Relationships among magnetic resonance imaging, histological findings, and IGF-I in steroid-induced osteonecrosis of the femoral head in rabbits

  • Xing-can Chen
  • Jian Weng
  • Xue-qun Chen
  • Ji-zeng Du
  • Miao-ping Zhu
  • Yong-qing Pan
  • Miao Liu
Article

Abstract

Objective

To study the relationships among magnetic resonance imaging (MRI), histological findings, and insulin-like growth factor-I (IGF-I) in steroid-induced osteonecrosis of the femoral head in rabbits.

Methods

Thirty rabbits were randomly divided into experimental Group A (n=15) and control Group B (n=15). The 7.5 mg/kg (2 ml) of dexamethasone (DEX) and physiological saline (2 ml) were injected into the right gluteus medius muscle twice at one-week intervals in animals of Groups A and B, respectively. At 4, 8 and 16 weeks after obtaining an MRI, the rabbits were sacrificed and the femoral head from one side was removed for histological study of lacunae empty of osteocytes, subchondral vessels, and size of fat cells under microscopy, and the femoral head from the other side was removed for enzyme-linked immunoadsorbent assay (ELISA) for IGF-I.

Results

At 4, 8 and 16 weeks after treatment, no necrotic lesions were detected in Group B, while they were detected in Group A. Light microscopy revealed that the fat cells of the marrow cavity were enlarged, subchondral vessels were evidently decreased, and empty bone lacunae were clearly increased. The IGF-I levels in Group A were significantly higher than those in Group B. At 8 weeks after the DEX injection, the MRI of all 20 femora showed an inhomogeneous, low signal intensity area in the femoral head, and at 16 weeks, the findings of all 10 femora showed a specific “line-like sign”. The MRI findings of all femora in Group B were normal.

Conclusion

MRI is a highly sensitive means of diagnosing early experimental osteonecrosis of the femoral head. However, the abnormal marrow tissues appeared later than 4 weeks when the expression of IGF-I increased. This reparative factor has an early and important role in response to steroid-induced osteonecrosis of the femoral head, and provides a theoretical foundation for understanding the pathology and designing new therapies.

Key words

Dexamethasone (DEX) Insulin-like growth factor-I (IGF-I) Magnetic resonance imaging (MRI) Osteonecrosis of the femoral head Pathology 

