Effects of a selective cyclooxygenase-2 inhibitor (celecoxib) on fracture healing in rats

Li, Kanghua; Cheng, Liang; Zhu, Yong; Deng, Guobing; Long, Haitao

doi:10.4103/0019-5413.114930

Cited by 7 publications

(5 citation statements)

References 30 publications

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“…Available animal studies in a rat model of periodontitis, however, have reported suppressive effects of etoricoxib on inflammation, osteoclastogenesis, and alveolar bone loss [ 60 , 61 ], which could, however, not be replicated in man [ 62 ], corresponding to our own results on human PDL fibroblasts. In contrary to the less COX-2-selective celecoxib [ 63 ], etoricoxib had no negative impact on alveolar bone healing in rats [ 64 ], whereas a reported antiangiogenetic effect in experimental lung cancer [ 65 ] was not observed at the etoricoxib concentrations used in our study.…”

Section: Discussioncontrasting

confidence: 89%

Effects of the Highly COX-2-Selective Analgesic NSAID Etoricoxib on Human Periodontal Ligament Fibroblasts during Compressive Orthodontic Mechanical Strain

Kirschneck

Küchler

Wolf

et al. 2019

Mediators of Inflammation

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Human periodontal ligament (hPDL) fibroblasts play a major role during periodontitis and orthodontic tooth movement, mediating periodontal inflammation, osteoclastogenesis, and collagen synthesis. The highly COX-2-selective NSAID etoricoxib has a favorable systemic side effect profile and high analgesic efficacy, particularly for orthodontic pain. In this in vitro study, we investigated possible side effects of two clinically relevant etoricoxib concentrations on the expression pattern of mechanically strained hPDL fibroblasts and associated osteoclastogenesis in a model of simulated orthodontic compressive strain occurring during orthodontic tooth movement. hPDL fibroblasts were incubated for 72 h under physiological conditions with etoricoxib at 0 μM, 3.29 μM, and 5.49 μM, corresponding to clinically normal and subtoxic dosages, with and without mechanical strain by compression (2 g/cm2) for the final 48 h, simulating conditions during orthodontic tooth movement in compressive areas of the periodontal ligament. We then determined gene and/or protein expression of COX-2, IL-6, PG-E2, RANK-L, OPG, ALPL, VEGF-A, P4HA1, COL1A2, and FN1 via RT-qPCR, ELISA, and Western blot analyses as well as apoptosis, necrosis, cell viability, and cytotoxicity via FACS, MTT, and LDH assays. In addition, hPDL fibroblast-mediated osteoclastogenesis was assessed by TRAP staining in coculture with RAW267.4 cells for another 72 h. Gene and protein expression of all evaluated factors was significantly induced by the mechanical compressive strain applied. Etoricoxib at 3.29 μM and 5.49 μM significantly inhibited PG-E2 synthesis, but not COX-2 and IL-6 gene expression nor RANK-L-/OPG-mediated osteoclastogenesis or angiogenesis (VEGF-A). Extracellular matrix remodeling (COL1A2, FN1) and bone anabolism (ALPL), by contrast, were significantly stimulated particularly at 5.49 μM. In general, no adverse etoricoxib effects on hPDL fibroblasts regarding apoptosis, necrosis, cell viability, or cytotoxicity were detected. Clinically dosed etoricoxib, that is, a highly selective COX-2 inhibition, did not have substantial effects on hPDL fibroblast-mediated periodontal inflammation, extracellular matrix remodeling, RANK-L/OPG expression, and osteoclastogenesis during simulated orthodontic compressive strain.

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Section: Discussioncontrasting

confidence: 89%

Effects of the Highly COX-2-Selective Analgesic NSAID Etoricoxib on Human Periodontal Ligament Fibroblasts during Compressive Orthodontic Mechanical Strain

Kirschneck

Küchler

Wolf

et al. 2019

Mediators of Inflammation

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“…Several studies that mainly focused on and discussed the effects of various drugs on bone healing process have been published in the literature [2, 5–12, 23]. Accelerating the union of a fractured bone has been the major purpose of such studies as well as identifying the agents that negatively affect its progression [5–7, 23]. Although the effects of gabapentin on wound healing in rats [24] and intestinal incision wound healing in rabbits [25] have been tested, no study has examined the direct relationship between bone metabolism and gabapentin monotherapy.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, the effects of gabapentin were assessed via radiographic, histological, and mechanical analysis of the fracture healing process. The standardized experimental fracture healing model applied in this study has been widely used in the literature [5–7, 29]. Standard drug administration was achieved by oral gavage twice a day by the same administrator at the same time every day of the study period.…”

Section: Discussionmentioning

confidence: 99%

Should orthopedic surgeons consider the effects of gabapentin administration on bone healing while treating a long bone fracture: experimental study in a rat model

Sofu

Koçkara

Aydın

et al. 2016

SICOT-J

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Objective: The main purpose of the present study was to assess the radiographic, histological, and mechanical effects of gabapentin on fracture healing in a rat model of femur fracture. Materials and methods: A standard transverse fracture of the mid-diaphysis was created. A total of 60 female Wistar-Albino rats with the mean age of 13.5 ± 1.2 weeks were used for this experimental trial. The rats were randomized into four groups with 15 animals included in each group. Group A and B were the control groups whereas C and D were the treatment groups. Drugs were delivered by oral gavage twice a day with the daily dosage calculated according to body surface area conversion to the human equivalent dosing regimen of 1200 mg/day. Radiographic, histological, and biomechanical evaluation was performed. Results: We could not detect any statistically significant difference between the control and gabapentin treatment groups according to the comparative assessment of radiographic scores on the 15th and 30th days. Although no significant differences were found between the groups on the 15th day, histological scores were better in the control group on the 30th day. According to the results of biomechanical testing, the fractured femurs resected from the control group exhibited significantly more strength on the 30th day. Conclusions: According to the data we acquired during the present study, administration of gabapentin negatively affects the fracture healing process especially in the aspects of histological progression as well as the biomechanical strength of the callus in a rat model.

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“…In an inflammatory state, high concentrations of the COX-2 inhibitor can reduce the content of alkaline phosphatase and calcium in bone marrow mesenchymal stem cells [40]. In a rat fracture model, short-term and long-term use of COX-2 inhibitors significantly interfered with bone adhesion and fracture healing [41]. In healthy Sprague Dawley rats, long-term use of COX-2 inhibitors stimulated bone resorption and reduced bone mass and mechanical properties of the femur [42].…”

Section: Discussionmentioning

confidence: 99%

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

Liu¹,

Ji²,

Shao³

et al. 2020

Preprint

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BackgroundEtoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA.MethodsOA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM).ResultsEtoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. ConclusionOur results demonstrate that although Etoricoxib can relieve the pain induced by OA, it also has adverse effects on subchondral bone in early OA.

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Effects of a selective cyclooxygenase-2 inhibitor (celecoxib) on fracture healing in rats

Cited by 7 publications

References 30 publications

Effects of the Highly COX-2-Selective Analgesic NSAID Etoricoxib on Human Periodontal Ligament Fibroblasts during Compressive Orthodontic Mechanical Strain

Effects of the Highly COX-2-Selective Analgesic NSAID Etoricoxib on Human Periodontal Ligament Fibroblasts during Compressive Orthodontic Mechanical Strain

Should orthopedic surgeons consider the effects of gabapentin administration on bone healing while treating a long bone fracture: experimental study in a rat model

Etoricoxib decreases mouse subchondral bone mass and biomechanical properties in early osteoarthritis

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