Temporomandibular disorders (TMDs) occur frequently within the general population and are the most common non-dental cause of orofacial pain. Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative joint disease (DJD). There have been several different methods of treatment of TMJ OA listed, including pharmacotherapy among others. Due to its anti-aging, antioxidative, bacteriostatic, anti-inflammatory, immuno-stimulating, pro-anabolic and anti-catabolic properties, oral glucosamine seems to be a potentially very effective agent in the treatment of TMJ OA. The aim of this review was to critically assess the efficacy of oral glucosamine in the treatment of TMJ OA on the basis of the literature. PubMed and Scopus databases were analyzed with the keywords: (temporomandibular joints) AND ((disorders) OR (osteoarthritis)) AND (treatment) AND (glucosamine). After the screening of 50 results, eight studies have been included in this review. Oral glucosamine is one of the symptomatic slow-acting drugs for osteoarthritis. There is not enough scientific evidence to unambiguously confirm the clinical effectiveness of glucosamine supplements in the treatment of TMJ OA on the basis of the literature. The most important aspect affecting the clinical efficacy of oral glucosamine in the treatment of TMJ OA was the total administration time. Administration of oral glucosamine for a longer period of time, i.e., 3 months, led to a significant reduction in TMJ pain and a significant increase in maximum mouth opening. It also resulted in long-term anti-inflammatory effects within the TMJs. Further long-term, randomized, double-blind studies, with a unified methodology, ought to be performed to draw the general recommendations for the use of oral glucosamine in the treatment of TMJ OA.
Overweight and obesity increase the risk of development and progression of knee osteoarthritis (OA), with higher levels of fat mass and lower levels of lean mass associated with poorer functional status. The aim was to assess changes in weight, body composition and physical function following weight loss or weight maintenance interventions in knee OA. A comprehensive search of four databases was conducted. The risk of bias was assessed using the Quality Criteria Checklist for primary research. Primary outcomes included weight, body composition and physical function; secondary outcomes were lipids, inflammatory biomarkers and muscle strength. Eleven studies were included utilizing diet and exercise (n = 4) or diet-only (n = 7) interventions, two of which were weight maintenance studies. Most studies (n = 10) reported improvements in physical function with significant weight loss, while the change in strength reported in three studies was variable. The diet and exercise studies reported an average reduction in weight of 6.7% and lean mass of 1.6 kg, with greater improvements in physical function. The diet-only studies, including weight maintenance interventions, reported greater average weight loss (7.8%) and reduction in LM (2.0 kg). Overall, better retention of lean mass and muscle strength was observed in participants with higher protein intake (≥37% of energy) and subsequently improved physical function.
OBJECTIVE: To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN: Systematic review and network meta-analysis of randomised trials.
DATA SOURCES: Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES: The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS: Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS: 192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS: Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION: PROSPERO number CRD42020213656.
OBJECTIVE: Current global guidelines regarding the first-line analgesics (acetaminophen, topical or oral non-steroidal anti-inflammatory drugs [NSAIDs]) for knee osteoarthritis remain controversial and their comparative risk-benefit profiles have yet to be adequately assessed.
DESIGN: Pubmed, Embase, Cochrane Library, and Web of Science were searched from database inception to March 2021 for randomized controlled trials (RCTs) comparing acetaminophen, topical NSAIDs and oral NSAIDs directly or indirectly in knee osteoarthritis. Bayesian network meta-analyses were conducted. A propensity-score matched cohort study was also conducted among patients with knee osteoarthritis in The Health Improvement Network database.
RESULTS: 122 RCTs (47,113 participants) were networked. Topical NSAIDs were superior to acetaminophen (standardized mean difference [SMD]=-0.29, 95% credible interval [CrI]: -0.52 to -0.06) and not statistically different from oral NSAIDs (SMD=0.03, 95% CrI: -0.16 to 0.22) for function. It had lower risk of gastrointestinal adverse effects (AEs) than acetaminophen (relative risk [RR]=0.52, 95%CrI: 0.35 to 0.76) and oral NSAIDs (RR=0.46, 95%CrI: 0.34 to 0.61) in RCTs. In real-world data, topical NSAIDs showed lower risks of all-cause mortality (hazard ratio [HR]=0.59, 95% confidence interval [CI]: 0.52 to 0.68), cardiovascular diseases (HR=0.73, 95%CI: 0.63 to 0.85) and gastrointestinal bleeding (HR=0.53, 95%CI: 0.41 to 0.69) than acetaminophen during the one-year follow-up (n=22,158 participants/group). A better safety profile was also observed for topical than oral NSAIDs (n=14,218 participants/group).
