Our institutional review board approved this retrospective study and waived the requirement for informed patient consent. Twenty-three of the 52 patients who underwent bone SPECT at our institution from April 2014 to November 2019 had uninfected nonunion of the femur, tibia, or humerus. Exclusion criteria were infectious diseases (osteomyelitis, purulent arthritis); nonunion cases with pelvic, fibular, clavicular, radial, and atypical femoral fractures; contralateral fracture cases; bone tumor cases (metastatic and primary); and unknown patient height and weight.
Patients’ medical records were evaluated to determine their characteristics and treatment progress. The average age at the time of bone SPECT scan was 43.8 ± 18.1 years (range, 16–76 years), with 13 men and 10 women. There were 15 femoral nonunions, 5 tibial nonunions, and 3 humeral nonunions. The implant types were intramedullary nails in 15 cases, plates in 6 cases, hemiarthroplasty + plate in 1 case, and no implant in 1 case. The average period from the injury to bone SPECT scan was 574 ± 854.3 days (range, 89–4330 days). The number of operations before the SPECT scan was 1.8 (1 in 11 cases, 2 in 6 cases, 3 in 5 cases, and conservative treatment in 1 case). Bone modifying agents (teriparatide acetate) for osteoporosis treatment were used in four cases. Low-intensity pulsed ultrasound treatment was used in 16 cases, and no cases received steroid medication. Autologous bone grafts were performed in 13 cases. Bone union was achieved in all cases after the operations following the SPECT scans.
There were 8 hypertrophic nonunions and 15 non-hypertrophic nonunions. We defined hypertrophic nonunion as elephant foot and horse hoof, and non-hypertrophic nonunion as oligotrophic, comminuted (torsion-wedge, dystrophic, necrotic), defect, and atrophic, according to the Weber classification of X-ray findings [9, 19]. Three senior orthopedic trauma surgeons classified the nonunions; 19/23 cases had the same classification by all three surgeons, but 4 cases had different opinions, so a consensus meeting was held, and the opinions were unified.
SPECT scans were performed before nonunion surgery. 99mTc-MDP or 99mTc-HMDP was injected intravenously, and SPECT imaging was performed 3 hours later. SPECT scans were obtained using a SPECT scanner (E.CAM; Canon Medical Systems Corp., Tokyo, Japan). The SPECT scan was acquired using a low-energy, high-resolution collimator at 140 keV photoenergy peak for 99mTc with a 128 × 128 matrix of 4.8 mm pixel size, and a total of 60 projections (30 steps) over 360° with a dwell time of 10 s/step. SPECT images were reconstructed using three-dimensional ordered subset expectation maximization (3D-OSEM) with six iterations, 15 subsets, and a Butterworth filter.
The quantitative SPECT parameters were calculated using the software, GI-BONE (AZE, Tokyo, Japan). The SUV was calculated for the quantitative analysis of 99mTc-MDP or 99mTc-HMDP uptake, as follows:
SUV = (tissue radioactivity/voxel volume)/(injected radioactivity/body weight), where tissue radioactivity means a tissue radioactivity concentration measured by SPECT. Tissue radioactivity concentration was obtained by multiplying the SPECT counts and Becquerel calibration factor, which was determined by scanning the cylindroid phantom filled with a known radioactivity concentration. Various SUV parameters were calculated using GI-BONE. The maximum value for SUV (SUVmax) = (maximum radioactivity/voxel volume)/(injected radioactivity/body weight). The mean value for SUV (SUVmean) = (total radioactivity/volume of interest (VOI))/(injected radioactivity/body weight). The peak value of SUV (SUVpeak) represents the average SUV obtained within a 1 cm3 sphere of the region of interest centered on the highest voxel of the target area.
The VOI size was defined as a sphere with a diameter of 19.2 mm sphere, considering the limit of spatial resolution of SPECT . Three parts of the VOI were placed on the healthy opposite extremity, and the average value was used as the control value; the SUV control ratio of the nonunion was used for evaluation. When comparing between patients, we considered that it is desirable to evaluate not by the absolute value of the target site but by the control ratio. The orthopedic trauma surgeon and the radiologist identified the nonunion site by observing plain X-ray, computed tomography (CT), and SPECT images, and identified and measured the hot and cold uptake areas.
Statistical analyses for the SPECT parameters of the nonunion lesions (hypertrophic nonunion and non-hypertrophic nonunion) were performed using the Mann–Whitney U test. All statistical analyses were performed using GraphPad Prism 7 (GraphPad Software Inc., La Jolla, CA). A p value less than 0.05 was considered statistically significant.