Introduction 1 3 2 5 6 9 The purpose of our study was to evaluate the use of FDG-PET in differentiating benign from malignant compression fractures. Materials and methods This study was approved by the institutional review board of our institution, which waived the need for informed consent. The study was compliant with the Health Insurance Portability and Accountability Act. A retrospective search was performed using Boolean operators (Folio; Open Market, Proto, UT, USA) to identify all patients who had undergone whole-body FDG-PET at our institution from 2003 to 2006 and had the finding of a compression fracture mentioned in the PET report. Imaging studies and reports, medical records, and pathology reports of selected cases were reviewed. Patients We identified 33 patients with compression fractures who underwent whole-body FDG-PET. There were 23 women and 10 men, aged 48–93 years, with a mean age of 72 years. Twenty-nine patients had a history of malignancy (1 had leukemia, 5 lung cancer, 1 ovarian cancer, 2 breast cancer , 5 colon cancer,  9 lymphoma, 1 sarcoma, 1 pancreatic cancer, 1 Klatskin tumor, 1 gastrointestinal stromal tumor,  1 laryngeal cancer, and 1 had esophageal cancer). The 4 patients without history of malignancy underwent whole body PET for work-up of indeterminate lung nodules detected on prior CT or radiographs. Sixteen patients underwent FDG-PET and 17 patients underwent FDG-PET/CT at time of evaluation. Nine patients underwent CT and 14 patients underwent MRI of the spine within 4 weeks of FDG-PET. Seventeen patients were followed up with serial FDG-PET studies. Nine patients underwent biopsy and the pathologic results were used as a standard of reference. Twenty-four patients who did not undergo biopsy were followed up clinically and with repeat imaging, with MRI, CT, or FDG-PET for a period of 1–3 years and findings at clinical follow-up and imaging studies were used for lesion verification. In these patients, the development of new lesions and/or progression of existing lesions on imaging were used as criteria for malignant compression fractures. Image acquisition Whole-body PET was performed using an ECAT HR+ scanner (CTI Molecular Imaging, Knoxville, TN, USA). All patients fasted for at least 6 h prior to image acquisition, and blood glucose levels were measured prior to the injection of FDG. A dose of 15–20 mCi (555–740 MBq) of FDG was administered intravenously 45 min to 1 h prior to scanning. Patients were positioned supine on the scanner and emission images were acquired in 6–7 bed positions from the mandible to the mid-thigh or to the level of the ankles in the case of lower extremity lesions. Transmission images obtained with a rotating germanium 68-rod source were used for attenuation correction. Images were reconstructed using the ordered-subset expectation maximization (OSEM) algorithm. Combined PET/CT studies were performed with a 16-section hybrid PET/CT gantry (Biograph Sensation 16; Siemens, Erlangen, Germany), which comprises a 16-section high-performance multi-detector row CT scanner with a lutetium oxyorthosilicate-based PET scanner. The PET image spatial resolution was 5.0 mm full width at half maximum, with a section thickness of 3.5 mm. Patients fasted for at least 6 h prior to image acquisition, and blood glucose levels were measured prior to the injection of FDG. Two 10-oz cups of water were administered as negative contrast material 1 h prior to scanning. A dose of 15–20 mCi (555–740 MBq) of FDG was administered intravenously 45 min to 1 h prior to scanning. Patients were positioned supine on the scanner and emission images were acquired in 6–7 bed positions from the mandible to mid-thigh or to the level of the ankles in the case of lower extremity lesions. Images were reconstructed with Fourier rebinning and attenuation-weighted ordered-subsets expectation maximization. A low-dose CT scan was performed prior to PET imaging primarily for attenuation correction, with patients holding their breath mid-expiration, and included an area from the mandible to the mid-thigh or to the level of the ankles in the case of lower extremity lesions. Slice thickness was 5 mm. A diagnostic contrast-enhanced CT was performed subsequent to the PET/CT following the administration of 100 mL intravenous contrast material (Isovue 300; Bracco Diagnostics, Princeton, NJ, USA) at an injection rate of 2 mL/s using 2.5-mm sections. Image analysis Semiquantitative and qualitative evaluation of PET images was performed on a high-resolution workstation (Reveal-MVS; Mirada Solutions, Oxford, UK) by one investigator, who was blinded to the clinical and pathological results (MAB). The images were displayed in rotating maximum intensity projections and in axial, coronal, and sagittal planes. Semiquantitative analysis of FDG uptake was performed by creating a region of interest over the area of maximal radiotracer activity. max (bw) tis inj max (bw) tis inj Statistical analysis t p Results Forty-three compression fractures were identified in 33 patients. Twenty-two fractures involved the thoracic and 21 fractures the lumbar spine. Nine patients underwent biopsy and 24 patients were followed up clinically and with repeat imaging. In the 9 patients who underwent biopsy, there were 3 benign and 6 malignant compression fractures. Of the 24 patients who were followed clinically and with repeat imaging, 6 patients were thought to have malignant and 18 patients were thought to have benign compression fractures. Overall, there were 21 patients with benign and 12 patients with malignant compression fractures. Out of the 43 compression fractures, there were 29 benign and 14 malignant fractures. Based on clinical history (acute onset of back pain often after minor trauma) and imaging characteristics on MRI (bone marrow edema) there were 5 acute benign compression fractures. Three patients were on bone marrow-stimulating therapy at the time of FDG-PET. Five patients were unable to undergo MRI because of pacemakers (3) or severe pain. Qualitative PET analysis 1 2 3 4 5 Fig. 1 a  arrow b arrows c arrow d arrow e white arrow black arrows  Fig. 2 a  arrow b arrow c arrow d arrow e arrow  Fig. 3 arrow  Fig. 4 a arrow b arrow c arrow  Fig. 5 a arrow arrowhead b arrow c arrows  6 7 8 Fig. 6 a arrow b arrow  Fig. 7 a  arrow b arrow arrowhead c arrows d arrow arrowhead  Fig. 8 a  arrow b arrowheads arrow c arrow  Quantitative PET analysis p t 9 Fig. 9 p t  Statistical analysis Sensitivity, specificity, positive and negative predictive values, and accuracy of FDG-PET in differentiating benign from malignant compression fractures were 86%, 83%, 84%, 71%, and 92% respectively. Discussion 10 13 12 14 16 8 9 In our study, malignant compression fractures demonstrated significantly increased FDG uptake compared with benign fractures. Mean SUV of malignant and benign fractures were 3.99 ± 1.52 SD for malignant lesions and 1.94 ± 0.97 SD for benign lesions. There were 2 false-negative results. In these cases there was moderately increased uptake of the compression fractures, which were thought to be acute benign fractures prospectively, but were found to represent metastatic disease on subsequent biopsy. SUV in these patients were 2.5 to 2.8 respectively. 17 18 Positron emission tomography and PET/CT were equally sensitive in differentiating benign from malignant compression fractures. However, the CT portion of the PET/CT improved the exact fracture localization and was able to provide additional information on fracture morphology, which can be helpful in diagnosing benign vs. malignant fractures. 8 19 20 In summary, FDG-PET is a useful method of differentiating between benign and malignant compression fractures and can serve as a problem solver in cases of equivocal MRI or CT findings, and in patients who are unable to undergo MRI. We do not recommend FDG-PET as a screening test, but rather as an additional imaging modality in problem cases, particularly in elderly patients with osteoporosis and a history of malignancy. In these patients, FDG-PET has the additional advantage of being able to evaluate the entire skeletal system and screen for metastatic disease.