Glucocorticoid treatment of ovariectomized sheep affects mineral density, structure, and mechanical properties of cancellous bone.
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.


BACKGROUND
The purpose of this study was to explore the effects of glucocorticoid treatment on cancellous bone density, microarchitecture, biomechanics, and formation of new bone.


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 (-19%) and mechanical competence (-45%) were reduced by glucocorticoid treatment (p < 0.1). BV/TV (-21%; p < 0.01) and trabecular thickness (-20%; p = 0.01) declined, whereas BS/BV increased (24%; p = 0.01). After 12 months, mineral density (-33%) and mechanical properties (-55%) were reduced even more profoundly (p < 0.05). Also, the structural parameters (BS/BV and Tb.Th.) still seemed to be affected by glucocorticoid treatment (p < 0.05). New bone formation, assessed by measurement of osteoid surface, was markedly reduced (-63%, p < 0.1) by glucocorticoid treatment. The differences between groups were generally more pronounced at the tibia and the femur than at the spine.


CONCLUSIONS
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.
Schorlemmer
Sandra
S
Institute of Orthopaedic Research and Biomechanics, University of Ulm, Ulm, Germany.
Gohl
Christine
C
Iwabu
Shohei
S
Ignatius
Anita
A
Claes
Lutz
L
Augat
Peter
P
D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005269:Femur / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D023421:Models, Animal; D010024:Osteoporosis / Q000188:drug therapy; D010052:Ovariectomy; D012756:Sheep; D013131:Spine / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D013977:Tibia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology
D005938:Glucocorticoids