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2.
Org Biomol Chem ; 17(46): 9913-9923, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31720670

RESUMO

Nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) inhibitors have been suggested as a potential treatment for calcium pyrophosphate dihydrate (CPPD) deposition disease. Here, we targeted the development of improved NPP1 inhibitors based on acyclic mimics of Pα,α-phosphorodithioate-substituted adenine nucleotides, 7-10. The latter were obtained in a facile two-step synthesis from adenine-(methoxy)ethanol. Among analogs 7-10, adenine-(methoxy)ethoxy-Pα,α-dithio-triphosphate, 8, was the most potent NPP1 inhibitor both with purified enzyme (IC50 0.645 µM) and in osteoarthritic human chondrocytes (IC50 0.033 µM). Furthermore, it efficaciously (10-fold vs. control) inhibited ATP-induced CPPD in human articular chondrocytes. Importantly, 8 was a highly selective NPP1 inhibitor which showed only minor inhibition of NPP3, CD39 and CD73, and did not inhibit TNAP (tissue nonspecific alkaline phosphatase) activity in human chondrocytes. Furthermore, 8 did not activate P2Y1,2,6 receptors. Analog 8 was not toxic to cultured chondrocytes at 100 µM. Therefore, 8 may be suitable for further development as a drug candidate for the treatment of CPPD arthritis and other NPP1-related diseases.


Assuntos
Adenina/farmacologia , Pirofosfato de Cálcio/antagonistas & inibidores , Condrócitos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Polifosfatos/farmacologia , Pirofosfatases/antagonistas & inibidores , Compostos de Sulfidrila/farmacologia , Adenina/síntese química , Adenina/química , Pirofosfato de Cálcio/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Estrutura Molecular , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Diester Fosfórico Hidrolases/metabolismo , Polifosfatos/química , Pirofosfatases/metabolismo , Relação Estrutura-Atividade , Compostos de Sulfidrila/química
3.
Medicine (Baltimore) ; 98(44): e17248, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689743

RESUMO

RATIONALE: Intra-articular corticosteroid injection (IACI) is a cost-effective conservative treatment of mild-to-moderate osteoarthritis. Adverse events after this procedure range from life-threatening systemic reactions to self-limiting local reactions. To our knowledge, this is the 1st report of osteonecrosis (ON) in the medial tibial plateau after IACI. PATIENT CONCERNS: An 81-year-old female visited our hospital due to left knee pain of increasing intensity. She presented the sudden onset of severe acute knee pain with long lasting knee pain for several years. DIAGNOSIS: The diagnosis was confirmed ON of medial tibial plateau of knee joint by pathologic finding. INTERVENTIONS: We conducted a posterior stabilized total-knee arthroplasty with no requirement for bone grafting or additional prosthesis, such as metal augments or stems. OUTCOMES: At the postoperative 1 year follow-up, the patient was satisfied with the surgery and had no pain during walking and active knee motion. LESSONS: This case especially stress the possibility of ON in medial tibia plateau after IACI. Therefore, clinicians should monitor symptoms after IACI to enable early detection of this complication.


Assuntos
Osteoartrite do Joelho/tratamento farmacológico , Osteonecrose/induzido quimicamente , Osteonecrose/cirurgia , Triancinolona/efeitos adversos , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Feminino , Humanos , Injeções Intra-Articulares , Triancinolona/uso terapêutico
4.
Expert Opin Drug Metab Toxicol ; 15(12): 1021-1032, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31709838

RESUMO

Introduction: Osteoarthritis (OA) is the leading cause of disability in the elderly, usually presenting with mono-or oligo-arthritis where local drug delivery by intra-articular (IA) injection may be more effective in terms of increased bioavailability, less systemic exposure and reduced adverse events. Several intra-articular medications for symptomatic are available on the market while the new disease-modifying drugs (DMOADs) are progressing into phase 3 pipeline of drug development.Areas covered: This narrative review covered the pharmacokinetic and pharmacodynamics of clinically available IA drugs which include corticosteroids, hyaluronic acid as well as injection techniques, efficacy, adverse effects and contraindications. In addition, the authors briefly describe the newer disease-modifying OA drugs (DMOAD) which are undergoing phase 3 pipeline of development such as Fibroblast growth factor (FGF-18) and Wnt inhibitor.Expert opinion: This is a rapidly evolving area with both new products and new trials regularly emerging. It is also a critically important area in a disease field that lacks for safe and effective treatments, where intra-articular delivery may enhance both local efficacy and reduce systemic toxicity.


