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1.
Rev. Flum. Odontol. (Online) ; 2(67): 75-87, mai-ago.2025.
Artigo em Português | LILACS, BBO - Odontologia | ID: biblio-1572996

RESUMO

A osteoporose é caracterizada pela perda óssea e pelo comprometimento da resistência do osso. Essa patologia afeta, também, os ossos da face e consequentemente interfere na atuação dos profissionais da odontologia. Assim sendo, o presente trabalho revisou a literatura acerca da relação entre osteoporose e odontologia. O levantamento dos dados se deu por consulta a livros e nas bases de dados Biblioteca Virtual em Saúde (BVS), PubMed e Scientific Eletronic Library Online (SciELO) e como Descritores em Ciência da Saúde (Decs) foram adotados os termos: "Odontologia", "Osteoporose" e "Saúde bucal". A osteoporose diminui a massa e aumenta a porosidade óssea na maxila e na mandíbula, podendo provocar até quatro vezes mais perda dentária. Os bifosfonatos, principal classe medicamentosa utilizada para o tratamento de osteoporose, estão associados à ocorrência de osteonecrose dos maxilares e ao aumento de tempo de tratamento ortodôntico. Assim, pode-se concluir que é imprescindível o conhecimento do cirurgião-dentista acerca da osteoporose para uma segura abordagem e execução de tratamento.


Osteoporosis is characterized by bone loss and compromised bone strength. This pathology also affects the bones of the face and consequently interferes with the work of dentists. Therefore, the present study reviewed the literature about the relationship between osteoporosis and dentistry. Data collection was carried out by consulting books and the databases Biblioteca Virtual em Saúde (BVS), PubMed and Scientific Electronic Library Online (SciELO) and as Medical Subjects Headings (MeSH) the terms adopted were: "Dentistry", "Osteoporosis" and "Oral health". Osteoporosis reduces bone mass and increases bone porosity in the maxilla and jaw, which can cause up to four times more tooth loss. Bisphosphonates, the main class of medications used to treat osteoporosis, are associated with the occurrence of osteonecrosis of the jaw (ONJ) and increase the time of orthodontic treatment. Thus, it can be concluded that the dentist's knowledge of osteoporosis is necessary for a safe approach and execution of treatment.


Assuntos
Osteoporose , Saúde Bucal , Odontologia , Difosfonatos
2.
J Appl Oral Sci ; 32: e20240224, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39356951

RESUMO

OBJECTIVE: For treatment of medication-related osteonecrosis of the jaw, one proposed approach is the use of a topical agent to block entry of these medications in oral soft tissues. We tested the ability of phosphonoformic acid (PFA), an inhibitor of bisphosphonate entry through certain sodium-dependent phosphate contransporters (SLC20A1, 20A2, 34A1-3) as well as Dynasore, a macropinocytosis inhibitor, for their abilities to prevent zoledronate-induced (ZOL) death in human gingival fibroblasts (HGFs). METHODOLOGY: MTT assay dose-response curves were performed to determine non-cytotoxic levels of both PFA and Dynasore. In the presence of 50 µM ZOL, optimized PFA and Dynasore doses were tested for their ability to restore HGF viability. To determine SLC expression in HGFs, total HGF RNA was subjected to quantitative real-time RT-PCR. Confocal fluorescence microscopy was employed to see if Dynasore inhibited macropinocytotic HGF entry of AF647-ZOL. Endosomal acidification in the presence of Dynasore was measured by live cell imaging utilizing LysoSensor Green DND-189. As a further test of Dynasore's ability to interfere with ZOL-containing endosomal maturation, perinuclear localization of mature endosomes containing AF647-ZOL or TRITC-dextran as a control were assessed via confocal fluorescence microscopy with CellProfiler™ software analysis of the resulting photomicrographs. RESULTS: 0.5 mM PFA did not rescue HGFs from ZOL-induced viability loss at 72 hours while 10 and 30 µM geranylgeraniol did partially rescue. HGFs did not express the SLC transporters as compared to the expression in positive control tissues. 10 µM Dynasore completely prevented ZOL-induced viability loss. In the presence of Dynasore, AF647-ZOL and FITC-dextran co-localized in endosomes. Endosomal acidification was inhibited by Dynasore and perinuclear localization of both TRITC-dextran- and AF647-ZOL-containing endosomes was inhibited by 30 µM Dynasore. CONCLUSION: Dynasore prevents ZOL-induced viability loss in HGFs by partially interfering with macropinocytosis and by inhibiting the endosomal maturation pathway thought to be needed for ZOL delivery to the cytoplasm.


