Impacto da administração tardia de bifosfonato oral sobre o processo de reparo peri-implantar em ratas osteopênicas: a funcionalização da superfície dos implantes pode melhorar esta resposta?
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Data
2023-02-16
Autores
Frigério, Paula Buzo [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A osteoporose é uma doença que atinge principalmente as mulheres na pós-menopausa. Atualmente, existem muitas terapias disponíveis para seu tratamento, entre elas os bifosfonatos orais que são fármacos com efeito anti-remodelação óssea, o que pode levar alguns efeitos adversos a longo prazo. Outras opções terapêuticas ou adjuvantes têm sido consideradas no intuito de melhorar as terapias anti-osteoporose, dentre elas, destacamos os fármacos osteoformadores, como a teriparatida, ou ainda suplementos como a vitamina K2. Deste modo, o objetivo desse projeto foi avaliar a qualidade óssea durante reparo peri-implantar em ratas osteoporóticas, numa situação em que o tratamento medicamentoso com alendronato de sódio ocorra após a instalação dos implantes funcionalizados com teriparatida ou vitamina K2. Foram utilizadas 96 ratas divididas em dois grandes grupos, conforme a cirurgia de indução da osteoporose e medicação sistêmica: 1 - OVX SAL: ratas submetidas à ovariectomia bilateral e tratadas com soro fisiológico e 2 - OVX ALE: ratas submetidas à ovariectomia bilateral e tratadas com alendronato de sódio. Dentro de cada grupo experimental, houve três subgrupos, conforme o tipo de tratamento local dos implantes: 1 – CONV (n = 8 por subgrupo): implantes convencionais que não tiveram nenhum tipo de tratamento local; 2 – TERI (n = 8 por subgrupo): implantes funcionalizados com teriparatida (PTH 1-34) e 3 – VK (n = 8 por subgrupo): implantes funcionalizados com vitamina K2. Após duas semanas da cirurgia de ovariectomia, todos os animais tiveram a instalação de implantes na metáfise tibial direita e esquerda (n = 192 implantes), sendo eles: convencionais (CONV), funcionalizados com teriparatida (TERI) ou vitamina K2 (VK). Passadas duas semanas, os animais receberam o tratamento medicamentoso por gavagem, sendo o soro fisiológico (0,7 mg/kg semanalmente) para os animais do grupo SAL e o alendronato de sódio (0,7 mg/kg semanalmente) para os animais do grupo ALE. A eutanásia ocorreu em dois períodos, a 6º e 10º semanas após a cirurgia de instalação dos implantes, respectivamente 44 e 74 dias. As tíbias coletadas foram utilizadas para a análise biomecânica (contra torque), microtomografia computadorizada (Micro-CT) utilizando os parâmetros para volume ósseo (BV), porcentagem de volume ósseo (BV.TV), espessura, número e separação das trabéculas (Tb.Th, Tb.N e Tb.Sp, respectivamente) e superfície de contato osso-implante (i.S). Os dados quantitativos foram submetidos ao teste de homocedasticidade para a seleção do teste estatístico adequado (paramétrico vs. não paramétrico), com nível de significância de 5%. Os resultados obtidos a partir do teste patenteado mostraram que a funcionalização dos implantes com teriparatida foi viável e apresentaram melhores resultados quando comparado aos implantes convencionais, o que justificou a dose de escolha. Para a análise biomecânica, os maiores torques de remoção dos implantes foram para os grupos tratados com teriparatida e o melhor valor obtido foi do grupo OVX SAL TERI (22,17 N/cm). Os parâmetros BV, BV.TV. Tb.Th, Tb.N, e i.S obtidos a partir do Micro-CT mostraram-se melhores para os grupos tratados com teriparatida e vitamina K2, sendo que estes grupos com implantes funcionalizados tiveram menor separação entre suas trabéculas ósseas (Tb.Sp). Conclui-se que a funcionalização com o PTH 1-34 e vitamina K2 promoveram melhores resultados a longo prazo, com superioridade para o primeiro tanto no torque de remoção como na microarquitetura do tecido ósseo reparacional. Mais estudos com a vitamina K2 se fazem necessários para encontrar uma dose eficaz correspondente.
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.
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.
Descrição
Palavras-chave
Implantes dentários, Teriparatida, Vitamina K 2, Difosfonatos, Diphosphonates