Skip to main content

Advertisement

Log in

Characterization of a new experimental model of osteoporosis in rabbits

  • ORIGINAL ARTICLE
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

To characterize an experimental model of osteoporosis in rabbits induced either by ovariectomy (OVX), glucocorticoids, or by a combination of both. Thirty-five rabbits were randomly allocated into five groups: bilateral OVX, daily methylprednisolone hemisuccinate (MPH) injections at a 1.5 mg/kg/day dose for 4 consecutive weeks (MPH group), or variable dose of MPH between 0.5 and 2 mg/kg/day in combination with OVX (OVX + MPH at low, medium, and high dose). Twenty-two animals were killed 6 weeks after OVX, and 13 were killed 16 weeks later. Dual-energy X-ray absorptiometry was obtained at baseline and 6 and 16 weeks after OVX. High-resolution magnetic resonance imaging (MRI) was carried out at 0 and 6 weeks after OVX. Glucose, total cholesterol, triglyceride, and oestradiol blood levels before and 16 weeks after OVX were determined. Bone mineral density (BMD) decreased significantly at lumbar spine in MPH and OVX + MPH medium-dose groups, and at global knee and subchondral bone of the knee in MPH, OVX + MPH low- and medium-dosage groups (P < 0.05). BMD variations in OVX rabbits were not significant in any of the three anatomical locations analyzed. BMD variation 16 weeks after OVX was significant at lumbar spine and global knee in the OVX + MPH medium-dose group and only at global knee in the OVX + MPH low-dose group (P < 0.05). MRI did not show bone or cartilage changes. Osteoporosis can be induced experimentally in rabbits through isolated MPH or by a combination of OVX and medium dose corticosteroid for 4 weeks. OVX alone was not sufficient to induce osteoporosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. AS Turner (2001) ArticleTitleAnimal models of osteoporosis-necessity and limitations Eur Cell Mater 1 66–81 Occurrence Handle14562261 Occurrence Handle1:CAS:528:DC%2BD3MXnsFyrsLw%3D

    PubMed  CAS  Google Scholar 

  2. RT Turner A Maran S Lotinun T Hefferan GL Evans M Zhang JD Sibonga (2001) ArticleTitleAnimal models for osteoporosis Rev Endocr Metab Disord 2 117–127 Occurrence Handle11704974 Occurrence Handle10.1023/A:1010067326811 Occurrence Handle1:CAS:528:DC%2BD3MXht1Wjt78%3D

    Article  PubMed  CAS  Google Scholar 

  3. AD Geddes (1996) Animal models of bone disease JP Bilezikian LG Raisz GA Rodan (Eds) Principles of Bone Biology Academic Press San Diego 1343–1354

    Google Scholar 

  4. DB Kimmel (2001) Animal models for in vivo experimentation in osteoporosis research R Marcus D Feldman J Kelsey (Eds) Osteoporosis, vol 2 Academic Press San Diego 29–47 Occurrence Handle10.1016/B978-012470862-4/50038-6

    Chapter  Google Scholar 

  5. DD Thompson HA Simmons CM Pirie HZ Ke (1995) ArticleTitleFDA Guidelines and animal models for osteoporosis Bone 17 IssueIDsuppl 4 125S–133S Occurrence Handle8579908 Occurrence Handle1:STN:280:DyaK287hvFWrsQ%3D%3D

    PubMed  CAS  Google Scholar 

  6. JB Rodgers MC Mounier-Faugere H Malluche (1993) ArticleTitleAnimal models for the study of bone loss after cessation of ovarian functions Bone (NY) 14 369–377 Occurrence Handle1:STN:280:DyaK3szntFyrtQ%3D%3D

    CAS  Google Scholar 

  7. Li Mosekilde (1995) ArticleTitleAssessing bone quality animal models in preclinical osteoporosis research Bone (NY) 17 IssueIDsuppl 4 343S–352S Occurrence Handle1:STN:280:DyaK287hvFaisA%3D%3D

    CAS  Google Scholar 

  8. DN Kalu (1991) ArticleTitleThe ovariectomized rat as a model of postmenopausal osteopenia Bone Miner 15 175–191 Occurrence Handle1773131 Occurrence Handle10.1016/0169-6009(91)90124-I Occurrence Handle1:STN:280:DyaK387islWrtg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  9. TJ Wronski CF Yen (1992) ArticleTitleThe ovariectomized rat as an animal model for postmenopausal bone loss Cell Mater 1 IssueIDsuppl 1 69–74

