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Influence of Factors Regulating Bone Formation and Remodeling on Bone Quality in Osteonecrosis of the Femoral Head

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Abstract

Osteonecrosis of the femoral head (ONFH) usually affects young individuals and has a major impact on lifestyle. Notably, the pathogenetic mechanisms of osteonecrosis are unresolved and no effective treatment exists. The objective of this study was to assess the gene expression levels of factors regulating bone formation and remodeling (bone morphogenetic protein [BMP]-2, BMP-7, Runx2, osteocalcin, osteoprotegerin [OPG]) in patients with ONFH and to compare them to those of patients with primary osteoarthritis (OA). The cellular and macromolecular composition of the bone matrix was assessed by osteocalcin immunohistochemistry, and the three-dimensional organization of trabecular bone was characterized by micro-computed tomographic analysis. Our results demonstrate that gene expression of BMP-2, BMP-7, and Runx2 is elevated in patients with ONFH. We observed increased extracellular osteocalcin deposition, presumably caused by a higher number of osteoblasts in concordance with increased activity of Runx2. Constant gene expression level of OPG implies an unchanged osteoclast differentiation rate in ONFH bone. We found no significant change in bone volume, connectivity, and structural model index; further, no significant differences were detected for trabecular properties in ONFH bone. In conclusion, we have shown increased gene expression of factors regulating bone formation and remodeling in the femoral head and/or neck of patients with ONFH. Further, we observed an increase in osteocalcin immunoreactivity and osteoblast/osteocyte cell number, while no significant changes in trabecular microarchitecture were detected. This study increases our understanding of the pathophysiology and repair process following ONFH and might help in the development of new treatment strategies in the future.

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References

  1. Calder JD, Pearse MF, Revell PA (2001) The extent of osteocyte death in the proximal femur of patients with osteonecrosis of the femoral head. J Bone Joint Surg Br 83:419–422

    Article  PubMed  CAS  Google Scholar 

  2. Mont MA, Hungerford DS (1995) Non-traumatic avascular necrosis of the femoral head. J Bone Joint Surg Am 77:459–474

    PubMed  CAS  Google Scholar 

  3. Tingart M, Bathis H, Perlick L, Lerch K, Luring C, Grifka J (2004) Therapy of femoral head osteonecrosis: results of a national survey [in German]. Z Orthop Ihre Grenzgeb 142:553–558

    Article  PubMed  CAS  Google Scholar 

  4. Radke S, Battmann A, Jatzke S, Eulert J, Jakob F, Schutze N (2006) Expression of the angiomatrix and angiogenic proteins CYR61, CTGF, and VEGF in osteonecrosis of the femoral head. J Orthop Res 24:945–952

    Article  PubMed  CAS  Google Scholar 

  5. Karsenty G (2000) How many factors are required to remodel bone? Nat Med 6:970–971

    Article  PubMed  CAS  Google Scholar 

  6. Chen HL, Panchision DM (2007) Concise review. Bone morphogenetic protein pleiotropism in neural stem cells and their derivatives–alternative pathways, convergent signals. Stem Cells 25:63–68

    Article  PubMed  CAS  Google Scholar 

  7. Li X, Cao X (2006) BMP signaling and skeletogenesis. Ann N Y Acad Sci 1068:26–40

    Article  PubMed  CAS  Google Scholar 

  8. Einhorn TA, Trippel SB (1997) Growth factor treatment of fractures. Instr Course Lect 46:483–486

    PubMed  CAS  Google Scholar 

  9. Boden SD (2005) The ABCs of BMPs. Orthop Nurs 24:49–52

    Article  PubMed  Google Scholar 

  10. Friedlaender GE (2004) Osteogenic protein-1 in treatment of tibial nonunions: current status. Surg Technol Int 13:249–252

    PubMed  Google Scholar 

  11. Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T (1997) Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell 89:755–764

    Article  PubMed  CAS  Google Scholar 

  12. Satija NK, Gurudutta GU, Sharma S, Afrin F, Gupta P, Verma YK, Singh VK, Tripathi RP (2007) Mesenchymal stem cells: molecular targets for tissue engineering. Stem Cells Dev 16:7–23

    Article  PubMed  CAS  Google Scholar 

  13. Karsenty G (2000) Role of Cbfa1 in osteoblast differentiation and function. Semin Cell Dev Biol 11:343–346

    Article  PubMed  CAS  Google Scholar 

  14. Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G (1997) Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. Cell 89:747–754