CLC number

R68 

References

  1. Brody, A.S., Strong, M., Babikian, G., 1991. Avascular necrosis: early MR imaging and histologic findings in a canine model. AJR, 157(2):341–345.PubMedGoogle Scholar
  2. Catanese, V.M., Svfiavolino, P.J., Lango, M.N., 1993. Discordant, organspecific regulation of insulin-like growth factor-I messenger ribonucleic acid in insulin-deficient diabetes in rats. Endocrinology, 132(2):496–503. [doi:10.1210/en.132.2.496]PubMedCrossRefGoogle Scholar
  3. Cheng, M.Z., Simon, C.F., Rawlinsine, A.A., 2002. Human osteoblast proliferative responses to strain and 17beta2 estrodiol are mediated by the estrogen receptor and the receptor for lnsulin-like growth factor I. J. Bone Miner. Res., 17(4):593–602. [doi:10.1359/jbmr.2002.17.4.593]PubMedCrossRefGoogle Scholar
  4. Cui, Q., Wang, G.J., Balian, G., 1997. Steroid-induced adipogenesis in a pluripotential cell line from bone marrow. J. Bone Joint Surg., 79(7):1054–1063.PubMedGoogle Scholar
  5. D’Ercole, A.J., Stiles, A.D., Underwood, L.E., 1984. Tissue concentrations of somatomedin-C: further evidence for multiple sites of synthesis and paracrine or autocrine mechanisms of action. Proc. Natl. Acad. Sci. USA, 81(3): 935–939. [doi:10.1073/pnas.81.3.935]PubMedCrossRefGoogle Scholar
  6. Duda, S.H., Laniado, M., Schick, F., 1993. The double-line sign of osteonecrosis: evaluation on chemical shift MR images. Eur. J. Radiol., 16(3):233–238. [doi:10.1016/0720-048X(93)90081-W]PubMedCrossRefGoogle Scholar
  7. Fan, F., Molina, P.E., Gelato, M.C., Lang, C.H., 1994. Differential tissue regulation of insulin-like growth factor-I content and binding proteins after endotoxin. Endocrinology, 134(4):1685–1692. [doi:10.1210/en.134.4.1685]PubMedCrossRefGoogle Scholar
  8. Gelato, M.C., Vassalotti, J., Spatola, E., Carlson, H.E., Rulherford, C., Marsh, K., 1991. Differential tissue regulation of the insulin-like growth factors in rats bearing the MStT/W15 pituitary tumor. Neuroendocrinology, 561(6): 765–774.Google Scholar
  9. Gimble, J.M., Robinson, C.E., Wu, X., Kelly, K.A., 1996. The function of adipocytes in the bone marrow stroma: an update. Bone, 19(5):421–428. [doi:10.1016/S8756-3282 (96)00258-X]PubMedCrossRefGoogle Scholar
  10. Hawker, F.H., Stewart, P.M., Baxter, R.C., Borkmann, M., Tan, K., 1987. Relationship of somatomedin-C/1 insulin-like growth factor I levels to conventional nutritional indices in critically ill patients. Crit. Care Med., 15(8): 732–736. [doi:10.1097/00003246-198708000-00004]PubMedCrossRefGoogle Scholar
  11. Jia, D.A., Heersche, J.N.M., 2000. Insulin like growth factor-1 and 2 stimulate osteoprogenitor proliferation and differentiation and adipocyte formation in cell populations derived from adult rat bone. Bone, 27(6):785–794. [doi:10.1016/S8756-3282(00)00400-2]PubMedCrossRefGoogle Scholar
  12. Koo, K.H., Ahn, I.O., Kim, R., 1999. Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images. Radiology, 213(3):715–722.PubMedGoogle Scholar
  13. Krause, U., Wegener, G., Hewsholme, E.A., 1992. Effects of insulin-like growth factor I on the rates of glucose transport and utilization in rat skeletal muscle in vifro. Biochem. J., 285(Pt 1):269–274.PubMedGoogle Scholar
  14. Mitchell, D.G., 1989. Using MR imaging to probe the pathophysiology of osteonecrosis. Radiology, 171(1):25–26.PubMedGoogle Scholar
  15. Mitchell, M.D., Kundel, H.L., Steinberg, M.E., Kressel, H.Y., Alavi, A., Axel, L., 1986. Avascular necrosis of the hip: comparison of MR, CT, and scintigraphy. AJR, 147(1): 67–71.PubMedGoogle Scholar
  16. Miyanishi, K., Yamamoto, T., Irisa, T., Yamashita, A., Jingushi, S., Noguchi, Y., Iwamoto, Y., 2001. A high LDL/HDL cholesterol ratio as a potential risk factor for corticosteroid-induced osteonecrosis in rabbits. Rheumatology, 40(2):196–201. [doi:10.1093/rheumatology/40.2.196]PubMedCrossRefGoogle Scholar