Assuntos
Sobrevivência Celular , Difosfonatos , Endossomos , Fibroblastos , Gengiva , Hidrazonas , Imidazóis , Ácido Zoledrônico , Ácido Zoledrônico/farmacologia , Humanos , Fibroblastos/efeitos dos fármacos , Gengiva/efeitos dos fármacos , Gengiva/citologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Endossomos/efeitos dos fármacos , Hidrazonas/farmacologia , Células Cultivadas , Fatores de Tempo , Reação em Cadeia da Polimerase em Tempo Real , Conservadores da Densidade Óssea/farmacologia , Reprodutibilidade dos Testes , Microscopia Confocal , Relação Dose-Resposta a Droga , Pinocitose/efeitos dos fármacos
3.
Artigo em Inglês | MEDLINE | ID: mdl-39304414

RESUMO

OBJECTIVE: The study aimed to evaluate digoxin, an RORγt inhibitor, in Medication-Related Osteonecrosis of the Jaws (MRONJ) in male rats treated with zoledronic acid (ZA). STUDY DESIGN: Forty male Wistar rats were divided into a negative control group (0.1 mL/kg saline), a positive control group (ZA, 0.20 mg/kg), and three test groups treated with ZA and digoxin at 1 (DG1), 2 (DG2), or 4 (DG4) mg/kg. These groups received treatment three times weekly. ZA was administered intravenously on days 0, 7, and 14, followed by extraction of the left lower first molar on day 42, a final ZA dose on day 49, and euthanasia on day 70. Analyses included radiographic, histomorphometric, and immunohistochemical evaluation of the mandibles, western blotting of gingiva, and mechanical tests on femurs. Statistical analysis was performed using ANOVA/Bonferroni tests (P < .05). RESULTS: Digoxin reduced radiolucency of MRONJ (P < .001), inflammatory cells, empty osteocyte lacunae (P < .001), apoptotic osteoclasts (P < .001), and Caspase-3-positive osteocytes (P = .021). ZA increased immunoreactivity for most markers except c-Fos, while digoxin reduced interleukin 17, TNF-α, IL-6, IL-2, FOXP3, c-Jun, NFκB (P < .001), TGF-ß (P = .009), RANKL (P = .035), and OPG (P = .034). Digoxin also reversed RORγt expression (P < .001), increased diarrhea scores (P = .028), renal and cardiac indexes (P < .001), and enhanced femur mechanical properties (P < .013). CONCLUSIONS: Digoxin attenuated MRONJ by inhibiting RORγt and reducing the Th17 response.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Digoxina , Difosfonatos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares , Ratos Wistar , Células Th17 , Ácido Zoledrônico , Animais , Digoxina/farmacologia , Masculino , Ratos , Células Th17/efeitos dos fármacos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Ácido Zoledrônico/farmacologia , Difosfonatos/farmacologia , Imidazóis/farmacologia , Western Blotting , Imuno-Histoquímica , Conservadores da Densidade Óssea/farmacologia , Modelos Animais de Doenças
4.
Int J Mol Sci ; 25(16)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39201648

RESUMO

Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.


