The effect of anti-retroviral therapy on fracture healing

Abstract

Aims A number of anti-retroviral therapies (ART) have been implicated in potentially contributing to HIV-associated bone disease. The aim of this study was to evaluate the effect of combination ART on the fracture healing process. Methods A total of 16 adult male Wistar rats were randomly divided into two groups (n = eight each): Group 1 was given a combination of Tenfovir 30 mg, Lamivudine 30 mg, and Efavirenz 60 mg per day orally, whereas Group 2 was used as a control. After one week of medication preload, all rats underwent a standardized surgical procedure of mid-shaft tibial osteotomy fixed by intramedullary nail with no gap at the fracture site. Progress in fracture healing was monitored regularly for eight weeks. Further evaluations were carried out after euthanasia by micro-CT, mechanically and histologically. Two blinded orthopaedic surgeons used the Radiological Union Scoring system for the Tibia (RUST) to determine fracture healing. Results The fracture healing process was different between the two groups at week 4 after surgery; only two out of eight rats showed full healing in Group 1 (ART-treated), while seven out of eight rats had bone union in Group 2 (control) (p = 0.040). However, at week eight postoperatively, there was no statistical difference in bone healing; seven out of eight progressed to full union in both groups. Conclusion This study demonstrated that combination ART resulted in delayed fracture healing at week 4 after surgery in rats, but did not result in the development of nonunion. Cite this article: Bone Joint Res 2022;11(8):585–593.

Effects of Tenofovir Disoproxil Fumarate on Bone Quality beyond Bone Density—A Scoping Review of the Literature

“…While an initial decrease in fracture healing union rate was observed at week 4, no significant differences in biomechanical strength were noted between the ART and control groups at week 8. This underscores the importance of studying the temporal dynamics of bone healing under ART regimens [ 29 ].…”

“…It is also important to note that TDF treatment delays the process of bone healing due to its mechanism of inhibiting osteoblast-mediated bone formation and promoting osteoclast-mediated bone resorption, as evidenced by a study by Graham et.al, where the fractured tibias of Wistar rats treated with TDF, lamivudine and efavirenz for four weeks showed a significantly lower union rate as compared with the rats in the control group. These ununited fracture sites also revealed a clear gap at the fracture ends filled with fibrous tissue where no woven bone nor cartilaginous callus was found in the inter-fragmentary area, which further highlights TDF’s ability to suppress osteoblast-mediated bone formation [ 29 ].…”