Isotretinoin induced achilles tendinopathy: Histopathological and biomechanical evaluation on rats

Abstract

Objective: The aim of the present study was to evaluate histopathological and biomechanical effects of isotretinoin on Achilles tendon.

Materials & methods: Sixteen rats were divided into two groups including the control group (n = 8) and isotretinoin group (n = 8). The control group received 1.42 ml/kg soy oil per day whereas the isotretinoin group received 15 mg/kg/day (gavage dose 1.42 ml/kg) isotretinoin dissolved in soy oil through gavage method for 6 weeks. Achilles tendons were excised at the end of week 6. The tendon samples were evaluated by hematoxylin-eosin under a light microscope. Quantitative evaluation was performed via Movin and Bonar scoring. A computer-monitored tensile testing machine was utilised for biomechanical testing. Biomechanical characteristics of the tendon samples (elastic modulus, yield force, ultimate tensile force) were measured.

Results: Histopathological evaluation revealed a significantly higher Movin and Bonar scores in histopathological evaluation. Movin score in isotretinoin group was 4.1 ± 2.5 and it was 2.3 ± 1.0 in control group (p = 0.032). Bonar score in isotretinoin group was 2.9 ± 1.4 and it was 1.6 ± 0.7 in control group (p = 0.022). In line with histopathological evaluation, biomechanical measurements in isotretinoin group (elastic modulus, yield force, ultimate tensile force) were significantly lower than the control group. Elastic modulus in isotretinoin group was 227 ± 27.7 N/mm² and in control group it was 281.7 ± 38.7 N/mm² (p = 0.006). In isotretinoin group; yield force was 33.7 ± 4.3 Pa and in control group it was 40.8 ± 5.9 Pa (p = 0.021). Ultimate tensile force in isotretinoin group was 35.7 ± 4.2 Pa and in control group it was 44 ± 7 Pa (p = 0.009).

Conclusion: The present study detected histopathological and biomechanical negative effect of isotretinoin on Achilles tendon. Therefore, isotretinoin should be questioned in medical history of patients with tendinopathy.

Keywords: Biomechanic; Isotretinoin; Rat; Tendinopathy; Tendon.

Fig. 1

The pulling device used for the rupture test (AG IS-50 kN,Shimadzu).

Fig. 2

Spindle shaped nuclei and indistinct cytoplasm in tenocytes (C4- H.E X 400).

Fig. 3

Increase in cellularity, minimally round, and ovoidnuclei in tenocytes (E1- H.E X 400).

Fig. 4

Tenocytes with round nuclei and distinct cytoplasm (E3- H.E X 400).

Fig. 5

Increase in vascularity (E7- H.E X 400).