Department of Diagnosis and Surgery-Periodontics Division, São Paulo State University (Unesp), St. José Bonifácio 1193 - Vila Mendonça, Araçatuba, SP, 16015-050, Brazil.
Nucleus of Study and Research in Periodontics and Implantology (NEPPI), School of Dentistry, São Paulo State University (Unesp), Araçatuba, SP, Brazil.
Clin Oral Investig. 2022 Mar;26(3):2681-2692. doi: 10.1007/s00784-021-04239-2. Epub 2021 Oct 23.
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.
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.
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/mm 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.
Both antineoplastic agents interfered negatively in the bone turnover around osseointegrated titanium implants.
Closer and more careful follow-up of patients with osseointegrated implants that will undergo chemotherapy with either CIS or 5-FU shall be performed.
用于治疗癌症的抗肿瘤药物与非靶组织之间的相互作用仍未得到充分评估,而这种相互作用可能对维持治疗期间和治疗后的患者生活质量至关重要。本临床前研究评估了顺铂(CIS)和 5-氟尿嘧啶(5-FU)对植入物周围组织的影响在接受治疗的大鼠胫骨中整合钛植入物周围的修复过程。
使用 90 只雄性大鼠,随机分为三组(n=30):生理盐水溶液(PSS)、CIS 和 5-FU。所有动物在第 0 天在双侧胫骨中插入 4.0×2.2mm 的钛植入物。动物在第 35 天和第 37 天分别接受 PSS、CIS 或 5-FU。手术后 50、65 和 95 天进行安乐死。进行组织学(骨/植入物接触[BIC])和骨面积分数占有率(%BAFO)、组织学和免疫组织化学(骨形态发生蛋白 2/4[BMP2/4]、 runt 相关转录因子 2[RUNX2]、骨钙素[OCN]和抗酒石酸酸性磷酸酶[TRAP])分析。数据进行了统计学分析。
与 PSS 组相比,CIS 和 5-FU 组在所有时间点的 BIC 和 BAFO 均较低。CIS 和 5-FU 组的 BMP2/4、RUNX2 和 OCN 阳性细胞/mm 数较低,TRAP 阳性细胞/mm 数较高,表明骨转换失衡在所有时间点均较 PSS 组更为明显。CIS 和 5-FU 组均观察到持续性和加剧的炎症。
两种抗肿瘤药物均对骨整合钛植入物周围的骨转换产生负面影响。
应密切并更仔细地随访接受 CIS 或 5-FU 化疗的骨整合植入物患者。