title: Anti-inflammatory treatment increases angiogenesis during early fracture healing.
abstract: OBJECTIVE
  Both inflammation and angiogenesis are crucial for normal fracture healing. The goal of this work was to determine how anti-inflammatory treatment affects angiogenesis during early stages of fracture repair.
  
  
  METHODS
  Tibia fractures were created in adult mice and animals were treated with indomethacin (2 mg/kg/day), a non-steroidal anti-inflammatory drug, or PBS once a day beginning from 1 day before fracture and continuing to 6 days after fracture. Animals were killed at 7, 14, and 28 days after injury for histomorphometric analysis of fracture healing. A second group of animals were killed at 3 and 7 days after injury to measure tissue levels of VEGF and interleukin-1 beta (IL-1β). A third group of animals were killed at 3 and 7 days after injury for stereology analysis of macrophage and neutrophil infiltration and tissue vascularization.
  
  
  RESULTS
  Indomethacin significantly decreased bone and cartilage formation at 7 days after fracture compared to controls. Indomethacin decreased the tissue levels of IL-1β at 3 days after fracture but did not affect the recruitment of macrophages or neutrophils to injured limbs. Indomethacin-treated fractures had similar length density and surface density of vasculature as the controls at 3 days after injury. At 7 days after fracture, vasculature in indomethacin-treated fractures exhibited higher length density and surface density than that in controls. By 28 days after injury, indomethacin-treated fractures still exhibited defects in fracture repair.
  
  
  CONCLUSIONS
  Anti-inflammatory treatments using indomethacin impair bone and cartilage formation and increase tissue vascularization in the callus during early fracture healing.
authors.affiliation: Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA 94110, USA.
authors.forename: Chuanyong
authors.initials: C
authors.lastname: Lu
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Xing
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Wang
authors.forename: Jeremy
authors.initials: J
authors.lastname: Mao
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Marcucio
authors.forename: Theodore
authors.initials: T
authors.lastname: Miclau
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D017102:Fracture Healing / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D018919:Neovascularization, Physiologic / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D007213:Indomethacin