Evaluation of the influence of antineoplastic agents over peri‐implant tissues around osseointegrated implants

Background Together with the increase in the number of rehabilitations using osseointegrated titanium implants, the occurrence of new cases of cancer has become more prevalent. The treatment of the disease usually encompasses administration of antineoplastic agents, such as Cisplatin and 5-Fluorouracil. The lack of specificity to tumor cells produces harmful effects over tissues. These effects over the peri-implant tissues of osseointegrated implants remains uncertain. Aim/Hypothesis To evaluate the influence of Cisplatin (CIS) and 5-Fluorouracil (5-FU) over the peri-implant tissues of osseointegrated titanium implants installed in the tibiae of rats. Materials and Methods ninety male Wistar rats were randomly assigned to three experimental groups (n = 30). Animals received 0.5 ml of sodium chloride 0.9% (SS) subcutaneously for 30 days before and after surgery. After that, animals received the titanium implants (DSP Biomedical®, 4 mm x 2.2 mm) in both tibiae. At 30 days after surgery, SS was interrupted. At 35 and 37 days, CIS, 5FU or 0.5 ml SS were intraperitoneally administered. For CIS, 5 mg kg and 2,5 mg kg, and 5-FU, 60 mg kg and 40 mg kg, respectively. SS-SS- received exclusively SS. NIC-SS- received NIC and SS. NIC- CIS- received NIC and CIS. NIC-5FU- received NIC and 5-FU. Ten animals per group period were euthanized at 50, 65 and 95 days. Specimens were processed and assigned for analyses of bone implant contact (BIC), percentage of newly-formed bone (PNFB), histologic and immunohistochemistry for detection of BMP2 4, RUNX2, OCN and TRAP. Other processed for ultrastructural analysis under scanning electron microscopy (SEM). Results SS-SS showed higher BIC when compared with the other groups. Group SS-CIS showed higher BIC when compared with group SS-5FU in all experimental periods. SS-SS showed higher PNFB when compared with the other groups. SS-SS presented the most arranged peri-implant structure. SS-CIS and SS-CIS presented similar histologic features of the peri-implant tissues, with thin trabeculae, and in a considerable proportion, connective tissues in the interface bone implant. SS-SS showed higher number of BMP2 4, RUNX2 and OCN-positive cells mm2 when compared with the other groups. SS-SS showed lower number of TRAP-positive cells mm when compared with the other groups. SS-CIS showed lower number of TRAP-positive cells mm when compared with SS-5FU in all experimental periods. Groups SS-CIS and SS-5Fu presented a gap in the interface bone implant, as well as scarce and isolated osteocytes. Conclusion and Clinical Implications Within the limits of the present study, it can be concluded that the antineoplastic agents CIS and 5FU harm the peri-implant tissues around osseointegrated implants. The features of peri-implant tissues in animals that received antineoplastic treatment may be relevant determine the most appropriate approach in a clinical scenario.