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Contrast-Enhanced MRI and Micro-CT Adopted for Evaluation of a Lipid-Lowering and Anticoagulant Herbal Epimedium-Derived Phytoestrogenic Extract for Prevention of Steroid-Associated Osteonecrosis

  • Ling QinEmail author
  • Ge Zhang
  • Hui Sheng
  • James F. Griffth
  • Ka Wai Yeung
  • Kwok-Sui Leung
Chapter
  • 2k Downloads

Abstract

We developed an alternative steroid-associated osteonecrosis (ON) rabbit model using a combination of a single injection of low-dose lipopolysaccharide (LPS) and three subsequent injections of pulsed high-dose methylprednisolone (MPS).The usefulness of this experimental ON model was evaluated using both conventional and advanced bio-imaging techniques, including contrast-enhanced dynamic MRI and a high-resolution micro-CT. Details on establishment of methodology are described, which were adopted into an efficacy study on a herbal Epimedium-derived phytoestrogenic extract (HEPE) developed for prevention of steroid-associated ON using an established rabbit model. The underlying mechanisms of HEPE for prevention of steroid-associated ON were found to be associated with inhibition of both intravascular thrombosis and extravascular bone marrow lipid deposition, the two known mechanistic pathways in pathogenesis of ON. Our experimental results provide for potential clinical trials or applications of HEPE in the prevention of ON among hig-hrisk patients undergoing steroid treatment.

