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1.
Artigo em Inglês | MEDLINE | ID: mdl-33353034

RESUMO

The purpose of the present study was to estimate the prevalence of cyclin-dependent kinase (CDK) 4/6 inhibitors use among cancer patients from the medication-related osteonecrosis of the jaw (MRONJ) cohort of the University of Messina. We retrospectively reviewed the records of all patients with either intravenous bisphosphonates or denosumab-related MRONJ reported in the electronic health records of the Unit of Oral Surgery, School of Dentistry, University of Messina between the first quarter of 2018 and the first quarter 2020 to identify eligible patients. We observed six cases of MRONJ associated with CDK4/6 inhibitors concomitantly with intravenous bisphosphonates and/or denosumab in breast cancer patients. The CDK4/6 inhibitors registered were palbociclib (n = 5) and abemaciclib (n = 1). Data of cancer patients diagnosed with MRONJ in the same period (n = 10) were extracted for comparison. The comparative assessment with this group of patients showed a similar distribution of MRONJ stage ranged and clinical course after treatment. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and close monitoring. The role of premedication dental evaluation as a prevention strategy has been acknowledged for cancer patients about to initiate intravenous bisphosphonates and/or denosumab for treatment of bone metastasis, but additional attention should be paid to whom are assuming CDK4/6 inhibitors because of their oral adverse events.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/metabolismo , Quinase 4 Dependente de Ciclina/metabolismo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Arcada Osseodentária , Masculino , Estudos Retrospectivos
2.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(10): 783-788, 2020 Oct 09.
Artigo em Chinês | MEDLINE | ID: mdl-33045792

RESUMO

Bisphosphonate (BP), a group of anti-resorptive drugs, has been widely used for the treatments of osteoporosis and metastatic bone diseases. Medication-related osteonecrosis of the jaw (MRONJ), a serious well-recognized complication of patients receiving BP, adversely affects patients' oral health and quality of life. Its clinical signs include pain, bone exposure and necrosis of the jaws. Invasive oral treatments, which may affect the repair of jaws in patients using BP, could cause the occurrence of MRONJ. Therefore, it is important to avoid the risk factors of MRONJ and to standardize the operations in order to reduce the occurrence of MRONJ in oral treatments for patients receiving BP. After reviewing the related literature, this article aims to conclude the research progress on the standardized oral treatments of patients receiving BP and to provide clinical instructions for clinicians to treat these patients.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Osteoporose , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Difosfonatos/efeitos adversos , Humanos , Arcada Osseodentária , Osteoporose/tratamento farmacológico , Qualidade de Vida
3.
Tokai J Exp Clin Med ; 45(3): 126-130, 2020 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-32901900

RESUMO

We present a case of osteomyelitis of the condyle secondary to bisphosphonate-related osteonecrosis of the jaw. A 77-year-old female was referred to our clinic with complaints of swelling in the left mandibular molar regions. The patient had been suffering from myeloperoxidase anti-neutrophil cytoplasmic antibody (MPOANCA) associated vasculitis and had been treated with glucocorticoids for 8 years, and oral bisphosphonates had been prescribed to prevent osteopenia secondary to glucocorticoids. Imaging examinations showed radiolucency of the left mandibular body. Based on the diagnosis of osteomyelitis of the mandibular body secondary to bisphosphonate-related osteonecrosis, the patient received antimicrobial therapy and was well-healed. However, the patient returned 8 weeks later complaining of acute left preauricular swelling. Computed tomography showed the destructive changes in the mandibular condyle. We speculated that the infection was caused by the local spread from osteomyelitis of the left mandibular body. The risk of jaw necrosis related to antiresorptive therapy is well known. In recent years, the number of older patients being administered glucocorticoids with bisphosphonates has increased; therefore, we must be attentive to the signs of infectious diseases of the jawbone in the aging because it can easily shift to osteomyelitis or osteonecrosis and spread infection through the marrow.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Arcada Osseodentária , Côndilo Mandibular , Osteomielite/etiologia , Idoso , Antibacterianos/administração & dosagem , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Feminino , Glucocorticoides/efeitos adversos , Humanos , Imagem por Ressonância Magnética , Côndilo Mandibular/diagnóstico por imagem , Osteomielite/diagnóstico por imagem , Osteomielite/terapia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
4.
Artigo em Inglês | MEDLINE | ID: mdl-32723683

