title: A comparison of the effects of ibuprofen and rofecoxib on rabbit fibula osteotomy healing.
abstract: OBJECTIVE
  Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) activity, which is the rate-limiting enzyme in the synthesis of prostaglandins. Previous studies have indicated that NSAID therapy, and in particular NSAIDs that specifically target the inflammatory cyclooxygenase (COX-2), impair bone healing. We compared the effects of ibuprofen and rofecoxib on fibula osteotomy healing in rabbits to determine whether nominal, continuous inhibition of COX-2 with rofecoxib would differentially affect fracture healing more than cyclical inhibition of COX-2 using ibuprofen, which inhibits COX-1 and COX-2 and has a short half-life in vivo.
  
  
  METHODS
  Bilateral fibula osteotomies were done in 67 skeletally mature male New Zealand white rabbits. The rabbits were treated with placebo, rofecoxib (12.5 mg once a day), or ibuprofen (50 mg 3 times a day) for 28 days after surgery. Plasma ibuprofen levels were measured by HPLC analysis. Bone healing was assessed by histomorphometry at 3 and 6 weeks after osteotomy, and at 6 and 12 weeks by torsional mechanical testing.
  
  
  RESULTS
  Plasma ibuprofen levels peaked and declined between successive doses. Fracture callus morphology was abnormal in the rofecoxib-treated rabbits and torsional mechanical testing showed that fracture healing was impaired. Ibuprofen treatment caused persistence of cartilage within the fracture callus and reduced peak torque at 6 weeks after osteotomy as compared to the fibulas from the placebo-treated rabbits. In the specimens allowed to progress to possible healing, non-union was seen in 5 of the 26 fibulas from the rofecoxib-treated animals as compared to 1 of 24 in the placebo group and 1 of 30 in the ibuprofen treatment group.
  
  
  CONCLUSIONS
  Continuous COX-2 inhibition as modeled by rofecoxib treatment appears to be more deleterious to fracture repair than cyclical cyclooxygenase inhibition as modeled by ibuprofen treatment. Ibuprofen treatment appeared to delay bone healing based upon the persistence of cartilage within the fracture callus and diminished shear modulus. Despite the ibuprofen-induced delay, rofecoxib treatment produced worse fracture (osteotomy) healing than ibuprofen treatment.
authors.affiliation: Department of Biochemistry, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, NJ, USA. oconnojp@umdnj.edu
authors.forename: J Patrick
authors.initials: JP
authors.lastname: O'Connor
authors.forename: John T
authors.initials: JT
authors.lastname: Capo
authors.forename: Virak
authors.initials: V
authors.lastname: Tan
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Cottrell
authors.forename: Michaele B
authors.initials: MB
authors.lastname: Manigrasso
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bontempo
authors.forename: J Russell
authors.initials: JR
authors.lastname: Parsons
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001696:Biomechanical Phenomena; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D005360:Fibula / Q000187:drug effects / Q000473:pathology / Q000601:surgery*; D017102:Fracture Healing / Q000187:drug effects*; D050723:Fractures, Bone / Q000188:drug therapy / Q000601:surgery*; D007052:Ibuprofen / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D007783:Lactones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010027:Osteotomy; D011817:Rabbits; D013450:Sulfones / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D007783:Lactones; D013450:Sulfones; C116926:rofecoxib; D007052:Ibuprofen