Keywords

Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Severe Acute Respiratory Syndrome Patient Lead Chromate Pulse Steroid Treatment 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Aaron RK (1998) Osteonecrosis: etiology, pathophysiology and diagnosis. In: Callaghan JJ, Rosenberg AG, Rubash HE (eds) The adult hip. Lippincott-Raven, Philadelphia, p 457Google Scholar
  2. Anderson JW, Johnstone BM, Cook-Newell ME (1995) Meta-analysis of the effects of soy protein intake on serum lipids. N Engl J Med 333:276–282PubMedCrossRefGoogle Scholar
  3. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME (2002) Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 32:94–124PubMedGoogle Scholar
  4. Bentley MD, Ortiz MC, Ritman EL, Romero JC (2002) The use of microcomputed tomography to study microvasculature in small rodents. Am J Physiol Regul Integr Comp Physiol 282:1267–1279Google Scholar
  5. Choo MK, Park EK, Yoon HK, Kim DH (2002) Antithrombotic and antiallergic activities of daidzein, a metabolite of puerarin and daidzin produced by human intestinal microflora. Biol Pharm Bull 25:1328–1332PubMedCrossRefGoogle Scholar
  6. Clifton-Bligh PB, Baber RJ, Fulcher GR, Nery ML, Moreton T (2001) The effect of isoflavones extracted from red clover (Rimostil) on lipid and bone metabolism. Menopause 8:259–265PubMedCrossRefGoogle Scholar
  7. Cooke PS, Naaz A (2005) Effects of estrogens and the phytoestrogen genistein on adipogenesis and lipogenesis in males and females. Birth Defects Res A Clin Mol Teratol 73:472–473PubMedCrossRefGoogle Scholar
  8. Dang Z, Lowik CW (2004) The balance between concurrent activation of ERs and PPARs determines daidzein-induced osteogenesis and adipogenesis. J Bone Miner Res 19:853–861PubMedCrossRefGoogle Scholar
  9. Dang ZC, Audinot V, Papapoulos SE, Boutin JA, Lowik CW (2003) Peroxisome proliferator-activated receptor gamma (PPARgamma) as a molecular target for the soy phytoestrogen genistein. J Biol Chem 278:962–967PubMedCrossRefGoogle Scholar
  10. Duvall CL, Robert Taylor W, Weiss D, Guldberg RE (2004) Quantitative microcomputed tomography analysis of collateral vessel development after ischemic injury. Am J Physiol Heart Circ Physiol 287:302–310CrossRefGoogle Scholar
  11. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (adult treatment panel III) (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) J Am Med Assoc 285:2486–2497CrossRefGoogle Scholar
  12. Glueck CJ, Freiberg RA, Sieve L, Wang P (2005) Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res 435:164–170PubMedCrossRefGoogle Scholar
  13. Griffith JF, Antonio GE, Kumta SM, Hui DS, Wong JK, Joynt GM, Wu AK, Cheung AY, Chiu KH, Chan KM, Leung PC, Ahuja AT (2005) Osteonecrosis of hip and knee in patients with severe acute respiratory syndrome treated with steroids. Radiology 235:168–175PubMedCrossRefGoogle Scholar
  14. Hong N, Du XK (2004) Avascular necrosis of bone in severe acute respiratory syndrome. Clin Radiol 59:602–608PubMedCrossRefGoogle Scholar
  15. Irisa T, Yamamoto T, Miyanishi K, Yamashita A, Iwamoto Y, Sugioka Y, Sueishi K (2001) Osteonecrosis induced by a single administration of low-dose lipopolysaccharide in rabbits. Bone 28:641–649PubMedCrossRefGoogle Scholar
  16. Jorgensen SM, Demirkaya O, Ritman EL (1998) Three-dimensional imaging of vasculature and parenchyma in intact rodent organs with X-ray micro-CT. Am J Physiol Heart Circ Physiol 275:1103–1114Google Scholar
  17. Koller E, Mann M, Malozowski S, Bacsanyi J, Gibert C (2000) Aseptic necrosis in HIV seropositive patients: a possible etiologic role for megestrol acetate. AIDS Patient Care STDS 14:405–410PubMedCrossRefGoogle Scholar
  18. Lamon-Fava S (2000) Genistein activates apolipoprotein A-I gene expression in the human hepatoma cell line Hep G2. J Nutr 130:2489–2492PubMedGoogle Scholar
  19. Lang P, Jergesen JE, Genant HK, Moseley ME, Schuylte-Monting J (1989) Magnetic resonance imaging of the ischemic femoral head in pigs. Dependency of signal intensities and relaxation times on elapsed time. Clin Orthop Relat Res 244:272–280PubMedGoogle Scholar
  20. Lau TF, Leung PC (2005) Using herbal medicine as a means of prevention experience during the SARS crisis. Am J Chinese Med 33:345–356CrossRefGoogle Scholar
  21. Lee SH, Jung BH, Kim SY, Chung BC (2004) Determination of phytoestrogens in traditional medicinal herbs using gas chromatography-mass spectrometry. J Nutr Biochem 15:452–460PubMedCrossRefGoogle Scholar
  22. Li X, Jin L, Cui Q, Wang GJ, Balian G (2005) Steroid effects on osteogenesis through mesenchymal cell gene expression. Osteoporos Int 16:101–108PubMedCrossRefGoogle Scholar
  23. Li ZR, Sun W, Qu H, Zhou YX, Dou BX, Shi ZC, Zhang NF, Cheng XG, Wang DL, Guo WS (2005) Clinical research of correlation between osteonecrosis and steroid. Zhonghua Wai Ke Za Zhi 43:1048–1053PubMedGoogle Scholar
  24. Lieberman JR, Berry DJ, Montv MA, Aaron RK, Callaghan JJ, Rayadhyaksha A, Urbaniak JR (2002) Osteonecrosis of the hip: nanagement in the twenty-first century. J Bone Joint Surg Am 84:834–853Google Scholar
