Anti-inflammatory treatment increases angiogenesis during early fracture healing

Chuanyong Lu, Zhiqing Xing, Xiaodong Wang, Jeremy Mao, Ralph S. Marcucio, Theodore Miclau

Research output: Contribution to journalArticlepeer-review

14 Scopus citations


Objectives: 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 indomethacintreated 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.

Original languageEnglish (US)
Pages (from-to)1205-1213
Number of pages9
JournalArchives of Orthopaedic and Trauma Surgery
Issue number8
StatePublished - Aug 2012
Externally publishedYes


  • Angiogenesis
  • Fracture repair
  • Indomethacin
  • Inflammation

ASJC Scopus subject areas

  • Surgery
  • Orthopedics and Sports Medicine


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