Differences According to the Type of Exogenous Hyaluronic Acid and its Frequency of Infiltration in the Treatment of Temporomandibular Osteoarthritis / Diferencias Según el Tipo de Ácido Hiaurónico Exógeno y su Frecuencia de Infiltración en el Tratamiento de la Osteoartritis Temporomandibular

SUMMARY: One of the most important minimally invasive treatments today in temporomandibular joint osteoarthritis (TMJ- OA) is the intra-articular exogenous hyaluronic acid (HA) injection, which has yielded good results in pain relief and improves mandibular function with few side effects. However, the effectiveness of HA continues to be controversial, partly due to the heterogeneity in the injection protocols in their molecular weight, viscosity and frequency of infiltration, among other properties. The aim of this review is to identify the differences in the histological and clinical effects of the different types of HA and the frequency of infiltration on TMJ-OA treatment. Materials and methods: A bibliographic search was performed in the PubMed, Web of Science and Scopus databases. The search was limited up to September 2022. Search terms included "osteoarthritis", "hyaluronic acid, "molecular weight", "concentration", "viscosity", "dose" and "temporomandibular", using AND/OR as Boolean terms. Results: Exogenous HA in its different molecular weights offers an improvement in histological and clinical characteristics. Apparently, low and medium molecular weight HA presents better results. No clinical studies related to the degree of HA viscosity were found. Respect to the frequency of infiltration, single injection, weekly injections for 3 weeks, weekly injections for 5 weeks and other protocols are used. However, their comparison is complex. There seems to be differences in the effects of the different HA preparations for the treatment of TMJ-OA, mainly in their molecular weight. However, the evidence remains scant.

Uno de los tratamientos mínimamente invasivos más importantes en la actualidad en la artrosis de la articulación temporomandibular (OATM) es la inyección intraarticular de ácido hialurónico (AH) exógeno, que ha dado buenos resultados en el alivio del dolor y mejora la función mandibular con pocos efectos secundarios. Sin embargo, la efectividad del AH continúa siendo controversial, en parte debido a la heterogeneidad en los protocolos de inyección en cuanto a su peso molecular, viscosidad y frecuencia de infiltración, entre otras propiedades. El objetivo de esta revisión fue identificar las diferencias en los efectos histológicos y clínicos de los diferentes tipos de HA y la frecuencia de infiltración en el tratamiento de TMJ-OA. Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Web of Science y Scopus. La búsqueda se limitó hasta septiembre de 2022. Los términos de búsqueda incluyeron "osteoartritis", "ácido hialurónico", "peso molecular", "concentración", "viscosidad", "dosis" y "temporomandibular", utilizando AND/OR como términos booleanos. El HA exógeno en sus diferentes pesos moleculares ofrece una mejora en las características histológicas y clínicas. Aparentemente, el AH de bajo y medio peso molecular presenta mejores resultados. No se encontraron estudios clínicos relacionados con el grado de viscosidad del HA. Respecto a la frecuencia de infiltración, se utilizan inyecciones únicas, inyecciones semanales durante 3 semanas, inyecciones semanales durante 5 semanas y otros protocolos. Sin embargo, su comparación es compleja. Parece haber diferencias en los efectos de las diferentes preparaciones de HA para el tratamiento de la OA-TMJ, principalmente en su peso molecular. Sin embargo, la evidencia sigue siendo escasa.

Utilização da cannabis sativa para tratamento de dor crônica em cães / Use of cannabis sativa for the treatment of chronic pain in dogs / Uso de cannabis sativa para el tratamiento del dolor crónico en perros

A Cannabis sativa é uma planta que apresenta vários benefícios terapêuticos para animais, como tratamento da dor neuropática, inflamatória e osteoartrose. A dor é bastante recorrente na rotina clínica, sendo importante seu manejo para que seja ofertada uma melhor qualidade e conforto de vida para o paciente. O estudo objetivou identificar, a partir de evidências científicas, as características da utilização medicinal do uso de Cannabis Sativa no tratamento da dor crônica no cão, utilizando um dos seus princípios ativos, canabidiol (CBD). Foi feito uma revisão bibliográfica onde foi realizada a busca de estudos experimentais e relatos de caso em bases de dados eletrônicos, sendo incluídas fontes contendo a utilização do CBD em animais, que abordaram controle da dor, assim como escore avaliativo da dor antes, durante e após o tratamento proposto. Após eleger e analisar 54 estudos percebe-se que na medicina veterinária o uso do canabidio é insuficiente, uma vez que o foco da maior parte dos estudos clínicos é voltado para medicina humana. Ainda assim, a utilização de CBD mostrou-se eficaz, confirmando uma nova alternativa para o controle da dor em animais.(AU)

Cannabis sativa is a plant that has several therapeutic benefits for animals, such as the treatment of neuropathic and inflammatory pain and osteoarthritis. Pain is quite recurrent in the clinical routine, and its management is important to offer a better quality and comfort of life for the patient. The study aimed to identify, based on scientific evidence, the characteristics of the medicinal use of Cannabis Sativa in the treatment of chronic pain in dogs, using one of its active principles, cannabidiol (CBD). A bibliographical review was carried out in which experimental studies and case reports were searched in electronic databases, including sources containing the use of CBD in animals, which addressed pain control, as well as pain assessment score before, during and after the proposed treatment. After choosing and analyzing 54 studies, it is clear that in veterinary medicine the use of CBD is few, and the focus of clinical studies is on human medicine. The use of CBD proved to be effective, thus confirming a new alternative for pain control in animals.(AU)

