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Arch Orthop Trauma Surg. 2012 Aug;132(8):1205-13. doi: 10.1007/s00402-012-1525-4. Epub 2012 May 24.

Anti-inflammatory treatment increases angiogenesis during early fracture healing.

Author information

1
Department of Orthopaedic Surgery, Orthopaedic Trauma Institute, San Francisco General Hospital, University of California at San Francisco, San Francisco, CA 94110, USA.

Abstract

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.

PMID:
22622792
DOI:
10.1007/s00402-012-1525-4
[Indexed for MEDLINE]

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