  25. Liu X, Zhang M, He L, Li YP, Kang YK (2006) Chinese herbs combined with Western medicine for severe acute respiratory syndrome (SARS). Cochrane Database Syst Rev 1:CD004882Google Scholar
  26. Martin JL, Fry ET, Sanderink GJ, Atherley TH, Guimart CM, Chevalier PJ, Ozoux ML, Pen-syl CE, Bigonzi F (2004) Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: the pharmacokinetics of enoxaparin in PCI (PEPCI) study. Catheter Cardiovasc Interv 61:163–170PubMedCrossRefGoogle Scholar
  27. Meng FH, Li YB, Xiong ZL, Jiang ZM, Li FM (2005) Osteoblastic proliferative activity of Epimedium brevicornum Maxim. Phytomedicine 12:189–193PubMedCrossRefGoogle Scholar
  28. Miller KD (2002) High prevalence of osteonecrosis of the femoral head in HIV infected adults. Ann Intern Med 137:17–25PubMedGoogle Scholar
  29. Motomura G, Yamamoto T, Miyanishi K, Jingushi S, Iwamoto Y (2004) Combined effects of an anticoagulant and a lipid-lowering agent on the prevention of steroid-induced osteonecrosis in rabbits. Arthritis Rheum 50:3387–3391PubMedCrossRefGoogle Scholar
  30. National Osteonecrosis Foundation website. http://www.nonf.org/index.htmlGoogle Scholar
  31. Pritchett JW (2001) Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res 386:173–178PubMedCrossRefGoogle Scholar
  32. Prophet EB, Mills B, Arrington JB, Sobin LH (eds) (1992) Armed Forces Institute of Pathology Laboratory Methods in Histotechnology. American Registry of pathology, Washington DC, p 98Google Scholar
  33. Qin L, Zhang G, Shi YY, Lee KM, Leung PC (2005a) Prevention and treatment of osteoporosis with traditional herbal medicine. In: Deng HW et al. (eds) Current topics of osteoporosis. World Scientific, UK, pp 513–531Google Scholar
  34. Qin L, Zhang G, Hung WY (2005b) Phytoestrogen-rich Herb Formula “XLGB” prevents OVX-induced deterioration of musculoskeletal tissues at hip in old rats. J Bone Miner Metabol 23S:55–61CrossRefGoogle Scholar
  35. Qin L, Zhang G, Sheng H (2006) Multiple imaging modalities in evaluation of experimental osteonecrosis induced by a combination of lippolysaccharide and methylprednisolone. Bone 39:863–871PubMedCrossRefGoogle Scholar
  36. Saito S, Saito M, Nishina T, Ohzono K, Ono K (1989) Long-term results of total hip arthroplasty for osteonecrosis of the femoral head. A comparison with osteoarthritis. Clin Orthop Relat Res 244:198–207PubMedGoogle Scholar
  37. Schulman S (1999) The effect of the duration of anticoagulation and other risk factors on the recurrence of venous thromboembolisms. Duration of Anticoagulation Study Group. Wien Med Wochenschr 149:66–69PubMedGoogle Scholar
  38. Scribner AN, Troia-Cancio PV, Cox BA, Marcantonio D, Hamid F, Keiser P, Levi M, Allen B, Murphy K, Jones RE, Skiest DJ (2000) Osteonecrosis in HIV: a case-control study. J Acquir Immune Defic Syndr 25:19–25PubMedCrossRefGoogle Scholar
  39. Shen J, Liang BL, Zeng QS, Chen JY, Liu QY, Chen RC, Zhong NS (2004) Report on the investigation of lower extremity osteonecrosis with magnetic resonance imaging in recovered severe acute respiratory syndrome in Guangzhou. Zhonghua Yi Xue Za Zhi 84:1814–1817PubMedGoogle Scholar
  40. Simopoulos DN, Gibbons SJ, Malysz J, Szurszewski JH, Farrugia G, Ritman EL, Moreland RB, Nehra A (2001) Corporeal structural and vascular micro-architecture with X-ray micro-computerized tomography in normal and diabetic rabbits: histopathological correlation. J Urol 165:1776–1782PubMedCrossRefGoogle Scholar
  41. So LK, Lau AC, Yam LY, Cheung TM, Poon E, Yung RW, Yuen KY (2003) Development of a standard treatment protocol for severe acute respiratory syndrome. Lancet 361:1615–1617PubMedCrossRefGoogle Scholar
  42. Wang GJ (2000) The pathogenesis and prevention of steroid-induced osteonecrosis. Clin Or-thop 370:295–310CrossRefGoogle Scholar
  43. Wang W, Zhu GJ, Zu SY (2004) Effects of 17/β Estradiol and Phytoestrogen α-Zearalanolon coagulation and fibrinolysis in Rats. Chin J Arterioscler 12:139–142Google Scholar
  44. Wortmann RL (2002) Lipid-lowering agents and myopathy. Curr Opin Rheumatol 14:643–647PubMedCrossRefGoogle Scholar
  45. Yamamoto T (1997) Effects of pulse methylprednisolone on bone and marrow tissues: corticosteroid-induced osteonecrosis in rabbits. Arthritis Rheum 40:2055–2064PubMedCrossRefGoogle Scholar
  46. Yamamoto T, Hirano K, Tsutsui H, Sugioka Y, Sueishi K (1995) Corticosteroid enhances the experimental induction of osteonecrosis in rabbits with Shwartzman reaction. Clin Orthop Relat Res 316:235–243PubMedGoogle Scholar
  47. Zhang G, Qin L, Hung WY (2006) Flavonoids derived from herbal Epimedium Brevicornum Maxim prevents OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption. Bone 38:818–825PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2007

Authors and Affiliations

  • Ling Qin
    • 1
    Email author
  • Ge Zhang
    • 1
  • Hui Sheng
    • 1
  • James F. Griffth
    • 2
  • Ka Wai Yeung
    • 2
  • Kwok-Sui Leung
    • 1
  1. 1.Department of Orthopaedics and TraumatologyThe Chinese University of Hong KongHong KongChina
  2. 2.Department of Radiology and Organ ImagingThe Chinese University of Hong KongHong KongChina

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