title: Osteoprotegerin treatment impairs remodeling and apparent material properties of callus tissue without influencing structural fracture strength.
abstract: The influence of osteoprotegerin (OPG) treatment on callus formation, callus tissue structural strength, apparent material properties, and histology of tibia fractures in rats was investigated after 3 weeks and 8 weeks of healing. OPG was given intravenously (10 mg/kg twice weekly) during the entire observation period, and control animals with fractures received vehicle only. When compared with control fractures after 3 weeks of healing, OPG treatment reduced the number of osteoclasts in the callus tissue (93%, P < 0.001) and hampered resorption of genuine cortical bone in the fracture line; OPG treatment did not influence callus dimensions, callus bone mineral content (BMC), fracture structural strength, or callus tissue apparent material properties. When compared with control fractures after 8 weeks of healing; OPG treatment reduced the number of osteoclasts in callus tissue (92%, P < 0.001), augmented callus dimensions (anteriorposterior diameter: 12%, P = 0.034, mediolateral diameter: 13%, P = 0.013), and increased callus BMC (50%, P = 0.007); OPG treatment hampered deposition of new woven bone at the fracture line of the genuine cortical bone (new woven bone present in all vehicle animals, but only in 13% of the OPG-treated animals (P < 0.001)); OPG treatment did not influence structural strength of the fractures, but decreased apparent material properties of the callus tissue (ultimate stress: 51%, P < 0.001; elastic modulus: 42%, P = 0.033). The experiment demonstrates that OPG treatment does not influence the early callus expansion and fracture strength. However, during the subsequent period of remodelling, OPG treatment impairs the normal remodeling and consolidation processes.
authors.affiliation: Department of Orthopaedics, Aarhus University Hospital, Aarhus, Denmark. michaelulrich@mail.dk
authors.forename: M
authors.initials: M
authors.lastname: Ulrich-Vinther
authors.forename: T T
authors.initials: TT
authors.lastname: Andreassen
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D002146:Bony Callus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019245:Compressive Strength / Q000187:drug effects; D005260:Female; D017102:Fracture Healing / Q000187:drug effects* / Q000502:physiology; D006023:Glycoproteins / Q000494:pharmacology*; D007275:Injections, Intravenous; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D053244:Osteoprotegerin; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D013314:Stress, Mechanical; D013977:Tibia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016474:Weight-Bearing
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat