Osteoporosis International

, Volume 22, Issue 6, pp 2003–2006 | Cite as

Bone fracture and bone fracture repair

  • N. L. Fazzalari
Bone Quality Seminars: Bone Fracture Healing and Strengthening


Fracture healing is a multistage repair process that involves complex, well-orchestrated steps initiated in response to tissue injury. The early upregulation of IL-6, osteoprotegerin (OPG), VEGF, and BMPs indicates a central role for these factors in the initiation of cartilage and periosteal woven bone formation. In both callus fracture repair and stress fracture repair, the RANKL/OPG ratio is initially reduced, but peaks earlier in stress fracture healing than callus fracture healing. Though the understanding of the biological processes and molecular signals that coordinate fracture repair has advanced, the cause of variability observed in fracture repair is poorly understood.


Fracture Fracture repair Microdamage Stress fracture 



The publication of the proceedings of the 5th Bone Quality Seminar 2010 has been made possible through an educational grant from Servier.

Conflicts of interest



  1. 1.
    Goldhahn J, Little D, Mitchell P, Fazzalari NL, Reid IR, Aspenberg P, Marsh D (2010) Evidence for anti-osteoporosis therapy in acute fracture situations—recommendations of a multidisciplinary workshop of the International Society for Fracture Repair. Bone 46:267–271PubMedCrossRefGoogle Scholar
  2. 2.
    AI-Aql ZS, Alagl AS, Graves DT, Gerstenfeld LC, Einhorn TA (2008) Molecular mechanisms controlling bone formation during fracture healing and distraction osteogenesis. J Dent Res 87:107–118PubMedCrossRefGoogle Scholar
  3. 3.
    Barth HD, Launey ME, MacDowell AA, Ager JW III, Ritchie RO (2010) On the effect of X-ray irradiation on the deformation and fracture behaviour of human cortical bone. Bone 46:1475–1485PubMedCrossRefGoogle Scholar
  4. 4.
    Zarrinkalam KH, Kuliwaba JS, Martin RB, Wallwork MAB, Fazzalari NL (2005) New insights into the propagation of fatigue damage in cortical bone using confocal microscopy and chelating fluorochromes. Eur J Morph 42:81–90CrossRefGoogle Scholar
  5. 5.
    Einhorn TA (1998) The cell and molecular biology of fracture healing. Clin Orthop Relat Res 335:S7–S21CrossRefGoogle Scholar
  6. 6.
    Colopy SA, Benz-Dean J, Barrett JG, Sample SJ, Lu Y, Danova NA et al (2004) Response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to cyclic fatigue loading. Bone 35:881–891PubMedCrossRefGoogle Scholar
  7. 7.
    Verborgt O, Gibson GJ, Schaffler MB (2000) Loss of osteocyte integrity in association with microdamage and bone remodeling after fatigue in vivo. J Bone Miner Res 15:60–67PubMedCrossRefGoogle Scholar
  8. 8.
    Burr DB, Forwood MR, Fyhrie DP, Martin RB, Schaffler MB, Turner CH (1997) Bone microdamage and skeletal fragility in osteoporotic and stress fractures. J Bone Miner Res 12:6–15PubMedCrossRefGoogle Scholar
  9. 9.
    Tsangari H, Findlay DM, Zannettino AC, Pan B, Kuliwaba JS, Fazzalari NL (2006) Evidence for reduced bone formation surface relative to bone resorption surface in female femoral fragility fracture patients. Bone 39:1226–1235PubMedCrossRefGoogle Scholar
  10. 10.
    Fazzalari NL, Kuliwaba JS, Atkins GJ, Forwood MR, Findlay DM (2001) The ratio of messenger RNA levels of receptor activator of nuclear factor kappaB ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis. J Bone Miner Res 16:1015–1027PubMedCrossRefGoogle Scholar
  11. 11.
    Dimitriou R, Tsiridis E, Giannoudis PV (2005) Current concepts of molecular aspects of bone healing. Injury 36:1392–1404PubMedCrossRefGoogle Scholar
  12. 12.
    Gerstenfeld LC, Alkhiary YM, Krall EA, Nicholls FH, Stapleton SN, Fitch JL et al (2006) Three-dimensional reconstruction of fracture callus morphogenesis. J Histochem Cytochem 54:1215–1228PubMedCrossRefGoogle Scholar
  13. 13.
    Gerstenfeld LC, Cullinane DM, Barnes GL, Graves DT, Einhorn TA (2003) Fracture healing as a post-natal developmental process: molecular, spatial, and temporal aspects of its regulation. J Cell Biochem 88:873–884PubMedCrossRefGoogle Scholar
  14. 14.
    Cho TJ, Gerstenfeld LC, Einhorn TA (2002) Differential temporal expression of members of the transforming growth factor beta superfamily during murine fracture healing. J Bone Miner Res 17:513–520PubMedCrossRefGoogle Scholar
  15. 15.
    Kidd LJ, Stephens AS, Kuliwaba JS, Fazzalari NL, Wu ACK, Forwood MR (2010) Temporal pattern of gene expression and histology of stress fracture healing. Bone 46:369–378PubMedCrossRefGoogle Scholar
  16. 16.
    Frost HM (1983) The regional acceleratory phenomenon: a review. Henry Ford Hosp Med J 31:3–9PubMedGoogle Scholar
  17. 17.
    Schilling T, Muller M, Minne HW, Ziegler R (1998) Influence of inflammation-mediated osteopenia on the regional acceleratory phenomenon and the systemic acceleratory phenomenon during healing of a bone defect in the rat. Calcif Tissue Int 63:160–166PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2011

Authors and Affiliations

  1. 1.Bone and Joint Research LaboratorySA Pathology and Hanson InstituteAdelaideAustralia
  2. 2.Discipline of PathologyUniversity of AdelaideAdelaideAustralia

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