Skip to main content
SpringerLink
Log in

Vitamin-D Binding Protein Does Not Enhance Healing in Rat Bone Defects: A Pilot Study

  • Symposium: Tribute to Dr. Marshall Urist: Musculoskeletal Growth Factors
  • Published:
Clinical Orthopaedics and Related Research®

    We’re sorry, something doesn't seem to be working properly.

    Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.

Abstract

Vitamin D-binding protein (DBP) has an anabolic effect on the skeleton and reportedly enhances bone ingrowth. We used an in vivo critical bone defect model to determine whether local administration of DBP promotes bone defect healing. We created a 5-mm segmental bone defect in the radial shaft in a rat model. Forty-eight rats were assigned to eight groups: local application of 1 μg, 5 μg, 10 μg, or 50 μg DBP (DBP-1, DBP-5, DBP-10, DBP-50), autogenous bone marrow mononuclear cells with or without 10 μg DBP (BM-DBP-10, BM), 80 μg BMP-2 delivered in gelatin sponge (BMP-2), and the sham operated group. Radiographic evaluation, histological stains, and epifluorescence microscopy were performed. Grossly, all bone gaps of the BMP-2 group were solidly bridged by callus, while all those in the sham operated group remained unhealed by 9 weeks. Only one specimen of the BM-DBP-10 and DBP-50 groups and three specimens of the BM group were solidly healed; pseudarthroses occurred in all of the other specimens. Histological study and radiographs of the specimens showed similar results. We did not observe the enhanced bone healing reported in a previous study.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2A–H
Fig. 3
Fig. 4A–C
Fig. 5A–D

Similar content being viewed by others

References

  1. Allen HL, Wase A, Bear WT. Indomethacin and aspirin: effect of nonsteroidal anti-inflammatory agents on the rate of fracture repair in the rat. Acta Orthop Scand. 1980;51:595–600.

    Article  CAS  PubMed  Google Scholar 

  2. Bostrom MP, Saleh KJ, Einhorn TA. Osteoinductive growth factors in preclinical fracture and long bone defects models. Orthop Clin North Am. 1999;30:647–658.

    Article  CAS  PubMed  Google Scholar 

  3. Chin KR, Nagarkatti DG, Miranda MA, Santoro VM, Baumgaertner MR, Jupiter JB. Salvage of distal tibia metaphyseal nonunions with the 90 degrees cannulated blade plate. Clin Orthop Relat Res. 2003;409:241–249.

    Article  PubMed  Google Scholar 

  4. den Boer FC, Wippermann BW, Blokhuis TJ, Patka P, Bakker FC, Haarman HJ. Healing of segmental bone defects with granular porous hydroxyapatite augmented with recombinant osteogenic protein-1 or autologous bone marrow. J Orthop Res. 2003;21:521–528.

    Article  CAS  Google Scholar 

  5. Fattah HA, Halaa EE, Shary THA. Nonunion of the humeral shaft: a report on 25 cases. Injury. 1982;14:225–262.

    Article  Google Scholar 

  6. Foulk DA, Szabo RM. Diaphyseal humerus fractures natural history and occurrence of nonunion. Orthopedics. 1995;18:333–335.

    CAS  PubMed  Google Scholar 

  7. Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 2001;83:S151–S158.

    PubMed  Google Scholar 

  8. Geesink RG, Hoefnagels NH, Bulstra SK. Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. J Bone Joint Surg Br. 1999;81:710–718.

    Article  CAS  PubMed  Google Scholar 

  9. Healy WL, White GM, Mick CA, Brooker AF Jr, Weiland AJ. Nonunion of the humeral shaft. Clin Orthop Relat Res. 1987;219:206–221.

    PubMed  Google Scholar 

  10. Jones CB, Sabatino CT, Badura JM, Sietsema DL, Marotta JS. Improved healing efficacy in canine ulnar segmental defects with increasing recombinant human bone morphogenetic protein-2/allograft ratios. J Orthop Trauma. 2008;22:550–559.

    Article  PubMed  Google Scholar 

  11. Kruyt MC, de Bruijn JD, Wilson CE, Oner FC, van Blitterswijk CA, Verbout AJ, Dhert WJ. Viable osteogenic cells are obligatory for tissue-engineered ectopic bone formation in goats. Tissue Eng. 2003;9:327–336.

    Article  CAS  PubMed  Google Scholar 

  12. Kruyt MC. Dhert WJ. Yuan H. Wilson CE. van Blitterswijk CA. Verbout AJ. de Bruijn JD. Bone tissue engineering in a critical size defect compared to ectopic implantations in the goat. J Orthop Res. 2004;22:544–451.

