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Defective bone repair in diclofenac treated C57Bl6 mice with and without lipopolysaccharide induced systemic inflammation
Author(s) -
RamirezGarciaLuna Jose L.,
Wong Timothy H.,
Chan Daniel,
AlSaran Yazeed,
Awlia Ayman,
AbouRjeili Mira,
Ouellet Suzie,
Akoury Elie,
Lemarié Catherine A.,
Henderson Janet E.,
Martineau Paul A.
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27128
Subject(s) - medicine , inflammation , bone healing , diclofenac , lipopolysaccharide , angiogenesis , systemic administration , systemic inflammation , osteoclast , pharmacology , immunology , surgery , receptor , in vivo , biology , microbiology and biotechnology
Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. Nonsteroidal anti‐inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non‐selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide‐induced systemic inflammation. Repair of femoral window defects was characterized using micro computed tomography imaging and histological analyses at 2 weeks postoperative. The data indicate (a) impaired bone regeneration associated with reduced osteoblast, osteoclast, and macrophage activity; (b) changes in the number, activity, and distribution of mast cells in regenerating bone; and (c) impaired angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and exacerbates the negative effects of systemic inflammation on the repair process.