El cannabis sativa es una planta que tiene varios beneficios terapéuticos para los animales, como el tratamiento del dolor neuropático e inflamatorio y la osteoartritis. El dolor es bastante recurrente en la rutina clínica, y su manejo es importante para ofrecer una mejor calidad y comodidad de vida al paciente. El estudio tuvo como objetivo identificar, con base en la evidencia científica, las características del uso medicinal de Cannabis Sativa en el tratamiento del dolor crónico en perros, utilizando uno de sus principios activos, el cannabidiol (CBD). Se realizó una revisión bibliográfica en la que se buscaron estudios experimentales y reportes de casos en bases de datos electrónicas, incluyendo fuentes que contengan el uso de CBD en animales, que abordaran el control del dolor, así como la puntuación de evaluación del dolor antes, durante y después del tratamiento propuesto. Después de elegir y analizar 54 estudios, queda claro que en medicina veterinaria el uso de cannabidio es insuficiente, ya que el foco de la mayoría de los estudios clínicos está en la medicina humana. Aun así, el uso de CBD demostró ser efectivo, confirmando una nueva alternativa para el control del dolor en animales.(AU)

Eficácia e segurança da combinação Glicosamina e Condroitina comparada a medicamentos disponíveis no SUS para o tratamento de osteoartrite: revisão rápida / Effectiveness and safety of Glucosamine and Chondroitin combination compared to drugs available in Brazilian Public Health System for the treatment of Osteoarthritis: rapid review

Tecnologia: Combinação de glicosamina e condroitina. Indicação: Tratamento de osteoartrite em adultos. Pergunta: O tratamento com a combinação de glicosamina e condroitina é mais eficaz e seguro que os demais tratamentos para osteoartrite disponíveis no SUS? Métodos: Uma revisão rápida de evidências, uma revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2. Resultados: Foi selecionada uma revisão sistemática, que atendiam aos critérios de inclusão. Conclusão: A combinação de glicosamina com condroitina, comparados ao placebo, mostrou ser mais eficaz para tratamento da dor e função e alcançou o segundo lugar nas alternativas terapêuticas para tratamento da dor e função

Technology: Combination of glucosamine and chondroitin. Indication: Treatment of osteoarthritis in adults. Question: Is the treatment with the combination of glucosamine and chondroitin more effective and safer than the other treatments for osteoarthritis available in the Brazilian Public Health System? Methods: A rapid review of evidence, a overview of systematic reviews, with bibliographic search done in PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed using AMSTAR-2. Results: A systematic review was selected, which met the inclusion criteria. Conclusion: The combination of glucosamine and chondroitin, compared to placebo, proved to be more effective for the treatment of pain and function and reached second place in therapeutic alternatives for the treatment of pain and function

Effectiveness of hyaluronic acid in the treatment of degenerative diseases of the temporomandibular joint: literature review / Efectividad del ácido hialurónico en el tratamiento de enfermedades degenerativas de la articulación temporomandibular: revisión de literatura

Objetive: The degenerative diseases of the tempo-romandibular joint (TMJ) are characterized by a progressive destruction of the articular tissues of the condyle and the glenoid fossa. The main aim of this review is to describe the effectiveness of the hyaluronic acid (HA) in the treatment of degenerative diseases of the TMJ in accordance with the available scientific evidence. Material and Methods: A literature search was made in the following databases EBSCO, Pubmed, Cochraneand Trip Database, using the keywords hyaluronic, hyaluronan, NaH, hyaluronate, TMJ, TMD, CMD, craniomandibular, orofacial pain and temporomandibular. There were no date or language restrictions applied. Results: After applying inclusion and exclusion criteria, 14 studies were included in this review (11 randomized controlled clinical trials and 3 non-randomized clinical trials). Conclusion: The studies reported a decrease in pain and improvement in functional parameters after treatment of TMJ osteoarthritis with HA . The use of arthrocentesis associated with the administration of HA provides effects synergistic, reaching a superiority the protocols with multiple injections with respect to those of a single session. The adverse effects related to the injection of HA with or without associated arthrocentesis were minor and transitory.

Resumen: Objetivo: Las enfermedades degenerativas de la articulación temporomandibular (ATM) se caracterizan por una destrucción progresiva de tejidos articulares en el cóndilo y la fosa glenoidea. El objetivo principal de esta revisión es describir la efectividad del uso de ácido hialurónico en el tratamiento de enfermedades degenerativas de la articulación temporomandibular de acuerdo con la evidencia científica disponible. Material y Métodos: Se realizó una búsqueda de la literatura en las bases de datos electrónicas EBSCO, PubMed, Cochrane y Trip Database, utilizando las palabras claves hyaluronic, hyaluronan, NaH, hyaluronate, tmj, tmd, cmd, craniomandibular, orofacial pain y temporomandibular, sin límite de fecha ni de idioma hasta Mayo del año 2020, complementada con una búsqueda retrógrada. Resultados: Con base en los criterios de inclusión y exclusión, 14 estudios fueron incluidos en esta revisión (11 ensayos clínicos controlados aleatorizados y 3 ensayos clínicos controlados no aleatorizados). Conclusión: Los estudios reportaron una disminución del dolor y mejora en los parámetros funcionales luego del tratamiento de osteoartritis de la ATM con AH. El uso de artrocentesis asociada a la administración del AH provee efectos sinérgicos, alcanzando una superioridad los protocolos con múltiples inyecciones con respecto a aquellos de una sola sesión. Los efectos adversos relacionados con la inyección de AH con o sin artrocentesis asociada fueron menores y transitorios.