    Google Scholar 

  13. Lisignoli G, Fini M, Giavaresi G, Nicoli AN, Toneguzzi S, Facchini A. Osteogenesis of large segmental radius defects enhanced by basic fibroblast growth factor activated bone marrow stromal cells grown on non-woven hyaluronic acid-based polymer scaffold. Biomaterials. 2002;23:1043–1051.

    Article  CAS  PubMed  Google Scholar 

  14. Ozturk AM, Cila E, Kanatli U, Isik I, Senkoylu A, Uzunok D, Piskin E. Treatment of segmental bone defects in rats by the stimulation of bone marrow osteo-progenitor cells with prostaglandin E2. Int Orthop. 2005;29:73–77.

    Article  CAS  PubMed  Google Scholar 

  15. Reddi AH. Role of morphogenetic proteins in skeletal tissue engineering and regeneration. Nature Biotechnology. 1998;16:247–252.

    Article  CAS  PubMed  Google Scholar 

  16. Schneider GB, Grecco KJ, Safadi FF, Popoff SN. The anabolic effects of vitamin D-binding protein-macrophage activating factor (DBP-MAF) and a novel small peptide on bone. Crit Rev Eukaryot Gene Expr. 2003;13:277–284.

    Article  CAS  PubMed  Google Scholar 

  17. Sipos W, Duvigneau JC, Schmoll F, Exel B, Hofbauer G, Baravalle G, Hartl RT, Dobretsberger M, Pietschmann P. Characterization of the cytokine pattern of porcine bone marrow-derived cells treated with 1alpha,25(OH)D. J Vet Med A Physiol Pathol Clin Med. 2005;52:382–387.

    CAS  PubMed  Google Scholar 

  18. Tsuang Y-H, Lin F-H, Tai H-C, Sun J-S, Liu H-C, Hang Y-S. Biocompatibility and osteoconductivity of the Pyrost bone substitutes. Histol Histopathol. 1997;12:19–24.

    CAS  PubMed  Google Scholar 

  19. Urist MR. Bone: formation by autoinduction. Clin Orthop Relat Res. 2002;395:4–10.

    Article  PubMed  Google Scholar 

  20. Wang J, Wenig L. Treatment of distal femoral nonunion with internal fixation, cortical allograft struts, and autogenous bone grafting. J Bone Joint Surg Am. 2003;85:436–440.

    Article  PubMed  Google Scholar 

  21. Younger EM, Chapman MW. Morbidity at bone graft donor site. J Orthop Trauma. 1989;3:192–195.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the staff of the Second Core Lab, Department of Medical Research, National Taiwan University Hospital, for technical support during the study. We also thank Miss Margaret Man-Ger SUN for her help in the editing and preparation of this manuscript.

Author information

Authors and Affiliations

  1. Institute of Clinical Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong St., Beitou District, Taipei, 11221, Taiwan, ROC

    Jui-Sheng Sun MD, PhD

  2. Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan, ROC

    Pei-Yu Chen MD

  3. Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan, ROC

    Jui-Sheng Sun MD, PhD & Pei-Yu Chen MD

  4. Department of Orthopedic Surgery, Taipei City Hospital, Taipei, Taiwan, ROC

    Yang-Hwei Tsuang MD, PhD

  5. Institute of Biomedical Engineering, National Yang-Ming University, Taipei, Taiwan, ROC

    Ming-Hong Chen MD, PhD

  6. Department of Orthopedic Surgery, Min-Sheng General Hospital, Taoyuang, Taiwan, ROC

    Po-Quang Chen MD, PhD

Authors
  1. Jui-Sheng Sun MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pei-Yu Chen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yang-Hwei Tsuang MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ming-Hong Chen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Po-Quang Chen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jui-Sheng Sun MD, PhD.

Additional information

One or more of the authors (J-S Sun and P-Y Chen) have received funding from the Industrial Technology Research Institute, Shin-Chiu, Taiwan, ROC.

Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

This work was performed at Institute of Clinical Medicine, National Yang-Ming University, Taipei City, Taiwan.

Appendix

Appendix

Appendix 1 Observer classification of radiographic healing (Allen et al. [1])
Full size table

About this article

Cite this article

Sun, JS., Chen, PY., Tsuang, YH. et al. Vitamin-D Binding Protein Does Not Enhance Healing in Rat Bone Defects: A Pilot Study. Clin Orthop Relat Res 467, 3156–3164 (2009). https://doi.org/10.1007/s11999-009-0864-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11999-009-0864-0

Keywords

Search

Navigation