RESUMO

OBJECTIVE: The aim of this study was to investigate the frequency of osteoradionecrosis/medication-related osteonecrosis of the jaw (ORN/MRONJ) after dental extraction with use of postextraction antibiotic coverage without prophylactic hyperbaric oxygen (HBO) in patients who received radiotherapy to head and neck (RT-HN) or antiresorptive medications and to determine possible associated factors. STUDY DESIGN: A retrospective study was conducted in patients who had a history of RT-HN or exposure to antiresorptives and who underwent dental extractions from 2003 to 2019. According to the clinical protocol, patients received amoxicillin 500 mg, 3 times daily (TID) for at least 14 days, and chlorhexidine 0.12% rinses, 2 times daily (BID), after extraction (or an alternative antibiotic if allergic to amoxicillin). HBO was not used for patients with RT-HN. RESULTS: Ninety patients underwent a total of 243 extractions. Fifty patients (55.5%) received a median of 54.1 Gray to the extraction site and 40 (44.4%) were on antiresorptives. None of the patients received both RT and antiresorptives. Of 40 patients, 3 (7.5%) developed MRONJ, and of 50 patients, 1 (2%) developed ORN. Among those at risk for MRONJ, male gender and concomitant immunosuppressant medications were associated with MRONJ development (P < .05). CONCLUSIONS: In our patient cohort, the rate of postextraction ORN/MRONJ was lower and comparable with the rates reported in the literature. Larger prospective studies are required to validate the efficacy of postextraction antibiotics in reducing ONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteonecrose , Osteorradionecrose , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Humanos , Masculino , Estudos Prospectivos , Estudos Retrospectivos
5.
Med. oral patol. oral cir. bucal (Internet) ; 25(3): e326-e336, mayo 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-196318

RESUMO

BACKGROUND: The aim of the present study was to analyse the incidence, risk ratio (RR) and prognoses of two types of medication-related osteonecrosis of the jaws (MRONJ): denosumab-related osteonecrosis of the jaws (DRONJ) and Bisphosphonate-Related Osteonecrosis of the Jaws (BRONJ) in cancer patients under treatment with deno-sumab or zoledronic acid (ZA). MATERIAL AND METHODS: An electronic and manual search was conducted for randomized controlled trials (RCTs) until May 2019. Assessment of the identified studies, risk of bias and data extraction were performed independently by two reviewers. The incidence of DRONJ and BRONJ and the RR to develop MRONJ were calculated at 1 year, 2 years and 3 years of exposure. It was also calculated the odds ratio (OR) of their respective prognoses. They were calculated normalizing the values of the individual studies to 1 year, 2 years or 3 years when necessary through robust regression models using a statistical program. RESULTS: From 1.277 references identified, 8 RCTs were included, which comprised a total of 13.857 patients with a variety of neoplasms. The incidence of DRONJ in cancer patients under treatment with denosumab ranged from 0.5 to 2.1% after 1 year, 1.1 to 3.0% after 2 years, and 1.3 to 3.2% after 3 years of exposure. The incidence of BRONJ in cancer patients under treatment with ZA ranged from 0.4 to 1.6% after 1 year of exposure, 0.8 to 2.1% after 2 years, and 1.0 to 2.3% after 3 years of exposure. Statistically significant differences were found between de-nosumab and ZA in the risk of developing MRONJ after 1, 2 and 3 years of exposure. Nevertheless, there were no significant differences in terms of patient prognosis. CONCLUSIONS: Denosumab is associated with a significantly higher risk of developing MRONJ compared to ZA. Nevertheless, no differences were found in its prognoses


No disponible


Assuntos
Humanos , Masculino , Feminino , Osteonecrose/induzido quimicamente , Denosumab/efeitos adversos , Ácido Zoledrônico/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Doenças Maxilomandibulares/induzido quimicamente , Medição de Risco , Fatores de Risco , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias/tratamento farmacológico , Fatores de Tempo
6.
Support Care Cancer ; 28(9): 4019-4029, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32307659

