Risk Of Tendinopathy Research Articles

Clinical Association of Achilles Tendinopathy and Hypertension Mediated by CaV1.2 Voltage-gated Ca2+ Channel

Category: Basic Sciences/Biologics; Hindfoot Introduction/Purpose: The Achilles tendon is subject to acute- and overuse-injuries, which may result in degenerative tendinopathy. Achilles tendinopathy is associated with pain, disability, and functional limitations. While some patients benefit from therapy and conservative measures, many progress to operative intervention. The pathogenic mechanisms of Achilles tendinopathy are largely unknown. Using novel transgenic mouse models with CaV1.2 (a voltage gated calcium channel) wildtype or a gain-of-function mutant channel, we observed potent regulatory effects of increased Ca2+ influx through CaV1.2 on Achilles tendinopathy development. CaV1.2 expression and activity has also been shown to contribute to hypertension amongst other systemic disease. We hypothesized that aberrant CaV1.2 function is a common pathogenic mechanism both hypertension and Achilles tendinopathy. To test this hypothesis, we performed an association study between two diseases. Methods: A case-control study was performed to investigate the association between Achilles tendinopathy and hypertension using TriNetX mulit-center clinical database. We identified Achilles tendinopathy and hypertension patients based on their ICD-10 codes. Chi-squared test, odds ratio (OR) and 95% confidence interval (CI) were used to detect the correlation between these two diseases. To elucidate the role of CaV1.2 in the association of Achilles tendinopathy and hypertension, we performed a retrospective cohort study with the exposure cohort defined as all subjects with hypertension and a calcium channel blocker (CCB) prescription preceding a diagnosed tendinopathy from January 1, 2011 to December 31, 2015. A matched cohort was defined as the subjects with hypertension but on medications other than CCBs. A 7-year follow-up was obtained for the outcome Achilles tendinopathy. Relative risk (RR) and hazard ratio (HR) were used to detect the effect of CCBs and other anti- hypertensives on the development of tendinopathy. Results: We determined that hypertension is more prevalent in patients with Achilles tendinopathy (42.4%) compared to those without (12.6%). The incidence of Achilles tendinopathy is significantly correlated with hypertension (p < 0.0001; OR=3.17, 95%CI=3.11-3.22). Furthermore, hypertension patients on CCBs had a 28% decrease in Achilles tendinopathy risk when compared with hypertensive patients on medications other than CCBs (RR=0.72, 95%CI=0.60-0.86, p< 0.0001). A cox proportional hazards model corroborated the findings, with hypertensive patients on CCBs having 26% decreased incidence of Achilles tendinopathy than patients on other medications (HR=0.74, 95%CI=0.62-0.88, p< 0.0001). In contrast, we found no significant effect of angiotensin-converting enzyme inhibitors (no direct effect on Calcium channel activity) on the incidence of Achilles tendinopathy (HR=0.99, 95%CI=0.88-1.10, p=0.8273). Conclusion: There may be a correlation between Achilles tendinopathy and other common systemic diseases such as hypertension, as well as potential treatment pathways. Our study of the TriNetX clinical database provides evidence that CaV1.2 expression/activity is a potential molecular mechanism underlying Achilles tendinopathy. Additionally, an effect of CCBs in hypertensive patients may be to lower the incidence of Achilles tendinopathy by inhibiting L-type voltage-gated Ca2+ channel (including CaV1.2) signaling in tenocytes. Our finding will provide a rationale for further investigation of this association, including a potential for repurposing FDA-approved generic CCBs to prevent or treat Achilles tendinopathy.

Effect of sex on muscle-tendon imbalances and tendon micromorphology in adolescent athletes-A longitudinal consideration.

