Glucocorticoid-treated sheep as a model for osteopenic trabecular bone in biomaterials research.

Abstract

The purpose of this study was to determine the alterations in ovine trabecular bone induced by a combination of ovariectomy and steroid treatment. Twenty-four female skeletally mature Merino sheep were randomly assigned to ovariectomy alone (OVX), ovariectomy combined with glucocorticoid treatment for 6 months (OVX + GC), or no treatment (control). Biopsies of trabecular bone were harvested 6 and 12 months after the beginning of the study from the proximal tibia. The biopsies were scanned for apparent bone mineral density by quantitative computed tomography and were mechanically tested. Three-dimensional bone reconstructions were obtained by micro-computed tomography. Trabecular bone from the OVX + GC animals had a markedly reduced apparent bone mineral density (27% less than control), bone volume (34%), and elastic modulus (36%) at 6 months. At 12 months, the reductions in apparent bone mineral density (33%), bone volume (37%), and elastic modulus (62%) appeared to be even more pronounced. Ovariectomy alone did not result in a perceptible reduction in any parameter. The combination of ovariectomy and glucocorticoid treatment in sheep resulted in a successful induction of substantial loss of trabecular bone and thus may serve as a large-animal model for osteopenic trabecular bone for the development and testing of orthopedic implants and techniques under osteoporotic conditions.