title: Biological perspectives of delayed fracture healing.
abstract: Fracture healing is a complex biological process that requires interaction among a series of different cell types. Maintaining the appropriate temporal progression and spatial pattern is essential to achieve robust healing. We can temporally assess the biological phases via gene expression, protein analysis, histologically, or non-invasively using biomarkers as well as imaging techniques. However, determining what leads to normal versus abnormal healing is more challenging. Since the ultimate outcome of fracture healing is to restore the original functions of bone, assessment of fracture healing should include not only monitoring the restoration of structure and mechanical function, but also an evaluation of the restoration of normal bone biology. Currently few non-invasive measures of biological factors of healing exist; however, recent studies that have correlated non-invasive measures with fracture healing outcome in humans have shown that serum TGFbeta1 levels appear to be an indicator of healing versus non-healing. In the future, developing additional measures to assess biological healing will improve the reliability and permit us to assess stages of fracture healing. Additionally, new functional imaging technologies could prove useful for better understanding both normal fracture healing and predicting dysfunctional healing in human patients.
authors.affiliation: Department of Clinical Studies New Bolton Center, School of Veterinary Medicine and Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, United States. Electronic address: kdhank@vet.upenn.edu.
authors.forename: K D
authors.initials: KD
authors.lastname: Hankenson
authors.affiliation: Department of Orthopedic and Trauma Surgery, University of Heidelberg, Theresienkrankenhaus, Mannheim, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Zimmerman
authors.affiliation: Department of Orthopaedic Surgery, University of California, San Francisco, United States.
authors.forename: R
authors.initials: R
authors.lastname: Marcucio
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D016326:Extracellular Matrix Proteins / Q000097:blood*; D017102:Fracture Healing / Q000502:physiology*; D050723:Fractures, Bone / Q000097:blood* / Q000628:therapy*; D005599:Fractures, Ununited / Q000097:blood; D006801:Humans; D051379:Mice; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood*; D000099222:betaIG-H3 Protein
chemical_list: D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein
keywords: Bone healing; Mediators; Non-union; TGFbeta1; Vascularity