Assuntos
Osteoporose , Ácido Zoledrônico , Animais , Ratos , Feminino , Ácido Zoledrônico/administração & dosagem , Ácido Zoledrônico/farmacologia , Osteoporose/tratamento farmacológico , Microtomografia por Raio-X , Osseointegração/efeitos dos fármacos , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Difosfonatos/administração & dosagem , Osteogênese/efeitos dos fármacos
5.
Acta Cir Bras ; 39: e393724, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39016360

RESUMO

PURPOSE: To evaluate collagen fibers during the bone repair process in critical defects created in the tibias of rats, treated with zoledronic acid (AZ) associated with low-level laser therapy (LLLT). METHODS: Ten rats were distributed according to treatment: group 1) saline solution; group 2) LLLT; group 3) AZ; group 4) AZ and LLLT. AZ was administered at the dose of 0.035 mg/kg at fortnightly intervals over eight weeks. Next, 2-mm bone defects were created in the tibias of all animals. The bone defects in groups 2 and 4 were irradiated LLLT in the immediate postoperative period. After periods 14 and 28 of application, the animals were euthanized, and birefringence analysis was performed. RESULTS: Approximately 90% of the total area was occupied by collagen fibers within the red color spectrum, this area being statistically larger in relation to the area occupied by collagen fibers within the green and yellow spectrum, in the four groups. Over the 14-day period, there was no statistically significant difference between the groups. In the 28-day period, group 2 (14.02 ± 15.9%) was superior in quantifying green birefringent fibers compared to group 1 (3.06 ± 3.24%), with p = 0.009. CONCLUSIONS: LLLT associated with ZA is effective in stimulating the neoformation of collagen fibers. The LLLT group without the association with ZA showed a greater amount of immature and less organized matrix over a period of 28 days.


Assuntos
Conservadores da Densidade Óssea , Colágeno , Difosfonatos , Imidazóis , Terapia com Luz de Baixa Intensidade , Ratos Wistar , Ácido Zoledrônico , Animais , Ácido Zoledrônico/farmacologia , Ácido Zoledrônico/uso terapêutico , Terapia com Luz de Baixa Intensidade/métodos , Imidazóis/farmacologia , Difosfonatos/farmacologia , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Colágeno/efeitos dos fármacos , Colágeno/efeitos da radiação , Masculino , Tíbia/efeitos dos fármacos , Tíbia/efeitos da radiação , Tíbia/cirurgia , Regeneração Óssea/efeitos dos fármacos , Regeneração Óssea/efeitos da radiação , Fatores de Tempo , Ratos , Reprodutibilidade dos Testes
6.
Bone ; 187: 117211, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39053792

RESUMO

Osteonecrosis of the jaw (ONJ) is a relatively rare side effect after prolonged use of bisphosphonates, which are drugs used to treat bone resorption in osteoporosis and certain cancers. This study introduces a novel ONJ model in rats by combining exposure to bisphosphonates, oral surgery, and bacterial inoculation. Potential ONJ preventive effects of polyguanidine (GuaDex) or antibiotics were evaluated. The study consisted of twenty-four male Wistar rats were divided into four groups. Groups 1 to 3 were given weekly doses of i.v. Zoledronic acid (ZA), four weeks before and two weeks after an osteotomy procedure on their left mandibular first molar. Group 4 was a negative control. Streptococcus gordonii bacteria were introduced into the osteotomy pulp chamber and via the food for seven days. On day eight, the rats were given different treatments. Group 1 was given a GuaDex injection into the osteotomy socket, Group 2 was given an intramuscular (i.m.) injection of clindamycin, Group 3 (positive control) was given an i.m. injection of saline, and Group 4 was given an i.m. injection of saline. Blood samples were taken two weeks after the osteotomy procedure, after which the rats were euthanized. Bone healing, bone mineral density, histology, and blood status were analyzed. The results showed that Group 1 (GuaDex) had no ONJ, extensive ongoing bone regeneration, active healing activity, vascularization, and no presence of bacteria. Group 2 (clindamycin) showed early stages of ONJ, avascular areas, and bacteria. Group 3 showed stages of ONJ, inflammatory infiltrates, defective healing, and bacterial presence, and Group 4 had normal healing activity and no bacterial presence. Conclusion: ZA treatment and bacterial inoculation after tooth extraction inhibited bone remodeling/healing and induced ONJ characteristic lesions in the rats. Only GuaDex apparently prevented ONJ development, stimulated bone remodeling, and provided an antimicrobial effect.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Ratos Wistar , Animais , Masculino , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Ratos , Difosfonatos/farmacologia , Difosfonatos/efeitos adversos , Guanidinas/farmacologia , Guanidinas/uso terapêutico
7.
Int. j. odontostomatol. (Print) ; 18(2): 141-147, jun. 2024. tab, ilus
Artigo em Espanhol | LILACS | ID: biblio-1564649