Effect of Gancao Fuzi Decoction on osteoarthritis and proteomics of articular cartilage in rats / 中国中药杂志

The rat osteoarthritis model was replicated by injection of sodium iodoacetate into the knee joint cavity, and the effects of Gancao Fuzi Decoction on rat osteoarthritis and the proteome of articular cartilage were investigated. Sixty SD rats weighing 230-250 g were randomly divided into normal group, model group, glucosamine sulfate group, and Gancao Fuzi Decoction high, medium and low dose groups. Osteoarthritis model was induced by intra-articular injection of sodium iodoacetate(3 mg on each leg) in all groups except the normal group. After modeling, each administration group was given intragastric administration for 1 month. During the administration period, joint pain test and joint width measurement were performed every week to observe the autonomous behavior of rats. Enzyme linked immunosorbent assay(ELISA) method was used to detect the contents of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), matrix metalloproteinase-3(MMP-3), and matrix metalloproteinase tissue inhibitor(TIMP-1) in rat joint lavage fluid. Hematoxylin-eosin(HE) staining was used to observe bone and joint morphology. Nano-LC-LTQ-Orbitrap system was used to detect arti-cular cartilage proteins. The results showed that, compared with the model group, Gancao Fuzi Decoction could significantly improve joint pain and joint swelling in osteoarthritis rats, significantly reduce the contents of TNF-α, IL-1β and MMP-3 in the joint cavity la-vage fluid, increase the content of TIMP-1, and relieve inflammatory diseases such as enlarged joint space, rough cartilage edge, different thickness of cartilage layer, and disordered arrangement of chondrocytes. After comparing the proteins between the groups, 273 differential proteins were screened out. KEGG analysis found that the above differential proteins involved 43 signaling pathways such as systemic lupus erythematosus, among which 11 signaling pathways were related to osteoarthritis. The above results indicated that Gancao Fuzi Decoction had a preventive effect on osteoarthritis, and its mechanism of action may be accomplished by regulating the protein expression of osteoarthritis-related signal pathways.

Reducción de la cobertura social para los fármacos antiartrósicos sintomáticos de acción lenta: una iniciativa de desinversión en Argentina, 2015-2017 / Reduction of social coverage for symptomatic slow-acting drugs for osteoarthritis: a disinvestment initiative in Argentina, 2015-2017

RESUMEN En abril de 2016, el Instituto Nacional de Servicios Sociales para Jubilados y Pensionados excluyó del subsidio social la cobertura al 100% de 159 fármacos, entre ellos, los antiartrósicos sintomáticos de acción lenta o symptomatic slow-acting drugs for osteoarthritis (SySADOA), por insuficiente evidencia de beneficio clínico significativo. Evaluamos el efecto de esta medida sobre la utilización de SySADOA y de los antiinflamatorios no esteroides (AINE), no afectados por la medida. Se compararon las dispensas ambulatorias de los SySADOA y los AINE de 2015 a 2017, midiendo unidades dispensadas, precio de venta al público y gasto de bolsillo del beneficiario para cada mes. Luego de la medida, descendieron un 61,6% los envases de SySADOA dispensados y un 63,4% el monto total del precio de venta al público, medido en valores constantes. La dispensa no se reorientó hacia los AINE, que descendieron un 6,1%. Disminuyó tanto la incidencia de nuevos tratamientos (de 6,4 a 3,3 tratamientos por 1.000 beneficiarios por mes) como su continuidad. El gasto de bolsillo de los beneficiarios en SySADOA aumentó un 75,8% (a valores constantes). La desinversión en intervenciones de valor terapéutico cuestionable es una herramienta valiosa para la sustentabilidad de los sistemas de salud.

ABSTRACT In April 2016, the National Institute of Social Services for Retirees and Pensioners discontinued its policy of 100% coverage for 159 drugs (the "social subsidy"), including symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), due to insufficient evidence of significant clinical benefit. We evaluated the effect of this measure on the use of SYSADOAs as well as non-steroidal anti-inflammatory drugs (NSAIDs), which were unaffected by this policy change. We compared outpatient dispensations of SYSADOAs and NSAIDs from 2015 to 2017, measuring dispensed units, retail price, and out-of-pocket expenses for beneficiaries each month. After the change in coverage, there was a 61.6% total decrease in SYSADOA units dispensed, and a 63.4% decrease in the final sales price to the public, measured in constant values. Dispensation was not reoriented towards NSAIDs, which fell by 6.1%. The incidence of new treatments decreased (from 6.4 to 3.3 treatments per 1,000 beneficiaries per month), as did their continuity. Beneficiaries' out-of-pocket spending on SYSADOAs increased by 75.8% (at constant values). Disinvestment in interventions with questionable therapeutic value is an important tool in working toward the sustainability of health systems.

A standardized extract of Centella asiatica (ECa 233) prevents temporomandibular joint osteoarthritis by modulating the expression of local inflammatory mediators in mice

Abstract Objectives To investigate the effect of a standardized extract of Centella asiatica (ECa 233), which has anti-inflammatory properties, on the local expression of the transient receptor potential vanilloid 1 (TRPV1), the acid-sensing ion channel subunit 3 (ASIC3), and the calcitonin gene-related peptide (CGRP) in the temporomandibular joint (TMJ) structure 21 days after injecting the TMJ with complete Freund's adjuvant (CFA). Methodology A mouse model was induced by analyzing the CFA-injected TMJ on days 7, 14, and 21. We assessed TMJ histology by the osteoarthritis cartilage grade score. Then, we observed the effect of different ECa 233 concentrations (30, 100, and 300 mg/kg) and of 140 mg/kg ibuprofen doses on TRPV1, ASIC3, and CGRP local expression on day 21. Results Osteoarthritis cartilage scores were 1.17±0.37 and 3.83±0.68 on days 14 and 21, respectively, in the CFA group (n=5). On day 21, TRPV1, ASIC3, and CGRP expression significantly increased in the CFA group. In the ibuprofen-treated group, TRPV1 expression significantly decreased, but ASIC3 and CGRP showed no significant difference. All ECa 233 doses reduced TRPV1 expression, but the 100 mg/kg ECa 233 dose significantly decreased ASIC3 expression. Conclusions TRPV1, ASIC3, and CGRP expression increased in mice with TMJ-OA on day 21. All ECa 233 and ibuprofen doses inhibited pathogenesis by modulating the local expression of TRPV1 and ASIC3. Therefore, ECa 233 was more effective than ibuprofen.

