A sheep model for fracture treatment in osteoporotic bone

SummaryThe histomorphometrical cancellous bone parameters of osteoporotic ewes were examined to establish a large animal model for the investigation of fracture treatment and healing in osteoporotic bone. Eighteen animals were divided into 2 groups. Group 1 (n = 8, age 3 to 5 years) served as an untreated control. In Group 2 (n = 10, age 7 to 9 years) osteoporosis was induced by means of ovariectomy, methylprednisolone application (average dose 160 mg/week) and Ca./Vit.D restricted diet during 7 months. Biopsies from iliac crest, femoral head and lumbar spine were harvested. Structural parameters from the biopsies were determined using μCT. In order to investigate static and dynamic parameters of bone remodelling, undecalcified sections were digitized and evaluated by means of image analysing software. Morphologically, bone area and trabecular thickness were reduced in osteoporotic sheep. Bone perimeter (−20%), trabecular number (−16%) and separation (+39%) showed a significant change in the iliac crest. The structure model index indicated a shift from the plate-to the rodmodel. At different skeletal sites of osteoporotic sheep bone resorption was significantly increased (250-675%), and bone formation significantly decreased (77-89%). Osteoid thickness (O.Th) was reduced (28-62%). In osteoporotic sheep the mean length of single labels was significantly shortened (64-73%) and the mineralising surface showed a significant decrease (80-92%). The mineralisation of the osteoid was comparable to the control group. The histomorphometrical changes in this sheep model of osteoporosis are comparable to the human situation of a combined post-menopausal and steroid-induced osteoporosis.

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Sheep Model for Fracture Treatment in Osteoporotic Bone: A Pilot Study About Different Induction Regimens

Journal of Orthopaedic Trauma ◽

10.1097/00005131-200011000-00008 ◽

2000 ◽

Vol 14 (8) ◽

pp. 565-566 ◽

Cited By ~ 2

Author(s):

Thomas A. Einhorn

Keyword(s):

Pilot Study ◽

Osteoporotic Bone ◽

Fracture Treatment ◽

Sheep Model

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Analysis of microscopic bone properties in an osteoporotic sheep model: a combined biomechanics, FE and ToF-SIMS study

Journal of The Royal Society Interface ◽

10.1098/rsif.2018.0793 ◽

2019 ◽

Vol 16 (151) ◽

pp. 20180793 ◽

Cited By ~ 3

Author(s):

R. Müller ◽

A. Henss ◽

M. Kampschulte ◽

M. Rohnke ◽

A. C. Langheinrich ◽

...

Keyword(s):

Biomechanical Testing ◽

Tissue Level ◽

Osteoporotic Bone ◽

Compression Tests ◽

Micro Computed Tomography ◽

Deficient Diet ◽

Element Analysis ◽

Sheep Model ◽

Tissue Properties ◽

Bone Properties

The present study deals with the characterization of bone quality in a sheep model of postmenopausal osteoporosis. Sheep were sham operated ( n = 7), ovariectomized ( n = 6), ovariectomized and treated with deficient diet ( n = 8) or ovariectomized, treated with deficient diet and glucocorticoid injections ( n = 7). The focus of the study is on the microscopic properties at tissue level. Microscopic mechanical properties of osteoporotic bone were evaluated by a combination of biomechanical testing and mathematical modelling. Sample stiffness and strength were determined by compression tests and finite-element analysis of stress states was conducted. From this, an averaged microscopic Young’s modulus at tissue level was determined. Trabecular structure as well as mineral and collagen distribution in samples of sheep vertebrae were analysed by micro-computed tomography and time-of-flight secondary ion mass spectrometry. In the osteoporotic sheep model, a disturbed fibril structure in the triple treated group was observed, but bone loss only occurred in form of reduced trabecular number and thickness and cortical decline, while quality of the residual bone was preserved. The preserved bone tissue properties in the osteoporotic sheep model allowed for an estimation of bone strength which behaves similar to the human case.

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A sheep model for fracture treatment in osteoporosis: Benefits of the model versus animal welfare

Laboratory Animals ◽

10.1258/la.2007.007001 ◽

2008 ◽

Vol 42 (4) ◽

pp. 453-464 ◽

Cited By ~ 29

Author(s):

M Egermann ◽

J Goldhahn ◽

R Holz ◽

E Schneider ◽

C A Lill

Keyword(s):

Side Effects ◽

Animal Welfare ◽

Combined Treatment ◽

Biological Response ◽

Biomechanical Properties ◽

Osteoporotic Bone ◽

Antibody Testing ◽

Mineral Density ◽

Deficient Diet ◽

Sheep Model

Summary Animal models are necessary to evaluate new options for the treatment of fractures in osteoporotic bone. They permit both the biological response of a living system and the influence of the pathological processes to be taken into account. A sheep model for osteoporosis was established by combining oestrogen deficiency, calcium and vitamin D-deficient diet with steroid medication. Bone mineral density (BMD) was reduced by >30% after 12 weeks of combined treatment. Osteoporosis similar to the human situation with corresponding changes in the micro-architecture and mechanical properties of bone was observed. This publication focuses on the impressive results obtained with the model and contrasts them with considerations of animal welfare. Considerable side-effects associated with steroid medication became manifest. Animals in the treatment groups showed signs of infection of various degrees due to the immunosuppressive effect of the medication. The infections were mostly caused by Corynebacterium pseudotuberculosis. Antibody testing revealed a 100% prevalence of infection in this breed of sheep. A modification of the steroid treatment, i.e. less-frequent injections, reduced the incidence of side-effects. This sheep model shows a significant and reproducible reduction in cancellous BMD of >30%, including relevant changes in biomechanical properties and increased fracture risk. However, the severity of the side-effects cannot be overlooked. The model must be improved if it is to be used in the future. Options to reduce the side-effects are discussed.

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