Histologic evaluation of femoral nerve demyelinating and axonal neuropathy in Wistar rats due to alendronate intake: a randomised study

Abstract

Background: Bisphosphonates (BPs) are forceful inhibitors of osteoclast-mediated bone resorption. Long-term BP use is associated with multiple rare but severe adverse effects. The objective of this study was to investigate the possible effects of BPs in the structure of femoral nerve. Specimens from the femoral nerve of ten female 12-month old Wistar rats were used as control group and ten female 12-month old Wistar rats to which Alendronate (Fosamax, Merck) was administered per os for 13 weeks, were used as research group. Samples were observed under a Transmission Electron Microscope. G ratio measurements and statistical analysis with SPSS program were also performed. Results:The control group showed no major changes of the nerve's histologic image, with the exception of some spots of thickness of the nerve myelin sheath. The research group showed major morphological changes which varied from partial disorganization or thickening of the myelin to severe myelin thickening and axon strangulation. A statistically significant difference of the G ratio between the two groups was observed. Conclusions:The reported values (found in literature) for the morphologic measurements of the femoral nerve in Wistar rats are not complying with the ones we found in our study. There was a significant reduction of all three variables (the mean axon like diameter, the myelin thickness, G ratio) studied in the femoral nerve of the research group in contrast to control group. Our study demonstrates a possible correlation between alendronate administration and femoral nerve's function, nevertheless due to the small specimen further research is needed.

Immunohistochemical Femoral Nerve Study Following Bisphosphonates Administration

“…Immunohistochemical staining for Sox10 showed that samples extracted from rats given alendronate were more positive (++) compared to samples of the control group, where the marker's expression was not so intense (+). Our results are in agreement with a previous study conducted under transmission electron microscope, suggested ultrastructural alterations of the femoral nerve [38], and confirm that degenerative changes in the myelin sheath occur following BP administration. Study of the inferior alveolar nerve under the same conditions evidenced myelin vacuolization, axonal detachment, local thickening, and/or myelin disruption ( Figure 5) [15].…”