Imbalances between muscle strength and tendon stiffness may cause high-level tendon strain during maximum effort muscle contractions and lead to tendon structural impairments and an increased risk for tendinopathy in adolescent athletes. However, it remains unclear whether the development of musculotendinous imbalances is influenced by sex. At four measurement time points during a competitive season, we measured quadriceps femoris muscle strength and patellar tendon mechanical properties in 15 female (14.3 ± 0.7 years) and 13 male (16.0 ± 0.6 years) elite handball players of similar maturity using dynamometry and ultrasonography. To estimate the tendon's structural integrity, the peak spatial frequency (PSF) of proximal tendon ultrasound scans was determined. Females demonstrated significantly lower muscle strength (p < 0.001) and patellar tendon stiffness (p < 0.001) than males with no significant changes over time (p > 0.05). Tendon strain during isometric maximum voluntary contractions and PSF neither differed between sexes nor changed significantly over time (p > 0.05). We found lower fluctuations in muscle strength (p < 0.001) in females during the season but no differences in the fluctuations of tendon strain, stiffness, and PSF (p > 0.05). Descriptively, there was a similar frequency (~40%) of athletes with high-level tendon strain (>9%) in both sexes. These findings suggest that the lower strength capacity of female athletes is paralleled by lower tendon stiffness. Thereby, muscle-tendon imbalances occur to a similar extent in both sexes leading to increased strain levels during the season, which indicates the need for specific tendon training.

Longitudinal Evidence for High-Level Patellar Tendon Strain as a Risk Factor for Tendinopathy in Adolescent Athletes

BackgroundHigh tendon strain leads to sub-rupture fatigue damage and net-catabolic signaling upon repetitive loading. While high levels of tendon strain occur in adolescent athletes at risk for tendinopathy, a direct association has not yet been established. Therefore, in this prospective longitudinal study, we examined the hypothesis that adolescent athletes who develop patellar tendon pain have shown increased levels of strain in advance.MethodsIn 44 adolescent athletes (12–17 years old), patellar tendon mechanical properties were measured using ultrasonography and inverse dynamics at four time points during a season. Fourteen athletes developed clinically relevant tendon pain (SYM; i.e., reduction of the VISA-P score of at least 13 points), while 23 remained asymptomatic (ASYM; VISA-P score of > 87 points). Seven cases did not fall into one of these categories and were excluded. Tendon mechanical properties of SYM in the session before the development of symptoms were compared to a randomly selected session in ASYM.ResultsTendon strain was significantly higher in SYM compared to ASYM (p = 0.03). The risk ratio for developing symptoms was 2.3-fold higher in athletes with tendon strain ≥9% (p = 0.026). While there was no clear evidence for systematic differences of the force applied to the tendon or tendon stiffness between SYM and ASYM (p > 0.05), subgroup analysis indicated that tendon force increased prior to the development of symptoms only in SYM (p = 0.034).DiscussioThe study provides novel longitudinal evidence that high tendon strain could be an important risk factor for patellar tendinopathy in adolescent athletes. We suggest that inadequate adaptation of tendon stiffness to increases in muscle strength may occur if adolescent athletes are subject to mechanical loading which does not provide effective tendon stimulation.

Neutrophil to lymphocyte ratio may be used as a predictor in tendinopathy

Objectives: Tendinopathy is a very common clinical disorder and a complex inflammation and degeneration process. Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) have been studied and accepted as biomarkers of inflammation, predictors of progression and prognosis in several studies. We aimed to show that NLR and PLR levels can help predict prognosis for tendinopathy by comparing NLR and PLR levels of patients with tendinopathy with healthy control groups. Methods: Tendinopathy and healthy cases whose complete blood test was requested, were included in the study. Age, gender, white blood cell (WBC), neutrophil, lymphocyte, platelet counts, NLR and PLR of these cases were examined. Results: There is a statistically significant difference between the tendinopathy (n = 140) and control (n = 51) groups in WBC and NLR values (p &amp;lt; 0.001). One unit increase in WBC and NLR levels increases the risk of tendinopathy 1.74 and 10.616 times respectively. According to the results of the ROC analysis, the threshold value of the WBC and NLR values to increase the risk of tendinopathy is 6.47, and 1.64 respectively. Conclusions: Our study suggested NLR and WBC values are significant indicators of tendinopathy. We consider these results to be a guide for all physicians, especially sports medicine physicians.

Effects of Statin Treatment on the Development of Tendinopathy: A Nationwide Population-Based Cohort Study.