Fatores de risco pré-operatórios associados a complicações após artroplastia primária total de joelho até o 30o dia de pós-operatório / Preoperative risk factors associated with complications after primary total knee arthroplasty up to the 30th postoperative day

A artroplastia total de joelho (ATJ) é um procedimento cirúrgico bem estabelecido, com altas taxas de sucesso para o tratamento da osteoartrite avançada do joelho que resulta, na maioria dos pacientes, em alívio da dor e melhora funcional da articulação. Embora a ATJ seja uma cirurgia eletiva segura, podem ocorrer complicações que resultam em maior tempo de internação e necessidade de readmissão hospitalar. Uma forma de reduzir o impacto das intercorrências é a identificação de possíveis fatores de risco para desenvolver complicações. A adoção de estratégias preventivas voltadas para controlar os fatores de risco potencialmente reduz a morbidade, a mortalidade e os custos diretos e indiretos com a ATJ. O objetivo do presente estudo foi determinar os fatores de risco para a ocorrência de complicações até trinta dias após realização de artroplastia total primária do joelho, a prevalência e o impacto das complicações sobre o tempo de internação e a necessidade de readmissão hospitalar. Foram incluídos no estudo 1.035 procedimentos de ATJ primária unilateral realizados no Instituto Nacional de Traumatologia e Ortopedia Jamil Haddad, no período de setembro de 2011 até fevereiro de 2016. Os parâmetros préoperatórios (idade, gênero, índice de massa corporal, ASA e comorbidades) e a ocorrência de complicações sistêmicas e locais até o 30º dia de pós-operatório foram obtidos por busca ativa nos prontuários. A identificação dos possíveis fatores de risco para ocorrência de qualquer complicação e a relação entre a ocorrência de complicação com o tempo de internação e com a necessidade de readmissão foi feita através de análise univariada. Em 4,3% dos procedimentos houve associação com algum tipo de complicação pósoperatória, sendo 2,8% complicações sistêmicas e 1,5% locais. Do total das complicações apresentadas pelos pacientes, 1,8% foram classificadas como graves e 2,5% como de baixa gravidade. Não foi registrado nenhum óbito no período pós-operatório de 30 dias. Diabetes e história de evento cardíaco prévio foram identificados como fatores de risco para complicação pós-operatória. Os pacientes que complicaram, permaneceram mais de 10 dias internados e/ou necessitaram de reinternação hospitalar. O baixo índice de complicações até trinta dias após a realização de ATJ, incluindo ausência de óbito, pode ser atribuído à estruturação multidisciplinar do atendimento médico realizado na instituição, a adoção de protocolos eficazes de anticoagulação e de reabilitação e o rastreamento de infecção no pré-operatório. Apesar dos baixos índices de complicações, nossos resultados mostram a importância de considerar a associação de fatores de risco com complicações pós-operatórias em pacientes que serão submetidos a ATJ. A adoção de estratégias preventivas voltadas para controlar os fatores de risco terá um impacto direto sobre o tempo de internação e readmissão hospitalar e, consequentemente, sobre os custos do procedimento para o sistema de saúde

Total knee arthroplasty (TKA) is a well-established surgical procedure with high success rates for the treatment of advanced knee osteoarthritis that results in pain relief and functional joint improvement in most patients. Although TKA is safe elective surgery, complications may occur that result in longer hospital stays and the need for hospital readmission. A way to reduce the impact of complications is to identify possible risk factors associated with complications. The adoption of prevention strategies designed to control risk factors potentially reduces morbidity, mortality, and direct and indirect costs regarding TKA. The aims of the present study were to determine the risk factors for complications occurring within 30 days of primary total knee arthroplasty (TKA), the prevalence and impact of complications on length of stay, and the need for hospital readmission. The study included 1,035 procedures of unilateral primary TKA at the Jamil Haddad National Institute of Traumatology and Orthopedics, from September 2011 to February 2016. Preoperative parameters (age, gender, body mass index, ASA and comorbidities) and the occurrence of systemic and local complications up to the 30th postoperative day were obtained by an active search of patients' medical records. The identification of possible risk factors for the occurrence of any complication and the relationship between the occurrence of complication with the length of stay and the need for readmission was performed through univariate analysis. In 4.3% of the procedures, there was an association with some type of postoperative complication of which 2.8% were systemic and 1.5% local. Of the total complications presented by patients, 1.8% were classified as severe whereas 2.5% were classified as low severity. No deaths were recorded in the 30-day postoperative period. Diabetes and history of the previous cardiac events were significantly associated with the risk of postoperative complications. Affected patients remained in the hospital for more than 10 days and/or required hospital readmission. The low complication rate up to 30 days after TKA, including the absence of death, can be attributed to the multidisciplinary structure of medical care provided at the institution, the adoption of effective anticoagulation and rehabilitation protocols and preoperative infection screening. Despite the low complication rates, our results show the importance of considering the association of risk factors with postoperative complications in patients undergoing TKA. The adoption of prevention strategies for the control of risk factors will have a direct impact on the length of hospital stay and readmission and, consequently, on the health system costs

