Inflammation, Bone Healing, and Anti-Inflammatory Drugs: An Update

Summary: Fracture healing is a unique multifaceted process requiring the presence of cells, molecular mediators, and angiogenic factors. The state of in fl ammation dominates the initial phase, but the ideal magnitude and duration of the process for an optimal outcome remains obscure. Biological response modi fi ers, such as platelet-rich plasma (PRP) preparations, have been used to reconstitute the desirable early in fl ammatory state, but the results obtained remain inconclusive. Ongoing research to characterize and quantify the in fl ammatory response after bone fracture is essential in order to better understand the molecular insights of this localized reaction and to expand our armamentarium in the management of patients with an impaired fracture healing response. Non-steroidal anti-in fl ammatory drugs frequently administered for analgesia after trauma procedures continue to be a cause of concern for a successful bone repair response.

[1]  J. M. Guimarães,et al.  The effect of autologous concentrated bone-marrow grafting on the healing of femoral shaft non-unions after locked intramedullary nailing. , 2014, Injury.

[2]  P. Giannoudis,et al.  Can we enhance fracture vascularity: What is the evidence? , 2014, Injury.

[3]  W. Walsh,et al.  Can platelet-rich plasma (PRP) improve bone healing? A comparison between the theory and experimental outcomes , 2013, Archives of Orthopaedic and Trauma Surgery.

[4]  P. Giannoudis,et al.  Physiological Challenges of Bone Repair , 2012, Journal of orthopaedic trauma.

[5]  G. Duda,et al.  Inflammatory phase of bone healing initiates the regenerative healing cascade , 2012, Cell and Tissue Research.

[6]  P. Giannoudis,et al.  Diabetes and fracture healing: the skeletal effects of diabetic drugs , 2012, Expert opinion on drug safety.

[7]  D. Hutmacher,et al.  Biomimetic tubular nanofiber mesh and platelet rich plasma-mediated delivery of BMP-7 for large bone defect regeneration , 2012, Cell and Tissue Research.

[8]  M. Bracken.  Steroids for acute spinal cord injury. , 2012, The Cochrane database of systematic reviews.

[9]  Antonios G Mikos,et al.  Harnessing and modulating inflammation in strategies for bone regeneration. , 2011, Tissue engineering. Part B, Reviews.

[10]  Thomas A Einhorn,et al.  The biology of fracture healing. , 2011, Injury.

[11]  Rozalia Dimitriou,et al.  Bone regeneration: current concepts and future directions , 2011, BMC medicine.

[12]  L. Koenderman,et al.  Systemic inflammation and fracture healing , 2011, Journal of leukocyte biology.

[13]  Ya-Dong Zhang,et al.  Combination of platelet-rich plasma with degradable bioactive borate glass for segmental bone defect repair. , 2011, Acta orthopaedica Belgica.

[14]  M. Betsch,et al.  Combined use of platelet-rich plasma and autologous bone grafts in the treatment of long bone defects in mini-pigs. , 2010, Injury.

[15]  G. Duda,et al.  Fracture healing is accelerated in the absence of the adaptive immune system , 2010, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  E. Park,et al.  Angiogenic factor-enriched platelet-rich plasma enhances in vivo bone formation around alloplastic graft material , 2010, The journal of advanced prosthodontics.

[17]  P. Giannoudis,et al.  NSAIDS inhibit in vitro MSC chondrogenesis but not osteogenesis: implications for mechanism of bone formation inhibition in man , 2010, Journal of cellular and molecular medicine.

[18]  B. Lindsey,et al.  An animal model for open femur fracture and osteomyelitis—Part II: Immunomodulation with systemic IL‐12 , 2009, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[19]  L. Tagliabue,et al.  Application of rhBMP-7 and platelet-rich plasma in the treatment of long bone non-unions: a prospective randomised clinical study on 120 patients. , 2008, Injury.

[20]  T. Szczepański,et al.  Benefit of Percutaneous Injection of Autologous Platelet-Leukocyte-Rich Gel in Patients with Delayed Union and Nonunion , 2008, European Surgical Research.

[21]  J. Folkman,et al.  Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet alpha granules and differentially released. , 2008, Blood.

[22]  P. Giannoudis,et al.  Molecular aspects of fracture healing: which are the important molecules? , 2007, Injury.

[23]  O. Reikerås,et al.  Lipopolysaccharide impairs fracture healing: An experimental study in rats , 2005, Acta orthopaedica.

[24]  Paquita Nurden,et al.  Autologous platelets as a source of proteins for healing and tissue regeneration , 2003, Thrombosis and Haemostasis.

[25]  G. Zimmerman,et al.  The platelet-activating factor signaling system and its regulators in syndromes of inflammation and thrombosis , 2002, Critical care medicine.

[26]  Thomas A Einhorn,et al.  Differential Temporal Expression of Members of the Transforming Growth Factor β Superfamily During Murine Fracture Healing , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[27]  T. Einhorn,et al.  Impaired Intramembranous Bone Formation during Bone Repair in the Absence of Tumor Necrosis Factor-Alpha Signaling , 2001, Cells Tissues Organs.

[28]  D. Macdonald,et al.  Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal anti-inflammatory drugs. , 2000, The Journal of bone and joint surgery. British volume.

[29]  R. Marx,et al.  Platelet-rich plasma: Growth factor enhancement for bone grafts. , 1998, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[30]  T. Rőszer,et al.  Inflammation as death or life signal in diabetic fracture healing , 2010, Inflammation Research.

[31]  Bert R. Mandelbaum,et al.  From Basic Science to Clinical Applications , 2009 .

[32]  L. Cooper,et al.  Macrophage cell lines produce osteoinductive signals that include bone morphogenetic protein-2. , 2002, Bone.