Comparison of the effects of dexketoprofen trometamol, meloxicam and diclofenac sodium on fibular fracture healing, kidney and liver: An experimental rat model
Introduction
Nonsteroidal anti-inflammatory drugs (NSAIDs) are especially useful in patients with bone fractures due to their excellent analgesic and anti-inflammatory effects. However, these drugs can significantly delay fracture healing [1], [2], [3], [4], [5], [6]. Endogenous prostaglandins (PGs), which are commonly found in bone, have beneficial effects on fracture healing [7], [8], [9], [10]. The effect of NSAIDs is focused on the inhibition of cyclooxygenase (COX). As a result of this inhibition, the PGs lose their effects as mediators in the bone fracture healing process [7], [11], [12]. However, in vitro studies have focused on the activity of osteoblasts and have shown that NSAIDs impair the bone turnover, regeneration, and proliferation of osteoblasts [13], [14], [15], [16]. There are limited studies on whether one NSAID shows superiority over another in the bone fracture healing process and with respect to kidney and liver toxicity [1], [17], [18], [19], [20], [21].
The aim of this study was to use histopathological and biochemical parameters to determine whether there are differences between the effects of the clinical dosages of dexketoprofen trometamol (DEXT), meloxicam (MEL), and diclofenac sodium (DIC) on the healing of closed fibular fractures with respect to toxicity of both the liver and kidney.
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Materials and methods
The experimental protocols were approved by the institutional animal ethics committee. The animals were obtained from the medical and surgical experimental research centre of the institute. All of the rats were housed in polycarbonate cages in a room with controlled temperature (22 ± 2 °C) and humidity (50 ± 5%) and a 12-hour(h)/12-h light/dark cycle. The rats were fed laboratory pellet chow, and water was provided ad libitum. All of the following experiments followed the Guiding Principles for the
Fibular union histopathology
The histological scores of the DEXT and MEL study groups were significantly lower than those of the control group (p < 0.05). The scores of the DIC group were equal to those of the control group (p = 1.00). The comparison of the study groups revealed that all of the groups exhibited significant differences (DEXT-MEL, p < 0.05; DEXT-DIC, p < 0.05; and MEL-DIC, p < 0.05). The lowest scores were found in the MEL group. The histological scores and descriptive data are presented in Table 2, Table 3.
Discussion
Bone fracture healing is one of the most complex cascades of events that results to union [28]. Many factors, such as the use of NSAIDs for the prevention of bone fracture pain, can affect this process. Recent studies have shown that these drugs affect the process of bone fracture healing [29], [30], [31]. NSAIDs interfere with the arachidonic acid mechanism by blocking the formation of PGs through the inhibition of the cyclooxygenase pathway, which plays a fundamental role in the bone healing
Conclusion
At present, there is no strong scientific evidence that supports discarding of the use of NSAIDs for the treatment of fracture-related pain. Our results suggest that DEXT and MEL impair the bone fracture healing process. In contrast, DIC did not histopathologically affect the bone fracture healing process. Because our findings in rats should not be extrapolated to humans, there is a need for further studies on the effects of NSAIDs on the fracture healing process in humans.
In clinical
Conflict of interest statement
None declared.
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