Generating evidence and understanding the treatment of osteoarthritis in Brazil: a study through Delphi methodology

OBJECTIVES: This study aimed to provide evidence for understanding how to treat osteoarthritis (OA) in our country. Therefore, it was necessary to match information and investigations related to the treatment of the disease from the three main types of specialists involved: physiatrists, orthopedists and rheumatologists. METHODS: The authors acted as a scientific advisory committee. From the initial discussions, a structured questionnaire was developed for use with a group of specialists on OA using the Delphi technique. The questionnaire was sent to 21 experts appointed by the authors, and the results obtained were critically analyzed and validated. RESULTS: The prevalence of OA was 33% in Brazil, corresponding to one-third of the individuals in the reference population, which included individuals over 25 years of age. Another significant finding was that most patients did not receive any form of treatment in the early stages of OA. CONCLUSION: The committee pointed to the need for early intervention and that the available medicinal resources can fulfil this important role, as is the case with SYSADOA treatments. Glucosamine-based medicinal products with or without chondroitin could also fulfill this need for early treatment. The other generated evidence and included investigations were then grouped together and are the subject of this publication.

Consideraciones clínicas e imagenológicas de la osteoartrosis en la articulación temporomandibular / Clinical and imaging remarks on temporomandibular joint osteoarthrosis

La osteoartrosis es una enfermedad degenerativa que, instalada en la articulación temporomandibular, genera efectos deletéreos en los tejidos blandos y óseos que la constituyen. En los tejidos duros se destaca la aparición de procesos osteolíticos a nivel condilar y de la cavidad glenoidea con cambios morfológicos importantes. Estas modificaciones están íntimamente relacionadas con el debilitamiento y/o destrucción de los tejidos blandos que ocurren previamente. Los síntomas que se presentan con mayor frecuencia en esta afección son la alteración del rango de movimiento, el dolor y, el más característico, la crepitación durante el examen con estetoscopio. La frecuencia de aparición alcanza entre un 8% y un 18%. Las causas para su documentación son variables y están vinculadas al desplazamiento discal, el trauma, hormonales y la inestabilidad oclusal, siendo el aumento de carga (bruxismo) la de mayor significación. El examen imagenológico puede documentar aplanamiento de los componentes óseos, disminución del espacio articular, discontinuidad de las corticales, esclerosis subcondral, osteofitos, quistes subcondrales y cuerpos libres periarticulares. En ocasiones la radiografía panorámica puede ser poco demostrativa para la documentación de esas particularidades; por el contrario, la tomografía computada es un excelente procedimiento diagnóstico. El aporte de la IRM es relevante en la ubicación del disco articular; asimismo, posibilita la observación de colección de fluido en los espacios articulares, generando una señal hiperintensa. Tratamiento: actuar principalmente para disminuir la carga sobre la ATM y,`por lo tanto, concientizar al paciente de la presencia del bruxismo, instalar un dispositivo oclusal miorrelajante (DOM) y suplementar con analgésicos, antiinflamatorios y antiartrósicos. Cuando la OA está asociada al desplazamiento discal, debe indicarse un dispositivo oclusal de desplazamiento anterior mandibular (DODAM) (AU)

Osteoarthrosis is a degenerative disease. When is located in the TMJ produces deleterious effects in its soft and hard tissues, osteolytic processes on condyle and glenoid cavity in the latter, with significant morphological changes, closely related to weakening and destruction of the tissues that had happened previously. Symptoms most frequent are alteration of the range of movement, pain and,the most characterystic, cracking while examination through stethoscope. Its frequency is between 8 and 18%.Causes for its documentation are variable and related to disc displacement, trauma, hormones and occlusal unsteadiness, being de increase of charge (clenching) the most relevant. Imaging can show flattening on osseusparts,, the articular space, discontinuation of cortexes, subchondral sclerosis, osteophytes, subchondral cysts,and loose particular bodies. Sometimes orthopantomograph may be barely demonstrative to document these phenomena, conversely CT is an excellent diagnostic procedure. The contribution of MRI is relevant to locate articular disc, and facilitate visualize fluid collection within the articular spaces, producing a hiperintense signal. Treatment: to act mainly for diminishing charge on the TMJ, so to raise patients conscience of the presence of clenching, install a myorelaxant occlusal device (DOM) and additionally analgesics, antiinflamatories and antiarthrosis When osteoarthrosis is associated with disc displacement and occlusal device for anterior mandibular displacement (DODAM) is suitable(AU)

Diacerein, its beneficial impact on chondrocytes and notable new clinical applications

Diacerein (DCN) was obtained by diacetylation of an anthraquinone derivative rhein and was approved by FDA in 2008, in the treatment of osteoarthritis due to its inhibitory effect on proinflammatory cytokines, including IL-6 and IL-1ß. It was synthesized in 1980s and marketed as a tablet in some European Union and Asian countries from 1994. Along with its great potential in the treatment of osteoarthritis, its other applications are also being explored day by day, such as in the treatment of psoriasis, epidermolysis bullosa, breast cancer, type 2 diabetes and periodontitis. The main aim of this review is to explore mechanism of action, various applications and side effects associated with DCN. This has been reviewed that apart from the risk of diarrhea on long-term administration of DCN, various clinical studies has also shown its modest benefits in treatment of various pathological conditions. Hence, DCN is emerging as a new and potentially safe derivative with maximum therapeutic efficacies and minimum side effects which can results in improving the living status of patients suffering from various inflammatory diseases

Strontium ranelate as a possible disease-modifying osteoarthritis drug: a systematic review