Assuntos
Antirreumáticos/administração & dosagem , Desenvolvimento de Medicamentos , Osteoartrite do Joelho/tratamento farmacológico , Idoso , Antirreumáticos/efeitos adversos , Antirreumáticos/farmacologia , Glucocorticoides/administração & dosagem , Humanos , Ácido Hialurônico/administração & dosagem , Injeções Intra-Articulares , Osteoartrite do Joelho/patologia
5.
BMC Infect Dis ; 19(1): 887, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651256

RESUMO

BACKGROUND: Arthroscopic partial meniscectomy is a common procedure in orthopedic practice. Infections are uncommon complications of this procedure with an incidence rate of 0,01% - 3,4%. Staphylococcus spp are the predominant causative agents in such cases. We present a case of knee septic arthritis caused by α-hemolytic Streptococcus. CASE PRESENTATION: A 22-year-old woman diagnosed with obesity (body mass index [BMI] 35 kg/m2) but with no other major comorbidities underwent an arthroscopic selective meniscectomy with administration of intravenous cefazolin for antibiotic prophylaxis. After an uneventful period of 2 months, the patient returned with pain, fever and a discharging sinus at the site of anterolateral arthroscopic portal. Blood tests and magnetic resonance imaging revealed osteomyelitis involving the tibial plate. Cultures of synovial fluid obtained from the knee and a pharyngeal swab yielded α-hemolytic Streptococcus. Five days later, the patient underwent arthroscopic debridement with partial synovectomy. Intraoperative specimens yielded α-hemolytic Streptococcus. The patient received intravenous piperacillin/tazobactam, followed by an associative regimen of amoxicillin and clindamycin with clinical, laboratory and instrumental evidence of symptom resolution. CONCLUSION: The incidence of knee septic arthritis after arthroscopic partial meniscectomy is 0.01-3.4%. This infection is usually caused by Staphylococcus spp. and in rare cases by commensal bacteria, such as α-hemolytic streptococci, secondary to transient bacteremia. Screening of the colonized area is important to prevent possible transient bacteremia. Diagnosis is based on isolation of the causative organisms from synovial fluid cultures, and treatment comprises arthroscopic debridement with individualized systemic antibiotic therapy based on the results of an antibiogram.


Assuntos
Artrite Infecciosa/microbiologia , Artroscopia/efeitos adversos , Bacteriemia/tratamento farmacológico , Meniscectomia/efeitos adversos , Osteoartrite do Joelho/microbiologia , Infecções Estreptocócicas/tratamento farmacológico , Administração Intravenosa , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Artrite Infecciosa/tratamento farmacológico , Artrite Infecciosa/etiologia , Bacteriemia/etiologia , Desbridamento/métodos , Feminino , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/microbiologia , Streptococcus/isolamento & purificação , Streptococcus/patogenicidade , Líquido Sinovial/microbiologia , Adulto Jovem
6.
Artigo em Russo | MEDLINE | ID: mdl-31626158

RESUMO

Osteoarthritis (OA) is a serious sociomedical problem, one of the leading causes of persistent disability and reduced quality of life. Modern publications on the use of transdermal drug formulations for OA evaluate the efficiency and safety of isolated drug administration. Pulse magnetotherapy is a modern method for potentiating the therapeutic effects of both the drug and the magnetic field (MF) in the single magnetophoretic technique. AIM: to determine the effect of pulsed MF on the clinical efficacy and tolerability of magnetophoretic transdermal diclofenac delivery in patients with gonarthrosis. SUBJECTS AND METHODS: A clinical randomized placebo-controlled study was conducted in 65 patients with Kellgren-Lawrence grade 2-3 knee OA, who were divided into 3 groups. Group 1 including 25 patients received magnetophoretic diclofenac gel delivery using a traveling MF (intensity, 20 mT; frequency, 6.25 Hz; exposure. 20 min, 12 sessions); Group 2 consisting of 20 patients used placebo magnetotherapy with diclofenac without MF; Group 3 comprising 20 patients had low-frequency pulse magnetotherapy with traveling MF without topical diclofenac therapy. VAS and WOMAC and the EQ-5D questionnaire were used during the examination. The results of treatment were analyzed according to the OMERACT-OARSI criterion. RESULTS: According to VAS and WOMAC scores, combination therapy showed a marked analgesic effect in the patients who had received magnetotherapy (p<0.01), as well as a significant reduction in stiffness and an improvement in functional characteristics, which were more pronounced in those who had magnetophoresis (p<0.001). According to the EQ-5D questionnaire, magnetotherapy was noted to have a positive impact on quality-of-life indicators. Analysis according the OMERACT-OARSI criterion demonstrated a high rate (67.8%) of response to magnetophoretic sis using diclofenac application formulations. CONCLUSION: Magnetophoretic transdermal diclofenac delivery using low-frequency pulsed MF is effective and safe for patients with knee OA and causes no serious adverse events.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Diclofenaco/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Fenômenos Magnéticos , Osteoartrite do Joelho/tratamento farmacológico , Administração Cutânea , Humanos , Qualidade de Vida , Resultado do Tratamento
7.
Rev Prat ; 69(5): 515-519, 2019 May.
Artigo em Francês | MEDLINE | ID: mdl-31626455

