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Validation of the sheep as a large animal model for the study of vertebral osteoporosis

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Abstract

Rats have long been the animal of choice for research in the field of osteoporosis. In the search for a complementary large animal model the sheep appears useful but hitherto the extent of bone loss from the spine has failed to reach a level that is generally accepted as osteoporotic in humans. Osteoporosis was induced in ten sheep using ovariectomy, low calcium diet and steroid injection for 6 months. Bone samples of iliac crest (IC), lumbar spine (LS), and proximal femur (PF) from the osteoporotic sheep were compared with those from four normal sheep using densitometry, histomorphometry, biochemistry and basic mechanical testing. The differences were examined using an analysis of variance with Tukey–Kramer test. Overall, the bone mineral density at LS and PF decreased more than 25% after treatment. Trabecular bone volume decreased by 29.2, 33.4 and 42.6% in IC, LS and PF, respectively. The failure load of the LS in axial compression was reduced to 2,003 from 6,140 N. The extent of bone loss was sufficient to categorise these sheep as osteoporotic although the pattern of bone loss varied between sites. Reduced mechanical competence in LS confirmed the suitability of this model for evaluation of potential treatments for osteoporosis.

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Acknowledgments

The authors thank Dr Ian Parkinson for assistance in statistical analysis; Mr Adnan Mulaibrahimovic for the ash weight analyses; the staff of the Veterinary Services Division, IMVS for animal husbandry; Ms Olga Theodorakakos for assistance with bone histomorphometry and Dr Nick Burgan for advice and assistance with mechanical testing.

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Authors and Affiliations

  1. The Adelaide Centre for Spinal Research, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, Adelaide, SA, 5000, Australia

    M. R. Zarrinkalam, H. Beard & R. J. Moore

  2. Hanson Institute, Institute of Medical and Veterinary Science, PO Box 14, Rundle Mall, Adelaide, SA, 5000, Australia

    M. R. Zarrinkalam, H. Beard & R. J. Moore

  3. Department of Nuclear Medicine and Bone Densitometry, Royal Adelaide Hospital, Adelaide, Australia

    C. G. Schultz

  4. Discipline of Pathology, University of Adelaide, Adelaide, Australia

    R. J. Moore

Authors
  1. M. R. Zarrinkalam
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  2. H. Beard
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  3. C. G. Schultz
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  4. R. J. Moore
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Correspondence to M. R. Zarrinkalam.

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The contribution of the second author “H. Beard” in this paper was as equal to the contribution of the first author “M. R. Zarrinkalam”.

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Zarrinkalam, M.R., Beard, H., Schultz, C.G. et al. Validation of the sheep as a large animal model for the study of vertebral osteoporosis. Eur Spine J 18, 244–253 (2009). https://doi.org/10.1007/s00586-008-0813-8

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  • DOI: https://doi.org/10.1007/s00586-008-0813-8

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