Cyclooxygenase-2 inhibitors in human skeletal fracture healing.
This article identifies the underlying molecular events responsible for fracture nonunions in a subset of fracture patients. Expression profiling of fracture callus tissue from both uneventful fracture repair and nonunion outcomes showed a decrease of COX-2 expression and an inability to mount an immune response in nonunion fractures. Validation in vitro with Saos-2 osteoprogenitor cell lines showed a decrease in osteogenesis potential after the cells were treated with celecoxib, a COX-2 specific inhibitor and anti-inflammatory agent. This article recapitulates that an initial immune response is crucial to fracture healing and suggests limited usage of COX-2 inhibitors in patients with healing fractures.
Daluiski
Aaron
A
Hospital for Special Surgery, New York, NY, USA.
Ramsey
Keri E
KE
Shi
Yuexian
Y
Bostrom
Mathias P
MP
Nestor
Bryan J
BJ
Martin
George
G
Hotchkiss
Robert
R
Stephan
Dietrich A
DA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002146:Bony Callus / Q000166:cytology / Q000378:metabolism; D000068579:Celecoxib; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000187:drug effects / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D005260:Female; D017102:Fracture Healing / Q000187:drug effects*; D005599:Fractures, Ununited / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D016861:Cyclooxygenase Inhibitors; D008565:Membrane Proteins; D011720:Pyrazoles; D011994:Recombinant Proteins; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D000068579:Celecoxib