DOS BULLETIN - Dansk Ortopædisk Selskab

2010-378_DOS nr. 3 2010 29/09/10 10:08 Side 128
The effects of glucocorticoid on microarchitecture,
collagen, mineral and mechanical properties of sheep
femur cortical bone –
Validation of large animal model for tissue engineering
and biomaterial research
Ming Ding, Carl Christian Danielsen, Søren Overgaard
Orthopaedic Research Unit, Odense University Hospital;
Institute of Anatomy, University of Aarhus
Background: Osteopenia in sheep has been successfully induced by glucocorticoid
treatment and the changes in properties of cancellous bone were comparable
with those observed in humans after long-term glucocorticoid treatment.
However, the influence on cortical bone has not been thoroughly elucidated.
Purpose: This study aimed to investigate the influence of glucocorticoid on
sheep cortical bone after long-term treatment. Specifically, we quantify the
microarchitecture, mechanical properties, collagen and mineral quality of sheep
cortical bone. We hypothesized that glucocorticoid treatment also had significant
influences on cortical bone that might increase risk of fracture.
Methods: In this study, 18 female skeletal mature sheep were randomly allocated
into 3 groups of 6 each. Group 1 (glucocorticoid-1) received prednisolone
treatment (0.60 mg/kg/day, 5 times weekly) for 7 months. Group 2 (glucocorticoid-2)
received the same treatment regime followed by observation of 3 months
without treatment. Group 3 was left untreated and served as the controls. All
sheep received restricted diet with low calcium and phosphorus. At sacrifice,
cortical bone samples from the femur midshaft of sheep were harvested, micro-
CT scanned and tested in 3 point bending and in tensile. Bone collagen and mineral
were determined.
Findings: Cortical porosity was significantly increased in the glucocorticoid-2
compared with the glucocorticoid-1 and the controls. Apparent density was significantly
decreased in the glucocorticoid-2 compared with the glucocorticoid-
1. Collagen content was significantly increased in the glucocorticoid-2 compared
with the glucocorticoid-1 and the controls. Bone mineral content did not
differ between the groups. Neither the three-point bending mechanical properties,
nor the tensile mechanical properties differed significantly between the
groups, while there was a trend towards decreasing bending mechanical properties
in the glucocorticoid-2.
Conclusion: In conclusion, 7 months glucocorticoid treatment with malnutrition
had significant impact on cortical microarchitecture of sheep femur midshaft.
These changes occurred particularly 3 months after the glucocorticoid cessation
suggesting a delayed effect of glucocorticoid on cortical bone. Thus, changes in
cortical bone beyond cancellous bone might further increase fracture risk.
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