    Google Scholar 

  10. HM Frost WSS Jee (1992) ArticleTitleOn the rat model of human osteopenias and osteoporoses Bone Miner 18 227–236 Occurrence Handle1392696 Occurrence Handle10.1016/0169-6009(92)90809-R Occurrence Handle1:STN:280:DyaK3s%2FgsF2ktA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  11. E Newman AS Turner JD Wark (1995) ArticleTitleThe potential of sheep for the study of osteopenia: current status and comparison with other animal models Bone (NY) 16 277S–284S Occurrence Handle1:STN:280:DyaK2Mzlt1ejtQ%3D%3D

    CAS  Google Scholar 

  12. P Zarco C Maestre G Herrero-Beaumont E González R García-Hoyo FJ Navarro P Braquet J Egido (1992) ArticleTitleInvolvement of platelet-activating factor and tumor necrosis factor in the pathogenesis of joint inflammation in rabbits Clin Exp Immunol 88 318–323 Occurrence Handle1315229 Occurrence Handle1:CAS:528:DyaK38XktVGqsLk%3D Occurrence Handle10.1111/j.1365-2249.1992.tb03080.x

    Article  PubMed  CAS  Google Scholar 

  13. O Sánchez-Pernaute MJ López-Armada P Hernández I Palacios F Navarro J Martínez J Egido G Herrero-Beaumont (1997) ArticleTitleAntifibroproliferative effect of tenidap in chronic antigen-induced arthritis Arthritis Rheum 40 2147–2156 Occurrence Handle9416851 Occurrence Handle10.1002/art.1780401208

    Article  PubMed  Google Scholar 

  14. H Mori M Manabe Y Kurachi M Nagumo (1997) ArticleTitleOsteointegration of dental implants in rabbit bone with low mineral density J Oral Maxillofac Surg 55 351–361 Occurrence Handle9120698 Occurrence Handle10.1016/S0278-2391(97)90124-5 Occurrence Handle1:STN:280:DyaK2s3lsl2ktg%3D%3D

    Article  PubMed  CAS  Google Scholar 

  15. TE Southard KA Southard KE Krizan SL Hillis JW Haller J Keller MW Vannier (2000) ArticleTitleMandibular bone density and fractal dimension in rabbits with induced osteoporosis Oral Surg Oral Med Oral Pathol Oral Radiol Endod 89 244–249 Occurrence Handle10673664 Occurrence Handle1:STN:280:DC%2BD3c7jvFKgsA%3D%3D Occurrence Handle10.1067/moe.2000.102223

    Article  PubMed  CAS  Google Scholar 

  16. T Cao T Shirota M Yamazaki K Ohno KI Michi (2001) ArticleTitleBone mineral density in mandibles of ovariectomized rabbits Clin Oral Implants Res 12 604–608 Occurrence Handle11737104 Occurrence Handle10.1034/j.1600-0501.2001.120608.x Occurrence Handle1:STN:280:DC%2BD3MnptVWnsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  17. T Cao T Shirota K Ohno KI Michi (2004) ArticleTitleMineralized bone loss in partially edentulous trabeculae of ovariectomized rabbit mandibles J Periodont Res 39 37–41 Occurrence Handle14687226 Occurrence Handle10.1111/j.1600-0765.2004.00703.x Occurrence Handle1:STN:280:DC%2BD3sngs1ejsw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  18. V Gilsanz TF Roe DT Gibbens EE Schulz ME Carlson O Gonzalez MI Boechat (1988) ArticleTitleEffect of sex steroids on peak bone density of growing rabbits Am J Physiol Endocrinol Metab 255 E416–E421 Occurrence Handle1:CAS:528:DyaL1cXmt1aksbo%3D

    CAS  Google Scholar 

  19. S Castañeda R Largo E Calvo F Rodríguez ME Marcos Díaz Curiel G Herrero-Beaumont (2006) ArticleTitleBone mineral measurements of subchondral and trabecular bone in healthy and osteoporotic rabbits Skeletal Radiol 35 34–41 Occurrence Handle16247642 Occurrence Handle10.1007/s00256-005-0022-z

    Article  PubMed  Google Scholar 

  20. M Warman AL Boskey (1983) ArticleTitleEffect of high levels of corticosteroids on the lipids of the long bones of the mature rabbit Metab Bone Dis Relat Res 4 319–324 Occurrence Handle6621357 Occurrence Handle10.1016/S0221-8747(83)80006-X Occurrence Handle1:CAS:528:DyaL3sXls12rs78%3D

