Diclofenac, a NSAID, delays fracture healing in aged mice.

Autor: Menger MM; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany; Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, Saar, Germany. Electronic address: maximilian.menger@uks.eu., Stief M; Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, Saar, Germany., Scheuer C; Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, Saar, Germany., Rollmann MF; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany., Herath SC; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany., Braun BJ; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany., Ehnert S; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany; Department of Trauma and Reconstructive Surgery, BG Trauma Center Tuebingen, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany., Nussler AK; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany; Department of Trauma and Reconstructive Surgery, BG Trauma Center Tuebingen, Siegfried Weller Institute for Trauma Research, Eberhard Karls University Tuebingen, 72076 Tuebingen, Germany., Menger MD; Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, Saar, Germany., Laschke MW; Institute for Clinical & Experimental Surgery, Saarland University, 66421 Homburg, Saar, Germany., Histing T; Department of Trauma and Reconstructive Surgery, Eberhard Karls University Tuebingen, BG Trauma Center Tuebingen, 72076 Tuebingen, Germany.
Jazyk: angličtina
Zdroj: Experimental gerontology [Exp Gerontol] 2023 Jul; Vol. 178, pp. 112201. Date of Electronic Publication: 2023 May 23.
DOI: 10.1016/j.exger.2023.112201
Abstrakt: Nonsteroidal anti-inflammatory drugs (NSAIDs), such as diclofenac, belong to the most prescribed analgesic medication after traumatic injuries. However, there is accumulating evidence that NSAIDs impair fracture healing. Because bone regeneration in aged patients is subject to significant changes in cell differentiation and proliferation as well as a markedly altered pharmacological action of drugs, we herein analyzed the effects of diclofenac on bone healing in aged mice using a stable closed femoral facture model. Thirty-three mice (male n = 14, female n = 19) received a daily intraperitoneal injection of diclofenac (5 mg/kg body weight). Vehicle-treated mice (n = 29; male n = 13, female n = 16) served as controls. Fractured mice femora were analyzed by means of X-ray, biomechanics, micro computed tomography (μCT), histology and Western blotting. Biomechanical analyses revealed a significantly reduced bending stiffness in diclofenac-treated animals at 5 weeks after fracture when compared to vehicle-treated controls. Moreover, the callus tissue in diclofenac-treated aged animals exhibited a significantly reduced amount of bone tissue and higher amounts of fibrous tissue. Further histological analyses demonstrated less lamellar bone after diclofenac treatment, indicating a delay in callus remodeling. This was associated with a decreased number of osteoclasts and an increased expression of osteoprotegerin (OPG) during the early phase of fracture healing. These findings indicate that diclofenac delays fracture healing in aged mice by affecting osteogenic growth factor expression and bone formation as well as osteoclast activity and callus remodeling.
Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest.
(Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: