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 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.
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 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: Luke G McVeigh; Anthony J Perugini; Jill C Fehrenbacher; Fletcher A White; Melissa A Kacena Journal: Curr Osteoporos Rep Date: 2020-10 Impact factor: 5.096
Authors: D A Behrends; D Hui; C Gao; A Awlia; Y Al-Saran; A Li; J E Henderson; P A Martineau Journal: Clin Orthop Relat Res Date: 2016-11-14 Impact factor: 4.176