structure visibility (4.83 ± 0.70, 4.17 ± 0.73 versus 3.83 ± 1.05), image sharpness (3.83 ± 1.12, 3.53 ± 0.90 versus 3.27 ± 1.16), and artifacts (3.83 ± 0.90, 3.42 ± 0.37 versus 3.10 ± 0.83). The CT value, image noise, contrast noise ratio, and image artifacts in DLIR-M and DLIR-H outperformed ASiR-V50% and FBP (P<0.001), whilst it showed no statistically significant between DLIR-L and ASiR-V50% (P>0.05). The prevalence of osteoporosis was 74 (24.67%) in women and 49 (11.79%) in men, whilst the osteoporotic vertebral fracture rate was 26 (8.67%) in women and (5.29%) in men.ConclusionImage quality with DLIR was high-qualified without affecting the accuracy of BMD measurement. It has a potential clinical utility in osteoporosis screening.