RESUMO

Knee osteoarthritis -OA- is one of the most common musculoskeletal diseases. It frequently induces intense pain and functional impairment. To date, there is no treatment able to slow down the structural progression. Only the symptomatic part of knee OA is accessible to treatment. The management should be global including non-pharmacological treatments -weight loss, physiotherapy, physical exercises, orthoses, braces- and pharmacological treatments combining general and local treatments. In this review, we will discuss the benefits and risks of the main oral treatments -acetaminophen, non-steroidal anti-inflammatory drugs, weak and strong opioids- and local treatments including topics -local anti-inflammatory drugs, capsaicin- and intra-articular injections of corticosteroids, hyaluronic acid and platelet- rich plasma. The potential interest of joint irrigation will also be mentioned. Finally, we will propose a therapeutic strategy encompassing these different treatments.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Ácido Hialurônico/uso terapêutico , Osteoartrite do Joelho , Acetaminofen , Humanos , Injeções Intra-Articulares , Osteoartrite do Joelho/tratamento farmacológico
8.
Medicine (Baltimore) ; 98(39): e17386, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574892

RESUMO

INTRODUCTION: The purpose of this study was to use meta-analysis techniques to evaluate the efficacy and safety of polydeoxyribonucleotide (PDRN) injections for knee osteoarthritis (OA) treatment. METHODS: Multiple comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched in November 2018 for studies that compared the effectiveness and safety of intra-articular PDRN injection for the knee joint with hyaluronic acid (HA) injection. Two reviewers independently determined study inclusion and they extracted data using a standardized data extraction form. The predefined primary outcome was Visual Analogue Scale. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS), and adverse events. RESULTS: Five randomized controlled trials were included in the meta-analysis. After 1 and 2 months, patients in the PDRN group showed significantly better improvement in pain than the HA group (P = .04 and P = .02, respectively). There was no significant difference in pain after 4 months. The pooled analysis showed that no significant differences were seen in function (KOOS and KSS) scores between the PDRN and HA groups (all P > .05) at all time points. There was no significant difference in adverse events between 2 groups (relative risks = 2.15, 95% confidential interval: 0.17-26.67, P = .55). CONCLUSION: The intra-articular use of PDRN was similar in function to HA, and the pain-relief effect was superior to HA for 2 months post-injection. Therefore, it could be a favorable alternative to HA to treat persistent pain associated with knee OA while avoiding side effects.Level of evidence I.


Assuntos
Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Polidesoxirribonucleotídeos/administração & dosagem , Viscossuplementos/administração & dosagem , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
9.
JAMA ; 322(14): 1360-1370, 2019 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-31593273

RESUMO

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug. Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis. Design, Setting, and Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites. Eligible participants were aged 40 to 85 years with symptomatic, radiographic knee osteoarthritis and Kellgren-Lawrence grade 2 or 3. Enrollment began in July 2013 and ended in May 2014; the last participant visit occurred on May 8, 2017. The primary outcome at 2 years and a follow-up analysis at 3 years are reported. Interventions: Participants were randomized to 1 of 5 groups: intra-articular injections of 100 µg of sprifermin administered every 6 months (n = 110) or every 12 months (n = 110), 30 µg of sprifermin every 6 months (n = 111) or every 12 months (n = 110), or placebo every 6 months (n = 108). Each treatment consisted of weekly injections over 3 weeks. Main Outcomes and Measures: The primary end point was change in total femorotibial joint cartilage thickness measured by quantitative magnetic resonance imaging at 2 years. The secondary end points (of 15 total) included 2-year change from baseline in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores. The minimal clinically important difference (MCID) is unknown for the primary outcome; for total WOMAC score in patients with hip and knee osteoarthritis, the absolute MCID is 7 U (95% CI, 4 to 10 U) and the percentage MCID is 14% (95% CI, 9% to 18%). Results: Among 549 participants (median age, 65.0 years; 379 female [69.0%]), 474 (86.3%) completed 2-year follow-up. Compared with placebo, the changes from baseline to 2 years in total femorotibial joint cartilage thickness were 0.05 mm (95% CI, 0.03 to 0.07 mm) for 100 µg of sprifermin administered every 6 months; 0.04 mm (95% CI, 0.02 to 0.06 mm) for 100 µg of sprifermin every 12 months; 0.02 mm (95% CI, -0.01 to 0.04 mm) for 30 µg of sprifermin every 6 months; and 0.01 mm (95% CI, -0.01 to 0.03 mm) for 30 µg of sprifermin every 12 months. Compared with placebo, there were no statistically significant differences in mean absolute change from baseline in total WOMAC scores for 100 µg of sprifermin administered every 6 months or every 12 months, or for 30 µg of sprifermin every 6 months or every 12 months. The most frequently reported treatment-emergent adverse event was arthralgia (placebo: n = 46 [43.0%]; 100 µg of sprifermin administered every 6 months: n = 45 [41.3%]; 100 µg of sprifermin every 12 months: n = 50 [45.0%]; 30 µg of sprifermin every 6 months: n = 40 [36.0%]; and 30 µg of sprifermin every 12 months: n = 48 [44.0%]). Conclusions and Relevance: Among participants with symptomatic radiographic knee osteoarthritis, the intra-articular administration of 100 µg of sprifermin every 6 or 12 months vs placebo resulted in an improvement in total femorotibial joint cartilage thickness after 2 years that was statistically significant, but of uncertain clinical importance; there was no significant difference for 30 µg of sprifermin every 6 or 12 months vs placebo. Durability of response also was uncertain. Trial Registration: ClinicalTrials.gov Identifier: NCT01919164.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Fatores de Crescimento de Fibroblastos/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cartilagem Articular/patologia , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Fatores de Crescimento de Fibroblastos/efeitos adversos , Seguimentos , Humanos , Injeções Intra-Articulares , Articulação do Joelho , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia
10.
Med Arch ; 73(3): 173-177, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31404121