RESUMO

El objetivo de esta revisión sistemática consistió en la búsqueda de medidas preventivas y de tratamiento de osteonecrosis asociada a medicamentos y anticuerpos monoclonales para proponer un nuevo protocolo en caso de ser necesario. Esta revisión bibliográfica se realizó en PubMed/MedLine, Cochrane, SciELO y EBSCO; delimitando la búsqueda desde el 1 de enero de 2017 al 22 de septiembre de 2022. Se incluyeron un total de 8 artículos. A pesar de que se incluyó la mayor cantidad de evidencia certera se obtuvieron resultados no significativos, actualmente hay un protocolo de la Asociación Americana de Cirugía Oral y Maxilofacial sin embargo se necesita más evidencia clínica.


The objective of this systematic review was to search for preventive and treatment measures for osteonecrosis associated with medications and monoclonal antibodies to propose a new protocol if necessary. This literature review was conducted in PubMed/MedLine, Cochrane, SciELO, and EBSCO; limiting the search from January 1, 2017 to September 22, 2022. A total of 8 articles were included. Although the greatest amount of accurate evidence was included, non-significant results were obtained. There is currently a protocol from the American Association of Oral and Maxillofacial Surgery, however, more clinical evidence is needed.


Assuntos
Humanos , Osteonecrose , Osteoporose/tratamento farmacológico , Teriparatida , Difosfonatos/efeitos adversos , Denosumab/efeitos adversos , Antibacterianos/uso terapêutico
8.
Biointerphases ; 19(3)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38836787

RESUMO

Titanium (Ti) is widely utilized as an implant material; nonetheless, its integration with bone tissue faces limitations due to a patient's comorbidities. To address this challenge, we employed a strategic approach involving the growth of thin films by spin-coating and surface functionalization with etidronate (ETI), alendronate (ALE), and risedronate (RIS). Our methodology involved coating of Ti cp IV disks with thin films of TiO2, hydroxyapatite (HA), and their combinations (1:1 and 1:2 v/v), followed by surface functionalization with ETI, ALE, and RIS. Bisphosphonate-doped films were evaluated in terms of surface morphology and physical-chemical properties by techniques such as electron microscopy, confocal microscopy, and x-ray photoelectron spectroscopy. The antibacterial potential of bisphosphonates alone or functionalized onto the Ti surface was tested against Staphylococcus aureus biofilms. Primary human bone mesenchymal stem cells were used to determine in vitro cell metabolism and mineralization. Although RIS alone did not demonstrate any antibacterial effect as verified by minimum inhibitory concentration assay, when Ti surfaces were functionalized with RIS, partial inhibition of Staphylococcus aureus growth was noted, probably because of the physical-chemical surface properties. Furthermore, samples comprising TiO2/HA (1:1 and 1:2 v/v) showcased an enhancement in the metabolism of nondifferentiated cells and can potentially enhance the differentiation of osteoblastic precursors. All samples demonstrated cell viability higher than 80%. Addition of hydroxyapatite and presence of bisphosphonates increase the metabolic activity and the mineralization of human bone mesenchymal cells. While these findings hold promise, it is necessary to conduct further studies to evaluate the system's performance in vivo and ensure its long-term safety. This research marks a significant stride toward optimizing the efficacy of titanium implants through tailored surface modifications.


