Effects of efavirenz and tenofovir on bone tissue in Wistar rats

Adv Clin Exp Med. 2020 Nov;29(11):1265-1275. doi: 10.17219/acem/127684.

Abstract

Background: Clinical trials indicate an increased risk of osteoporosis and bone fractures in people infected with human immunodeficiency virus (HIV). The pathogenesis of bone disturbances in HIV-positive patients is unknown, but it is suggested that antiretroviral drugs may be involved.

Objectives: To assess the effects of efavirenz (EF) and tenofovir (T) on bone remodeling in rats.

Material and methods: The study involved 36 male Wistar rats divided into 3 groups, receiving normal saline (control group - group C), efavirenz (group EF) or tenofovir disoproxil (group T).

Results: After 24 weeks of the study, the following observations were made: In blood serum of the EF group compared to group C, there were increased levels of tartrate-resistant acid phosphatase form 5b (TRAP) and inorganic phosphorus. In the densitometric examination, group T showed a lower total body (TB) bone mineral density (BMD) than group C. In the immunohistochemical assessment, group EF showed a higher intensity and extension of anti-tartrate resistant acid phosphatase antibodies (abTRAP) compared to group C. In the histopathological examination of the second lumbar vertebra (L2), group EF showed a lower bone surface/volume ratio (BS/BV) and higher trabecular thickness (Tb.Th) than the control group. In the histopathological examination of the femur, a lower bone surface/tissue volume (BS/TV) and lower trabecular number (Tb.N) were found in group T compared to in group C. A lower value of the Young's modulus was observed in the four-point bending trial in groups EF and T compared to group C.

Conclusions: The results of this study indicate that EF affects bone microarchitecture and leads to impaired biomechanical properties of bones in rats. Additionally, the negative effect of T on bone tissue was confirmed.

Keywords: antiretroviral drug; bone; efavirenz; rat model; tenofovir.

MeSH terms

  • Alkynes
  • Animals
  • Benzoxazines
  • Bone Density*
  • Bone and Bones*
  • Cyclopropanes
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Tenofovir

Substances

  • Alkynes
  • Benzoxazines
  • Cyclopropanes
  • Tenofovir
  • efavirenz