Evaluation of BP-ONJ in osteopenic and healthy sheep: comparing ZTE-MRI with µCT

Abstract

Objectives: Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side effect of antiresorptive treatment that is increasingly prescribed for patients with osteoporosis or malignant diseases with bone metastases. Surgical treatment of BP-ONJ requires adequate pre-operative imaging. To date, CT is the imaging standard in clinical routine; however, defining the extent of the pathological area is difficult and soft tissues are poorly displayed. MRI with zero echo time (ZTE-MRI) to display hard tissues enables a precise display of calcified structures and soft tissues for the delineation of bone necrosis and soft-tissue reactions.

Methods: BP-ONJ was induced in eight sheep by extraction of two premolars in the left mandible and zoledronate (ZOL) administration. Eight sheep without ZOL administration served as the control group. Four sheep of each main group underwent osteopenia induction via ovariectomy, glucocorticoid administration and a calcium-free diet. After sacrifice, the area of tooth extraction was harvested and scanned with micro-CT (µCT) and ZTE-MRI. Two trained dentists analyzed digital imaging and communications in medicine data sets using three-dimensional imaging software. The periosteal reaction and the remaining extraction sockets were measured.

Results: BP-ONJ was evident, and the remaining extraction sockets were observed in all animals treated with ZOL. Periosteal reactions were more pronounced in animals treated with ZOL, and they appeared broader in ZTE-MRI.

Conclusions: BP-ONJ lesions in the sheep mandible can be detected using µCT and ZTE-MRI. Although illustration of sequester was more consistent using the µCT, ZTE-MRI was advantageous in evaluation of periosteal reaction.

Keywords: animal model; bisphosphonate-associated osteonecrosis of the jaw; magnetic resonance imaging; periosteum; x-ray microtomography.

Figure 1

Overview of the time schedule of interventions in each group [Group 1a (G1a), Group 1b (G1b), Group 2a (G2a) and Group 2b (G2b)] in which each square represents 2 weeks (yellow = low calcium diet, dexamethasone infusion; X = ovariectomy, green = zoledronate infusion, tx = tooth extraction, E = euthanasia). For colour image see online.

Figure 2

Coronal cross-section of a specimen scanned using micro-CT with anatomical and pathological structures. a, remaining extraction socket; b, periostal reaction; c, bone marrow; and d, cortical bone.

Figure 3

Coronal cross-section scanned using zero echo time MRI. a, remaining extraction socket; b, periostal reaction; c, bone marrow; and d, cortical bone.

Figure 4

Alignment of the specimen scanned within an individual co-ordinate system. The x-axis is oriented axial to the mandible at the most caudal point of the mandible, the y-plane is oriented sagittal to the mandible and located in the centre of the extraction socket (vertical lines). The periosteal reaction is measured in the coronal cross-sections of micro-CT (left) and MRI (right) with a distance of 3 mm between each measuring plane (horizontal lines).

Figure 5

Bland–Altman plots of the difference between the mean MRI and mean micro-CT (μCT) measurements on the vestibular and oral aspects. Each dot represents a measurement of one examiner at one time point (overall two examiners at each three time points). SD, standard deviation; ZTE-MRI, zero echo time MRI.