Impact of late administration of oral bisphosphonate on the peri-implant repair process in osteopenic rats: can implant surface functionalization improve this response?

Author(s)

Paula Buzo Frigério

• Document type: Master's Dissertation
• Press: Araçatuba. 2023-02-22.
• Institution: Universidade Estadual Paulista (Unesp). Faculdade de Odontologia. Araçatuba
• Defense date: 2023-02-16
• Advisor: Roberta Okamoto; Danielle Botticelli

Abstract

Osteoporosis is a disease that affects mainly postmenopausal women. Currently, there are many therapies available for its treatment, including oral bisphosphonates, which are drugs with an anti-bone remodeling effect, which may lead to some adverse effects in the long term. Other therapeutic or adjuvant options have been considered in order to improve anti-osteoporosis therapies, among them, we highlight osteoforming drugs, such as teriparatide, or supplements such as vitamin K2. Thus, the aim of this project was to evaluate bone quality during peri-implant repair in osteoporotic rats, in a situation in which drug treatment with alendronate sodium occurs after the installation of implants functionalized with teriparatide or vitamin K2. Ninety-six rats were used, divided into two large groups, according to the osteoporosis induction surgery and systemic medication: 1 - OVX SAL: rats submitted to bilateral ovariectomy and treated with saline solution, and 2 - OVX ALE: rats submitted to bilateral ovariectomy and treated with sodium alendronate. Within each experimental group there were three subgroups, according to the type of local treatment of the implants: 1 - CONV (n = 8 per subgroup): conventional implants that did not receive any type of local treatment; 2 - TERI (n = 8 per subgroup): implants functionalized with teriparatide (PTH 1-34) and 3 - VK (n = 8 per subgroup): implants functionalized with vitamin K2. Two weeks after the ovariectomy surgery, all animals had implants installed in the right and left tibial metaphysis (n = 192 implants), either conventional (CONV), functionalized with teriparatide (TERI) or vitamin K2 (VK). After two weeks, the animals received drug treatment by gavage, being saline (0.7 mg/kg weekly) for the animals in the SAL group and sodium alendronate (0.7 mg/kg weekly) for the animals in the ALE group. Euthanasia occurred in two periods, at the 6th and 10th week after implant installation surgery, respectively 44 and 74 days. The collected tibiae were used for biomechanical analysis (counter-torque), computerized microtomography (Micro-CT) using the parameters for bone volume (BV), percentage of bone volume (BV.TV), thickness, number and separation of trabeculae (Tb.Th, Tb.N, and Tb.Sp, respectively), and bone-implant contact surface (i.S). Quantitative data were submitted to the homoscedasticity test for the selection of the appropriate statistical test (parametric vs. nonparametric), with a significance level of 5%. The results obtained from the patented test showed that functionalization of the implants with teriparatide was feasible and showed better results when compared to conventional implants, which justified the dose of choice. For the biomechanical analysis, the highest implant removal torques were for the groups treated with teriparatide, and the best value obtained was from the OVX SAL TERI group (22.17 N/cm). The parameters BV, BV.TV. Tb.Th, Tb.N, and i.S obtained from Micro-CT were better for the groups treated with teriparatide and vitamin K2, and these groups with functionalized implants had less separation between their bone trabeculae (Tb.Sp). It is concluded that functionalization with PTH 1-34 and vitamin K2 promoted better long-term results, with superiority for the former in both removal torque and microarchitecture of the reparational bone tissue. Further studies with vitamin K2 are needed to find a corresponding effective dose. (AU)

• FAPESP's process: 21/06050-6 - Impact of late administration of oral biphosphonate on perimplantar repair process in osteopenic rats. Can the implant's functionalization act favorably on this response?
• Grantee: Paula Buzo Frigério
• Support Opportunities: Scholarships in Brazil - Master