OVARIECTOMISED AND LONG TERM INDUCED (OLI) RAT MODEL FOR PRECLINICAL ASSESSMENT OF OSTEOPOROTIC THERAPEUTICS.
Abstract
Osteoporosis affects millions of people, especially the aged population and numerous researchers focus on developing novel pharmacotherapeutic agents for the prevention and treatment of osteoporosis. Animal models have become an indispensable part of the pre-clinical assessment of osteoporotic therapeutics and rat models have been widely preferred. The majority of studies so far reported have used young or short-term induced rat models, but they do not mimic the pathological condition in senile osteoporosis. Hence this study has focused on developing an ovariectomised and long term induced (OLI) aged rat model for the preclinical assessment studies. Long term osteoporosis was induced in Wistar rats by ovariectomy followed by the maintenance period of 10 months. Histological evaluation and Micro-CT analysis substantiated the extensive bone loss in the OLI rats compared to Control and ovariectomised and short term induced (OSI) rat model. OLI rats also exhibited impairment in the healing of 3 x 1.5 mm femoral cortical bone defect even after 8 weeks of surgery. Histomorphometric analyses indicated that OLI rats exhibited a poor regeneration efficiency (RE) ratio of 0.67 ± 0.2 compared to 0.95 ± 0.1 in the Control group. Chronic bone loss in the OLI rats together with the impaired osteogenic efficacy has been successfully demonstrated which proposes OLI rat models to be utilized for investigating novel pharmacotherapy’s or novel biomaterials intended for osteoporotic applications.
Keywords: Osteoporosis, Rat osteoporotic model, long-term osteoporosis induction, oestrogen deficiency.Â
Â
DOI
https://doi.org/10.22270/jddt.v7i2.1400References
Kanis JA, Borgstrom F, De Laet C, Johansson H, Johnell O, Jonsson B, et al. Assessment of fracture risk. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2005; 16(6):581–9.
Colón-Emeric CS, Saag KG. Osteoporotic fractures in older adults. Best Pract Res Clin Rheumatol. 2006 Aug; 20(4):695–706.
Das S, Crockett JC. Osteoporosis - a current view of pharmacological prevention and treatment. Drug Des Devel Ther. 2013; 7:435–48.
Omi N, Ezawa I. [Animal models for bone and joint disease. Low calcium diet-induced rat model of osteoporosis]. Clin Calcium. 2011 Feb; 21(2):173–80.
Lasota A, Danowska-Klonowska D. Experimental osteoporosis--different methods of ovariectomy in female white rats. Rocz Akad Med W Białymst 1995. 2004; 49 Suppl 1:129–31.
Marie PJ, Kassem M. Extrinsic mechanisms involved in age-related defective bone formation. J Clin Endocrinol Metab. 2011 Mar; 96(3):600–9.
Jiang G, Matsumoto H, Fujii A. Mandible bone loss in osteoporosis rats. J Bone Miner Metab. 2003; 21(6):388–95.
Kubo T, Shiga T, Hashimoto J, Yoshioka M, Honjo H, Urabe M, et al. Osteoporosis influences the late period of fracture healing in a rat model prepared by ovariectomy and low calcium diet. J Steroid Biochem Mol Biol. 1999 Mar;68(5–6):197–202.
Rabbits F working group on revision of guidelines for health monitoring of rodents and, (Convenor) MM, Berard M, Feinstein R, Gallagher A, Illgen-Wilcke B, et al. FELASA recommendations for the health monitoring of mouse, rat, hamster, guinea pig and rabbit colonies in breeding and experimental units. Lab Anim. 2014 Jul 1;48(3):178–92.
Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG, National Centre for the Replacement, Refinement and Reduction of Amimals in Research. Animal research: reporting in vivo experiments--the ARRIVE guidelines. J Cereb Blood Flow Metab Off J Int Soc Cereb Blood Flow Metab. 2011 Apr;31(4):991–3.
Mohan BG, Shenoy SJ, Babu SS, Varma HK, John A. Strontium calcium phosphate for the repair of leporine (Oryctolagus cuniculus) ulna segmental defect. J Biomed Mater Res A. 2013 Jan; 101(1):261–71.
Habermann B, Kafchitsas K, Olender G, Augat P, Kurth A. Strontium Ranelate Enhances Callus Strength More Than PTH 1-34 in an Osteoporotic Rat Model of Fracture Healing. Calcif Tissue Int. 2010 Jan; 86(1):82–9.