Previous longitudinal cohort studies have reported the conflicting results of the relationship between statin use and the development of tendinopathy disorder. It is unclear if there is a relationship between statin use, particularly the type or cumulative doses, and the development of tendinopathy disorder. To investigate an association between statin treatment and the development of tendinopathy. Cohort study; Level of evidence, 3. A total of 594,130 participants were enrolled in this study in 2002 and evaluated until 2015. There were 84,102 statin users and 168,204 nonusers (controls) selected at a ratio of 1:2 using propensity score matching analysis. The types of included tendinopathy were as follows: (1) trigger finger, (2) radial styloid tenosynovitis, (3) elbow epicondylitis, (4) rotator cuff tendinopathy, and (5) Achilles tendinitis. Cox proportional hazards models with time-varying covariates were constructed to identify the association between statin use and tendinopathy development. Statin treatments regardless of statin types were associated with a significantly greater risk of all types of tendinopathy development (hazard ratio, 1.435; 95% CI, 1.411-1.460) compared with no statin treatment. A trend toward risk reduction was observed according to cumulative statin doses, which was indicated by hazard ratios of 2.337 (95% CI, 2.269-2.406), 2.210 (95% CI, 2.132-2.290), and 1.1 (95% CI, 1.098-1.146) in patients with cumulative defined daily doses of 90, 91-180, and >180, respectively. This nationwide population-based cohort study suggests that statin use regardless of the statin type was associated with a greater risk of tendinopathy compared with that of nonusers. The risk of tendinopathy development was diluted with the increasing cumulative defined daily dose.

Short-Term Exposure to Ciprofloxacin Reduces Proteoglycan Loss in Tendon Explants

Fluoroquinolone antibiotics are associated with increased risk of tendinopathy and tendon rupture, which can occur well after cessation of treatment. We have previously reported that the fluoroquinolone ciprofloxacin (CPX) reduced proteoglycan synthesis in equine tendon explants. This study aimed to determine the effects of CPX on proteoglycan catabolism and whether any observed effects are reversible. Equine superficial digital flexor tendon explant cultures were treated for 4 days with 1, 10, 100 or 300 µg/mL CPX followed by 8 days without CPX. The loss of [35S]-labelled proteoglycans and chemical pool of aggrecan and versican was studied as well as the gene expression levels of matrix-degrading enzymes responsible for proteoglycan catabolism. CPX suppressed [35S]-labelled proteoglycan and total aggrecan loss from the explants, although not in a dose-dependent manner, which coincided with downregulation of mRNA expression of MMP-9, -13, ADAMTS-4, -5. The suppressed loss of proteoglycans was reversed upon removal of the fluoroquinolone with concurrent recovery of MMP and ADAMTS mRNA expression, and downregulated TIMP-2 and upregulated TIMP-1 expression. No changes in MMP-3 expression by CPX was observed at any stage. These findings suggest that CPX suppresses proteoglycan catabolism in tendon, and this is partially attributable to downregulation of matrix-degrading enzymes.

The Burden and Risk Factors of Patellar and Achilles Tendinopathy in Youth Basketball: A Cohort Study.

This study aimed at evaluating the burden and risk factors of patellar and Achilles tendinopathy among youth basketball players. Patellar and Achilles tendinopathy were prospectively monitored in 515 eligible male and female youth basketball players (11–18 years) through a competitive season. Overall, the season prevalence of patellar tendinopathy was 19.0% (95% CI: 15.7–22.7%), 23.2% (95% CI: 18.6–28.2%) in males and 12.5% (95% CI: 8.3–17.9%) in females. The season prevalence of Achilles tendinopathy was 4.3% (95% CI: 2.7–6.4%), 4.1% (95% CI: 2.2–7.0%) in males and 4.5% (95% CI: 2.1–8.4%) in females. Median proportion of symptoms duration was 83% of average total weeks of basketball exposure for patellar tendinopathy and 75% for Achilles tendinopathy. Median time to patellar tendinopathy onset was 8 weeks for male players and 6 weeks for female players. Higher odds of patellar tendinopathy risk were seen in males (OR: 2.23, 95% CI: 1.10–4.69) and players with previous anterior knee pain had significantly elevated odds (OR: 8.5, 95% CI: 4.58–16.89). The burden and risk of patellar tendinopathy is high among competitive youth basketball players. Risk factors include sex and previous anterior knee pain. These findings provide directions for practice and future research.

