Abstract This study aimed to determine whether absolute quantification obtained with a high-speed CZT SPECT/CT system provides consistent results on phantom and in bone scintigraphy-based longitudinal monitoring of patients with vertebral fractures and/or fracture cascades. Materials and Methods. SPECT images were reconstructed as recommended for clinical routine. Both image quality and accuracy of measured activity were evaluated using an IEC body phantom. The optimized reconstruction process was applied to routine ≤ 15 min 99m Tc-HDP SPECT spine recordings, which had been previously acquired from 25 patients (74±12 years old) at both early (1.3±1.1 months) and late (5.2±2.3 months) stage assessments of an acute vertebral fracture of a traumatic and/or osteoporotic origin. Results. A SPECT reconstruction with 32 equivalent iterations was used based on high levels of foci detectability in spheres as small as 0.6 mL in volume, and accuracy of measured activity, although the latter was affected by partial volume effect for spheres ≤ 5.8 mL. SUVmax from patients’ intact T1 vertebrae, used as a reference, remained stable between 1 st and 2 nd SPECT recordings (5.7±1.1 vs. 5.8±1.1, p=0.76). SUVmax from the initially fractured vertebrae were 3-fold higher on 1 st SPECT (21.0±8.5, p<0.001 vs. T1 SUVmax) and markedly decreased on 2 nd SPECT (11.2±4.2, p<0.001 vs. 1 st SPECT). Inverse changes in SUVmax were documented for newly compacted fractures apparent on the 2 nd SPECT (1 st SPECT: 7.4±2.0 vs. 2 nd SPECT: 21.8±10.3, p=0.002) together with an increased bone density on CT (in mean Hounsfield Units: 121±28 vs.190±39, p=0.003). Rate of SUVmax > 7.5 was 98% (56/57) for measurements obtained in vertebrae fractured in the preceding 7-months, whereas this rate was only 4% for the reference intact vertebrae (2/50). Conclusion. High-speed recordings with this CZT-SPECT/CT system provide reliable SUV measurements that may attest to longitudinal changes in vertebral bone metabolism and especially changes related to fracture healing or recurrence.