The effects of cholesterol accumulation on Achilles tendon biomechanics: A cross-sectional study.
ABSTRACT: Familial hypercholesterolemia, a common genetic metabolic disorder characterized by high cholesterol levels, is involved in the development of atherosclerosis and other preventable diseases. Familial hypercholesterolemia can also cause tendinous abnormalities, such as thickening and xanthoma (tendon lipid accumulation) in the Achilles, which may impede tendon biomechanics. The objective of this study was to investigate the effect of cholesterol accumulation on the biomechanical performance of Achilles tendons, in vivo. 16 participants (10 men, 6 women; 37±6 years) with familial hypercholesterolemia, diagnosed with tendon xanthoma, and 16 controls (10 men, 6 women; 36±7 years) underwent Achilles biomechanical assessment. Achilles biomechanical data was obtained during preferred pace, shod, walking by analysis of lower limb kinematics and kinetics utilizing 3D motion capture and an instrumented treadmill. Gastrocnemius medialis muscle-tendon junction displacement was imaged using ultrasonography. Achilles stiffness, hysteresis, strain and force were calculated from displacement-force data acquired during loading cycles, and tested for statistical differences using one-way ANOVA. Statistical parametric mapping was used to examine group differences in temporal data. Participants with familial hypercholesterolemia displayed lower Achilles stiffness compared to the control group (familial hypercholesterolemia group: 87±20 N/mm; controls: 111±18 N/mm; p = 0.001), which appeared to be linked to Achilles loading rate rather than an increased strain (FH: 5.27±1.2%; controls: 4.95±0.9%; p = 0.413). We found different Achilles loading patterns in the familial hypercholesterolemia group, which were traced to differences in the centre of pressure progression that affected ankle moment. This finding may indicate that individuals with familial hypercholesterolemia use different Achilles loading strategies. Participants with familial hypercholesterolemia also demonstrated significantly greater Achilles hysteresis than the control group (familial hypercholesterolemia: 57.5±7.3%; controls: 43.8±10%; p<0.001), suggesting that walking may require a greater metabolic cost. Our results indicate that cholesterol accumulation could contribute to reduced Achilles function, while potentially increasing the chance of injury.
Project description:<h4>Background</h4>Familial hypercholesterolemia is a genetic condition characterized by life-long elevations of plasma low-density lipoprotein cholesterol. In addition to life-threatening cardiovascular complications, intratendinous cholesterol deposits (xanthomas) can lead to pain and tendon thickening, particularly in the Achilles. Clinical detection of xanthomas currently relies upon visual assessment and palpation, or ultrasound-based measures of tendon thickening or echotexture. Misdiagnosis of xanthoma can delay the commencement of potentially life-saving lipid-lowering therapy. Our primary purpose was to determine whether analysis of separated fat and water magnetic resonance images may be able to differentiate between xanthomatic and nonxanthomatic Achilles tendons through quantification of intratendinous fat content. The main hypothesis was that Achilles tendon xanthomas will demonstrate greater lipid content than Achilles tendinopathy or healthy control tendons.<h4>Methods</h4>Bilateral MRI scans of Achilles tendons from 30 participants (n = 10 Achilles tendon xanthoma, n = 10 Achilles overuse tendinopathy, n = 10 healthy controls) were analyzed for total lipid content using the Dixon method of fat and water signal separation. Secondary outcome measures included tendon water content, as well as ultrasound characterization of tendon tissue organization and thickness.<h4>Results</h4>Fat content was greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p < 0.0001). Water content was also greater in Achilles tendon xanthomas compared to the tendinopathy (p < 0.0001) and control groups (p = 0.0002). Ultrasound tissue characterization revealed worse tissue organization in Achilles tendon xanthoma tendons compared to Achilles tendinopathy (p < 0.05) but demonstrated largely overlapping distributions. Achilles tendon xanthoma tendons were, on average, significantly thicker than the tendons of the other two groups (p < 0.01 and p < 0.001, respectively).<h4>Conclusion</h4>MRI-derived measures of Achilles tendon fat content may be able to distinguish xanthomas from control and tendinopathic tissue. Dixon method MRI warrants further evaluation in an adequately powered study to develop and test clinically relevant diagnostic thresholds.