RESUMO

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is an infrequent, but potentially serious, adverse event that can occur after exposure to bone-modifying agents (BMAs; e.g., bisphosphonates, denosumab, and antiangiogenic therapies). BMAs are typically used at higher doses to prevent skeletal-related events in cancer patients and at lower doses for osteoporosis/bone loss. MRONJ can cause significant pain, reduce quality of life, and can be difficult to treat, requiring a multiprofessional approach to care. METHODS: We reviewed the literature and guidelines to summarize a practical guide on MRONJ for nurses and other allied healthcare professionals. RESULTS: While there is a risk of MRONJ with BMAs, this should be considered in relation to the benefits of treatment. Nurses and other allied healthcare professionals can play a key role alongside physicians and dentists in assessing MRONJ risk, identifying MRONJ, counseling the patient on the benefit-risk of BMA treatment, preventing MRONJ, and managing the care pathway of these patients. Assessing patients for MRONJ risk factors before starting BMA treatment can guide preventative measures to reduce the risk of MRONJ. Nurses can play a pivotal role in facilitating multiprofessional management of MRONJ by communicating with patients to ensure compliance with preventative measures, and with patients' physicians and dentists to ensure early detection and referral for prompt treatment of MRONJ. CONCLUSIONS: This review summarizes current evidence on MRONJ and provides practical guidance for nurses, from before BMA treatment is started through to approaches that can be taken to prevent and manage MRONJ in patients receiving BMAs.


Assuntos
Pessoal Técnico de Saúde/normas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Enfermeiras e Enfermeiros/normas , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de Risco
7.
J Stomatol Oral Maxillofac Surg ; 121(5): 556-562, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32156673

RESUMO

BACKGROUND: Bisphosphonates (BPs) contrast the bone fragility and improve bone density in some metastatic cancers and bone diseases, such as Osteogenesis Imperfecta (OI). BPs use has been associated with osteonecrosis of the jaws (BRONJs) in adults needing for invasive dental procedures. AIM: To conduct a systematic review on BRONJ occurrence after dental surgery in paediatric population under BPs therapy for OI, so as to identify the pre-surgical protocols adopted. DESIGN: According to PRISMA guidelines, Pubmed, Web of Science (WoS) and Cochrane were investigated on September 2018, and re-checked on July 2019. Inclusion criteria were English-language papers on children/young adults (until 24 years old) reporting dental/oral surgery procedures. RESULTS: Totally, 60 articles were found. After title/abstract reviews and duplicates exclusion, 22 eligible titles underwent full-text evaluation. Finally, 10 studies were included. CONCLUSIONS: The lack of BRONJ occurrence in paediatric population suffering OI and treated with BPs, was confirmed, but the reasons are still debated, being the BPs therapies and the surgical strategies various and not standardized. Longitudinal studies should evaluate what happens to those former children once adult, to evaluate the delayed BRONJs onset associated with the occurrence of comorbidities during the adulthood.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Procedimentos Cirúrgicos Bucais , Osteogênese Imperfeita , Adolescente , Adulto , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Criança , Difosfonatos/efeitos adversos , Humanos , Procedimentos Cirúrgicos Bucais/efeitos adversos , Osteogênese Imperfeita/diagnóstico , Adulto Jovem
8.
Sci Rep ; 10(1): 5620, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32221325