Assuntos
Antibacterianos , Difosfonatos , Células-Tronco Mesenquimais , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Propriedades de Superfície , Titânio , Titânio/química , Titânio/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus/efeitos dos fármacos , Difosfonatos/química , Difosfonatos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Células Cultivadas , Durapatita/química , Durapatita/farmacologia
9.
J Dent ; 148: 105051, 2024 09.
Artigo em Inglês | MEDLINE | ID: mdl-38763386

RESUMO

OBJECTIVE: To map the current scientific landscape regarding the association/causality of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction under bisphosphonate (BF) therapy to identify knowledge gaps and guide future research. DATA: This review used the PCC strategy (P = Patient; C = Concept; C = Context). SOURCES: The MEDLINE/PubMed, Scopus, Web of Science/Clarivate Analytics, and gray literature databases were used. STUDY SELECTION: Searches were conducted by two independent reviewers until April 2024. Studies involving prior BF use and tooth extraction in humans or animals were included. Among the 176 studies, 73 (41.4 %) were in animals, and 103 (58.5 %) were in humans. Brazil led in animal studies (n = 14; 19.1 %), while Italy led in human studies (n = 14; 13.6 %). Zoledronic acid was the most cited BF (79.4 % in animals; 34.9 % in humans), with intravenous administration being most frequent (38.3 % in animals; 35.9 % in humans). The mandible was the main extraction site (n = 36 in animals; n = 41 in humans). In 91.7 % of the animal studies, sequelae compatible with osteonecrosis signs and symptoms were observed, with bone necrosis being most common (n = 39; 53.4 %). In humans, 93.2 % of studies presented 239 sequelae, with bone necrosis (n = 53; 22.1 %) being the most cited. The main location of sequelae was the mandible (n = 36 in animals; n = 41 in humans). CONCLUSIONS: Animal studies highlighted bone exposure, notably using murine models, with a significant Brazilian contribution. In human studies, bone necrosis was the main sequela of MRONJ, which has been reported by researchers in the Italy. CLINICAL SIGNIFICANCE: These findings underscore the importance of careful consideration and monitoring of patients who have a history of bisphosphonate use and who are undergoing tooth extraction, highlighting the potential risk of MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Difosfonatos , Extração Dentária , Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Difosfonatos/efeitos adversos , Animais , Conservadores da Densidade Óssea/efeitos adversos , Ácido Zoledrônico/uso terapêutico , Ácido Zoledrônico/efeitos adversos , Brasil
10.
J Appl Oral Sci ; 32: e20230447, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38695448

RESUMO

OBJECTIVE: To evaluate whether antimicrobial photodynamic therapy (aPDT) repairs bisphosphonate-related osteonecrosis of the jaw (BRONJ) modulated by the reduction of NF-kB protein in a murine model. METHODOLOGY: Male Wistar rats (N=30) were divided into the following groups (n=6/group): negative control (NC); experimental osteonecrosis (ONE); ONE + photosensitizer (PS); ONE + photobiomodulation (PBM); and ONE + aPDT. Over 8 weeks, ONE was induced by zoledronic acid 250 µg/kg injections, except in the NC group, which received sterile 0.9% saline, followed by extraction of the lower left first molar. Red light laser irradiation (wavelength ~660 nm, power 50 mW, energy of 2 J, energy dose of 66.67 J/cm2 for 40 s) was performed once a week for 4 weeks. Methylene blue 0.3% was used as PS. The animals were euthanized and examined macroscopically for the presence of exposed bone and epithelial repair and microscopically by histochemical (hematoxylin-eosin and Masson's trichrome staining) and immunohistochemical (anti-NF-kB) methods. Macroscopic and histomorphometric data were analyzed by one-way ANOVA and Tukey's post-test (p<0.05). RESULTS: Mucosal repair, viable osteocytes, and NF-kB immunostaining were observed in the NC, ONE+PS, ONE+PBM, and ONE+aPDT groups. The ONE group showed no mucosal repair, showing empty lacunae and multifocal immunostaining for NF-kB. The ONE+PBM and ONE+aPDT groups had greater deposition of extracellular matrix and less necrotic bone tissue (p<0.05). CONCLUSION: PBM and aPDT treatments for BRONJ were effective for bone and epithelial repair, in addition to reducing inflammation mediated by the decrease of NF-kB protein in the irradiated regions.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Modelos Animais de Doenças , Imuno-Histoquímica , NF-kappa B , Fotoquimioterapia , Fármacos Fotossensibilizantes , Ratos Wistar , Animais , Masculino , Fotoquimioterapia/métodos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , NF-kappa B/análise , Fármacos Fotossensibilizantes/farmacologia , Fatores de Tempo , Reprodutibilidade dos Testes , Ácido Zoledrônico/farmacologia , Resultado do Tratamento , Imidazóis/farmacologia , Difosfonatos/farmacologia , Terapia com Luz de Baixa Intensidade/métodos , Azul de Metileno/farmacologia , Azul de Metileno/uso terapêutico , Análise de Variância , Distribuição Aleatória , Conservadores da Densidade Óssea/farmacologia
11.
Eur J Clin Pharmacol ; 80(8): 1121-1132, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38691138