RESUMO

Introduction: Osteoarthritis (OA) is a chronic joint disease characterized by degeneration of the articular cartilage, changes in the physico-chemical properties of the synovial fluid and macroscopical modifications of the joint. Patients with Classes I and II of Knee OA can be treated with pharmacologic therapy. Vitamin C is key for both preventing inflammatory arthritis and maintaining healthy joints with OA. Aim: The aim of our paper is to verify the effectiveness of the addition of vitamin c in nutriceutical drugs for the therapy of the knee arthritis in the young adult. Results: Group B has a lower VAS score at 6 and 12 months with p<0.05. Not statistical difference we found in KSS during all follow up. A better quality of life was founded in Group B at 12 months in group B(p<0.05) and less use of pain killers/monthly(p<0.05). Conclusion: There is no denying that vitamin C benefits everybody, whether they have arthritis or not. Therefore, it is a good idea to maintain a healthy balance of vitamin C. Without a doubt, vitamin C benefits most people with early OA.


Assuntos
Antioxidantes/uso terapêutico , Ácido Ascórbico/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Adolescente , Adulto , Analgésicos/uso terapêutico , Suplementos Nutricionais , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Dor Musculoesquelética/tratamento farmacológico , Dor Musculoesquelética/etiologia , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Adulto Jovem
11.
Medicine (Baltimore) ; 98(34): e16956, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441895

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a common disease in elderly individuals. Many medications for KOA have the potential to cause side effects. We used Juglandis semen complex extract (JCE) consisting of 4 herbs derived from Cheong-A-Won, which has been commonly used for KOA treatment. In this study, we will evaluate whether JCE improves symptoms in patients with KOA and will identify the changes in the inflammation factor. METHODS: This study will be a single-center, randomized, double-blind, and placebo-controlled trial. Three groups, JCE 1000 mg, 2000 mg, and placebo, will be randomly allocated. Total duration of the clinical trial will be 12 to 14 weeks. Study participants will be followed up every 6 weeks and the effect and safety will be assessed at the 2, 3, and 4 visit. All participants were asked to maintain a dosage schedule for this protocol. The primary outcomes will be measured using Korean Western Ontario and McMaster Universities Questionnaire and the secondary outcomes will include pain Visual analog scale score, EuroQol Five Dimensions questionnaire, Patient Global Impression of Change, and the changes in the laboratory test parameters of inflammation. Repeated-measure analysis will be used to measure primary efficacy based on full analysis set. DISCUSSION: This study has limited inclusion and exclusion criteria and a well-controlled intervention, and it will be the first randomized controlled trial to assess the efficacy and safety of JCE in patients with KOA. This study provides insights into the mechanisms that explain the therapeutic effects of JCE in KOA and will lay the groundwork for further studies.


Assuntos
Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Método Duplo-Cego , Humanos , Medicina Tradicional Coreana/métodos , Projetos Piloto , Ensaios Clínicos Controlados Aleatórios como Assunto , República da Coreia
12.
BMC Musculoskelet Disord ; 20(1): 376, 2019 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-31421686

RESUMO

BACKGROUND: Obesity and radiological severity have been identified to be independent predictors of a low rate of response to viscosupplementation (VS), in patients with knee osteoarthritis (OA). Is that enough to formally refute VS in such patients in whom surgery is sometimes contraindicated? OBJECTIVES: To compare pain and function scores before and 6 months after knee VS, according to the weight status (obese versus non obese), the radiological severity (mild/moderate versus severe) and both combined. METHODS: Post-hoc analysis of a prospective, double blind, randomized, multicentre trial, comparing 2 viscosupplements, in patients with symptomatic knee OA. Patients were classified according to body mass index (BMI < or ≥ 30 kg.- 2), OARSI radiological grade (1-2 versus 3) and OMERACT-OARSI response criteria (Yes/No). WOMAC between-group comparisons (obese versus non-obese, OARSI 1-2 versus 3, and both combined) in all patients and in OMERACT-OARSI Responders, were achieved using Mannn-Whitney U test. RESULTS: One-hundred and sixty-six patients were analyzed: 28.3% were obese, 44% were OARSI grade 3, 42,2% were neither obese nor OARSI 3, whereas 14.5% were obese and OARSI 3. At baseline WOMAC pain score did not differ according to the patients sub-groups (p > 0.05). Six months after VS, WOMAC pain decreased significantly in all patient sub-groups (all p < 0.01). At month 6, WOMAC pain sub-score was significantly lower in non-obese than in obese patients (4.9 ± 4.1 versus 7.1 ± 4.9; p = 0.008) and in patients OARSI 1-2 versus 3 (4.8 ± 4.3 versus 6.4 ± 4.5; p = 0.009). However, in responder patients there was no difference in pain score and pain decrease related to the weight status and the radiological score. CONCLUSION: These results do not confirm our previous conclusions that recommended not performing VS in obese patients with severe knee OA. Although the chances of being a responder were much reduced in these patients, the benefit of patients who respond to treatment was similar to that of subjects with normal weight and mild/moderate OA. Different pain phenotypes, more than overweight and advanced disease, might be the main reason for the success or failure of VS.