Considering that osteoarthritis (OA) is the most prevalent joint disease worldwide, multiple pharmacological treatments have been proposed to alter the articular structure with potential benefit in the progression of the disease. The so-called disease-modifying OA drugs have been frequently investigated but conclusive findings are rare. Strontium ranelate (SrRan) is a drug usually prescribed to treat osteoporosis, with proven effects in decreasing the risk of fractures and possible effect in reducing the progression of OA. The objective of this review was to demonstrate the current panorama of knowledge on the use of SrRan in clinical and experimental models, clarifying its mechanisms of action and describing possible anti-nociceptive and anti-inflammatory effects. The systematic review was based on the PRISMA statement and included articles that are indexed in scientific databases. Fifteen studies were included: seven pre-clinical and eight clinical studies. Despite the limited number of studies, the results suggest a positive effect of SrRan in patients with OA, through changes in functional capacity and reduction of progression of morphological parameters and joint degradation, with moderate quality of evidence for those clinical outcomes. Novel studies are necessary to elucidate the molecular targets of SrRan, focusing on anti-inflammatory effects and histological changes promoted by SrRan, which seemed to reduce the progression of OA in the experimental and clinical studies.

Role of hyaluronic acid in the homeostasis and therapeutics of temporomandibular joint osteoarthritis / Rol del ácido hialurónico en la homeostasis y terapéutica de la osteoartritis de articulación temporomandibular

The aim of this study was to perform a literature review regarding the role of hyaluronic acid (HA) in the homeostasis and therapeutics of temporomandibular joint (TMJ) osteoarthritis (OA). The TMJ has characteristics that give it special adaptation and recovery abilities, where HA plays a fundamental role in helping to maintain joint homeostasis, which is affected in pathological processes like OA. OA is a chronic degenerative multi-factor disease that can affect all the components of the synovial joints, causing degradation of the articular cartilage, extracellular matrix and breakage in the HA molecules. HA is a non-branched linear polysaccharide with viscosupplementation, anti-inflammatory, lubrication and pain relief effects; it also activates the intrinsic repair processes of the cartilage and normalizes the endogenous production of HA by the synoviocytes. In recent years, the therapeutic use of HA has shown evidence that supports its application in TMJ OA, improving viscosupplementation capacity, acting at the cellular and molecular levels, reducing various inflammatory mediators and improving the reparative characteristics. Its use has been studied in animal models and in humans. However, no consensus has been reached in terms of concentrations, dose, application frequency or molecular weight to be used.

El objetivo de este estudio fue realizar una revisión de la literatura respecto del rol del ácido hialurónico (AH) en la homeostasis y terapéutica de la osteoartritis (OA) de la articulación temporomandibular (ATM). La ATM presenta características que le confieren propiedades de adaptación y recuperación especiales, donde el AH juega un rol fundamental ayudando a mantener la homeostasis articular, la cual se ve afectada en procesos patológicos como la OA. La OA es una enfermedad multifactorial crónica degenerativa que puede afectar a todos los componentes de las articulaciones sinoviales, generando degradación del cartílago articular, matriz extracelular y quiebre de las moléculas de AH. El AH es un polisacárido lineal no ramificado que presenta efectos de viscosuplementación, antiinflamatorios, lubricantes, en el alivio del dolor, permite además, activar procesos intrínsecos de reparación del cartílago y normalizar la producción endógena de AH por parte de los sinoviositos. En los últimos años el uso terapéutico del AH ha presentado evidencia que sustenta su aplicación en OA de ATM mejorando la capacidad de viscosuplementación, actuando a nivel celular y molecular, disminuyendo diversos mediadores inflamatorios y mejorando las características reparativas. Su uso se ha estudiado en modelos animales y en humanos, sin embargo no existe consenso en cuanto a concentraciones, dosis, frecuencias de aplicación y peso molecular a utilizar.

Estudo Prospectivo Sobre o Impacto do Uso do Selante de Fibrina Humano Evicel® em Pacientes com Osteoartrite Submetidos à Artroplastia Total do Joelho / Prospective Study on the Impact of Using Evicel® Human Fibrin Sealant in Patients with Osteoarthritis that Underwent Total Knee Arthroplasty

A artroplastia total de joelho (ATJ) está associada a sangramento per operatório significativo, que é causa potencial de complicações. Por isso, medidas que possam minimizá-lo devem ser constantemente investigadas. Os agentes hemostáticos, tipo selantes de fibrina humano, têm se mostrado como alternativas para alcançar este objetivo, porém alguns componentes de suas formulações como o ácido tranexâmico e a aprotinina têm se associado a complicações alérgicas e irritativas ao sistema nervoso central, surgindo então um selante de fibrina humano livre de tais substâncias. O objetivo desse estudo foi avaliar os resultados do uso tópico intraoperatório do selante de fibrina humano Evicel® em pacientes com osteoartrite submetidos à ATJ, buscando diferenças entre os grupos em relação à perda sanguínea, necessidade transfusional, tempo de internação hospitalar, amplitude de movimento, percepção de dor e incidência de complicações de cicatrização de feridas, infecciosas e tromboembólicas. Foram analisados prospectivamente um grupo de intervenção com 32 pacientes e um grupo controle com 31 pacientes, com osteoartrite sintomática dos joelhos, submetidos à ATJ. Os resultados foram semelhantes entre os grupos, em relação à perda sanguínea visível no dreno em 24h (Controle 276,5 mL ± 46,24 vs. Evicel 365,9 mL ± 45,73), à perda sanguínea total em 24h (Controle 930 mL ± 78 vs. Evicel 890 mL ± 67) e em 60h de pós-operatório (Controle 1250 mL ± 120 vs. Evicel 1190 mL ± 96;), à necessidade de hemotransfusão (ocorreu em apenas um controle), ao tempo de permanência hospitalar (Controle 5,61 ± 0,50 n=31 vs. Evicel 4,81 ± 0,36), dor pósoperatória e amplitude de movimento. O uso do agente selante de fibrina não se relacionou à ocorrência de complicações da cicatrização de ferida, infecção ou à trombose venosa profunda. Concluímos que o agente hemostático de fibrina humana não foi eficaz em reduzir o volume de sangramento e a necessidade de hemotransfusão ou interferir sobre o tempo de internação hospitalar, percepção de dor e amplitude de movimento. Seu uso não se relacionou a nenhuma complicação

