A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: A cross sectional study comparing Osgood Schlatter disease with controls.

BACKGROUND: Osgood-Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. PURPOSE: This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. STUDY DESIGN: Cross-sectional study. METHODS: Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). RESULTS: Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the  tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2).  Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, -0.05, 95% CI: -0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, -0.09, 95% CI: -0.4 to 0.2, p = 0.04; distal mean difference, -0.6, 95% CI: -0.9 to -0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = -2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. CONCLUSION: Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. CLINICAL RELEVANCE: Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD.

Early differential diagnosis of ankylosing spondylitis among patients with low back pain in primary care.

Diagnosing and treating low back pain (LBP) is a worldwide major primary care challenge in which a differential diagnosis between non-specific LBP and conditions with a known pathology is essential for choosing the optimal treatment strategy. The time required for the diagnosis of a condition such as ankylosing spondylitis (AS) was previously found too long. However, a recently published paper by Bashir et al. found that distinct episodes of axial pain separated by more than 6 months seem more predictive than currently applied characteristics in reaching an early diagnosis of AS.

No beneficial effect of Polidocanol treatment in Achilles tendinopathy: a randomised controlled trial.

PURPOSE: Polidocanol injections have been used to treat chronic Achilles tendinopathy in clinical settings, but the few studies published show inconsistent results. The aim of this study was to evaluate the mid-term effect of Polidocanol in patients with chronic Achilles tendinopathy. It was hypothesised that patients treated with Polidocanol would have significant improvements in the outcome measures investigated compared to patients treated with a placebo treatment at mid-term follow-up. METHODS: This randomised controlled trial included forty-eight patients aged 32-77 years with a history of Achilles tendinopathy for at least 3 months and with neovascularisation demonstrated by ultrasonography was included. A minimum of 3 months of eccentric exercise treatment was required before participating. The patients were allocated to a maximum of two injection of either Polidocanol or Lidocaine (placebo). The primary outcome measure was pain during walking reported on a visual analogue scale. Secondary outcome measures were Foot and Ankle Outcome Score (FAOS), patient satisfaction with treatment and, shortly after inclusion, the Victorian Institute of Sports Assessment-Achilles questionnaire (VISA-A) was also included. Follow-up examinations were performed after 3 and 6 months. RESULTS: Pain during walking decreased during the 6-month follow-up period, but no significant differences were seen between the two groups. The same tendency was seen for FAOS and VISA-A in which both groups showed an improvement at 3- and 6-month follow-up, but no mid-term differences between the groups were seen. An equal number of patients in the two groups were satisfied with the treatment at follow-up. CONCLUSIONS: The results indicate that Polidocanol is a safe treatment, but the mid-term effects are the same as a placebo treatment. This further questions the use of Polidocanol in the treatment of chronic Achilles tendinopathy. LEVEL OF EVIDENCE: I.

High-load strength training improves outcome in patients with plantar fasciitis: A randomized controlled trial with 12-month follow-up.

The aim of this study was to investigate the effectiveness of shoe inserts and plantar fascia-specific stretching vs shoe inserts and high-load strength training in patients with plantar fasciitis. Forty-eight patients with ultrasonography-verified plantar fasciitis were randomized to shoe inserts and daily plantar-specific stretching (the stretch group) or shoe inserts and high-load progressive strength training (the strength group) performed every second day. High-load strength training consisted of unilateral heel raises with a towel inserted under the toes. Primary outcome was the foot function index (FFI) at 3 months. Additional follow-ups were performed at 1, 6, and 12 months. At the primary endpoint, at 3 months, the strength group had a FFI that was 29 points lower [95% confidence interval (CI): 6-52, P = 0.016] compared with the stretch group. At 1, 6, and 12 months, there were no differences between groups (P > 0.34). At 12 months, the FFI was 22 points (95% CI: 9-36) in the strength group and 16 points (95% CI: 0-32) in the stretch group. There were no differences in any of the secondary outcomes. A simple progressive exercise protocol, performed every second day, resulted in superior self-reported outcome after 3 months compared with plantar-specific stretching. High-load strength training may aid in a quicker reduction in pain and improvements in function.

Exercise during school hours when added to patient education improves outcome for 2 years in adolescent patellofemoral pain: a cluster randomised trial.

BACKGROUND: Patellofemoral pain (PFP) is common among adolescents and associated with long-lasting pain and disability. Patient education and exercise therapy are commonly used treatments in primary and secondary care but the effect of these treatments in adolescents is unknown. We aimed to determine the effect of exercise therapy as an add-on therapy to patient education compared with education alone. METHODS: 121 adolescents from 15-19 years of age were cluster randomised to patient education or patient education combined with exercise therapy. Patient education covered self-management of pain and information on PFP. Exercise therapy consisted of supervised exercises on school premises (3/week for 3 months) and instructions on home-based exercises. Adherence to exercises was assessed as attendance and weekly text messages. Primary outcome measure was self-reported recovery (seven-point Likert scale) at 12 months with additional follow-ups at 3, 6 and 24 months. RESULTS: Adolescents randomised to patient education and exercise therapy were more likely to have recovered at 12 months (OR, 1.73, 95% CI 1.02 to 2.93, number needed to treat (NNT) of 11). Similar results were observed at 3 and 6 months (OR 1.88 and 1.43) while the effect was further increased at 24 months (OR of 2.52, NNT of 5). A higher total number of weekly exercise sessions increased the odds of recovery. CONCLUSIONS: In adolescent PFP, the addition of exercise therapy for 3 months was more effective than patient education alone. The effect was apparent at 3 months and increased up to 2 years. Adherence to exercises was important and improved the odds of recovery. TRIAL REGISTRATION NUMBER: clinicaltrials.gov reference: NCT01438762.

