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Diclofenac, a NSAID, delays fracture healing in aged mice
Maximilian M Menger1, Maximilian Stief2, Claudia Scheuer2
1Department 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.
Abstract:
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.
Insights
Diclofenac, a common pain reliever, was found to significantly delay fracture healing in aged mice. This nonsteroidal anti-inflammatory drug (NSAID) impaired bone formation and remodeling, impacting recovery in older individuals.
Area of Science:
- Orthopedics and Regenerative Medicine
- Pharmacology and Drug Action
- Gerontology and Aging Research
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed for pain management following traumatic injuries.
- Accumulating evidence suggests NSAIDs may negatively impact fracture healing processes.
- Bone regeneration is significantly altered in aged individuals, affecting cellular functions and drug responses.
Purpose of the Study:
- To investigate the effects of diclofenac on bone healing in an aged mouse model.
- To analyze diclofenac's impact on fracture repair using a stable closed femoral fracture model in elderly mice.
Main Methods:
- A stable closed femoral fracture model was established in aged mice.
- Diclofenac was administered daily via intraperitoneal injection (5 mg/kg body weight).
- Fractured femora were analyzed using X-ray, biomechanics, micro computed tomography (μCT), histology, and Western blotting.
Main Results:
- Diclofenac treatment significantly reduced bending stiffness in fractured femora at 5 weeks post-fracture.
- Callus tissue in diclofenac-treated mice showed reduced bone and increased fibrous tissue content.
- Histological analysis revealed less lamellar bone, delayed callus remodeling, decreased osteoclast numbers, and increased osteoprotegerin (OPG) expression.
Conclusions:
- Diclofenac delays fracture healing in aged mice.
- The drug negatively affects bone formation, callus remodeling, and osteoclast activity.
- Findings suggest caution when prescribing NSAIDs like diclofenac for fracture recovery in elderly patients.