    Article  PubMed  CAS  Google Scholar 

  21. E Calvo I Palacios E Delgado J Ruiz-Cabello P Hernández O Sánchez-Pernaute J Egido G Herrero-Beaumont (2001) ArticleTitleHigh resolution MRI detects cartilage swelling at the early stages of experimental osteoarthritis Osteoarthritis Cartil 9 463–472 Occurrence Handle10.1053/joca.2001.0413 Occurrence Handle1:STN:280:DC%2BD3MvitVKhuw%3D%3D

    Article  CAS  Google Scholar 

  22. MR Simon (1984) ArticleTitleThe rat as an animal for the study of senile idiopathic osteoporosis Acta Anat (Basel) 119 248–250 Occurrence Handle1:STN:280:DyaL2c3ns1Olug%3D%3D

    CAS  Google Scholar 

  23. M Matsushita T Tsuboyama R Kasai H Okumura T Yamamuro K Higuchi K Higuchi A Kohno T Yonezu A Utani (1986) ArticleTitleAge-related changes in bone mass in the senescence-accelerated mouse (SAM) Am J Pathol 125 276–283 Occurrence Handle3789087 Occurrence Handle1:STN:280:DyaL2s%2FntlKmtA%3D%3D

    PubMed  CAS  Google Scholar 

  24. T Takeda (1999) ArticleTitleSenescence-accelerated mouse (SAM): a biogerontological resource in aging research Neurobiol Aging 20 105–110 Occurrence Handle10537019 Occurrence Handle10.1016/S0197-4580(99)00008-1 Occurrence Handle1:STN:280:DC%2BD3c%2FgsFCisw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  25. K Watanabe A Hishiya (2005) ArticleTitleMouse models of senile osteoporosis Mol Asp Med 26 221–231 Occurrence Handle10.1016/j.mam.2005.01.006

    Article  Google Scholar 

  26. SSJ Webster (1995) ArticleTitleAnimal models in the prevention and treatment of osteopenia: forward Bone (NY) 17 113S–114S

    Google Scholar 

  27. B Grardel B Sutter B Flautre E Viguier F Lavaste P Hardouin (1994) ArticleTitleEffects of glucocorticoids on skeletal growth in rabbits evaluated by dual-photon absorptiometry, microscopic connectivity and vertebral compressive strength Osteoporos Int 4 204–210 Occurrence Handle7949750 Occurrence Handle10.1007/BF01623240 Occurrence Handle1:STN:280:DyaK2M%2FjslSltw%3D%3D

    Article  PubMed  CAS  Google Scholar 

  28. RG Erben J Eberle K Stahr M Goldberg (2000) ArticleTitleAndrogen deficiency induces high turnover osteopenia in aged male rats: a sequential histomorphometric study J Bone Miner Res 15 1085–1098 Occurrence Handle10841177 Occurrence Handle10.1359/jbmr.2000.15.6.1085 Occurrence Handle1:CAS:528:DC%2BD3cXktFKhur0%3D

    Article  PubMed  CAS  Google Scholar 

  29. E Canalis (1996) ArticleTitleMechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis J Clin Endocrinol Metab 81 3441–3447 Occurrence Handle8855781 Occurrence Handle10.1210/jc.81.10.3441 Occurrence Handle1:CAS:528:DyaK28XmtlCmsbs%3D

    Article  PubMed  CAS  Google Scholar 

  30. RS Weinstein RL Jilka AM Parfitt SC Manolagas (1998) ArticleTitleInhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone J Clin Invest 102 274–282 Occurrence Handle9664068 Occurrence Handle1:CAS:528:DyaK1cXkslOktrc%3D

    PubMed  CAS  Google Scholar 

  31. RM Pereira AM Delany E Canalis (2001) ArticleTitleCortisol inhibits the differentiation and apoptosis of osteoblasts in culture Bone (NY) 28 484–490 Occurrence Handle1:CAS:528:DC%2BD3MXjtlChsLw%3D

    CAS  Google Scholar 

  32. RC Pereira AM Delany E Canalis (2002) ArticleTitleEffects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression Bone (NY) 30 685–691 Occurrence Handle1:CAS:528:DC%2BD38Xjtl2ltLc%3D

    CAS  Google Scholar 

  33. E Canalis JP Bilezikian A Angeli A Giustina (2004) ArticleTitlePerspectives on glucocorticoid-induced osteoporosis Bone (NY) 34 593–598 Occurrence Handle1:CAS:528:DC%2BD2cXisF2nt7c%3D