Project description:Background:Clinical diagnostic criteria of familial hypercholesterolemia (FH) in Japan include LDL cholesterol ?? ?180 ?mg/dL, Achilles tendon thickness ?? ?9.0 ?mm, and family history. However, few data exist regarding its validation. Design and Methods:A series of 680 participants, with a mean LDL cholesterol of 175 ?mg/dL were enrolled at Kanazawa University Hospital between 2006 and 2018. All had full assessments of, LDL cholesterol, Achilles tendon X-rays, family history records, and genetic analysis of FH-associated genes (LDLR, APOB, and PCSK9). The area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis predicting the presence of FH mutations by each clinical marker were assessed. Results:The optimal cutoff values predicting the presence of an FH-associated mutation were 181 ?mg/dL for LDL cholesterol and ?7.0 ?mm for Achilles tendon thickness. AUCs predicting FH mutations were 0.827 for Achilles tendon thickness ?9.0 ?mm, 0.889 for LDL cholesterol ?180 ?mg/dL, and 0.906 for family history. If Achilles tendon thickness ?7.0 ?mm was used as a clinical criterion, then 41 participants (6%) were newly diagnosed with FH and 86 (12%) were newly misclassified as FH. Conclusions:Current clinical diagnostic criteria of FH were validated in this cohort. We recommend considering a tentative diagnosis of "potential FH" if the Achilles tendon thickness is ?? ?7.0 ?mm and <9.0 ?mm rather than dismissing a diagnosis of FH.
Project description:BACKGROUND:Achilles tendinopathy is one of the most common overuse injuries in running, and forefoot pronation, seen in flatfeet participants, has been proposed to cause additional loading across the Achilles tendon. Foot orthoses are one of the common and effective conservative treatment prescribed for Achilles tendinopathy, it works by correcting the biomechanical malalignment and reducing tendon load. Previous studies have shown reduction of Achilles Tendon load (ATL) during running by using customized arch support orthosis (CASO) or an orthotic heel lift (HL). However, there are still little biomechanical evidence and comparative studies to guide orthotic prescriptions for Achilles tendinopathy management. Therefore, this study seeks to investigate the two currently employed orthotic treatment options for Achilles tendinopathy: CASO and HL for the reduction of ATL and Achilles tendon loading rate (ATLR) in recreational runners with flatfeet. METHODS:Twelve participants were recruited and run along the runway in the laboratory for three conditions: (1) without orthoses, (2) with CASO (3) with HL. Kinematic and kinetic data were recorded by 3D motion capturing system and force platform. Ankle joint moments and ATL were computed and compared within the three conditions. RESULTS:Participants who ran with CASO (p?=?0.001, d?=?0.43) or HL (p?=?0.001, d?=?0.48) associated with a significant reduction in ATL when compared to without orthotics while there was no significant difference between the two types of orthoses, the mean peak ATL of CASO was slightly lower than HL. Regarding the ATLR, both orthoses, CASO (p?=?0.003, d?=?0.93) and HL (p?=?0.004, d?=?0.78), exhibited significant lower value than the control but similarly, no significant difference was noted between them in which the use of CASO yielded a slightly lower loading rate than that of HL. CONCLUSIONS:Both CASO and HL were able to cause a significant reduction in peak ATL and ATLR comparing to without orthotics condition. There were subtle but no statistically significant differences in the biomechanical effects between the two types of orthoses. The findings help to quantify the effect of CASO and HL on load reduction of Achilles tendon and suggests that foot orthoses may serve to prevent the incidence of Achilles tendon pathologies. TRIAL REGISTRATION:NCT04003870 on clinicaltrials.gov 1 July 2019.
