Title: Imaging for detection of osteomyelitis: a systematic review and meta-analysis
Funder: Department of Health and Social Care

Abstract: Design: Systematic review and meta-analysis of diagnostic accuracy studies of medical imaging tests used to diagnose osteomyelitis. Review strategy: A search of MEDLINE, EMBASE and other databases will be used to identify all studies of imaging techniques to diagnose osteomyelitis that present diagnostic accuracy data. The potential for bias of these studies will be assessed using the QUADAS-2 tool. To ensure accuracy, two reviewers will undertake the reviewing process. Target Population: All patients with suspected osteomyelitis based on presented symptoms or blood tests. Adults and children, and all types, causes and locations of osteomyelitis will be included. Technologies: Any medical imaging test used to assess osteomyelitis, including: X-ray, MRI, CT scan, PET scan, SPECT scan, scintigraphy and ultrasound. Reference standards will include: biopsy of potentially infected bone, pus aspiration and surgically confirmed osteomyelitis. Outcomes: Measurements of diagnostic accuracy including sensitivity and specificity, positive and negative likelihood ratios and positive and negative predictive values. Tests will be compared using diagnostic odds ratios and areas under ROC curves. Synthesis: Studies will be pooled using bivariate meta-analysis methods for pooling sensitivity and specific estimates. Summary receiver operating characteristic curves will be produced. Data on implementation issues such as accessibility and cost of tests, ease of interpretation of results, and exposure to radiation will also be synthesised. Project timetable: The project will run over fifteen months, as follows: Months 1-3: Preliminary searches, protocol preparation, full database searches Months 3-7: Screening of searches, study selection, Months 7-10: Data extraction and quality assessment Months 10-12: Syntheses of studies and meta-analyses Months 11-15: Update searches, write report and papers. Expertise in team: Mark Simmonds is an expert in meta-analyses and reviews of diagnostic tests. He has successfully managed several diagnostic accuracy reviews, as part of HTA projects. Jeannette Kraft has more than 10 years’ experience specialising in musculoskeletal imaging in children. She was recently part of a group developing a novel MRI-based scoring system for children with Juvenile Dermatomyositis. Andrew Grainger has 17 years’ experience as a consultant musculoskeletal radiologist and has daily involvement with imaging bone and joint infection in adults using all imaging modalities. He also receives NIHR for research in musculoskeletal imaging. Nerys Woolacott has been the NICE TAR project manager at CRD for 10 years and is an expert in Health Technology Assessment and evidence synthesis. Alexis Llewellyn has been the main reviewer on a number of successful HTA reviews and NICE TAR projects including in the field of diagnostic and screening tests accuracy. CRD regularly undertakes high quality systematic reviews of healthcare interventions, and has published over 600 systematic reviews. Its methodological guidance on undertaking systematic reviews in health care is recommended as a source of good practice by national and international agencies. Other project staff will be drawn from across the CRD team.

Lay abstract: Osteomyelitis is a bacterial infection of bone and bone marrow. It is caused by infection reaching the bone through the blood stream, or as a result of an injury through direct spread. Untreated it may cause fever, swelling, pain, and in more severe cases, death of the bone which may lead to amputation, septicaemia and organ failure. It is treated with a course of antibiotics and surgical removal of dead bone and tissue, if required. A bone biopsy, where a sample is taken from the potentially infected bone for testing, is the most reliable means of diagnosis, but it is painful, and requires anaesthetic. Medical imaging of the affected area is also used to identify osteomyelitis and to rule out other causes of symptoms, such as fractures. A number of imaging methods are available including X-rays, ultrasound, magnetic resonance imaging (MRI) scans, computed tomography and positron emission tomography (PET) scans. Because of the range of types of patients who might get osteomyelitis, its various causes, and the number of types of imaging techniques available, there is some uncertainty as to which imaging technique is best in different circumstances. There have been few published systematic reviews in this area, and most reviews are either out-of-date, or focus on one imaging technique, or one type of patient. This project will formally review all the available literature on the effectiveness of medical imaging techniques for the diagnosis of osteomyelitis. Recommended guidance for conducting systematic reviews will be followed to ensure all relevant studies are identified, all relevant data is analysed, and the quality of each included study will be assessed and accounted for in analyses. The primary aim of the project is to summarise the diagnostic accuracy of the tests; that is, to determine how many people with osteomyelitis they correctly identify as requiring treatment, and how many people without osteomyelitis they correctly identify. This review will consider all plausible imaging techniques, including those listed above, and all types of patient (both adults and children), cause and location of osteomyelitis. The project will compare the various techniques, to identify which have the greatest accuracy in different circumstances. When comparing tests account will be taken of the practicalities of performing the tests, including costs, ease of use and interpretation, and potential for radiation exposure. The findings of the project will be published as an HTA report, and in two or three relevant medical journals, including one non-technical guidance document. To ensure medical professionals are aware of the findings results will be presented at two or more conferences attended by radiologists and experts in osteomyelitis.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION