Bone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis

Lill, C. A.; Gerlach, U. V.; Eckhardt, C.; Goldhahn, J.; Schneider, E.

Affiliations

¹AO Research Institute Davos, Clavadelerstrasse, Davos, Switzerland

²Department of Orthopaedic Surgery, University of Heidelberg, Schlierbacher Landstrasse 200a, Heidelberg, Germany

Abstract and keywords

In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy, calcium/vitamin Drestricted diet and steroid administration was found to generate the highest decrease in bone mineral density (BMD). The aim of the present study was to quantify the outcome of this triple treatment in an animal model of osteoporosis in terms of alteration in bone mass, bone structure and bone mechanics. A total of 32 sheep were divided into two equal groups. Group 1 (age 3–5 years) was used as a normal control. Group 2 (age 7–9 years) was ovariectomized, fed a calcium/vitamin D-restricted diet and injected with methylprednisolone (MP) over 7 months (22 weeks MP solution, 6 weeks MP suspension). The BMD at the distal radius and tibia was determined preoperatively and at repeated intervals bilaterally using quantitative computed tomography. Steroid blood levels were determined 4 and 24 h after selected injections. BMD was measured at L3 and L4 after 7 months. Biopsies were taken from iliac crests, vertebral bodies and femoral heads, and bone structure parameters investigated by three-dimensional micro-CT. Compressive mechanical properties of cancellous bone were determined from biopsies of vertebral bodies and femoral heads. After 7 months of osteoporosis induction the BMD of cancellous bone decreased 36 + 3% in the radius and 39 + 4% in the tibia. Steroid blood levels 24 h after injection of MP suspension were significantly higher than after injection of MP solution. Changes in structural parameters of cancellous bone from the iliac crest, lumbar spine and femoral head in group 2 indicated osteoporosis-associated changes. In group 2 there was a significant reduction in BMD of the lumbar spine and a significant reduction in stiffness and failure load in compression testing of biopsies of lumbar vertebrae. In sheep, changes in the structural parameters of bone such as trabecular number and separation during osteoporosis induction are comparable to the human situation. The sheep model presented seems to meet the criteria for an osteoporosis model for fracture treatment with respec

Keywords: Animal model; Mechanical testing; Micro-CT; Osteoporosis; Osteoporosis induction; Sheep

Links

DOI: 10.1007/s001980200047

PubMed: 12086352

WoS: 000176220900010

History

Received: 2001-05-04

Accepted: 2001-12-06

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Cited By (3)

Year	Entry
2007	Eswaran SK, Allen MR, Burr DB, Keaveny TM. A computational assessment of the independent contribution of changes in canine trabecular bone volume fraction and microarchitecture to increased bone strength with suppression of bone turnover. J Biomech. 2007;40(15):3424-3431.
2012	Liu X, Lei W, Wu Z, Cui Y, Han B, Fu S, Jiang C. Effects of glucocorticoid on BMD, micro-architecture and biomechanics of cancellous and cortical bone mass in OVX rabbits. Med Eng Phys. January 2012;34(1):2-8.
2008	Xu Q. Evaluation of Bone Quality Using Novel Image Analyses and Mechanical Testing Methods [PhD thesis]. Louisville, KY: University of Louisville; August 2008.