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) occurs in patients undergoing oral surgery while medicated with bisphosphonate, denosumab or anti-angiogenic agents. We employed a MRONJ-like rat model to investigate whether injecting fluvastatin at extraction sites prevents MRONJ-like lesion. A MRONJ-like model was created by treating rats with zoledronate and dexamethasone, extracting teeth, and immediately injecting fluvastatin at the extraction site. The experimental group comprised three subgroups treated with low (0.1 mg/kg; FS-L), medium (1.0 mg/kg; FS-M) and high concentrations (10 mg/kg; FS-H) of fluvastatin. Necrotic bone exposure was significantly lower in the FS-M (p = 0.028) and FS-H (p = 0.041) groups than in the MRONJ group. The distance between the edges of the epithelial surfaces was significantly shorter in the FS-M (p = 0.042) and FS-H (p = 0.041) groups. The area of necrotic bone and the necrotic bone ratio were significantly smaller in the FS-H group (p = 0.041 and p = 0.042 respectively). Bone volume fraction calculated on µ-CT images was significantly larger in the FS-H group than in the MRONJ group (p = 0.021). Our findings suggest that a single local injection of fluvastatin following tooth extraction can potentially reduce the chance of developing MRONJ-like lesion in rats.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Fluvastatina/farmacologia , Osteonecrose/prevenção & controle , Inibidores da Angiogênese/efeitos adversos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Osso e Ossos/diagnóstico por imagem , Denosumab/efeitos adversos , Difosfonatos/efeitos adversos , Modelos Animais de Doenças , Feminino , Osteonecrose/etiologia , Ratos , Ratos Wistar , Extração Dentária/efeitos adversos , Ácido Zoledrônico/efeitos adversos
9.
Oral Dis ; 26(5): 955-966, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32011077

RESUMO

OBJECTIVE: We reported the alveolar bone histology prior to dental extractions in cancer patients, who received bone-targeting agents (BTA). SUBJECTS AND METHODS: Fifty-four patients were included. Patients underwent extractions, and bone biopsies were taken. RESULTS: Extractions were performed due to pain, swelling, purulence, fistula, and numbness, not responding to treatment, in 40 patients (group A); extractions due to asymptomatic, non-restorable teeth, were performed in 14 patients (group B). Complete alveolar jaw bone histological necrosis was observed in 28 of 40 (70%) patients of group A and none of group B (p < .001). The development of clinical osteonecrosis (MRON) was assessed in 44 patients; 10 patients, who were also treated with Low Level Laser Treatments-LLLT, were excluded from this analysis, as the alternative therapies were a confounding factor. Twelve patients, with alveolar bone histological necrosis prior to extraction, developed medication-related osteonecrosis of the jaw (MRONJ) compared with two patients with vital or mixed vital/non-vital bone (p < .0007). BTAs >1 year and concurrent targeted therapy were also significantly associated with MRONJ (p = .016 and p = .050). CONCLUSION: Pain, swelling, purulence, fistula, and numbness were significantly associated with complete bone histological necrosis prior to extractions and increased MRONJ development. Research is justified to explore whether histological necrosis represents an early stage of osteonecrosis.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Neoplasias , Extração Dentária , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico por imagem , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos , Humanos
10.
J Bone Miner Metab ; 38(4): 581-588, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32076874

RESUMO

INTRODUCTION: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in patients with AID. MATERIALS AND METHODS: The study population comprised 232 patients treated with AR, AID or non-AID, who had undergone dental extraction from January 2011 to September 2017. The incidence and risk factors of ARONJ were analysed retrospectively. Additionally, the relationship between ARONJ and osteoporotic fracture (OF) and AR discontinuation during dental procedures was investigated. RESULTS: Of 232 patients, 10 developed ARONJ within 1 year of dental extraction. The incidence of ARONJ in patients with AID was higher than that in non-AID patients (2.0/100 person-year vs 0.5/100 person-year; p = 0.03). Among the AID patients, RA patients had strikingly high incidence of ARONJ (3.6/100 person-year). The incidence of neither ARONJ nor OF significantly differed between patients who continued and discontinued AR in the perioperative period. CONCLUSION: Patients with AID who undergo dental extraction are at high risk of ARONJ. Discontinuation of AR would not significantly contribute to reduce the incidence of ARONJ in those patients.


Assuntos
Doenças Autoimunes/complicações , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Extração Dentária/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/terapia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/complicações , Estudos Retrospectivos , Fatores de Risco , Suspensão de Tratamento , Adulto Jovem
11.
J Craniofac Surg ; 31(4): 1037-1041, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32102027

