Trabecular bone remodelling in the femur of C57BL/6J mice treated with diclofenac in combination with treadmill exercise

Abstract

Purpose: Analgesic treatment with diclofenac deteriorates bone structure and decreases biomechanical properties. This bone loss has been though to be reversed by training. The impact of exercise on bone treated with diclofenac (DF) has reminded elusive. In the present study, we assayed the combined impact of exercises and DF on mouse femur. Methods: The femur samples we obtained from 30 days treated C57BL/6J female mice. The training group ran on a horizontal treadmill at 12 m/min by 30 min a day (5% grade/slope). The group of ten mice treated with DF received the drug subcutaneously every day (5 mg/kg of body weight/day). The combined group ran on the treadmill and obtained DF. After 30 days, we sacrificed mice and studied their femurs using microcomputed tomography (µCT), dynamic mechanical analysis (DMA) and nanoindentation. Results: We observed that treadmill running and DF decreased trabecular bone volume and mineral density. Combined effect of training and DF was not additive. A significant interaction of both parameters suggested protective effect of training on bone loss provoked by DF. The femur cortical bone shell remained untouched by the training and treatment. The training and the DF treatment did not alter the storage modulus E' significantly. The unchanged storage modulus would be suggesting on the unaltered bone strength. Conclusions: We concluded that even relatively short time of training with concomitant DF treatment could be protective on trabecular bone. Although viscoelastic properties of the entire femur were not modulated, femur trabecular tissue was thinned by treatment with DF and protected by training.

Application of thermal analysis methods in biology and medicine

“…For sheep bones, a change could be observed and was especially marked in tan d decrease, significantly decreasing the damping (energy dissipating) ability of the bones (126). The influence of diclofenac treatment (known to deteriorate bone structure) and exercise on female mice bones was also investigated by DMA (127), but the results were mostly ambivalent, with no major statistical differences. This is not unusual for mechanical property testing, where a large number of measurements is needed to obtain satisfactory statistical analysis, which is not always feasible for long DMA measurements.…”

“…Thermal analysis methods are rarely used to characterize the mechanical properties of plants, but they found much wider applications on animal samples, due to the greater flexibility of the methods and small sample sizes needed for the analysis, as well as the ability to measure viscoelastic properties. Mechanical properties of biological samples expectedly show a large scatter (122,127): proper mechanical analysis of synthetic materials also requires a large number of samples, and the diversity in living organisms is comparably greater. A shortcoming of DMA and TMA in comparison with classical mechanical testing methods is a smaller number of measurements per sample, making statistical analysis less likely to find significant correlations or differences (127), even when they are perceptible from the data (143,152).…”

“…Mechanical properties of biological samples expectedly show a large scatter (122,127): proper mechanical analysis of synthetic materials also requires a large number of samples, and the diversity in living organisms is comparably greater. A shortcoming of DMA and TMA in comparison with classical mechanical testing methods is a smaller number of measurements per sample, making statistical analysis less likely to find significant correlations or differences (127), even when they are perceptible from the data (143,152).…”