Project description:Achilles tendon injuries affect both athletes and the general population, and their incidence is rising. In particular, the Achilles tendon is subject to dynamic loading at or near failure loads during activity, and fatigue induced damage is likely a contributing factor to ultimate tendon failure. Unfortunately, little is known about how injured Achilles tendons respond mechanically and structurally to fatigue loading during healing. Knowledge of these properties remains critical to best evaluate tendon damage induction and the ability of the tendon to maintain mechanical properties with repeated loading. Thus, this study investigated the mechanical and structural changes in healing mouse Achilles tendons during fatigue loading. Twenty four mice received bilateral full thickness, partial width excisional injuries to their Achilles tendons (IACUC approved) and twelve tendons from six uninjured mice were used as controls. Tendons were fatigue loaded to assess mechanical and structural properties simultaneously after 0, 1, 3, and 6 weeks of healing using an integrated polarized light system. Results showed that the number of cycles to failure decreased dramatically (37-fold, p<0.005) due to injury, but increased throughout healing, ultimately recovering after 6 weeks. The tangent stiffness, hysteresis, and dynamic modulus did not improve with healing (p<0.005). Linear regression analysis was used to determine relationships between mechanical and structural properties. Of tendon structural properties, the apparent birefringence was able to best predict dynamic modulus (R(2)=0.88-0.92) throughout healing and fatigue life. This study reinforces the concept that fatigue loading is a sensitive metric to assess tendon healing and demonstrates potential structural metrics to predict mechanical properties.
Project description:Mechanical loading affects tendon healing and recovery. However, our understanding about how physical loading affects recovery of viscoelastic functions, collagen production and tissue organisation is limited. The objective of this study was to investigate how different magnitudes of loading affects biomechanical and collagen properties of healing Achilles tendons over time. Achilles tendon from female Sprague Dawley rats were cut transversely and divided into two groups; normal loading (control) and reduced loading by Botox (unloading). The rats were sacrificed at 1, 2- and 4-weeks post-injury and mechanical testing (creep test and load to failure), small angle x-ray scattering (SAXS) and histological analysis were performed. The effect of unloading was primarily seen at the early time points, with inferior mechanical and collagen properties (SAXS), and reduced histological maturation of the tissue in unloaded compared to loaded tendons. However, by 4 weeks no differences remained. SAXS and histology revealed heterogeneous tissue maturation with more mature tissue at the peripheral region compared to the center of the callus. Thus, mechanical loading advances Achilles tendon biomechanical and collagen properties earlier compared to unloaded tendons, and the spatial variation in tissue maturation and collagen organization across the callus suggests important regional (mechano-) biological activities that require more investigation.
Project description:Therapy options for ruptured Achilles tendons need to take into account the right balance of timing, amount and intensity of loading to ensure a sufficient biomechanical resilience of the healing tendon on the one hand, and to enable an adequate tensile stimulus on the other hand. However, biomechanical data of human Achilles tendons after rupture during the separate healing stages are unknown. Shear wave elastography is an ultrasound technique that measures material elastic properties non-invasively, and was proven to have a very good correlation to biomechanical studies. Taking advantage of this technology, 12 patients who suffered from an acute Achilles tendon rupture were acquired and monitored through the course of one year after rupture. Nine of these patients were treated non-operatively and were included for the analysis of biomechanical behaviour. A significant increase of material elastic properties was observed within the first six weeks after trauma (up to 80% of baseline value), where it reached a plateau phase. A second significant increase occurred three to six months after injury. This pilot study suggests a time correlation of biomechanical properties with the biological healing phases of tendon tissue. In the reparative phase, a substantial amount of biomechanical resilience is restored already, but the final stage of biomechanical stability is reached in the maturation phase. These findings can potentially be implemented into treatment and aftercare protocols.
Project description:Familial homozygous hypercholesterolemia is one of the high risk factors that can result in premature coronary arterial disease leading to severe morbidity and premature death in children and young adults. We describe a rare example of extensive xanthoma tuberosum in a case of familial homozygous hypercholesterolemia.