CONCLUSIONS: Topical NSAIDs are more effective than acetaminophen but not oral NSAIDs for function improvement in people with knee osteoarthritis. Topical NSAIDs are safer than acetaminophen or oral NSAIDs in trials and real-world data.
OBJECTIVE: Despite an extensive body of research on NSAIDs in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.
METHODS: We searched MEDLINE, EMBASE, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. RCTs assessing the efficacy and/or safety of FDA-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences and risk ratios with 95% confidence intervals.
RESULTS: We included 72 RCTs (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [-0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of GI AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [1.21, 1.57]). The incidence of CV AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.
CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen. This article is protected by copyright. All rights reserved.
OBJECTIVE: Despite an extensive body of research on nonsteroidal antiinflammatory drugs (NSAIDs) in osteoarthritis, the duration of their efficacy and timeline of adverse event (AE) onset have been understudied. We conducted a systematic review and meta-analyses from 2 to 26 weeks to characterize the efficacy and AE trajectories of oral NSAIDs in knee osteoarthritis.METHODS: We searched MEDLINE, Embase, Web of Science, Google Scholar, and the Cochrane Database from inception to May 2018. Randomized controlled trials assessing the efficacy and/or safety of Federal Drug Administration-approved NSAIDs in knee osteoarthritis patients were included. Two independent reviewers assessed quality and extracted data. We calculated standardized mean differences (SMDs) and risk ratios (RRs) with 95% confidence intervals (95% CIs).RESULTS: We included 72 randomized controlled trials (26,424 participants). NSAIDs demonstrated moderate, statistically significant effects on pain that peaked at 2 weeks (SMD -0.43 [95% CI -0.48, -0.38]), but the magnitude of the effects decreased over time. The results for function were similar. The incidence of gastrointestinal (GI) AEs was significantly higher in NSAID users than placebo users as early as 4 weeks (RR 1.38 [95% CI 1.21, 1.57]). The incidence of cardiovascular (CV) AEs in NSAID users was not significantly different from placebo. Most GI and CV AEs were transient and of minor severity.CONCLUSION: NSAIDs produced significant pain and function improvements that peaked at 2 weeks but decreased over time. The incidence of minor GI and CV AEs consistently rose, reaching significance as early as 4 weeks. Clinicians should weigh the durability of efficacy with the early onset of minor AEs along with patient tolerability and preferences when formulating an NSAID regimen.
OBJECTIVE: Our aim was to assess the safety of cyclooxygenase-2 (COX-2) inhibitors in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials.
METHODS: A comprehensive literature search was undertaken in the databases MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL) and Scopus. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with COX-2 inhibitors in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatobiliary disorders, renal and urinary disorders, as well as overall severe and serious AEs, drug-related AEs and mortality. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once).
RESULTS: Database searches identified 2149 records from which, after exclusions, 40 trials were included in the meta-analysis. The use of COX-2 inhibitors in OA was associated with a significant increased risk of drug-related AEs compared with placebo (relative risk (RR) 1.26, 95% CI 1.09-1.46; I2 = 24%). The risk of upper gastrointestinal complications (including dyspepsia, gastritis and heartburn) was significantly increased with COX-2 inhibitors versus placebo (RR 1.19, 95% CI 1.03-1.38; I2 = 0%), particularly for abdominal pain, which increased by 40% with COX-2 inhibitors (RR 1.40, 95% CI 1.08-1.80; I2 = 0%). The risk of hypertension increased by 45% overall (RR 1.45, 95% CI 1.01-2.10; I2 = 25%); however, when rofecoxib was removed from the analysis the risk of hypertension in the COX-2 inhibitor group was no longer significant (RR 1.21, 95% CI 0.80-1.83; I2 = 20%). The overall risk of heart failure and edema was increased by nearly 70% with COX-2 inhibitors versus placebo (RR 1.68, 95% CI 1.22-2.31; 0%) and this level of risk did not change appreciably when rofecoxib was excluded (RR 1.67, 95% CI 1.21-2.29; 0%).
CONCLUSIONS: In our analysis, COX-2 inhibitors were associated with an increased risk of upper gastrointestinal AEs, especially abdominal pain. We also found an increased risk of cardiovascular AEs with COX-2 inhibitors, namely hypertension, heart failure and edema.
