Vertebral Fracture by Quantitative Morphometry
In quantitative morphometry vertebral fracture is determined by precisely measuring the shape of the vertebral bodies on lateral view radiographs. Various approaches have been used but the most common approach measures the posterior, middle and anterior height of the vertebral body. This is done by defining six points along the margin of the vertebra according to strictly standardized criteria. Prevalent and incident fractures are then determined by calculating the ratio of these heights to one another either on the same film or on sequential films and comparing the results to reference data and threshold criteria. Prevalent fracture is generally defined as a ratio more than 3 standard deviations below the normal ratio for the specific vertebral level. The success of quantitative morphometry for assessing prevalent vertebral fracture depends on the applicability of the reference data to the study population. Incident fracture is most often defined as a 20% reduction from baseline in vertebral height that is also at least 4 mm. Other thresholds have been used (e.g., 15% reduction) but Black has demonstrated that the 20% threshold provides the greatest power in clinical trials [DM Black et al, J Bone Miner Research 1999].
 In order to achieve precise measurements of vertebral body height the radiographic acquisition must be standardized and carefully controlled to ensure consistency and quality. Particular attention must be paid to factors affecting magnification in the radiographic image and the positioning of the patient. Care must be taken to ensure that the patient is positioned in such a manner to provide a clear depiction of the vertebral bodies, avoiding double projection of the vertebral body endplate due to oblique positioning. Synarc has developed a standardized approach for spinal radiography that can be taught to x-ray technologists and implemented at any radiology clinic. These procedures are in accordance with the recommendations of the National Osteoporosis Foundation Working Group on Vertebral Fractures (“Assessing Vertebral Fracture,” J Bone Miner Research 1995; 10(4):518-523).
The assessment of vertebral fracture by quantitative morphometry is not used routinely in clinical practice and thus can only be performed at a small number of centers around the world. Even fewer of these centers are capable of managing the volume of data collected in a study of a drug to treat osteoporosis, both with regard to the number of images received as well as the management of the data and study sites in accordance with regulatory guidelines. After years of experience in global clinical trials Synarc is able to combine expert and highly trained readers using sophisticated reading workstations with efficient data management systems to support even the largest clinical trials.
Combining the Semi-quantitative and Quantitative Approaches
The semi-quantitative and quantitative approaches can be combined in an osteoporosis clinical trial to take advantage of the merits of each technique. This approach has been used in several registration studies. The radiographs of the subjects are analyzed by both techniques and where those approaches disagree adjudication is performed using a third, independent assessment. Historically, the third approach has been a second visual assessment of fracture by a trained reader.
Synarc readers are fully trained in both reading approaches and meet high standards for reliability. Working with our proprietary Vfract™ reading system, the readers use customized image display and analysis software to evaluate the serial images from a clinical trial. The electronic scoresheets and signatures allow rapid and accurate data recording that adheres to the guidelines of regulatory agencies. This synergistic blend of reader and reading system increases capacity while enhancing the quality of the data.
Vertebral Fracture Assessment with DXA
The current generation of DXA scanners is capable of providing lateral images of the spine suitable for the assessment of vertebral fracture (VFA scans). While image quality of these DXA images falls short of conventional radiographs, the scans can be useful for fracture detection in some clinical trials. Synarc’s radiologists have been involved in the scientific evaluation of the diagnostic utility of VFA scans and have an advanced understanding of the technology. When desired, Synarc has systems ready for the receipt, archival and reading of VFA scans in the multi-center clinical trial setting.
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