Assuntos
Artralgia/tratamento farmacológico , Articulação do Joelho/patologia , Obesidade/epidemiologia , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/diagnóstico , Artralgia/etiologia , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico , Medição da Dor , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Viscossuplementação/métodos
13.
J Med Food ; 22(9): 875-884, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31381494

RESUMO

Osteoarthritis (OA) is a chronic condition that impacts quality of life and functionality for which consumers often seek dietary supplements to provide some relief. The purpose of this double-blind, placebo-controlled clinical trial was to assess the safety and efficacy of a water-soluble chicken eggshell membrane hydrosylate (WSEM) dietary supplement (BiovaFlex®) 450 mg daily on knee function, mobility, and general health and well-being in 88 adults with OA randomized into intervention (n = 44) or placebo (n = 44) groups. Outcomes were assessed periodically over 12 weeks, including the Western Ontario McMaster Osteoarthritis Index (WOMAC), the six-minute walk test (6MWT), knee range of motion (ROM) testing, and safety. Normalized analysis (improvement over baseline) showed that the poorest initial performers benefited the greatest from the WSEM by day 5 in the 6MWT, with the rest of the population showing significant improvement over placebo by week 12. The normalized WOMAC Stiffness score was also significantly improved over placebo by day 5 (P < .05). Without normalization, no statistically significant improvements were seen in WOMAC, 6MWT, and ROM testing. The Product was also found to be safe in this study. In conclusion, daily consumption of WSEM significantly enhanced average individual physical capacity (walking distance and ability), reduced stiffness by the fifth day of supplementation with the greatest benefit seen by the most compromised individuals, and was maintained over 12 weeks. A WSEM dietary supplement may offer a safe option for relief from symptoms and increased mobility for those with OA.


Assuntos
Casca de Ovo/química , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Animais , Galinhas , Suplementos Nutricionais/análise , Método Duplo-Cego , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Estudos Prospectivos , Amplitude de Movimento Articular , Resultado do Tratamento
15.
Phytother Res ; 33(9): 2378-2386, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31270886

RESUMO

Excessive oxidative stress, which can amplify inflammatory responses, is involved in the pathologic progression of knee osteoarthritis. Diosmin is known to possess a variety of biological functions such as antiinflammatory and antioxidant activities. We therefore demonstrated the chondroprotective potentials of diosmin on human articular chondrocytes under oxidative stress. The cytotoxicity of diosmin (5, 10, 50, and 100 µM) to chondrocytes was first evaluated. Subsequently, the cells were treated with diosmin (5 and 10 µM) after hydrogen peroxide (H2 O2 ) exposure. We found that the cytotoxicity of diosmin occurred in a dose-dependent manner (10, 50, and 100 µM), and low-dose diosmin (5 µM) slightly impaired cell viability. Diosmin supplementations (5 and 10 µM) did not show beneficial effects on mitochondrial activity, cytotoxicity, proliferation, and survival and the cell senescence was ameliorated in H2 O2 -exposed chondrocytes. On the other hand, diosmin down-regulated the mRNA levels of iNOS, COX-2, IL-1ß, COL1A1, MMP-3, and MMP-9; up-regulated TIMP-1 and SOX9; and improved COL2A1 in chondrocytes under oxidative stresses. Furthermore, diosmin also regulated glutathione reductase and glutathione peroxidase of H2 O2 -exposed chondrocytes. In conclusion, diosmin displayed a remarkable antiinflammatory effect compared with the antioxidant capacity on human chondrocytes. Diosmin can maintain the homeostasis of extracellular matrix of articular cartilage.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Diosmina/uso terapêutico , Osteoartrite do Joelho/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Idoso , Sobrevivência Celular , Diosmina/farmacologia , Humanos , Pessoa de Meia-Idade
16.
JAMA ; 322(1): 37-48, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31265100