Are subject-specific models necessary to predict patellar tendon fatigue life? A finite element modelling study

Patellar tendinopathy is an overuse injury that occurs from repetitive loading of the patellar tendon in a scenario resembling that of mechanical fatigue. As such, fatigue-life estimates provide a quantifiable approach to assess tendinopathy risk and may be tabulated using nominal strain (NS) or finite element (FE) models with varied subject-specificity. We compared patellar tendon fatigue-life estimates from NS and FE models of twenty-nine athletes performing countermovement jumps with subject-specific versus generic geometry and material properties. Subject-specific patellar tendon material properties and geometry were obtained using a data collection protocol of dynamometry, ultrasound, and magnetic resonance imaging. Three FE models were created for each subject, with: subject-specific (hyperelastic) material properties and geometry, subject-specific material properties and generic geometry, and generic material properties and subject-specific geometry. Four NS models were created for each subject, with: subject-specific (linear elastic) material properties and moment arm, generic material properties and subject-specific moment arm, subject-specific material properties and generic moment arm, and generic material properties and moment arm. NS- and FE-modelled fatigue-life estimates with generic material properties were poorly correlated with their subject-specific counterparts (r2 ≤0.073), while all NS models overestimated fatigue life compared to the subject-specific FE model (r2 ≤0.223). Furthermore, FE models with generic tendon geometry were unable to accurately represent the heterogeneous strain distributions found in the subject-specific FE models or those with generic material properties. These findings illustrate the importance of incorporating subject-specific material properties and FE-modelled strain distributions into fatigue-life estimations.

Ciprofloxacin reduces tenocyte viability and proteoglycan synthesis in short-term explant cultures of equine tendon.

Fluoroquinolones are an effective, broad-spectrum antibiotic used to treat an array of bacterial infections. However, they are associated with an increased risk of tendinopathy and tendon rupture even after discontinuation of treatment. This condition is known as fluoroquinolone-associated tendinopathy, the underlying mechanisms of which are poorly understood. While many factors may be involved in the pathophysiology of tendinopathies in general, changes in tenocyte metabolism and viability, as well as alteration of proteoglycan metabolism are prominent findings in the scientific literature. This study investigated the effects of ciprofloxacin, a common fluoroquinolone, on cell viability, proteoglycan synthesis, and proteoglycan mRNA expression in equine superficial digital flexor tendon explants after 96 h treatment with between 1–300 µg/mL ciprofloxacin, and again after 8 days discontinuation of treatment. Ciprofloxacin caused significant reductions in cell viability by between 25–33% at all dosages except 10 µg/mL, and viability decreased further after 8 days discontinuation of treatment. Proteoglycan synthesis significantly decreased by approximately 50% in explants treated with 100 µg/mL and 300 µg/mL, however this effect reversed after 8 days in the absence of treatment. No significant mRNA expression changes were observed after the treatment period with the exception of versican which was down-regulated at the highest concentration of ciprofloxacin. After the recovery period, aggrecan, biglycan and versican genes were all significantly downregulated in explants initially treated with 1–100 µg/mL. Results from this study corroborate previously reported findings of reduced cell viability and proteoglycan synthesis in a whole tissue explant model and provide further insight into the mechanisms underlying fluoroquinolone-associated tendinopathy and rupture. This study further demonstrates that certain ciprofloxacin induced cellular changes are not rapidly reversed upon cessation of treatment which is a novel finding in the literature.

Prevention of strain-induced impairments of patellar tendon micromorphology in adolescent athletes.

High-level patellar tendon strain may cause impairments of the tendon's micromorphological integrity in growing athletes and increase the risk for tendinopathy. This study investigated if an evidence-based tendon exercise intervention prevents high-level patellar tendon strain, impairments of micromorphology and pain in adolescent basketball players (male, 13-15years). At three time points over a season (M1-3), tendon mechanical properties were measured using ultrasound and dynamometry, proximal tendon micromorphology with a spatial frequency analysis and pain and disability using VISA-P scores. The control group (CON, n=19) followed the usual strength training plan, including sprint and change-of-direction drills. In the intervention group (INT, n=14), three sessions per week with functional exercises were integrated into the training, providing repetitive high-magnitude tendon loading for at least 3s per repetition. The frequency of high-level strain (ie, ≥9%) continuously decreased in INT, while tending to increase in CON since tendon force increased in both (p<0.001), yet tendon stiffness only in INT (p=0.004). In CON, tendon strain was inversely associated with tendon peak spatial frequency at all time points (p<0.05), indicating impairments of tendon micromorphological integrity with higher strain, but not at M2 and M3 in INT. Descriptively, the fraction of asymptomatic athletes at baseline was similar in both groups (~70%) and increased to 100% in M3 in INT, while remaining unchanged in CON. We suggest that functional high-load tendon exercises could reduce the prevalence of high-level patellar tendon strain and associated impairments of its micromorphology in adolescent athletes, providing new opportunities for tendinopathy prevention.

