title: Bone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis.
abstract: In a pilot experiment comparing four different modalities for inducing osteoporosis in the sheep, a combination of ovariectomy, calcium/vitamin D-restricted 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 respect to mechanical and morphometric bone properties.
authors.affiliation: AO Research Institute Davos, Switzerland. christoph.lill@ao-asif.ch
authors.forename: C A
authors.initials: CA
authors.lastname: Lill
authors.forename: U V
authors.initials: UV
authors.lastname: Gerlach
authors.forename: C
authors.initials: C
authors.lastname: Eckhardt
authors.forename: J
authors.initials: J
authors.lastname: Goldhahn
authors.forename: E
authors.initials: E
authors.lastname: Schneider
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000033:anatomy & histology / Q000187:drug effects*; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D005598:Fractures, Spontaneous / Q000209:etiology; D005938:Glucocorticoids / Q000009:adverse effects / Q000097:blood; D008775:Methylprednisolone / Q000009:adverse effects / Q000097:blood; D023421:Models, Animal; D010024:Osteoporosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000209:etiology*; D010052:Ovariectomy; D012756:Sheep; D013048:Specimen Handling; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D005938:Glucocorticoids; D008775:Methylprednisolone