Total knee arthroplasty is associated with significant per operative bleeding, which is a potential cause of complications. So, measures that may minimize it should be constantly investigated. Hemostatic agents, such as human fibrin sealants, have been shown as alternatives to achieve this goal, but some components of their formulations (tranexamic acid and aprotinin), have been associated with complications like allergy and irritative central nervous system reactions, and a fibrin sealant has emerged, free of these substances. The goal of this study was to evaluate the results of the intraoperative topical use of the Evicel® human fibrin sealant in total knee arthroplasties, looking for differences between groups in relation to blood loss, transfusional need, length of hospital stay, range of motion, pain perception and incidence of complications. We analyzed prospectively an intervention group with 32 patients and a control group with 31 patients with symptomatic knee osteoarthritis who underwent arthroplasty. The results were similar between the groups, in relation to the visible blood loss in the drain in 24h (Control 276.5 mL ± 46.24 vs. Evicel 365.9 mL ± 45.73), the total blood loss in 24h (Control 930 mL ± 78 vs. Evicel 890 mL ± 67) and in the postoperative 60h (Control 1250 mL ± 120 vs. Evicel 1190 mL ± 96), the need for blood transfusion (occurred in only one control), the length of hospital stay (Control 5.61 ± 0.50 n=31 vs. Evicel 4.81 ± 0.36), postoperative pain and range of motion. Its use was not related to the occurrence of wound healing complications, infection or to deep venous thrombosis. We conclude that the new hemostatic agent of human fibrin was not effective in reducing bleeding volume and the need for blood transfusion or interfering with hospital length of stay, pain perception and range of motion. Its use was not related to any complications.

Uso de ácido hialurónico en osteoartritis de articulación temporomandibular en paciente adolescente / Use of hyaluronic acid in osteoarthritis of temporomandibular joint in adolescent patient

La osteoartritis es un tipo de trastorno temporomadibular de origen articular, siendo uno de los procesos degenerativos óseos que más comúnmente afectan a la articulación temporomandibular. Se caracteriza por remodelación del hueso subcondral subyacente, deterioro y abrasión del tejido articular. Las infiltraciones intraarticulares de ácido hialurónico se consideran beneficiosas para el tratamiento del dolor y la recuperación de propiedades de los tejidos articulares. El objetivo de éste artículo es describir el uso de ácido hialurónico en el manejo de osteoartritis de articulación temporomandibular en un paciente adolescente. Paciente de sexo femenino, 15 años de edad, presenta dolor de un año de evolución en la región preauricularbilateral, con aumento de dolor en apertura máxima. Considerando el examen clínico e imagenológico se diagnostica una luxación discal con reducción con componente osteoartritico e inflamatorio bilateral. Se indica reposo mandibular, dieta líquida, AINEs y se realiza la aplicación intraarticular de ácido hialurónico(Suprahyalâ 25 mg/2,5 ml) bilateral. Se cita a control a las 2, 3 y 16 semanas donde la paciente se encuentra sin dolor espontaneo y a la palpación. El uso de ácido hialurónico es una de las alternativas terapeúticas más utilizadas para el manejo de la osteoartritis de articulación temporomandibular, sin embargo es necesario que la evidencia de su aplicación intraarticular en adolescentes y niños se consolide.

Osteoarthritis is a type of articular origin Temporomandibular disorders, being one of themost common degenerative processes affecting thetemporomandibular joint. It is characterized byremodeling of the underlying subchondral bone,deterioration and abrasion of articular tissue. Intra-articular injections of hyaluronic acid are considered beneficial for treatment of pain and recovery of joint tissues properties. The aim of this article is to describe the use of hyaluronic acid in the management of osteoarthritis of temporomandibular joint in an adolescent patient. Female patient, 15 years old,presented pain with a year of progress in the bilateral preauricular region, with increased pain at maximum aperture. Considering the clinical and imaging tests the patient was diagnosed with disk displacement with reduction with bilateral osteoarthritic and inflammatory component. Mandibular rest, liquid diet, NSAIDs were indicated and the application of intra-articular hyaluronicacid (Suprahyalâ 25 mg / 2.5 ml) bilaterally. Control was quoted at 2, 3 and 16 weeks where the patient has no spontaneous pain and tenderness. The use of hyaluronic acid is one of the most commonly usedtherapeutic alternatives for the management ofosteoarthritis of temporomandibular joint. However,further evidence of its use in intra-articular application in adolescents and children should be incorporated.