RESUMO

PURPOSE: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. METHODS: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. RESULTS: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. CONCLUSION: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women.


Assuntos
Conservadores da Densidade Óssea , Difosfonatos , Resultado da Gravidez , Humanos , Gravidez , Feminino , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Difosfonatos/administração & dosagem , Recém-Nascido , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Conservadores da Densidade Óssea/administração & dosagem , Aborto Espontâneo/induzido quimicamente , Aborto Espontâneo/epidemiologia , Complicações na Gravidez/tratamento farmacológico , Nascimento Prematuro
12.
Sci Rep ; 14(1): 8215, 2024 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-38589479

RESUMO

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.


Assuntos
Agaricus , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Animais , Ratos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Difosfonatos , Maxila/patologia , Extração Dentária , Via de Sinalização Wnt , Ácido Zoledrônico
13.
Spec Care Dentist ; 44(4): 1273-1279, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481370

RESUMO

OBJECTIVE: To identify radiographic findings suggestive of drug-induced osteonecrosis and evaluate radiomorphometric patterns indicative of changes in bone mineral density in individuals transplanted for liver disorders using bisphosphonates. STUDY DESIGN: The study group included panoramic x-rays of liver transplant patients who are being monitored and who present a clinical status of osteoporosis and use bisphosphonates. The control group was made up of liver transplant patients who did not have osteoporosis. On panoramic radiographs, mental index (MI) and mandibular cortical index (MCI) and the presence of radiographic anomalies suggestive of osteonecrosis were evaluated. RESULTS: There were significant statistical results when comparing the groups in relation to the decrease in bone mineral density (BMD) with MCI-C3 (p = 0.036), however, there were none in relation to MI (p = 0.14). There were no valid statistical results when relating MCI (p = 0.94) and MI (p = 0.66) with reduced BMD and use of bisphosphonates. CONCLUSION: Liver transplant individuals using bisphosphonates present greater radiographic signs of bone sclerosis suggestive of a greater propensity to develop osteonecrosis of the jaw and an increased risk of presenting changes suggestive of reduced bone mineral density on panoramic radiographs when compared to liver transplant individuals not using bisphosphonates.


Assuntos
Conservadores da Densidade Óssea , Densidade Óssea , Difosfonatos , Transplante de Fígado , Radiografia Panorâmica , Humanos , Feminino , Masculino , Difosfonatos/efeitos adversos , Densidade Óssea/efeitos dos fármacos , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/efeitos adversos , Osteoporose , Idoso , Adulto , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Estudos de Casos e Controles
16.
Clin Oral Investig ; 28(2): 151, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38360985