RESUMO

Importance: Patients with osteoarthritis (OA) may remain symptomatic with traditional OA treatments. Objective: To assess 2 subcutaneous tanezumab dosing regimens for OA. Design, Setting, and Participants: A randomized, double-blind, multicenter trial from January 2016 to May 14, 2018 (last patient visit). Patients enrolled were 18 years or older with hip or knee OA, inadequate response to OA analgesics, and no radiographic evidence of prespecified joint safety conditions. Interventions: Patients received by subcutaneous administration either tanezumab, 2.5 mg, at day 1 and week 8 (n = 231); tanezumab, 2.5 mg at day 1 and 5 mg at week 8 (ie, tanezumab, 2.5/5 mg; n = 233); or placebo at day 1 and week 8 (n = 232). Main Outcomes and Measures: Co-primary end points were change from baseline to week 16 in Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) Pain (0-10, no to extreme pain), WOMAC Physical Function (0-10, no to extreme difficulty), and patient global assessment of osteoarthritis (PGA-OA) (1-5, very good to very poor) scores. Results: Among 698 patients randomized, 696 received 1 or more treatment doses (mean [SD] age, 60.8 [9.6] years; 65.1% women), and 582 (83.6%) completed the trial. From baseline to 16 weeks, mean WOMAC Pain scores decreased from 7.1 to 3.6 in the tanezumab, 2.5 mg, group; 7.3 to 3.6 in the tanezumab, 2.5/5 mg, group; and 7.3 to 4.4 in the placebo group (least squares mean differences [95% CI] vs placebo were -0.60 [-1.07 to -0.13; P = .01] for tanezumab, 2.5 mg, and -0.73 [-1.20 to -0.26; P = .002] for tanezumab, 2.5/5 mg). Mean WOMAC Physical Function scores decreased from 7.2 to 3.7 in the 2.5-mg group, 7.4 to 3.6 in the 2.5/5-mg group, and 7.4 to 4.5 with placebo (differences vs placebo, -0.66 [-1.14 to -0.19; P = .007] for tanezumab, 2.5 mg, and -0.89 [-1.37 to -0.42; P < .001] for tanezumab, 2.5/5 mg). Mean PGA-OA scores decreased from 3.4 to 2.4 in the 2.5-mg group, 3.5 to 2.4 in the 2.5/5-mg group, and 3.5 to 2.7 with placebo (differences vs placebo, -0.22 [-0.39 to -0.05; P = .01] for tanezumab, 2.5 mg, and -0.25 [-0.41 to -0.08; P = .004] for tanezumab, 2.5/5 mg). Rapidly progressive OA occurred only in tanezumab-treated patients (2.5 mg: n = 5, 2.2%; 2.5/5 mg: n = 1, 0.4%). The incidence of total joint replacements was 8 (3.5%), 16 (6.9%), and 4 (1.7%) in the tanezumab, 2.5 mg; tanezumab, 2.5/5 mg; and placebo groups, respectively. Conclusions and Relevance: Among patients with moderate to severe OA of the knee or hip and inadequate response to standard analgesics, tanezumab, compared with placebo, resulted in statistically significant improvements in scores assessing pain and physical function, and in PGA-OA, although the improvements were modest and tanezumab-treated patients had more joint safety events and total joint replacements. Further research is needed to determine the clinical importance of these efficacy and adverse event findings. Trial Registration: ClinicalTrials.gov Identifier: NCT02697773.


Assuntos
Analgésicos/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Artralgia/tratamento farmacológico , Fator de Crescimento Neural/antagonistas & inibidores , Osteoartrite do Quadril/tratamento farmacológico , Osteoartrite do Joelho/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Analgésicos/efeitos adversos , Anticorpos Monoclonais Humanizados/efeitos adversos , Artroplastia de Substituição/estatística & dados numéricos , Progressão da Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Medição da Dor
17.
Cochrane Database Syst Rev ; 7: CD012128, 2019 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-31322289

