{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T16:43:31Z","timestamp":1781196211061,"version":"3.54.1"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T00:00:00Z","timestamp":1548806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["APMIS"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:p>Assessment of bone graft material efficacy is difficult in humans, since invasive methods like staged <jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> scans or biopsies are ethically unjustifiable. Therefore, we developed a novel large animal model for the verification of a potential transformation of synthetic bone graft substitutes into vital bone. The model combines multiple imaging methods with corresponding histology in standardized critical sized cancellous bone defect. Cylindrical bone voids (10\u00a0ml) were created in the medial femoral condyles of both hind legs (first surgery at right hind leg, second surgery 3\u00a0months later at left hind leg) in three merino\u2010wool sheep and either (i) left empty, filled with (ii) cancellous allograft bone or (iii) a synthetic, gentamicin eluting bone graft substitute. All samples were analysed with radiographs, <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content>, \u03bc<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content>,<jats:styled-content style=\"fixed-case\"> DEXA<\/jats:styled-content> and histology after sacrifice at 6\u00a0months. Unfilled defects only showed ingrowth of fibrous tissue, whereas good integration of the cancellous graft was seen in the allograft group. The bone graft substitute showed centripetal biodegradation and new trabecular bone formation in the periphery of the void as early as 3\u00a0months. \u03bc<jats:styled-content style=\"fixed-case\">CT<\/jats:styled-content> gave excellent insight into the structural changes within the defects, particularly progressive allograft incorporation and the bone graft substitute biodegradation process. <jats:styled-content style=\"fixed-case\">MRI<\/jats:styled-content> completed the picture by clearly visualizing soft tissue ingrowth into unfilled bone voids and presence of fluid collections. Histology was essential for verification of trabecular bone and osteoid formation. Conventional radiographs and <jats:styled-content style=\"fixed-case\">DEXA<\/jats:styled-content> could not differentiate details of the ongoing transformation process. This model appears well suited for detailed <jats:italic>in\u00a0vivo<\/jats:italic> and <jats:italic>ex\u00a0vivo<\/jats:italic> evaluation of bone graft substitute behaviour within large bone defects.<\/jats:p>","DOI":"10.1111\/apm.12918","type":"journal-article","created":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T12:09:05Z","timestamp":1548850145000},"page":"53-63","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Establishment and effects of allograft and synthetic bone graft substitute treatment of a critical size metaphyseal bone defect model in the sheep femur"],"prefix":"10.1111","volume":"127","author":[{"given":"Werner","family":"Hettwer","sequence":"first","affiliation":[{"name":"Musculoskeletal Tumor Section Department of Orthopedic Surgery Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Horstmann","sequence":"additional","affiliation":[{"name":"Musculoskeletal Tumor Section Department of Orthopedic Surgery Rigshospitalet University of Copenhagen Copenhagen Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Bischoff","sequence":"additional","affiliation":[{"name":"Central Experimental Animal Facility University Hospital Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"G\u00fcllmar","sequence":"additional","affiliation":[{"name":"Medical Physics Group Institute of Diagnostic and Interventional Radiology University Hospital Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen R.","family":"Reichenbach","sequence":"additional","affiliation":[{"name":"Medical Physics Group Institute of Diagnostic and Interventional Radiology University Hospital Jena Jena Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrina S. 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