RESUMO

OBJECTIVE: This study aimed to evaluate the efficacy of ozone therapy in the preoperative (prevention) and/or postoperative (treatment) of MRONJ. MATERIAL AND METHODS: Forty male Wistar rats were caudally treated with zoledronic acid (ZOL) and to ozone therapy before extraction (prevention, POG), after extraction (treatment, TOG), or both (prevention and treatment, TPOG), and treated with saline (SAL). The animals received intramuscular fluorochrome (calcein and alizarin), and 28 days postoperatively, they were euthanized, and the tissues were subjected to microtomographic computed tomography (microCT), LASER confocal, and histomorphometric analyses. RESULTS: Micro-CT showed a higher bone volume fraction average in all groups than that in the ZOL group (P < 0.001), the ZOL group showed high porosity (P = 0.03), and trabecular separation was greater in the TOG group than in the POG group (P < 0.05). The mineral apposition rate of the POG group was high (20.46 ± 6.31) (P < 0.001), followed by the TOG group (20.32 ± 7.4). The TOG group presented the highest mean newly formed bone area (68.322 ± 25.296) compared with the ZOL group (P < 0.05), followed by the SAL group (66.039 ± 28.379) and ZOL groups (60.856 ± 28.425). CONCLUSIONS: Ozone therapy modulated alveolar bone repair in animals treated with ZOL, mainly after surgery trauma, leading to bone formation as healing tissue. CLINICAL RELEVANCE: Osteonecrosis has been a challenge in dentistry, and owing to the lack of a consensus regarding therapy, studies presenting new therapies are important, and ozone has been one of the therapies explored empirically.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Ratos , Animais , Masculino , Difosfonatos , Imidazóis/farmacologia , Extração Dentária , Ratos Wistar , Ácido Zoledrônico , Microtomografia por Raio-X , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico
17.
Am J Case Rep ; 25: e942980, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38404023

RESUMO

BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious reaction to anti-resorptive drugs (ARDs) in patients treated for osteoporosis and conditions related to cancer. Treatment for MRONJ consists of the use of non-operative therapies according to the evolution of the disease, which consist of the use of antimicrobial mouthwashes, systemic antibiotics, and operative therapies, such as debridement of necrotic bone, marginal or segmental resection, and bone reconstruction of the jaws in more advanced stages of the disease. CASE REPORT This is a case series of 11 female patients treated for MRONJ, with a mean age of 76.5 years. Patients with malignant diseases of the jaws or those undergoing head and neck radiotherapy were excluded. Nine patients were medicated for osteoporosis with oral bisphosphonates and denosumab, and 2 patients used zoledronate to treat metastatic breast cancer. MRONJ prevailed in the mandible, most patients were classified as stage 2, and the most frequent triggers were tooth extraction and prosthetic trauma. All patients initially underwent non-operative therapies and were operated according to MRONJ stage, but none required segmental resection. Adjuvant treatments were used in 5 patients, and mean treatment and follow-up periods were 5 and 18.3 months, respectively. There was complete resolution of disease in all patients, with only 1 relapse. CONCLUSIONS This case series suggests that it is possible to treat MRONJ with conservative therapies in the early stages of the disease and minimally invasive surgeries in more advanced stages of the disease, thus avoiding segmental jaw resections.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteoporose , Humanos , Feminino , Idoso , Difosfonatos/efeitos adversos , Conservadores da Densidade Óssea/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Recidiva Local de Neoplasia/complicações , Osteoporose/induzido quimicamente , Osteoporose/complicações , Osteoporose/tratamento farmacológico , Arcada Osseodentária
18.
J Mol Med (Berl) ; 102(3): 353-364, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38302741

RESUMO

This study compiles the main hypotheses involved in the etiopathogenesis of medication-related osteonecrosis of the jaw (MRONJ). A narrative review of the literature was performed. The etiopathogenesis of MRONJ is multifactorial and not fully understood. The main hypothesis considers the disturbance of bone turnover caused by anti-resorptive drugs. Bisphosphonates and denosumab inhibit osteoclast activity through different action mechanisms, accumulating bone microfracture. Other hypotheses also consider oral infection and inflammation, the antiangiogenic effect and soft tissue toxicity of bisphosphonates, and the inhibition of lymphangiogenesis. Knowledge of the current theories for MRONJ is necessary to define future studies and protocols to minimize the incidence of this severe condition.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Humanos , Conservadores da Densidade Óssea/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Arcada Osseodentária
19.
Clin Oral Investig ; 28(1): 89, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38217802