  17. Miyanishi, K., Yamamoto, T., Irisa, T., Yamashita, A., Jingushi, S., Noguchi, Y., Iwamoto, Y., 2002. Bone marrow fat cell enlargement and a rise in intraosseous pressure in steroid-treated rabbits with osteonecrosis. Bone, 30(1): 185–190. [doi:10.1016/S8756-3282(01)00663-9]PubMedCrossRefGoogle Scholar
  18. Murphy, L.J., Bell, G.I., Friesen, H.G., Friesen, H.G., 1987. Tissue distribution of insulin like growth factor-I and-II messenger ribonucleic acid in the adult rat. Endocrinology, 120(4):1279–1282.PubMedCrossRefGoogle Scholar
  19. Ross, R., Miell, J., Freeman, E., Jones, J., Matthew, D., Buchanan, C., 1991. Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin-like growth factor-I. Clin. Endocrinol. (Oxf.), 35(1):47–54. [doi:10.1111/j.1365-2265.1991.tb03495.x]CrossRefGoogle Scholar
  20. Sakaia, T., Suganoa, N., Tsuji, T., Nishii, T., Yoshikawa, H., Ohzono, K., 2000. Serial magnetic resonance imaging in a non-traumatic rabbit osteonecrosis model: an experimental longitudinal study. Magnetic Resonance Imaging, 18(7):897–905. [doi:10.1016/S0730-725X(00)00175-2]PubMedCrossRefGoogle Scholar
  21. Schwander, J.C., Hauri, C., Zapf, J., Froesch, E.R., 1983. Synthesis and secretion of insulin-like growth factor and its binding protein by the perfused rat liver: dependence on growth hormone status. Endocrinology, 113(1): 297–305.PubMedGoogle Scholar
  22. Turkalj, I., Keller, U., Ninnis, R., 1992. Effect of increasing doses of recombinant human insulin-like growth factor-I on glucose, lipid and leucine metabolism in man. J. Clin. Endocrinol. Metab., 75(5):1186–1191. [doi:10.1210/jc.75.5.1186]PubMedCrossRefGoogle Scholar
  23. Uberoi, R., Tai, G., Hughes, P.M., 1994. Gadolinium-DTPA-enhanced MRI in the evaluation of osteonecrosis. Clin. Radiol., 49(9):645–648. [doi:10.1016/S0009-9260(05)81884-7]PubMedCrossRefGoogle Scholar
  24. Vande, B.C., Malghem, J., Lecouvet, F.E., Jamart, J., Maldague, B., 1999. Idiopathic bone marrow edema lesions of the femoral head: predictive value of MR imaging findings. Radiology, 212(2):527–535.Google Scholar
  25. Vande, B.E., Malghem, J.J., Labaisse, M.A., 1993. MR imaging of avascular necrosis and transient marrow edema of the femoral head. Radiographics, 13:501–520.Google Scholar
  26. Vande Berg, B., Gilon, R., Malghem, J., Lecouvet, F., Depresseux, G., Houssiau, F., 2006. Correlation between baseline femoral neck marrow status and the development of femoral head osteonecrosis in corticosteroid-treated patients: a longitudinal study by MR imaging. Eur. J. Radiol., 58(3):444–449. [doi:10.1016/j.ejrad.2006.01.009]CrossRefGoogle Scholar
  27. Wildemann, B., Schmidmaier, G., Brenner, N., 2004. Quantification, localization, and expression of IGF-I and TGF-β1 during growth factor-stimulated fracture healing. Calcif. Tissue Int., 74(4):388–397. [doi:10.1007/s00223-003-0117-2]PubMedCrossRefGoogle Scholar
  28. Yamamoto, T., Irisa, T., Sugioka, Y., Sueishi, K., 1997. Effects of pulse methylprednisolone on bone and marrow tissues. Arthritis Rheum, 40(11):2055–2064. [doi:10.1002/art.1780401119]PubMedCrossRefGoogle Scholar

Copyright information

© Zhejiang University and Springer-Verlag GmbH 2008

Authors and Affiliations

  • Xing-can Chen
    • 1
    • 2
  • Jian Weng
    • 1
  • Xue-qun Chen
    • 1
  • Ji-zeng Du
    • 1
  • Miao-ping Zhu
    • 2
  • Yong-qing Pan
    • 2
  • Miao Liu
    • 2
  1. 1.Division of Neurobiology and Physiology, Institute of Neuroscience, School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Department of Radiologythe 117 Hospital of the Chinese People’s Liberation ArmyHangzhouChina

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