Fluoroquinolones as a trigger for rupture of abdominal aortic aneurysm: A case-crossover analysis.

Fluoroquinolones (FQ) are associated with an increased risk of tendinopathy, including rupture. Our study aimed to investigate whether FQ use triggered the rupture of aortic aneurysms using a self-controlled design. We hypothesised that the use of FQ was associated with aortic rupture shortly after redeemed FQ prescriptions. Using nationwide data sources, we performed a case-crossover study of cases with ruptured aortic aneurysms. From 1996 to 2016, 58 persons presented with rupture of an aortic aneurysm and a redeemed prescription for any FQ within 28days. 67% were men, and the median age was 77years. Some 82.9% presented with a ruptured abdominal aneurysm. In our conditional regression, the crude OR for having rupture with a recent FQ redemption was 1.36 (CI 1.00-1.86). After adjusting for potential confounders, the OR was 1.35 (CI 0.98-1.85). Changing the hazard period to FQ redemption within 60 and 90days, the OR was 2.16 (CI 1.70-2.76) and 2.21 (CI 1.78-2.75), respectively. In conclusion, we demonstrated an association between FQ use within 60 and 90days and a diagnosis of ruptured aortic aneurysm.

Ultrasonographic Evaluation of the Shoulders and Its Associations with Shoulder Pain, Age, and Swim Training in Masters Swimmers.

Background and objectives: The long head of the biceps (LHB) and rotator cuff tendinopathy is the major cause of shoulder pain in competitive swimmers. The risk of tendinopathy increases with aging; however, the structural changes of LHB and rotator cuff in populations of masters swimmers have not been well examined. The purpose of this study was to investigate the prevalence of ultrasonographic abnormalities of the shoulders in masters swimmers, and the association of pain, age, and swim training with structural changes in this population. Materials and Methods: A total of 60 subjects participated in this study, with 20 masters swimmers with shoulder pain, 20 asymptomatic masters swimmers, and 20 sex- and age-matched controls. All swimmers completed a self-reported questionnaire for shoulder pain, their history of competition, and training volume. Each subject underwent ultrasonographic examination of both shoulders for pathologic findings in the LHB tendon, rotator cuff (supraspinatus (SSP) and subscapularis (SSC)) tendons, and subacromial bursa (SAB) of both shoulders and had thickness measured. Results: The prevalence of tendinosis (LHB, 48.8%; SSP, 17.5%; SSC, 15.9%), partial tear (SSP, 35.0%), and calcification (SSC, 10.0%) were higher in swimmers than in controls. LHB and SSP tendinosis were associated with shoulder pain. Older age and later start of competition were associated with an increased risk of LHB tendinosis and SSC calcification. Earlier initiation of swimming and longer history of competition were associated with an increased risk of SSP and SSC tendinosis. The thicker SSP tendon significantly increased the risk of tendinosis and partial tear. Conclusions: A high prevalence of structural changes in the rotator cuff and biceps tendons in masters swimmers reflects the effect of shoulder symptoms, aging, and swim training.