RESUMO

OBJECTIVE: To evaluate the osseointegration of implants with hydrophobic (HFB) and hydrophilic (HFL) surfaces in a murine model of high-dose bisphosphonates (BPs). MATERIALS AND METHODS: Sixty-four rats were randomly allocated into four groups: control group with HFB implants (CG-HFB), control group with HFL implants (CG-HFL), BP group with HFB implants (BP-HFB), and BP group with HFL implants (BP-HFL). Animals were euthanized after 15 and 45 days (n=8). The dependent variables assessed were the removal torque (biomechanical analysis), the bone volume around the implants (%BV/TV) (microtomographic analysis), the bone-implant contact (%BIC), the bone between the threads (%BBT) (histomorphometric analysis), and the expression of bone metabolism markers (immunohistochemistry analysis). RESULTS: The CG-HFL and BP-HFL groups presented higher removal torque than the CG-HFB and BP-HFB implants. The %BIC of the CG-HFL surfaces was slightly higher than that of the CG-HFB implants. The BP-HFB and BP-HFL groups presented a higher %BIC than that of the CG-HFB and CG-HFL groups (p<0.001). BP therapy also increased the %BBT at both implant surfaces. Higher levels of ALP were observed in the matrix region of bone tissue on the HFL surfaces than on the HFB surfaces. CONCLUSION: Both surfaces enable osseointegration in rats under BP therapy. CLINICAL RELEVANCE: The study demonstrates that hydrophobic (HFB) and hydrophilic (HFL) implant surfaces can promote osseointegration in rats undergoing bisphosphonate therapy. The HFL surfaces exhibited improved biomechanical performance, higher bone-implant contact, and increased bone volume, suggesting their potential clinical relevance for implant success in individuals on bisphosphonate treatment.


Assuntos
Implantes Dentários , Ratos , Camundongos , Animais , Osteogênese , Difosfonatos/farmacologia , Modelos Animais de Doenças , Propriedades de Superfície , Titânio/química , Osseointegração
20.
Oral Dis ; 30(3): 1462-1474, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-36807967

RESUMO

This study evaluated the effect of resveratrol (RES) on the prevention of medication-related osteonecrosis of the jaws (MRONJ) in ovariectomized (OVX) rats treated with zoledronate (ZOL). Fifty rats were distributed in five groups: SHAM (n = 10): non-ovariectomy + placebo; OVX (n = 10):ovariectomy + placebo; OVX + RES (n = 10):ovariectomy + resveratrol; OVX + ZOL (n = 10):ovariectomy + placebo + zoledronate; and OVX + RES + ZOL (n = 10):ovariectomy + resveratrol + zoledronate. The mandibles left sides were analyzed with micro-CT, histomorphometry, and immunohistochemistry. On the right side, bone markers gene expression was analyzed by qPCR. ZOL increased the percentage of necrotic bone and reduced the neo-formed bone compared to groups not receiving ZOL (p < 0.05). RES impacted the tissue healing pattern in OVX + ZOL + RES, reduced inflammatory cell infiltrate, and improved bone formation in the extraction site. Osteoblasts, alkaline phosphatase (ALP)-, and osteocalcin (OCN)-immunoreactive cells were lower in OVX-ZOL than in SHAM, OVX, and OVX-RES. The OXV-ZOL-RES had fewer osteoblasts and ALP- and OCN-cells than the SHAM and OVX-RES. The tartrate-resistant acid phosphatase (TRAP)-positive cells were reduced in the presence of ZOL (p < 0.05), while the TRAP mRNA levels increased with ZOL treatment, with or without resveratrol, compared with the other groups (p < 0.05). RES alone increased superoxide dismutase levels compared to OVX + ZOL and OVX + ZOL + RES (p < 0.05). In conclusion, resveratrol reduced the tissue impairment severity induced by ZOL; however, it could not prevent the occurrence of MRONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Resveratrol , Ácido Zoledrônico , Animais , Resveratrol/farmacologia , Resveratrol/uso terapêutico , Ratos , Feminino , Ácido Zoledrônico/uso terapêutico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Ovariectomia , Imidazóis/farmacologia , Estilbenos/uso terapêutico , Estilbenos/farmacologia , Difosfonatos/farmacologia , Conservadores da Densidade Óssea/farmacologia , Conservadores da Densidade Óssea/uso terapêutico , Ratos Wistar , Microtomografia por Raio-X , Osteocalcina , Fosfatase Alcalina , Osteoblastos/efeitos dos fármacos , Antioxidantes/uso terapêutico , Antioxidantes/farmacologia
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