title: The effects of glucocorticoid on microarchitecture, collagen, mineral and mechanical properties of sheep femur cortical bone.
abstract: In this study, 18 female skeletally mature sheep were randomly allocated into three groups of six each. Group 1 (glucocorticoid-1) received prednisolone treatment (0.60 mg/kg/day, five times weekly) for 7 months. Group 2 (glucocorticoid-2) received the same treatment regime followed by observation of 3 months without treatment. Group 3 was left untreated and served as controls. All sheep received a restricted diet with low calcium and phosphorus. At sacrifice, cortical bone samples from the femur midshaft of each sheep were harvested, micro-CT scanned and subjected to three-point bending and tensile strength testing. Bone collagen and mineral were determined. Cortical porosity was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Apparent density was significantly decreased in the glucocorticoid-2 compared with the glucocorticoid-1 group. Collagen content was significantly increased in the glucocorticoid-2 compared with the glucocorticoid-1 and control groups. Bone mineral content did not differ between the groups. Neither the three-point bending mechanical properties nor the tensile mechanical properties differed significantly between the groups, while there was a trend towards decreasing bending mechanical properties in the glucocorticoid-2 group. In conclusion, 7 months of glucocorticoid treatment with malnutrition had a significant impact on the cortical microarchitecture of the sheep femur midshaft. These observed changes occurred 3 months after glucocorticoid cessation, suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in cortical bone beyond cancellous bone might further increase fracture risk in patients treated with glucocorticoids. This model might be used as a glucocorticoid-induced osteoporotic model for orthopaedic biomaterial, joint prosthesis and medical device researches.
authors.affiliation: Orthopaedic Research Laboratory, Department of Orthopaedics and Traumatology, Odense University Hospital, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. ming.ding@ouh.regionsyddanmark.dk
authors.forename: Ming
authors.initials: M
authors.lastname: Ding
authors.forename: Carl Christian
authors.initials: CC
authors.lastname: Danielsen
authors.forename: Søren
authors.initials: S
authors.lastname: Overgaard
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects; D003094:Collagen / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000502:physiology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008422:Materials Testing; D008903:Minerals / Q000378:metabolism*; D012756:Sheep; D013718:Tensile Strength / Q000187:drug effects; D055114:X-Ray Microtomography
chemical_list: D005938:Glucocorticoids; D008903:Minerals; D003094:Collagen