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.

Review of Nonprimate, Large Animal Models for Osteoporosis Research

“…(90) 3D histomorphometric analysis of ovine tibial bone biopsies yielded data showing only slight reductions in trabecular parameters between OVX and sham animals; however, OVX sheep administered glucocorticoids did present with significant cancellous bone loss.…”

Microarchitectural adaptations in aging and osteoarthrotic subchondral bone issues

“…Right: A typical stress-strain curve from a destructive test. Ultimate stress and ultimate strain are derived from the first maximum of the curve, Young's modulus is determined as the tangent to the point on the loading curve intersecting the 0.6% strain line, failure energy (fracture toughness) as the area underneath the compression curve between zero strain and ultimate strain (IV,V) [7]. The linear portion of the stress strain curve is called the elastic region.…”

“…Micro-CT in vitro scanning has been widely used for bone samples obtained from all sizes of animal, such as mouse [2,[75][76][77], rat [175], guinea pig [44], rabbit [52,149], dog [28,46,85,101,102], pig [106,107] sheep [7,37], and human [29,51,[64][65][66][67]. In vivo micro-CT imaging can now also be applied to all sizes of animals depending on the location to be scanned.…”

A reversal phase arrest uncoupling the bone formation and resorption contributes to the bone loss in glucocorticoid treated ovariectomised aged sheep

“…In an attempt to mimic the clinical situation in osteoporotic patients researchers have used sheep models in which osteoporosis was induced by a combination of ovariectomy (OVX) and glucocorticoid treatment [6][7][8]. Nevertheless, the underlying cellular mechanisms responsible for the bone loss in those sheep models have been considered different from cellular mechanism responsible for osteoporotic bone loss in humans, questioning its relevance to human osteoporosis [6,9,10]. Furthermore, most of these studies focused, mainly on microarchitectural changes such as bone mineral density, trabecular thickness (Tb.Th.)…”