RESUMO

BACKGROUND: Osteoarthritis affecting the knee is common and represents a continuum of disease from early cartilage thinning to full-thickness cartilage loss, bony erosion, and deformity. Many studies do not stratify their results based on the severity of the disease at baseline or recruitment. OBJECTIVES: To assess the benefits and harms of surgical intervention for the management of symptomatic mild to moderate knee osteoarthritis defined as knee pain and radiographic evidence of non-end stage osteoarthritis (Kellgren-Lawrence grade 1, 2, 3 or equivalent on MRI/arthroscopy). Outcomes of interest included pain, function, radiographic progression, quality of life, short-term serious adverse events, re-operation rates and withdrawals due to adverse events. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase up to May 2018. We also conducted searches of ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform for ongoing trials. Authors of trials were contacted if some but not all their participants appeared to fit our inclusion criteria. SELECTION CRITERIA: We included randomised controlled trials that compared surgery to non-surgical interventions (including sham and placebo control groups, exercise or physiotherapy, and analgesic or other medication), injectable therapies, and trials that compared one type of surgical intervention to another surgical intervention in people with symptomatic mild to moderate knee osteoarthritis. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data using standardised forms. We analysed the quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. MAIN RESULTS: A total of five studies involving 566 participants were identified as eligible for this review. Single studies compared arthroscopic partial meniscectomy to physical therapy (320 participants), arthroscopic surgery (debridement ± synovectomy ± chondroplasty) to closed needle joint lavage with saline (32 participants) and high tibial osteotomy surgery to knee joint distraction surgery (62 participants). Two studies (152 participants) compared arthroscopic surgery (washout ± debridement; debridement) to a hyaluronic acid injection. Only one study was at low risk of selection bias, and due to the difficulty of blinding participants to their treatment, all studies were at risk of performance and detection bias.Reporting of results in this summary has been restricted to the primary comparison: surgical intervention versus non-surgical intervention.A single study, included 320 participants with symptoms consistent with meniscal tear. All subjects had the meniscal tear confirmed on knee MRI and radiographic evidence of mild to moderate osteoarthritis (osteophytes, cartilage defect or joint space narrowing). Patients with severe osteoarthritis (KL grade 4) were excluded. The study compared arthroscopic partial meniscectomy and physical therapy to physical therapy alone (a six-week individualised progressive home exercise program). This study was at low risk of selection bias and outcome reporting biases, but was susceptible to performance and detection biases. A high rate of cross-over (30.2%) occurred from the physical therapy group to the arthroscopic group.Low-quality evidence suggests there may be little difference in pain and function at 12 months follow-up in people who have arthroscopic partial meniscectomy and those who have physical therapy. Evidence was downgraded to low quality due to risk of bias and imprecision.Mean pain was 19.3 points on a 0 to 100 point KOOS pain scale with physical therapy at 12 months follow-up and was 0.2 points better with surgery (95% confidence interval (CI) 4.05 better to 3.65 points worse with surgery, an absolute improvement of 0.2% (95% CI 4% better to 4% worse) and relative improvement 0.4% (95% CI 9% better to 8% worse) (low quality evidence). Mean function was 14.5 on a 0 to 100 point KOOS function scale with physical therapy at 12 months follow-up and 0.8 points better with surgery (95% CI 4.3 better to 2.7 worse); 0.8% absolute improvement (95% CI 4% better to 3% worse) and 2.1% relative improvement (95% CI 11% better to 7% worse) (low quality evidence).Radiographic structural osteoarthritis progression and quality of life outcomes were not reported.Due to very low quality evidence, we are uncertain if surgery is associated with an increased risk of serious adverse events, incidence of total knee replacement or withdrawal rates. Evidence was downgraded twice due to very low event rates, and once for risk of bias.At 12 months, the surgery group had a total of three serious adverse events including fatal pulmonary embolism, myocardial infarction and hypoxaemia. The physical therapy alone group had two serious adverse events including sudden death and stroke (Peto OR 1.58, 95% CI 0.27 to 9.21); 1% more events with surgery (95% CI 2% less to 3% more) and 58% relative change (95% CI 73% less to 821% more). One participant in each group withdrew due to adverse events.Two of 164 participants (1.2%) in the physical therapy group and three of 156 in the surgery group underwent conversion to total knee replacement within 12 months (Peto OR 1.76, 95% CI 0.43 to 7.13); 1% more events with surgery (95% CI 2% less to 5% more); 76% relative change (95% CI 57% less to 613% more). AUTHORS' CONCLUSIONS: The review found no placebo-or sham-controlled trials of surgery in participants with symptomatic mild to moderate knee osteoarthritis. There was low quality evidence that there may be no evidence of a difference between arthroscopic partial meniscectomy surgery and a home exercise program for the treatment of this condition. Similarly, low-quality evidence from a few small trials indicates there may not be any benefit of arthroscopic surgery over other non-surgical treatments including saline irrigation and hyaluronic acid injection, or one type of surgery over another. We are uncertain of the risk of adverse events or of progressing to total knee replacement due to very small event rates. Thus, there is uncertainty around the current evidence to support or oppose the use of surgery in mild to moderate knee osteoarthritis. As no benefit has been demonstrated from the low quality trials included in this review, it is possible that future higher quality trials for these surgical interventions may not contradict these results.


Assuntos
Artroscopia , Osteoartrite do Joelho/cirurgia , Artroscopia/efeitos adversos , Humanos , Osteoartrite do Joelho/tratamento farmacológico , Medição da Dor , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Índice de Gravidade de Doença
18.
Sports Health ; 11(5): 461-466, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31340715

