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. 2022 Mar;26(3):2681-2692.
doi: 10.1007/s00784-021-04239-2. Epub 2021 Oct 23.

The influence of antineoplastic agents on the peri-implant bone around osseointegrated titanium implants: an in vivo histomorphometric and immunohistochemical study

Henrique Rinaldi Matheus  1   2 , Edilson Ervolino  2   3 , David Jonathan Rodrigues Gusman  1   2 , Luiz Guilherme Forin  1   2 , Bianca Rafaeli Piovezan  1   2 , Juliano Milanezi de Almeida  4   5
Affiliations

The influence of antineoplastic agents on the peri-implant bone around osseointegrated titanium implants: an in vivo histomorphometric and immunohistochemical study

Henrique Rinaldi Matheus et al. Clin Oral Investig. 2022 Mar.

Abstract

Background and objective: The interaction between antineoplastic drugs used for treating cancer and non-affected tissues remains poorly assessed and may be critical for maintaining the quality of life for patients during and after treatment. This pre-clinical study evaluated the effects of cisplatin (CIS) and 5-fluorouracil (5-FU) on the peri-implant repair process around osseointegrated titanium implants installed in the tibiae of rats.

Material and methods: Were used 90 male rats, randomly divided into three groups (n = 30): physiological saline solution (PSS), CIS, and 5-FU. Titanium implants (4.0 × 2.2 mm) were inserted in both tibiae of all animals at day 0. The animals received either PSS, CIS, or 5-FU at 35 and 37 days. Euthanasia was performed at 50, 65, and 95 days after surgery. Histometric (bone/implant contact [BIC]) and bone area fraction occupancy (% BAFO), histological, and immunohistochemical (for bone morphogenetic protein 2/4 [BMP2/4], Runt-related transcription factor 2 [RUNX2], osteocalcin [OCN], and tartrate-resistant acid phosphatase [TRAP]) analyses were performed. Data were statistically analyzed.

Results: Groups CIS and 5-FU presented lower BIC and lower BAFO as compared with PSS in all time points. The imbalance in bone turnover was observed by the lower number of BMP2/4-, RUNX2-, and OCN-positive cells/mm2 and the higher number of TRAP-positive cells/mm in groups CIS and 5-FU as compared with PSS in all time points. Persistent and exacerbated inflammation was observed in groups CIS and 5-FU.

Conclusions: Both antineoplastic agents interfered negatively in the bone turnover around osseointegrated titanium implants.

Clinical relevance: Closer and more careful follow-up of patients with osseointegrated implants that will undergo chemotherapy with either CIS or 5-FU shall be performed.

Keywords: Antineoplastic agents; Bone implant interface; Cisplatin; Fluorouracil; Osseointegration.

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