    Article  PubMed  CAS  Google Scholar 

  15. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93:165–176

    Article  PubMed  CAS  Google Scholar 

  16. Nakagawa N, Kinosaki M, Yamaguchi K, Shima N, Yasuda H, Yano K, Morinaga T, Higashio K (1998) RANK is the essential signaling receptor for osteoclast differentiation factor in osteoclastogenesis. Biochem Biophys Res Commun 253:395–400

    Article  PubMed  CAS  Google Scholar 

  17. Simonet WS, Lacey DL, Dunstan CR, Kelley M, Chang MS, Luthy R, Nguyen HQ, Wooden S, Bennett L, Boone T, Shimamoto G, DeRose M, Elliott R, Colombero A, Tan HL, Trail G, Sullivan J, Davy E, Bucay N, Renshaw-Gegg L, Hughes TM, Hill D, Pattison W, Campbell P, Sander S, Van G, Tarpley J, Derby P, Lee R, Boyle WJ (1997) Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 89:309–319

    Article  PubMed  CAS  Google Scholar 

  18. Ficat RP (1985) Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. J Bone Joint Surg Br 67:3–9

    PubMed  CAS  Google Scholar 

  19. Kim YH, Kim JS (2004) Histologic analysis of acetabular and proximal femoral bone in patients with osteonecrosis of the femoral head. J Bone Joint Surg Am 86-A:2471–2474

    PubMed  Google Scholar 

  20. Hildebrand T, Laib A, Muller R, Dequeker J, Ruegsegger P (1999) Direct three-dimensional morphometric analysis of human cancellous bone: microstructural data from spine, femur, iliac crest, and calcaneus. J Bone Miner Res 14:1167–1174

    Article  PubMed  CAS  Google Scholar 

  21. Hofstaetter JG, Wang J, Yan J, Glimcher MJ (2006) Changes in bone microarchitecture and bone mineral density following experimental osteonecrosis of the hip in rabbits. Cells Tissues Organs 184:138–147

    Article  PubMed  Google Scholar 

  22. Altman DG, Gore SM, Gardner MJ, Pocock SJ (1983) Statistical guidelines for contributors to medical journals. BMJ 286:1489–1493

    PubMed  CAS  Google Scholar 

  23. Lang TA, Secic M (1997) How to report statistics in medicine: annotated guidelines for authors, editors, and reviewers. American College of Physicians, Philadelphia, pp 81–92

    Google Scholar 

  24. Johnson EE, Urist MR, Finerman GA (1992) Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone. Clin Orthop Relat Res 277:229–237

    PubMed  Google Scholar 

  25. Sandhu HS, Kanim LE, Kabo JM, Toth JM, Zeegan EN, Liu D, Seeger LL, Dawson EG (1995) Evaluation of rhBMP-2 with an OPLA carrier in a canine posterolateral (transverse process) spinal fusion model. Spine 20:2669–2682

    Article  PubMed  CAS  Google Scholar 

  26. Mazieres B, Marin F, Chiron P, Moulinier L, Amigues JM, Laroche M, Cantagrel A (1997) Influence of the volume of osteonecrosis on the outcome of core decompression of the femoral head. Ann Rheum Dis 56:747–750

    Article  PubMed  CAS  Google Scholar 

  27. Scully SP, Aaron RK, Urbaniak JR (1998) Survival analysis of hips treated with core decompression or vascularized fibular grafting because of avascular necrosis. J Bone Joint Surg Am 80:1270–1275

    PubMed  CAS  Google Scholar 

  28. Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047

    PubMed  CAS  Google Scholar 

  29. Weinreb M, Shinar D, Rodan GA (1990) Different pattern of alkaline phosphatase, osteopontin, and osteocalcin expression in developing rat bone visualized by in situ hybridization. J Bone Miner Res 5:831–842

    Article  PubMed  CAS  Google Scholar 

  30. Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452

    Article  PubMed  CAS  Google Scholar 

  31. Assouline-Dayan Y, Chang C, Greenspan A, Shoenfeld Y, Gershwin ME (2002) Pathogenesis and natural history of osteonecrosis. Semin Arthritis Rheum 32:94–124

    PubMed  Google Scholar 

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Acknowledgements

We appreciate the financial support of the Deutsche Forschungsgemeinschaft for this study, assigned to M. T. and S. G. (Az: TI 305/2-1). We also thank Claudia Göttl and Mandy Vogel for their superior technical support.

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Correspondence to Susanne Grässel.

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Tingart, M., Beckmann, J., Opolka, A. et al. Influence of Factors Regulating Bone Formation and Remodeling on Bone Quality in Osteonecrosis of the Femoral Head . Calcif Tissue Int 82, 300–308 (2008). https://doi.org/10.1007/s00223-008-9111-z

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  • DOI: https://doi.org/10.1007/s00223-008-9111-z

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