Glucocorticoid Treatment of Ovariectomized Sheep Affects Mineral Density, Structure, and Mechanical Properties of Cancellous Bone

Abstract

Thus far, orthopedic research lacks a suitable animal model of osteoporosis. In OVX sheep, 6 months of steroid exposure reduced bone density and mechanical competence. Bone properties and bone formation did not recover for another 6 months. Therefore, steroid-treated OVX sheep may serve as a large animal model for osteopenic bone. Introduction:The purpose of this study was to explore the effects of glucocorticoid treatment on cancellous bone density, microarchitecture, biomechanics, and formation of new bone. Materials and Methods: Sixteen ovariectomized merino sheep received either a 6-month glucocorticoid treatment (GLU; 0.45 mg/kg methylprednisolone) or were left untreated (control). Cancellous bone biopsy specimens from the tibia were harvested 6 months after ovariectomy. After 12 months, the animals were killed, and biopsy specimens were obtained from the contralateral tibia and the lumbar spine. All biopsy specimens were scanned for apparent bone mineral density by peripheral quantitative computed tomography (pQCT) and tested mechanically in uniaxial compression. Three-dimensional bone reconstructions were obtained by microcomputed tomography. Formation of new bone was analyzed using histologies of the femoral condyles. Results: After 6 months, mineral density (Ϫ19%) and mechanical competence (Ϫ45%) were reduced by glucocorticoid treatment (p Ͻ 0.1). BV/TV (Ϫ21%; p Ͻ 0.01) and trabecular thickness (Ϫ20%; p ϭ 0.01) declined, whereas BS/BV increased (24%; p ϭ 0.01). After 12 months, mineral density (Ϫ33%) and mechanical properties (Ϫ55%) were reduced even more profoundly (p Ͻ 0.05). Also, the structural parameters (BS/BV and Tb.Th.) still seemed to be affected by glucocorticoid treatment (p Ͻ 0.05). New bone formation, assessed by measurement of osteoid surface, was markedly reduced (Ϫ63%, p Ͻ 0.1) by glucocorticoid treatment. The differences between groups were generally more pronounced at the tibia and the femur than at the spine. Conclusion: The effects of short-term high-dose steroid administration on bone mineral in this animal model were comparable with those observed in humans after long-term corticoid treatment. Reduction in bone quality and bone formation rate persisted after the cessation of steroid administration. Glucocorticoid treatment of ovariectomized sheep may therefore serve as a large animal model for steroid-induced osteopenia.

The experimental osteoporosis in sheep – clinical approach

“…The parameters specifying changes of bone density (BV/TV, Tb.N, Tb.Th, Conn.Dn) and changes of porosity (Po.tot, Po.cl, Po.op, BS/BV) were determined. Similar parameters were monitored by Turner et al (1995) and Schorlemmer et al (2003). By analysing the obtained results, it can be observed that in the group of sheep treated with ovariectomy (PC) in relation to the negative control group (NC), based on the samples from the proximal femoral bone epiphyses, the group is characterised by a general increase in bone density parameters and a decrease in porosity, including total density of 15%.…”

“…Guided by other researchers' insights, examinations of radiological density of bones were also made in the group of sheep treated with steroidal medications (SC). Schorlemmer et al (2003) in their studies proved that treatment with steroidal medications for a long time would lead to secondary osteoporosis and would intensify changes taking place in the skeletal system. After a six-month application of glucocorticosteroids, a biopsy of tibial bones showed a decrease in bone density of 19%.…”

Evaluation of bipolar hemiarthroplasty for the treatment of steroid-induced osteonecrosis of the femoral head

“…Moreover, steroid-induced ONFH in young patients directly inhibits osteoblastic bone formation and stimulates increased bone resorption [24,25]. Kindsfater et al [10] reported prosthesis survival rates up to eight years in a general group of patients with osteoarthritis, with intermediate-term clinical results of BHA being satisfactory independent of age and not related to underlying diagnosis.…”

Validation of the sheep as a large animal model for the study of vertebral osteoporosis

“…Bone loss has been reported previously at various skeletal sites in sheep following ovariectomy [5,16,27,28,42], chronic steroid therapy [7,10] or dietary manipulation [9], but in none of these studies, could these animals be classified as osteoporotic by standard definitions. Other studies have implemented combination treatments to induce osteoporosis in sheep [13, 14, 19-21, 29, 32, 33] and although such treatments have resulted in further bone loss compared to the single treatments, lumbar spine BMD was either not reduced significantly [13,29,32,33] or it did not achieve the minimum of 25% bone loss [20,21] required to classify them as osteoporotic. The current study was undertaken in an attempt to achieve more substantial bone loss in the lumbar spine of domestic sheep, a large animal that is frequently used for experimental studies.…”