High-fat diet, adipokines and low-grade inflammation are associated with disrupted tendon healing: a systematic review of preclinical studies.

BACKGROUND: The aetiopathogenesis of tendinopathy is uncertain, but inflammation may play a role in the early phase of tendinopathy and in tendon healing response. We investigated the most up-to-date evidence about the association between obesity, high-fat diet and tendinopathy, focusing on the role of adipokines, inflammatory pathways and molecular changes. SOURCES OF DATA: A systematic review was performed searching PubMed, Embase and Cochrane Library databases following the PRISMA guidelines. We included studies of any level of evidence published in peer-reviewed journals. The risk of bias (SIRCLE) was assessed, as was the methodological quality (CAMARADES) of the included studies. We excluded all the articles with a high risk of bias and/or low quality after the assessment. After applying the inclusion and exclusion criteria, we included 14 studies of medium or high quality. AREAS OF AGREEMENT: A high-fat diet negatively affects tendon quality, increasing the risk of rupture and tendinopathy. AREAS OF CONTROVERSY: Controversial evidence exists on both tendon fat infiltration secondary to a dysregulation of the lipid metabolism and of a molecular effect of inflammatory pathways. GROWING POINTS: The secretion of adipokines is strictly related to fat ingestion and body composition and can potentially act on tendon physiology and injury. AREAS TIMELY FOR DEVELOPING RESEARCH: Adipokines, low-grade inflammation and fat intake play a role in disrupting tendon healing and setting up tendinopathy. Further high-quality research is needed to better define the molecular pathways involved.

Obesity Increases the Risk of Tendinopathy, Tendon Tear and Rupture, and Postoperative Complications: A Systematic Review of Clinical Studies.

BACKGROUND: Inflammation and mechanical demands play a role in the development of tendon conditions and the dysregulation of tendon healing. In patients with obesity, high levels of pro-inflammatory cytokines and a high mechanical demand promote chronic low-grade inflammation. Although controversial results have been reported, we aimed to summarize current evidence while highlighting the role of obesity in tendinopathy. QUESTIONS/PURPOSES: (1) Do patients with obesity have a greater risk of tendinopathy, stratified by upper and lower extremity sites, than patients who do not have obesity? (2) Is obesity associated with a higher risk of upper and lower extremity tendon tear and ruptures? (3) Is obesity associated with an increased risk of complications after upper and lower extremity tendon surgery? METHODS: We performed a systematic review by searching the PubMed, Embase, and Cochrane Library databases, combining the term "tendon" with common terms for tendinopathy and rupture such as "tendon injury OR tendinopathy OR tendon rupture" and "obese" OR "obesity." We included studies with any level of evidence published from January 2000 to July 10, 2019 in peer-reviewed journals reporting clinical results. After we removed the duplicates, there were 365 records. Two independent authors screened these records and excluded 320 based on abstract and title screening. Of the remaining 45 studies, 23 were excluded because the topic did not address the research questions (n = 19), the article was outdated (n = 3), or because there was a serious risk of bias (n = 1). Finally, we included 22 studies with 49,914 participants (5984 with obesity), 31,100 (1884 with obesity) of whom had upper-extremity tendinopathy, while 18,814 (4010 with obesity) had lower-extremity tendinopathy. Obesity was defined as a BMI ≥ 30 kg/m according to the WHO's criteria. Data were extracted and analyzed critically. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were applied, and the risk of bias (ROBINS tool) of the studies was assessed, as was the methodological quality (Coleman score). The assessment was performed independently by two authors. Inter-rater agreement for the assessments of the risk of bias and methodological quality were 89% and 94%, respectively. All studies were observational, and most were retrospective case-control studies. Any discrepancy was discussed and solved by consensus. The articles had a moderate risk of bias (eight articles) or a low risk of bias (fourteen articles). We excluded one article because of a serious risk of bias. The mean (range) Coleman score was 53.5 (42-74). RESULTS: Obesity was associated with a greater risk of upper extremity tendinopathy (rotator cuff: odds ratio 1.25 [95% confidence interval 1.12 to 1.40]; p < 0.001; medial epicondylitis: OR 1.9 [95% CI 1.0 to 3.7]; p < 0.05) and lower-extremity tendinopathy (Achilles tendon: OR 3.81 [95% CI 2.57 to 5.63]; OR 3.77 [95% CI 2.24 to 6.34]; OR 6.56 [95% CI 3.18 to 13.55], for obesity Classes I, II and III, respectively; patellar tendon: OR 1.10 [95% CI 1.05 to 1.90]; p = 0.001; plantar fascia: OR 2.97 [95% CI 1.64 to 5.37]; p = 0.004). Obesity was associated with a greater risk of upper extremity tendon tear (rotator cuff: OR 2.35 [95% CI 1.62 to 3.40]; p < 0.001) and rupture leading to tendon surgery (rotator cuff in men: OR 3.13 [95% CI 1.29 to 7.61]; p < 0.001 and women: OR 3.51 [95% CI 1.80 to 6.85]; p < 0.001). However, no association was found between BMI and lower extremity rupture (Achilles mean BMI: 27.77 kg/m [95% CI 26.94 to 28.49] versus control: 26.66 kg/m [95% CI 26.06 to 27.27]; p = 0.047). Upper extremity complications (n = 359) after tendon repair surgery had a weighted incidence of 13.27% and 8.13% for rotator cuff surgery in patients with and without obesity, respectively. In the lower extremity (n = 21,152), the weighted incidence for Achilles tendon surgery was 11.28% and 8.6% in patients with and without obesity, respectively. CONCLUSIONS: Obesity is associated with a higher risk of tendinopathy, tendon tear and rupture, and complications after tendon surgery than non-obesity. However, the high heterogeneity and observational nature of the studies highlight the need to be cautious about the results of our study. We encourage researchers to perform clinical and preclinical studies to explore pathways related to the metabolic state of this population. LEVEL OF EVIDENCE: Level IV, prognostic study.

Frequency of use and adequacy of Cochrane risk of bias tool 2 in non-Cochrane systematic reviews published in 2020: Meta-research study.

Risk of bias (RoB) assessment is essential to the systematic review methodology. The new version of the Cochrane RoB tool for randomized trials (RoB 2) was published in 2019 to address limitations identified since the first version of the tool was published in 2008 and to increase the reliability of assessments. This study analyzed the frequency of usage of the RoB 2 and the adequacy of reporting the RoB 2 assessments in non-Cochrane reviews published in 2020. This meta-research study included non-Cochrane systematic reviews of interventions published in 2020. For the reviews that used the RoB 2 tool, we analyzed the reporting of the RoB 2 assessment. Among 3880 included reviews, the Cochrane RoB 1 tool was the most frequently used (N = 2228; 57.4%), followed by the Cochrane RoB 2 tool (N = 267; 6.9%). From 267 reviews that reported using the RoB 2 tool, 213 (79.8%) actually used it. In 26 (12.2%) reviews, erroneous statements were used to indicate the RoB 2 assessment. Only 20 (9.4%) reviews presented a complete RoB 2 assessment with a detailed table of answers to all signaling questions. The judgment of risk of bias by the RoB 2 tool was not justified by a comment in 158 (74.2%) reviews. Only in 33 (14.5%) of reviews the judgment in all domains was justified in the accompanying comment. In most reviews (81.7%), the RoB was inadequately assessed at the study level. In conclusion, the majority of non-Cochrane reviews published in 2020 still used the Cochrane RoB 1 tool. Many reviews used the RoB 2 tool inadequately. Further studies about the uptake and the use of the RoB 2 tool are needed.