Comelekoglu U, Bagis S, Yalin S, Ogenler O, Yildiz A, Sahin NO, et al. Biomechanical evaluation in osteoporosis: ovariectomized rat model. Clin Rheumatol. 2007 Mar; 26(3):380–4.
Kerschan-Schindl K, Mikosch P, Obermayer-Pietsch B, Gasser R, Dimai H-P, Fahrleitner-Pammer A, et al. Current Controversies in Clinical Management of Postmenopausal Osteoporosis. Exp Clin Endocrinol Diabetes. 2014 May 16; 122(08):437–44.
Syed FA, Melim T. Rodent models of aging bone: an update. Curr Osteoporos Rep. 2011 Dec; 9(4):219–28.
Dennison E, Cole Z, Cooper C. Diagnosis and epidemiology of osteoporosis. Curr Opin Rheumatol. 2005 Jul;17(4):456–61.
Kiebzak GM, Smith R, Howe JC, Gundberg CM, Sacktor B. Bone status of senescent female rats: chemical, morphometric, and biomechanical analyses. J Bone Miner Res Off J Am Soc Bone Miner Res. 1988 Aug; 3(4):439–46.
Fukuda S, Iida H. Age-related changes in bone mineral density, cross-sectional area and the strength of long bones in the hind limbs and first lumbar vertebra in female Wistar rats. J Vet Med Sci Jpn Soc Vet Sci. 2004 Jul; 66(7):755–60.
Vasikaran SD. Utility of biochemical markers of bone turnover and bone mineral density in management of osteoporosis. Crit Rev Clin Lab Sci. 2008; 45(2):221–58.
Sokoll LJ, Dawson-Hughes B. Effect of menopause and aging on serum total and ionized calcium and protein concentrations. Calcif Tissue Int. 1989 Mar; 44(3):181–5.
Compston J. Age-Related Changes in Bone Remodelling and Structure in Men: Histomorphometric Studies. J Osteoporos. 2011; 2011:1–4.
Laib DA, Barou O, Vico L, Lafage-Proust MH, Alexandre C, Rügsegger P. 3D micro-computed tomography of trabecular and cortical bone architecture with application to a rat model of immobilisation osteoporosis. Med Biol Eng Comput. 2000 May; 38(3):326–32.
Majumdar S, Genant HK, Grampp S, Newitt DC, Truong V-H, Lin JC, et al. Correlation of Trabecular Bone Structure with Age, Bone Mineral Density, and Osteoporotic Status: In Vivo Studies in the Distal Radius Using High Resolution Magnetic Resonance Imaging. J Bone Miner Res. 1997 Jan 1; 12(1):111–8.
Meyer RA, Tsahakis PJ, Martin DF, Banks DM, Harrow ME, Kiebzak GM. Age and ovariectomy impair both the normalization of mechanical properties and the accretion of mineral by the fracture callus in rats. J Orthop Res Off Publ Orthop Res Soc. 2001 May; 19(3):428–35.
Giannoudis P, Tzioupis C, Almalki T, Buckley R. Fracture healing in osteoporotic fractures: is it really different? A basic science perspective. Injury. 2007 Mar; 38 Suppl 1:S90-99.
Oliver RA, Yu Y, Yee G, Low AK, Diwan AD, Walsh WR. Poor histological healing of a femoral fracture following 12 months of oestrogen deficiency in rats. Osteoporos Int J Establ Result Coop Eur Found Osteoporos Natl Osteoporos Found USA. 2013 Oct; 24(10):2581–9.
Syftestad GT, Urist MR. Bone aging. Clin Orthop. 1982 Feb ; (162):288–97.
Shapiro F. Bone development and its relation to fracture repair. The role of mesenchymal osteoblasts and surface osteoblasts. Eur Cell Mater. 2008; 15:53–76.
Namkung-Matthai H, Appleyard R, Jansen J, Hao Lin J, Maastricht S, Swain M, et al. Osteoporosis influences the early period of fracture healing in a rat osteoporotic model. Bone. 2001 Jan; 28(1):80–6.
Chandran, S., Suresh B., Hari Krishanan VS, Varma, H.K., John A.. Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model. J. Biomater. Appl. 885328216647197. doi:10.1177/0885328216647197
Published
Abstract Display: 774 
PDF Downloads: 796 How to Cite
Issue
Section
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.