title: Effects of diclofenac on periosteal callus maturation in osteotomy healing in an animal model.
abstract: BACKGROUND
  Potential adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on bone metabolism and fracture healing are contradictive to their wide application in post-traumatic treatment. Our objective was to investigate changes to periosteal callus formation with respect to NSAID and central analgesic drug application. Our hypothesis was that callus formation is delayed in animals treated with the non-specific NSAID diclofenac.
  
  
  METHODS
  The left tibia of forty male Wistar rats were osteotomized, stabilized with a Kirschner wire, and randomized into four groups of ten animals. Group 1 received a placebo, group 2 received the central analgesic tramadol (20 mg/kg per day) throughout the study, and groups 3 and 4 were treated with sodium diclofenac (5 mg/kg per day). Group 3 received diclofenac for seven days, followed by placebo until sacrifice (short-term), while group 4 animals received diclofenac for the full period (long-term). Animals were sacrificed 21 days after osteotomy.
  
  
  RESULTS
  Under light microscopy, all osteotomies healed successfully and independently of the drug treatment. Histomorphometry revealed delayed callus maturation in long-term diclofenac treated animals, with significantly higher amounts of cartilage and less bone, particularly in the outermost region of periosteal callus. Short-term NSAID and tramadol application did not significantly alter callus differentiation.
  
  
  CONCLUSIONS
  Callus maturation in vivo was impaired after long-term application of diclofenac which corresponds to the in vitro findings of a dose-dependent effect of NSAIDs on osteoblast proliferation.
authors.affiliation: Department of Traumatology, Hand, Plastic, and Reconstructive Surgery, University of Ulm, Steinhoevelstr. 9, 89075 Ulm, Germany. gert.krischak@uniklinik-ulm.de
authors.forename: Gert D
authors.initials: GD
authors.lastname: Krischak
authors.forename: Peter
authors.initials: P
authors.lastname: Augat
authors.forename: Tobias
authors.initials: T
authors.lastname: Sorg
authors.forename: Robert
authors.initials: R
authors.lastname: Blakytny
authors.forename: Lothar
authors.initials: L
authors.lastname: Kinzl
authors.forename: Lutz
authors.initials: L
authors.lastname: Claes
authors.forename: Alexander
authors.initials: A
authors.lastname: Beck
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002146:Bony Callus / Q000187:drug effects* / Q000473:pathology; D004008:Diclofenac / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008297:Male; D023421:Models, Animal; D010027:Osteotomy / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014147:Tramadol / Q000494:pharmacology; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac; D014147:Tramadol