RESUMO

OBJECTIVES: The aim of the present study is to report a case series of patients with peri-implant medication-related osteonecrosis of the jaw (MRONJ), in particular describing the onset of the condition and surgical treatment outcome. MATERIAL AND METHODS: Fifteen consecutive patients with clinical diagnosis of peri-implant MRONJ were retrospectively included in the study. The sample was stratified on the base of oral, pharmacological, and general health variables. The number of affected implants was recorded in all patients, and MRONJ staging applied. Surgical treatment was performed with a standardized operative protocol, involving implant removal, sequestrectomy, debridement of soft tissue, and bone curettage. Follow-up evaluating surgical outcome was performed at twelve months after surgery. RESULTS: in our study sample, patients were almost equally distributed in terms of underlying diseases in osteoporotic and oncologic patients. All MRONJ lesions were symptomatic, and in 6 patients bone exposure was detected. 40 implants in total were evaluated, with MRONJ being present around 29 implants. 12 patients were diagnosed with Stage III MRONJ, and 3 patients with Stage II MRONJ. Surgical treatment leads to complete healing in 86.7% of cases, with 100% success for maxillary MRONJ. CONCLUSIONS: Surgical treatment seems to have a positive impact on MRONJ treatment also in cases of peri-implant involvement. However, monitoring and prevention are fundamental in patients under pharmacological treatment with anti-resorptive/antiangiogenic drugs, as peri-implant MRONJ can develop also in absence of specific traumatic events.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/cirurgia , Implantes Dentários/efeitos adversos , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cicatrização
12.
Yakugaku Zasshi ; 140(1): 63-79, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-31902887

RESUMO

Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone-resorptive effect. BPs are divided into nitrogen-containing BPs (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). N-BPs have far stronger anti-bone-resorptive effects than non-N-BPs, and BRONJ is caused by N-BPs. Our murine experiments have revealed the following. N-BPs, but not non-N-BPs, exhibit direct and potent inflammatory/necrotic effects on soft-tissues. These effects are augmented by lipopolysaccharide (the inflammatory component of bacterial cell-walls) and the accumulation of N-BPs in jawbones is augmented by inflammation. N-BPs are taken into soft-tissue cells via phosphate-transporters, while the non-N-BPs etidronate and clodronate inhibit this transportation. Etidronate, but not clodronate, has the effect of expelling N-BPs that have accumulated in bones. Moreover, etidronate and clodronate each have an analgesic effect, while clodronate has an anti-inflammatory effect via inhibition of phosphate-transporters. These findings suggest that BRONJ may be induced by phosphate-transporter-mediated and infection-promoted mechanisms, and that etidronate and clodronate may be useful for preventing and treating BRONJ. Our clinical trials support etidronate being useful for treating BRONJ, although additional clinical trials of etidronate and clodronate are needed.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Conservadores da Densidade Óssea/metabolismo , Conservadores da Densidade Óssea/uso terapêutico , Ensaios Clínicos como Assunto , Ácido Clodrônico/química , Ácido Clodrônico/metabolismo , Ácido Clodrônico/farmacologia , Ácido Clodrônico/uso terapêutico , Difosfonatos/química , Difosfonatos/metabolismo , Difosfonatos/uso terapêutico , Ácido Etidrônico/química , Ácido Etidrônico/metabolismo , Ácido Etidrônico/farmacologia , Ácido Etidrônico/uso terapêutico , Humanos , Inflamação , Arcada Osseodentária/metabolismo , Camundongos , Nitrogênio , Proteínas de Transporte de Fosfato/antagonistas & inibidores , Ratos
13.
Med Care ; 58(5): 419-426, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-31985584