3-D structural changes in subchondral bone and the effect of bisphosphonate intervention in early osteoarthritis / Cambios estructurales tridimensionales del hueso subcondral y el efecto de la intevención con bisfosfonato en la osteoartritis temprana

This study aims to observe the 3-D structural changes in subchondral bone and the effects of bisphosphonate intervention in the early unsteady stage of the knee joint. Sixty healthy male New Zealand white rabbits were divided into the model group (n= 24), the bisphosphonate (Bis) group (n= 24), and the control group (n= 12). The rabbits' right knees were used to evaluate the structural changes. The Bis group received subcutaneous injections of bisphosphonate, while the model and control groups received subcutaneous injections of isotonic saline solution. After surgical preparation, the knee joint was dissected for Micro-CT examination, and the Micro-CT results were compared using ANOVA. In the fourth postoperative week, the bone volume fraction (BVF), trabecular number (Tb.N), and trabecular thickness (Tb.Th) of the model group were significantly lower than those of the control group (P<0.01). There was no significant difference between the Bis and control groups. In the twelfth postoperative week, BVF, Tb.Th, and Tb.N of the model group were significantly higher than those of the control and Bis groups (P <0.05). Similarly, bone mineral density was higher in the model group (P <0.01), while the trabecular spacing was significantly lower (P <0.05). In the early unsteady stage of the knee joint, the subchondral bone had markedly decreased, while obvious bone formation was visible in the late stage. Bisphosphonates could protect the subchondral bone structure by inhibiting bone absorption.

El objetivo fue observar los cambios estructurales en 3-D del hueso subcondral y los efectos de la intervención con bifosfonatos en la etapa temprana de la inestabilidad de la articulación de la rodilla. Sesenta conejos blancos New Zealand machos sanos se dividieron en tres grupos: modelo (n= 24), bisfosfonato (Bis) (n= 24) y control (n= 12). Las rodillas derechas de los conejos se utilizaron para evaluar los cambios estructurales. El grupo Bis recibió inyecciones subcutáneas de bisfosfonato, mientras que los grupos modelo y control recibieron inyecciones subcutáneas de solución salina isotónica. Después de la preparación quirúrgica, la articulación de la rodilla fue disecada para su análisis mediante micro-TC, y los resultados se compararon mediante ANOVA. En la cuarta semana postoperatoria, la fracción del volumen óseo (GVF), el número trabecular (Tb.N) y el espesor trabecular (Tb.Th) del grupo modelo fueron significativamente más bajos que los del grupo control (P <0,01). No hubo diferencia significativa entre los grupos control y Bis. En la semana 12 postoperatoria, BVF, Tb.Th, y Tb.N del grupo modelo fueron significativamente mayores que los del grupo control y Bis (P <0,05). Del mismo modo, la densidad mineral ósea fue mayor en el grupo modelo (P <0,01), mientras que la separación trabecular fue significativamente menor (<0,05 P). En la etapa inestable temprana de la articulación de la rodilla, el hueso subcondral disminuyó notablemente, mientras que la formación ósea obvia fue visible en la etapa tardía. Los bisfosfonatos podrían proteger la estructura ósea subcondral mediante la inhibición de la absorción ósea.

Using agents that suppress bone remodeling to treat or prevent joint disease: quo vadis?

Treatment of osteoarthritis (OA) with antiremodeling agents has had a mixed record of results. It is likely that remodeling suppression is only effective when used in the early phases of OA, before significant progression. Animal and human studies largely bear this out. Treatment of young mice with a RANKL inhibitor suppresses bone resorption and prevents OA progression. Likewise, bisphosphonate treatments in rodents and rabbits with induced injury or inflammatory arthritis, reduced cartilage degeneration when administered preemptively, but later administration did not. The increased prevalence of OA in women after the menopause, and presence of estrogen receptors in joint tissues, suggests that treatment with estrogens or Selective Estrogen Receptor Modulators may be effective. However, in clinical trials of knee and hip, results show decreased or increased risk for OA, or no effect. Raloxifene had positive effects in animal models, but no effect in human studies. More recent potential treatments such as strontium ranelate or cathepsin-K inhibitors may be effective, but may work directly on the cartilage rather than through their well-known effects on bone. The conclusion from these studies is that anti-remodeling agents must be administered pre-emptively or in the very early stages of disease to be effective. This means that better imaging techniques or identification of early structural changes in bone that occur before progressive cartilage destruction must be developed. (AU)

Protective effects of tumor necrosis factor-α blockade by adalimumab on articular cartilage and subchondral bone in a rat model of osteoarthritis

We aimed to investigate the effects of an anti-tumor necrosis factor-α antibody (ATNF) on cartilage and subchondral bone in a rat model of osteoarthritis. Twenty-four rats were randomly divided into three groups: sham-operated group (n=8); anterior cruciate ligament transection (ACLT)+normal saline (NS) group (n=8); and ACLT+ATNF group (n=8). The rats in the ACLT+ATNF group received subcutaneous injections of ATNF (20 μg/kg) for 12 weeks, while those in the ACLT+NS group received NS at the same dose for 12 weeks. All rats were euthanized at 12 weeks after surgery and specimens from the affected knees were harvested. Hematoxylin and eosin staining, Masson's trichrome staining, and Mankin score assessment were carried out to evaluate the cartilage status and cartilage matrix degradation. Matrix metalloproteinase (MMP)-13 immunohistochemistry was performed to assess the cartilage molecular metabolism. Bone histomorphometry was used to observe the subchondral trabecular microstructure. Compared with the rats in the ACLT+NS group, histological and Mankin score analyses showed that ATNF treatment reduced the severity of the cartilage lesions and led to a lower Mankin score. Immunohistochemical and histomorphometric analyses revealed that ATNF treatment reduced the ACLT-induced destruction of the subchondral trabecular microstructure, and decreased MMP-13 expression. ATNF treatment may delay degradation of the extracellular matrix via a decrease in MMP-13 expression. ATNF treatment probably protects articular cartilage by improving the structure of the subchondral bone and reducing the degradation of the cartilage matrix.