RESUMO

CONTEXT: Viscosupplementation is widely used for management of knee osteoarthritis. Many formulations of hyaluronic acid (HA) are available, ranging from a single injection to a series of up to 5 injections per treatment. OBJECTIVE: To compare efficacy between single and multiple HA injection formulations. DATA SOURCES: MEDLINE, EMBASE, Cochrane, Web of Science, Scopus databases were all searched. STUDY SELECTION: Full-text prospective randomized and nonrandomized controlled human trials, cohort studies, and cost-effectiveness evaluations in the English language comparing different injection regimens of viscosupplementation were included. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Data were collected using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Four databases were searched by a librarian and the principal investigator, identifying 6196 articles for screening. RESULTS: Eleven studies met the inclusion criteria. Of the studies comparing single- with multiple-injection formulations of HA for treatment of knee osteoarthritis, there was no consistent difference in patient-reported outcomes. Furthermore, 5-injection formulations do not appear to be superior to 3-injection formulations. CONCLUSION: There are limited head-to-head trials comparing viscosupplementation formulations that differ based on number of injections, and in particular, there is a paucity of trials evaluating single-injection formulations. Based on the currently available data, there appears to be similar efficacy with the possibility for greater cost-effectiveness and less patient inconvenience with single-injection formulations.


Assuntos
Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Viscossuplementação , Humanos , Injeções Intra-Articulares , Medidas de Resultados Relatados pelo Paciente , Ensaios Clínicos Controlados Aleatórios como Assunto
19.
Trials ; 20(1): 377, 2019 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-31234919

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic musculoskeletal disorder that seriously affects quality of life. Patients with KOA frequently develop one or more of the following typical symptoms: joint pain, stiffness, joint friction noise and impaired functionality. Traditional Chinese medicine (TCM) has been shown to have a superior effect and a particular advantage in the treatment of KOA; among TCM, the Tong-luo Qu-tong plaster is the convenient and most commonly used method in China to improve symptoms including pain, stiffness and limited mobility in patients with KOA, as it causes few adverse effects. But there is a lack of high-quality clinical evidences to support the therapeutic effect that Chinese adhesive plaster can have in relieving pain and stiffness. The purpose of this study will be to evaluate the efficacy and safety of Tong-luo Qu-tong plaster in patients with KOA. METHODS/DESIGN: This study will be a randomized, double-blind, parallel positive controlled, multi-center clinical trial, a non-inferiority trial design was adopted. A total of 2000 participants older than 40 years, with KOA, will be randomly allocated into an experimental group (n = 1500) and a control group (n = 500). All participants will receive a conventional conservative treatment lasting for 14 days as two courses, once daily. Tong-luo Qu-tong plaster will be administered externally to participants in the experimental group, while the control group will receive a Qi-zheng Xiao-tong plaster. The outcome of the total Western Ontario and McMaster Universities Arthritis Index scores, TCM syndrome quantitative score and visual analog scale scores will be measured during the assessment visits (baseline and 1-week and 2-week follow up). In addition, adverse events related to clinical symptoms and signs and results of laboratory tests will be documented during the clinical trials. DISCUSSION: This study will provide reliable evidence of the effectiveness and safety of Tong-luo Qutong plaster in patients with KOA. If the results are favorable, it is expected that the patients with KOA will benefit from this study, many patients may have a good alternative treatment for KOA. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03309501 . Registered on 8 November 2017.


Assuntos
Artralgia/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa , Osteoartrite do Joelho/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Método Duplo-Cego , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Projetos de Pesquisa
20.
Int J Mol Sci ; 20(13)2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31248037

RESUMO

In recent years, first evidences emerged that sympathetic neurotransmitters influence osteoarthritis (OA) manifestation. Joint-resident stem cells might contribute to cartilage repair, however, their chondrogenic function is reduced. The neurotransmitter norepinephrine (NE) was detected in the synovial fluid of trauma and OA patients. Therefore, the aim of this study was to analyse how NE influences the chondrogenesis of synovial adipose tissue-derived stem cells (sASCs). sASCs were isolated from knee-OA patients synovia. After adrenoceptor (AR) expression analysis, proliferation and chondrogenic differentiation in presence of NE and/or α- and ß-AR antagonist were investigated. Cell count, viability, chondrogenic and hypertophic gene expression, sulfated glycosaminoglycan (sGAG) and type II collagen content were determined. Key AR-dependent signaling (ERK1/2, PKA) was analyzed via western blot. sASC expressed α1A-, α1B-, α2A-, α2B-, α2C-, and ß2-AR in monolayer and pellet culture. NE did not affect proliferation and viability, but 10-7 and 10-6 M NE significantly reduced sGAG and type II collagen content as well as ERK1/2 phosphorylation. These effects were fully reversed by yohimbine (α2-AR antagonist). Our study confirms the important role of NE in sASC chondrogenic function and provides new insights in OA pathophysiology. Future studies might help to develop novel therapeutic options targeting neuroendocrine pathways for OA treatment.


Assuntos
Tecido Adiposo/citologia , Condrogênese/efeitos dos fármacos , Norepinefrina/farmacologia , Receptores Adrenérgicos alfa 2/metabolismo , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Membrana Sinovial/citologia , Antagonistas de Receptores Adrenérgicos alfa 2/farmacologia , Biomarcadores , Diferenciação Celular , Expressão Gênica , Humanos , Imuno-Histoquímica , Imunofenotipagem , Sistema de Sinalização das MAP Quinases , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia
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