RESUMO

BACKGROUND: Discontinuation of bisphosphonates (BP) or a "drug holiday" after several years of treatment is increasingly common. However, the association of drug holiday duration with future fracture risk is unclear. OBJECTIVES: We evaluated the rate of fracture in relation to various lengths of drug holidays among women receiving long-term BP therapy. RESEARCH DESIGN: Observational cohort study using US Medicare data 2006-2016. Incidence rates (IRs) and Cox proportional hazards models were used to evaluate the rate and adjusted hazard ratios (aHRs) controlling for potential confounders. SUBJECTS: Women aged 65 years and above enrolled in fee-for-service Medicare who had been adherent (≥80%) to alendronate, risedronate, or zoledronate for ≥3 years. MEASURES: Hip, humerus, distal forearm, and clinical vertebral fracture. RESULTS: Among 81,427 eligible women observed for a median (interquartile range) of 4.0 (2.5, 5.3) years, 28% of women underwent a drug holiday. In the alendronate cohort (73% overall), the IR of hip fracture among women who discontinued BP for >2 years was 13.2 per 1000 person-years. Risk was increased (aHR=1.3, 1.1-1.4) versus continuing therapy (IR=8.8, referent). Rates were elevated for humerus fracture with discontinuation >2 years (aHR=1.3, 1.1-1.66) and for clinical vertebral fracture with discontinuation >2 years (aHR=1.2, 1.1-1.4). Results were similar for risedronate, zoledronate, and ibandronate for hip and clinical vertebral fracture. CONCLUSION: Discontinuing alendronate beyond 2 years was associated with increased risk of hip, humerus, and clinical vertebral fractures.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Fraturas do Quadril/epidemiologia , Fraturas do Úmero/epidemiologia , Fraturas da Coluna Vertebral/epidemiologia , Idoso , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Estudos de Coortes , Difosfonatos/efeitos adversos , Esquema de Medicação , Feminino , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/prevenção & controle , Humanos , Medicare , Osteoporose Pós-Menopausa/tratamento farmacológico , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Fatores de Tempo , Estados Unidos/epidemiologia , Suspensão de Tratamento
14.
Med. oral patol. oral cir. bucal (Internet) ; 25(1): e71-e83, ene. 2020. tab, ilus
Artigo em Inglês | IBECS | ID: ibc-196198

RESUMO

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a rare, but serious adverse effect of certain drugs, of which bisphosphonates are the most widely known. This pathology is also associated with other medications such as the biologic antiresorptive agent, denosumab and some antiangiogenics such as sunitinib, bevacizumab or aflibercept. Very recently, new medications have also been associated with osteonecrosis of the jaw (ONJ). The objectives were to update the list of medications associated with ONJ, to analyze the fundamental aspects of this list and to describe the level of evidence available. MATERIAL AND METHODS: A narrative bibliographic review was made, using the PubMed-MedLine, DOAJ and SCI-ELO databases. Additional information was obtained through the online Medication Information Centre of the Spanish Agency of Medicines and Medical Devices (AEMPS - CIMA), the websites of the US Food & Drugs Administration (Drugs@FDA) and the European Medicines Agency (EMA). RESULTS: The latest drugs identified as potential facilitators of this pathology include a number of anti-VEGF based antiangiogenic drugs and anti-TKI and different types of immunomodulators. Neither the level of evidence in this association nor the risk are equal for all these drugs. On the other hand, over the coming years, new drugs will be marketed with similar action mechanisms to those that are recognized as having this adverse effect. CONCLUSIONS: No effective therapy is currently known for the treatment of ONJ. Therefore, in order to prevent new cases of MRONJ, it is essential for all oral healthcare professionals to be fully up-to-date with the etiopathogenic aspects of this pathology and to be aware of those drugs considered to be a risk


No disponible


Assuntos
Humanos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Inibidores da Angiogênese/efeitos adversos , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Fatores de Risco , Denosumab/efeitos adversos , Bevacizumab/efeitos adversos , Sunitinibe/efeitos adversos
15.
Med Hypotheses ; 134: 109427, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31622920

RESUMO

There have been increasing numbers of reports that anti-osteoporosis drugs cause osteonecrosis. A typical example is medication-related osteonecrosis of the jaws (MRONJ) which can cause massive necrosis and defects of the jaws. Thus, the dosage and effects of anti-osteoporosis drugs should be re-examined. Our hypothesis is that primary moderate osteoporosis itself is beneficial for bones and should not be excessively treated other than vitamin D, calcium supplementation and functional exercises. The self-repair and anti-infection abilities of bone depend on its organic tissues including stem cells, blood vessels, osteoclastic and osteogenic factors in bone, which jointly fight against invading pathogens and repair bone damage. Recent evidence supports age-related changes in mesenchymal stem cell including loss of self-renewal and increases in senescent cell numbers. Thus, the number of MSCs and vessels need to be increased to achieve functions similar to those in young people. This requires dissolving a portion of inorganic materials and providing extra space to hold more cells and blood vessels. In contrast, anti-osteoporosis drugs prevent bone destruction, and increase mineralization that occupies the space of organic materials, reduces bone immunity and self-repair. Moreover, long term use of anti-osteoporosis drugs also have negative effects on long bones and cartilages. Therefore, moderate age-related osteoporosis is natural in humans to protect bones. Excessive treatment of osteoporosis weakens immunity and self-repair.


Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Osso e Ossos/metabolismo , Modelos Biológicos , Osteoporose/fisiopatologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Osso e Ossos/irrigação sanguínea , Osso e Ossos/citologia , Osso e Ossos/ultraestrutura , Cálcio/uso terapêutico , Autorrenovação Celular , Senescência Celular , Terapia Combinada , Implantes Dentários , Terapia por Exercício , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/fisiologia , Osteoporose/tratamento farmacológico , Osteoporose/terapia , Vitamina D/uso terapêutico
16.
Z Rheumatol ; 79(2): 203-209, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30796524

RESUMO

BACKGROUND AND OBJECTIVES: The aim of the present study was to assess the prevalence of medication-related osteonecrosis of the jaw (MRONJ) in osteoporosis patients suffering from inflammatory rheumatic diseases, as well as to assess the prevalence of relevant dental, behavioral, and medical risk factors for MRONJ. MATERIALS AND METHODS: A total of 198 patients with inflammatory rheumatic diseases and osteoporosis therapy were recruited from a tertiary rheumatological/immunological referral center between June 2015 and September 2016. They were assessed using a structured interview. A maxillofacial surgeon later examined patients complaining of possible symptoms of osteonecrosis. In cases of osteonecrosis, dental records were obtained and evaluated. Preventive measures taken and dental as well as other clinical risk factors were evaluated. RESULTS: Of the 198 patients, three suffered from osteonecrosis of the jaw, none of whom had any history of malignant disease or radiation therapy, resulting in a prevalence of 1.5%. Of these three patients, only one was given bisphosphonates intravenously (i.v.), whereas all three had been treated orally. All three diagnoses of MRONJ had been previously known to the patients and their maxillofacial surgeons. Two of the patients had rheumatoid arthritis, and one patient suffered from large vessel vasculitis. Long anti-osteoporotic treatment duration, low functional status, and low bone density of the femur were significantly associated with MRONJ development. CONCLUSION: Inflammatory rheumatic diseases constitute a risk factor for MRONJ in patients treated with bisphosphonates for osteoporosis. Patients should be counseled accordingly and should be offered dental screening and regular dental check-ups.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteoporose , Febre Reumática , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/tratamento farmacológico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêutico , Feminino , Humanos , Osteonecrose/induzido quimicamente , Osteoporose/tratamento farmacológico , Febre Reumática/tratamento farmacológico
17.
J Stomatol Oral Maxillofac Surg ; 121(4): 344-346, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31672685

RESUMO

INTRODUCTION: The objective of this study was to assess medical students' knowledge of "medication related osteonecrosis of the jaws" (MRONJ). METHODS: A questionnaire survey was administered to all the medical students in the last two years of school of medicine at the University of Eastern Piedmont between January 2019 and March 2019. The questionnaire contained a first section regarding demographic and personal data of the student and a second section regarding the knowledge on MRONJ. RESULTS: On the whole, 72 medical students agreed to participate to this study and filled in the questionnaire. As for indications for the use of bisphosphonates 45 students correctly answered "osteoporosis, osteogenesis imperfecta, multiple myeloma, or metastasis of some malignant tumors". Almost all students (71 out of 72) answered that a thorough examination of oral cavity and a dentist screening is needed and fundamental before starting bisphosphonate assumption. As for drugs responsible for MRONJ, only 12 students out of 72 correctly answered "bisphosphonates, denosumab, and antiangiogenic drugs". DISCUSSION: A better level of knowledge and awareness by medical doctors and young physicians may lead, in future, to minimize incidence of MRONJ as well as to a better resolution of ONJ cases. Theoretical and practical initiatives could be promoted to improve and consolidate the knowledge of future physicians about this important issue.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Conservadores da Densidade Óssea , Osteoporose , Estudantes de Medicina , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Humanos
18.
Aust Dent J ; 65(1): 100-103, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31769879