Project description:<h4>Introduction</h4>Statins are widely used to inhibit cholesterol production in the liver among people with hypercholesterolemia. A recent epidemiological study in the UK has shown that statin use (unlike elevated BMI) is not associated with an increased risk of Achilles tendon rupture. However, because of laboratory reports suggesting a negative influence of statins on tenocyte metabolism, we decided to directly compare the Achilles tendon structure (cross-sectional area and longitudinal collagen organization) in regular statin users compared to non-users.<h4>Methods</h4>We conducted ultrasound tissue characterization (UTC) of the Achilles tendon in statin users and a comparison group of similar age and gender. Statin users and control participants were recruited from May 10 2015 to February 17 2017 through a cardiovascular health centre and from the general community. Cross-sectional area of the Achilles tendon and longitudinal collagen organization (% type I echoes) were assessed using quantitative ultrasound tissue characterization by a blinded observer at a predetermined location (2 cm proximal to the calcaneus).<h4>Results</h4>Sixty-six individuals who were either taking statins for at least one year (ST, n = 33) or a comparison group who had never taken statins (CG, n = 33) were included in the study. The Achilles tendon cross-sectional area (ST 59.7 (13) mm2, CG 59.9 (8.5) mm2) and proportion of echo-type I patterns [ST 70 (10)%, CG 74 (13)%] were equivalent in the two groups. In contrast, there was a negative correlation between BMI (rs = -0.25, p = 0.042) and type I echo values. Obese individuals demonstrated a significantly lower percentage of type I echoes (62 (11)%) than individuals of normal body mass index (73 (10)% p<0.05).<h4>Conclusion</h4>These findings demonstrate that there is no evidence of a negative statin influence on Achilles tendon structure. Given earlier reports that the risk of Achilles injury is equivalent in statin users and non-users, weightbearing exercise may be prescribed without placing the Achilles tendon at a higher risk of injury than among the general population. The results of this study are consistent with the known negative effects of elevated BMI on tendon structure, suggesting that an assessment of the Achilles tendons prior to prescribing weightbearing exercise may be prudent in obese individuals.
Project description:Our goal was to develop a novel technique for inducing Achilles tendinopathy in animal models which more accurately represents the progressive histological and biomechanical characteristic of chronic Achilles tendinopathy in humans. In this animal research study, forty-five rabbits were randomly assigned to three groups and given bilateral Achilles injections. Low dose (LD group) (n = 18) underwent a novel technique with three low-dose (0.1mg) injections of collagenase that were separated by two weeks, the high dose group (HD) (n = 18) underwent traditional single high-dose (0.3mg) injections, and the third group were controls (n = 9). Six rabbits were sacrificed from each experimental group (LD and HD) at 10, 12 and 16 weeks. Control animals were sacrificed after 16 weeks. Histological and biomechanical properties were then compared in all three groups. At 10 weeks, Bonar score and tendon cross sectional area was highest in HD group, with impaired biomechanical properties compared to LD group. At 12 weeks, Bonar score was higher in LD group, with similar biomechanical findings when compared to HD group. After 16 weeks, Bonar score was significantly increased for both LD group (11,8±2,28) and HD group (5,6±2,51), when compared to controls (2±0,76). LD group showed more pronounced histological and biomechanical findings, including cross sectional area of the tendon, Young's modulus, yield stress and ultimate tensile strength. In conclusion, Achilles tendinopathy in animal models that were induced by serial injections of low-dose collagenase showed more pronounced histological and biomechanical findings after 16 weeks than traditional techniques, mimicking better the progressive and chronic characteristic of the tendinopathy in humans.
Project description:Background:Previously, scholars have concluded that the Achilles tendon and the plantar fascia were closely biomechanically related, although there is little clinical evidence of the relationship between the two. To investigate the biomechanical relationship between the Achilles tendon and the plantar fascia, the author used standing lateral ankle radiographs of patients with insertional Achilles tendonitis to determine the biomechanical relationship between the Achilles tendon and plantar fascia. Methods:The author collected standing lateral ankle radiographs from patients with insertional Achilles tendonitis who accepted surgical treatment in the author's hospital from March 2009 to July 2018. According to whether there were bone spurs on the posterior side of the calcaneus, patients were divided into group A (spur present on the posterior side) and group B (spur not present on the posterior side). The positive rates of spurs on the plantar side of the calcaneus were determined in group A and group B. The chi-square test was used to compare the measurement results between the two groups. Results:In group A, 13 heels were positive for calcaneal bone spurs, and the positive rate was 65.0%. In group B, 3 heels were positive for plantar calcaneal spurs, and the positive rate was 12%. Among all 16 patients with positive plantar calcaneal spurs, 13 had posterior calcaneal spurs (accounting for 81.3%), and 3 had negative results, accounting for 18.7%. There was a significant difference between the results in groups A and B (P < 0.05). Conclusion:There is a relationship between posterior calcaneal spurs and plantar calcaneal spurs in patients with insertional Achilles tendonitis, which can be inferred as resulting from the increasing tension in the biomechanically complex relationship between the Achilles tendon and the plantar fascia.