    CAS  Google Scholar 

  34. K Miyanishi T Yamamoto T Irisa G Motomura S Jingushi K Sueishi Y Iwamoto (2005) ArticleTitleEffects of different corticosteroids on the development of osteonecrosis in rabbits Rheumatology 44 332–336 Occurrence Handle15598709 Occurrence Handle10.1093/rheumatology/keh505 Occurrence Handle1:CAS:528:DC%2BD2MXhslSksLg%3D

    Article  PubMed  CAS  Google Scholar 

  35. T Yamamoto T Irisa Y Sugioka K Sueishi (1997) ArticleTitleEffect of pulse methylprednisolone on bone and marrow tissues. Corticosteroid-induced osteonecrosis in rabbits Arthritis Rheum 40 2055–2064 Occurrence Handle9365096 Occurrence Handle10.1002/art.1780401119 Occurrence Handle1:CAS:528:DyaK2sXns1ygsbo%3D

    Article  PubMed  CAS  Google Scholar 

  36. AW Eberhardt A Yeager-Jones HC Blair (2001) ArticleTitleRegional trabecular bone matrix degeneration and osteocyte death in femora of glucocorticoid-treated rabbits Endocrinology 142 1333–1340 Occurrence Handle11181552 Occurrence Handle10.1210/en.142.3.1333 Occurrence Handle1:CAS:528:DC%2BD3MXhsFemtbk%3D

    Article  PubMed  CAS  Google Scholar 

  37. L Mosekilde SE Weisbrode JA Safron HF Stills ML Jankowsky DC Ebert CC Danielsen CH Sogaard AF Franks ML Stevens (1993) ArticleTitleEvaluation of the skeletal effects of combined mild dietary calcium restriction and ovariectomy in Sinclair S-1 minipigs: a pilot study J Bone Miner Res 8 1311–1321 Occurrence Handle8266823 Occurrence Handle1:CAS:528:DyaK2cXktleru7s%3D Occurrence Handle10.1002/jbmr.5650081106

    Article  PubMed  CAS  Google Scholar 

  38. CA Lill AK Fluegel E Schneider (2002) ArticleTitleEffect of ovariectomy, malnutrition and glucocorticoid application on bone properties in sheep: a pilot study Osteoporos Int 13 480–486 Occurrence Handle12107662 Occurrence Handle10.1007/s001980200058 Occurrence Handle1:STN:280:DC%2BD38zmsFOrsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

  39. P Chavassieux A Buffet P Vergnaud P Garnero PJ Meunier (1997) ArticleTitleShort-term effects of corticosteroids on trabecular bone remodeling in old ewes Bone (NY) 20 451–455 Occurrence Handle1:CAS:528:DyaK2sXjsV2iu78%3D

    CAS  Google Scholar 

  40. M Egermann J Goldhahn E Schneider (2005) ArticleTitleAnimal models for fracture treatment in osteoporosis Osteoporos Int 16 S129–S138 Occurrence Handle15750681 Occurrence Handle10.1007/s00198-005-1859-7

    Article  PubMed  Google Scholar 

  41. WSS Jee WE Roberts HZ Park G Julian M Kramer (1972) Interrelated effects of glucocorticoid and parathyroid hormone upon bone remodeling RV Talmage PL Munson (Eds) Calcium, parathyroid hormone and the calcitonins Excerpta Medica Amsterdam 430–438

    Google Scholar 

  42. CA Lill UV Gerlach C Eckhardt J Goldhahn E Schneider (2002) ArticleTitleBone changes due to glucocorticoid application in an ovariectomized animal model for fracture treatment in osteoporosis Osteoporos Int 13 407–414 Occurrence Handle12086352 Occurrence Handle10.1007/s001980200047 Occurrence Handle1:STN:280:DC%2BD38zktlamsA%3D%3D

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriel Herrero-Beaumont.

Additional information

Part of this study was presented at the 28th annual meeting of the American Society for Bone and Mineral Research, Philadelphia, PA, USA, September 15–19, 2006 [J Bone Miner Res 2006;21(suppl 1):S178]

About this article

Cite this article

Castañeda, S., Calvo, E., Largo, R. et al. Characterization of a new experimental model of osteoporosis in rabbits. J Bone Miner Metab 26, 53–59 (2008). https://doi.org/10.1007/s00774-007-0797-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-007-0797-1

Key words

Navigation