Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing

Cottrell, Jessica; O’Connor, J. P.

doi:10.3390/ph3051668

Cited by 97 publications

(72 citation statements)

References 112 publications

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“…1,2 Bone fracture is one of the most common injuries, which is associated with high treatment costs exceeding billions of dollars, societal productivity loss, and individual disability. 3,4 With the development of orthopedic surgical techniques and implant materials, the prognosis of fracture is markedly improved.…”

Section: Introductionmentioning

confidence: 99%

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

Wang¹,

Li²,

Ren³

et al. 2017

IJN

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Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague–Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu 2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu 2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu 2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better fracture healing.

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Section: Introductionmentioning

confidence: 99%

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

Wang¹,

Li²,

Ren³

et al. 2017

IJN

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“…10,11 Diclofenac reduces inflammation, swelling, and arthritic pain by direct inhibition of cyclooxygenase isozymes (COX-1 and COX-2) peripherally in injured tissues as well as in the central nervous system, which leads to the inhibition of prostaglandins production from arachidonic acid. 12,13 In addition, diclofenac also exerts its action via the inhibition of the thromboxane-prostanoid receptor and lipoxygenase enzymes, and the activation of nitric oxide-cGMP antinociceptive pathway. 14 In the present study, antinociceptive activity of liposome-encapsulated and free-form diclofenac was evaluated in vivo via different nociceptive assay models.…”

mentioning

confidence: 99%

Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

Goh

Tang

Chiong

et al. 2014

IJN

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Diclofenac is a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, antinociceptive, and antipyretic activities. Liposomes have been shown to improve the therapeutic efficacy of encapsulated drugs. The present study was conducted to compare the antinociceptive properties between liposome-encapsulated and free-form diclofenac in vivo via different nociceptive assay models. Liposome-encapsulated diclofenac was prepared using the commercialized proliposome method. Antinociceptive effects of liposome-encapsulated and free-form diclofenac were evaluated using formalin test, acetic acid-induced abdominal writhing test, Randall–Selitto paw pressure test, and plantar test. The results of the writhing test showed a significant reduction of abdominal constriction in all treatment groups in a dose-dependent manner. The 20 mg/kg liposome-encapsulated diclofenac demonstrated the highest antinociceptive effect at 78.97% compared with 55.89% in the free-form group at equivalent dosage. Both liposome-encapsulated and free-form diclofenac produced significant results in the late phase of formalin assay at a dose of 20 mg/kg, with antinociception percentages of 78.84% and 60.71%, respectively. Significant results of antinociception were also observed in both hyperalgesia assays. For Randall–Sellito assay, the highest antinociception effect of 71.38% was achieved with 20 mg/kg liposome-encapsulated diclofenac, while the lowest antinociceptive effect of 17.32% was recorded with 0 mg/kg liposome formulation, whereas in the plantar test, the highest antinociceptive effect was achieved at 56.7% with 20 mg/kg liposome-encapsulated diclofenac, and the lowest effect was shown with 0 mg/kg liposome formulation of 8.89%. The present study suggests that liposome-encapsulated diclofenac exhibits higher antinociceptive efficacy in a dose-dependent manner in comparison with free-form diclofenac.

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“…In several studies, fracture healing was delayed in animals treated with NSAIDs in that intermediate measures of healing were reduced in the NSAID-treated animals but ultimate healing was not significantly affected. 2 In contrast, fracture healing was severely impaired in rats treated with COX-2-selective NSAIDs, such as rofecoxib and celecoxib. 12 Healing in the COX-2-selective NSAID-treated rats was characterized by abnormal callus cartilage morphology and an apparent failure of the callus chondrocytes to progress into hypertrophy based upon reduced type X collagen mRNA levels.…”

Section: The Role Of Lipid Mediator Synthesis Enzymes In Fracture Heamentioning

confidence: 99%

“…Indeed, nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit inflammation also impair fracture healing. 2 NSAIDs reduce the synthesis of lipid mediators that regulate inflammation by inhibiting cyclooxygenase activity. This indicates that cyclooxygenase-derived lipid mediators have a critical role in promoting fracture healing.…”

Section: Introductionmentioning

confidence: 99%

Fracture healing and lipid mediators

O’Connor¹,

Manigrasso²,

Kim³

et al. 2014

BoneKEy Reports

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Lipid mediators regulate bone regeneration during fracture healing. Prostaglandins and leukotrienes are well-known lipid mediators that regulate inflammation and are synthesized from the O-6 fatty acid, arachidonic acid. Cyclooxygenase (COX-1 or COX-2) and 5-lipoxygenase (5-LO) catalyze the initial enzymatic steps in the synthesis of prostaglandins and leukotrienes, respectively. Inhibition or genetic ablation of COX-2 activity impairs fracture healing in animal models. Genetic ablation of COX-1 does not affect the fracture callus strength in mice, suggesting that COX-2 activity is primarily responsible for regulating fracture healing. Inhibition of cyclooxygenase activity with nonsteroidal anti-inflammatory drugs (NSAIDs) is performed clinically to reduce heterotopic ossification, although clinical evidence that NSAID treatment impairs fracture healing remains controversial. In contrast, inhibition or genetic ablation of 5-LO activity accelerates fracture healing in animal models. Even though prostaglandins and leukotrienes regulate inflammation, loss of COX-2 or 5-LO activity appears to primarily affect chondrogenesis during fracture healing. Prostaglandin or prostaglandin analog treatment, prostaglandin-specific synthase inhibition and prostaglandin or leukotriene receptor antagonism also affect callus chondrogenesis. Unlike the O-6-derived lipid mediators, lipid mediators derived from O-3 fatty acids, such as resolvin E 1 (RvE1), have anti-inflammatory activity. In vivo, RvE1 can inhibit osteoclastogenesis and limit bone resorption. Although O-6 and O-3 lipid mediators have clear-cut effects on inflammation, the role of these lipid mediators in bone regeneration is more complex, with apparent effects on callus chondrogenesis and bone remodeling.

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Effect of Non-Steroidal Anti-Inflammatory Drugs on Bone Healing

Cited by 97 publications

References 112 publications

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

Evaluation of antinociceptive activity of nanoliposome-encapsulated and free-form diclofenac in rats and mice

Fracture healing and lipid mediators

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