Inhibition of cortical and cancellous bone formation in glucocorticoid-treated OVX sheep

Abstract

Introduction: Little is known about the effects of steroids on cortical bone. The purpose of this study was to explore the effects of glucocorticoid treatment on cortical bone density, strength, and formation of new bone in ovariectomized sheep and to compare it to cancellous bone. Materials and methods: Sixteen ovariectomized merino sheep either received a 6-month glucocorticoid treatment (GLU; 0.45 mg/kg/day Methylprednisolone s.c.) or were left untreated (control). After 2 and 4 months, newly formed bone was labeled by the administration of calceingreen and Tetracycline-hydrochloride. After 12 months, the animals were sacrificed and cortical specimens were obtained from the tibial diaphysis. Cancellous bone specimens were harvested from the proximal tibia. All specimens were scanned for apparent BMD by pQCT and tested mechanically. Formation of new bone was analyzed using histological slices of the femoral condyles and cross-sections of the mid-diaphysis of the tibia. Results: The intracortical formation of new bone in glucocorticoid-treated sheep was 70% lower after 2 months and 80% lower after 4 months. Six months after the termination of the steroid administration, the active bone area was 20% lower than in the control group. Cortical width and cortical bone area were reduced by 7–8% and marrow area increased by 8% in steroid-treated animals compared to control animals. Neither cortical apparent bone mineral density nor biomechanical parameters of cortical bone specimens differed between the groups. Cancellous bone formation in steroid-treated animals declined by 68% after 2 months and by 90% after 4 months. After 1 year, cancellous bone formation was reduced by 38% compared to control. The apparent cancellous bone mineral density and cancellous bone compressive stiffness were reduced by 34% and 55%, respectively. Conclusion: A six-month glucocorticoid treatment of ovariectomized sheep resulted in a substantial reduction of bone formation both in cortical and in cancellous bone and reduced cortical width by increased endosteal resorption. Beyond changes in cancellous bone, impaired cortical bone remodeling may add to the increased fracture risk at the hip or the distal radius in patients treated with steroids.