Differences in Achilles tendon stiffness in people with gout: a pilot study

BackgroundGout has been associated with weaker foot/leg muscles and altered gait patterns. There is also evidence of on-going foot pain and an increased risk of tendinopathy, with the Achilles and patella tendons most frequently affected in gout. Additionally, the inflammation associated with gout may change tissue elasticity. Ultrasound imaging utilising shear wave elastography (SWE) offers a non-invasive method of quantifying changes in tendon stiffness. SWE findings have not previously been reported in individuals with gout. We sought to determine differences in Achilles tendon stiffness in people with gout compared to controls (non-gout).MethodsA cross sectional study comparing 24 people with gout and 26 age/sex-matched controls. Clinical and demographic data were collated, and US imaging used to determine tendon thickness, presence of gouty tophi and/or aggregates and levels of angiogenesis. Ten shear wave elastography (SWE) measures were taken along the centre of a longitudinal section of the mid-portion of each Achilles tendon. Prior to data collection, intra-observer error was good (>0.69). Data were summarised using descriptive statistics and a repeated measures ANCOVA was used to compare SWE measures between the two groups for the left and right foot separately after accounting for Body Mass Index (BMI).ResultsA small proportion of those with gout presented with intra-tendon aggregates and/or intra-tendon tophi in one or both tendons. There was no statistically significant difference in tendon thickness between groups. Neo-vascularity was present in a third of gout participants. SWE findings demonstrated significantly reduced tendon stiffness in those with gout compared to controls: right Achilles mdiff =1.04 m/s (95% CI (0.38 to 1.7) p = 0.003 and left Achilles mdiff = 0.7 m/s (95% CI 0.09 to 1.32) p = 0.025. No relationship between the presence of tophi and SWE values were detected.ConclusionSubjects with chronic gout show significantly reduced Achilles tendon stiffness compared to non-gout controls. From a clinical standpoint, our findings were similar to SWE measurements in subjects with Achilles tendinopathy and who did not have gout.

Association of the matrix metalloproteinase 3 (MMP3) single nucleotide polymorphisms with tendinopathies: case-control study in high-level athletes.

Matrix metalloproteinases (MMPs) play an important role in matrix remodelling, as well as in tendon integrity. Due to overuse, athletes often develop chronic tendinopathies. If not treated, they lead to severe impairment, even complete tendon ruptures. The main purpose of this study was to investigate whether three functional polymorphisms within the MMP3 gene are associated with increased risk of developing tendinopathies in high-level Croatian athletes. We have recruited one hundred fifty-five (63 high-level athletes with diagnosed tendinopathies and 92 asymptomatic controls) unrelated Caucasians for this case-control genetic study. All participants were genotyped for three single nucleotide polymorphisms (SNP) within the MMP3 gene: rs591058 C/T, rs650108 A/G and rs679620 G/A using the pyrosequencing method. The MMP3 rs650108 GG (P = 0.0074) and rs679620 AA (P= 0.0119) genotypes were significantly over-represented in cases compared with controls, while rs591058 TT (P = 0.0759), as well as haplotype variant T - G - A (P = 0.06), implicated that there is an indication of predisposition for tendinopathies. These results support association between functional variants within the MMP3 gene and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in a larger population.

High Frequencies of TNC and COL5A1 Genotypes Associated With Low Risk for Superficial Digital Flexor Tendinopathy in Greek Indigenous Horse Breeds Compared With Warmblood Horses

Tendinopathies constitute a very common category of musculoskeletal disorders, causing economic losses in the equine industry and animal welfare issues in horse populations. Sport and racehorses are in general sensitive to tendinopathies, whereas local indigenous horse populations are often more tolerant to various disorders. Particularly, indigenous Greek horse breeds have evolved and adapted in the rough topographic features of mountainous and semimountainous Greek terrain and are less prone to develop tendinopathies. Susceptibility to tendinopathy has been proposed to be associated with three specific variants in the tenascin-C and collagen type 5 α-1 genes. The present study was designed to analyze these genes and estimate the frequency of the aforementioned variants in three indigenous Greek horse populations, namely the pinia (peneia) breed, the Messara breed, and the nondescript Macedonian pacer, in comparison with a population of warmbloods. Results revealed high frequencies of genotypes with high risk for tendinopathy in the warmblood population and high frequency of low risk genotypes in the Greek breeds. Apart from the three variants, two novel polymorphisms were detected, one of which may also be associated with risk for tendinopathy. Our findings (a) are in agreement with previous ones demonstrating that risk for tendinopathies is associated with particular gene variants and also (b) highlight the value of Greek indigenous horse breeds as a genetic resource that (c) may be used in selective breeding schemes for decreasing the risk for tendinopathies in genetically improved breeds.