RESUMO

Bisphosphonates (BPs) have long been used for the treatment of osteoporosis and diseases like bone malignancies, active Paget's disease of bone, severe osteogenesis imperfecta and fibrous dysplasia among others. They bond highly to the bone surface and inhibit bone resorption. As BPs have a long half-life in bone because of their irreversible binding to bone, patients retain their risk profile even after drug cessation. This property also explains the complications wherein the cessation of bone resorption leads to halt in bone turnover. Usually with alendronate the risk of bisphosphonate-related osteonecrosis of jaw (BRONJ) wears off after 12 months. Reporting of the development of BRONJ is commonly associated with the intravenous BPs. Invasive surgical procedure associated with the placement of implants has been shown to be a major reason for the occurrence or initiation of BRONJ in susceptible patients. The prognosis of implants placed in the jaws of patients under or past BP medication is still uncertain. The present case report describes a patient on long-term oral BP therapy with spontaneous exfoliation of implant supported bone due to osteonecrosis.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/efeitos adversos , Implantes Dentários/efeitos adversos , Osteonecrose/induzido quimicamente , Alendronato/efeitos adversos , Difosfonatos/efeitos adversos , Humanos
19.
J Stomatol Oral Maxillofac Surg ; 121(5): 523-526, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31863926

RESUMO

INTRODUCTION: The aim of the present study was to investigate the number of patients with Multiple Myeloma (MM) treated with intravenous Zoledronic Acid who presented an involvement of the jaws by Myeloma that mimicked an osteonecrosis. MATERIAL AND METHODS: A retrospective study was performed in a University Hospital reference for a population of 1.084.000 inhabitants. A 'case' Medication-Related Osteonecrosis of the jaw (MRONJ) was considered when the patient met diagnostic criteria established by the American Association of Oral and Maxillofacial Surgeons (AAOMS, 2014). We recorded data on the underlying disease, medications used, mode of Bisphosphonate administration (oral or intravenous), and timing of medication use. RESULTS: The sample size was 84 cases. 22 patients had MRONJ associated to MM treatment. Histopathological examination of pathological bone was characterized by the presence of necrotic osteitis in 82 patients. Only 2 patients with MRONJ suspicion were finally diagnosed as MM. These cases represented 9.09% of all patients with multiple myeloma initially labeled MRONJ in our hospital. CONCLUSION: The present study has shown that MM can be identified in jaw specimens of patients exposed to Bisphosphonates and clinically diagnosed as osteonecrosis. Biopsy examination should be considered in at least selected cases, for example, before surgical treatment in patients with MM and clinical stage 3 osteonecrosis (due to the detection of malignancy would alter the surgical strategy).


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos , Mieloma Múltiplo , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/diagnóstico , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Difosfonatos/efeitos adversos , Humanos , Mieloma Múltiplo/complicações , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Ácido Zoledrônico/efeitos adversos
20.
Future Oncol ; 15(30): 3503-3511, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31580147

RESUMO

Aim: To investigate the risk factors for developing osteonecrosis of jaw (ONJ) in advanced cancer patients with bone metastases underwent zoledronic acid (ZA) treatment. Materials & methods: Univariate and multivariate logistic regression analyses were performed to investigate factors associated with developing ONJ in advanced cancer patients. Results: A total of 2214 advanced cancer patients were included. Univariate and multivariate logistic regression analyses for risk factors associated with ONJ were older age (≥66 years, hazards ratio [HR]: 3.21; p = 0.007), anemia (HR: 3.29; p = 0.006) and duration of ZA exposure (between 1 and 2 years, HR: 3.91, p = 0.01; ≥2 years, HR: 8.07, p < 0.001), respectively. Conclusion: Patients with older age, anemia and/or more than 1 year of ZA treatment are at high risk of developing ONJ.


Assuntos
Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/epidemiologia , Conservadores da Densidade Óssea/administração & dosagem , Neoplasias Ósseas/tratamento farmacológico , Ácido Zoledrônico/administração & dosagem , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anemia/epidemiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/patologia , Conservadores da Densidade Óssea/efeitos adversos , Neoplasias Ósseas/secundário , Ensaios Clínicos Fase III como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ácido Zoledrônico/efeitos adversos
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