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

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

The Impact of Genistein Supplementation on Tendon Functional Properties and Gene Expression in Estrogen-Deficient Rats.

Tendinopathy risk increases with menopause. The phytoestrogen genistein prevents collagen loss during estrogen deficiency (ovariectomy [OVX]). The influence of genistein on tendon function and extracellular matrix (ECM) regulation is not well known. We determined the impact of genistein on tendon function and the expression of several genes important for the regulation of tendon ECM. Eight-week-old rats (n = 42) were divided into three groups: intact, OVX, or OVX-genistein (6 mg/kg/day) for 6 weeks. Tail fascicles were assessed with a Deben tensile stage. Achilles tendon mRNA expression was determined with digital droplet polymerase chain reaction. Compared to intact, fascicle stress tended to be lower in untreated OVX rats (P = .022). Furthermore, fascicle modulus and energy density were greater in genistein-treated rats (P < .05) compared to intact. Neither OVX nor genistein altered expression of Col1a1, Col3a1, Casp3, Casp8, Mmp1a, Mmp2, or Mmp9 (P > .05). Compared to intact, Tnmd and Esr1 expression were greater and Pcna and Timp1 expression were lower in OVX rats (P < .05). Genistein treatment returned Tnmd, Pcna, and Timp1 to levels of intact-vehicle (P < .05), but did not alter Scx or Esr1 (P > .05). Several β-catenin/Wnt signaling-related molecules were not altered by OVX or genistein (P > .05). Our findings demonstrate that genistein improves tendon function in estrogen-deficient rats. The effect of genistein in vivo was predominately on genes related to cell proliferation rather than collagen remodeling.

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

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. (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? 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). 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. 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 IV, prognostic study.

Statin treatment increases the clinical risk of tendinopathy through matrix metalloproteinase release \u2013 a cohort study design combined with an experimental study

Recent experimental evidence indicates potential adverse effects of statin treatment on tendons but previous clinical studies are few and inconclusive. The aims of our study were, first, to determine whether statin use in a cohort design is associated with tendinopathy disorders, and second, to experimentally understand the pathogenesis of statin induced tendinopathy. We studied association between statin use and different tendon injuries in two population-based Swedish cohorts by time-dependent Cox regression analysis. Additionally, we tested simvastatin in a 3D cell culture model with human tenocytes. Compared with never-users, current users of statins had a higher incidence of trigger finger with adjusted hazard ratios (aHRs) of 1.50 for men (95% confidence interval [CI] 1.21–1.85) and 1.21 (1.02–1.43) for women. We also found a higher incidence of shoulder tendinopathy in both men (aHR 1.43; 1.24–1.65) and women (aHR 1.41; 0.97–2.05). Former users did not confer a higher risk of tendinopathies. In vitro experiments revealed an increased release of matrix metalloproteinase (MMP)-1 and MMP-13 and a weaker, disrupted matrix after simvastatin exposure. Current statin use seems to increase the risk of trigger finger and shoulder tendinopathy, possibly through increased MMP release, and subsequently, a weakened tendon matrix which will be more prone to injuries.

Low prevalence of patellar tendon abnormality and low incidence of patellar tendinopathy in female collegiate volleyball players

ABSTRACTThe prevalence of patellar tendinopathy has been reported to be as high as 50% in elite male volleyball (VB) players; however, the rate of injury in female collegiate VB athletes is unknown. The purpose of this study was to 1) identify the prevalence of ultrasonographic evidence of patellar tendon abnormality at the start of the preseason in female collegiate VB players; 2) report the incidence of tendinopathy during the season; and 3) determine if the preseason presence of tendon abnormality is associated with onset of disease. One hundred and six female collegiate VB players had both patellar tendons imaged. Incidence of patellar tendinopathy was tracked during the course of the 4-month season. Twenty-two athletes presented with ultrasonographic evidence of patellar tendon abnormality in at least one knee at the start of the preseason. The incidence of time-loss patellar tendinopathy was 0.26 (95% CI: 0.04, 0.85) per 1000 athletic exposures. This study was unable to determine if preseason presence of tendon abnormality was associated with a greater risk of tendinopathy due to power. The prevalence of tendon abnormality in the preseason and the incidence of patellar tendinopathy in female collegiate VB players are lower than that observed in other populations.