The influence of time-of-day variation and loading on the aponeurosis plantaris pedis: an ultrasonographic study.

AIM: The aim of this paper was to investigate the effect of time-of-day on the thickness of the the aponeurosis plantaris pedis, and to examine the acute effects of high-load strength training and long distance running on the thickness of the aponeurosis plantaris pedis. METHODS: Proximal aponeurosis plantaris pedis thickness was assessed with a 13-MHz linear-array transducer. In sub-study 1, ten participants (ten aponeurosis') were measured five times during 24 hours. In sub-study 2, ten participants (ten aponeurosis') were measured just before, immediately after and again three hours after 3x12 unilateral heel-rises. In sub-study 3, 11 healthy experienced runners (11 aponeurosis') were measured just before, immediately after and two hours after a 15km run. The average thickness of three scans of each foot was used in the analysis. The data was analysed using repeated measures one-way ANOVA. RESULTS: The mean thickness of the aponeurosis plantaris pedis' fluctuated significantly during the 24 hours (p=0,02), but it did not change in relation to the high-load strength training (p=0,86) or 15km of running (p = 0,70). CONCLUSION: High-load strength training and long distance running do not induce changes in the thickness of the aponeurosis plantaris pedis. Time-of-day influences the thickness of the aponeurosis plantaris pedis, but the changes are not larger than measurement uncertainty.

Effects of resistance training on endurance capacity and muscle fiber composition in young top-level cyclists.

Equivocal findings exist on the effect of concurrent strength (S) and endurance (E) training on endurance performance and muscle morphology. Further, the influence of concurrent SE training on muscle fiber-type composition, vascularization and endurance capacity remains unknown in top-level endurance athletes. The present study examined the effect of 16 weeks of concurrent SE training on maximal muscle strength (MVC), contractile rate of force development (RFD), muscle fiber morphology and composition, capillarization, aerobic power (VO2max), cycling economy (CE) and long/short-term endurance capacity in young elite competitive cyclists (n=14). MVC and RFD increased 12-20% with SE (P<0.01) but not E. VO2max remained unchanged. CE improved in E to reach values seen in SE. Short-term (5-min) endurance performance increased (3-4%) after SE and E (P<0.05), whereas 45-min endurance capacity increased (8%) with SE only (P<0.05). Type IIA fiber proportions increased and type IIX proportions decreased after SE training (P<0.05) with no change in E. Muscle fiber area and capillarization remained unchanged. In conclusion, concurrent strength/endurance training in young elite competitive cyclists led to an improved 45-min time-trial endurance capacity that was accompanied by an increased proportion of type IIA muscle fibers and gains in MVC and RFD, while capillarization remained unaffected.

Effect of unloading followed by reloading on expression of collagen and related growth factors in rat tendon and muscle.

Tendon tissue and the extracellular matrix of skeletal muscle respond to mechanical loading by increased collagen expression and synthesis. This response is likely a secondary effect of a mechanically induced expression of growth factors, including transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-I (IGF-I). It is not known whether unloading of tendon tissue can reduce the expression of collagen and collagen-inducing growth factors. Furthermore, the coordinated response of tendon and muscle tissue to disuse, followed by reloading, is unclear. Female Sprague-Dawley rats were subjected to hindlimb suspension (HS) for 7 or 14 days, followed by 2, 4, 8, or 16 days of reload (RL) (n = 8 in each group). Age-matched controls were included for day 0, day 14 HS, and day 16 RL (n = 8). mRNA expression levels for collagen I (COL1A1), collagen III (COL3A1), TGF-beta1, connective tissue growth factor (CTGF), myostatin, and IGF-I isoforms were measured by real-time RT-PCR in Achilles tendon and soleus muscle. The tendon mass was unchanged, while the muscle mass was reduced by 50% after HS (P < 0.05) and returned to control levels during RL. Collagen I and III, TGF-beta1, and CTGF mRNA levels were unaltered by HS, although collagen III tended to decrease in muscle at day 7 HS. IGF-I isoforms were significantly induced in tendon after 7 days of HS (P < 0.001), and mechanogrowth factor increased in muscle at day 14 HS (P < 0.05). Reload increased muscle collagen I and III mRNA (>10-fold) (P < 0.001) and growth factor expression (P < 0.05), while the tendon response was limited to a moderate induction of collagen expression (2-fold) (P < 0.05). Unloading of tendon and muscle tissue did not reduce expression of collagen and collagen-inducing growth factors, indicating that the response to unloading is not opposite that of loading. Furthermore, the tendon response was clearly different and less pronounced than the muscle tissue response.

Short-term strength training and the expression of myostatin and IGF-I isoforms in rat muscle and tendon: differential effects of specific contraction types.

In skeletal muscle, an increased expression of insulin like growth factor-I isoforms IGF-IEa and mechano-growth factor (MGF) combined with downregulation of myostatin is thought to be essential for training-induced hypertrophy. However, the specific effects of different contraction types on regulation of these factors in muscle are still unclear, and in tendon the functions of myostatin, IGF-IEa, and MGF in relation to training are unknown. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric, or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve during general anesthesia. mRNA levels for myostatin, IGF-IEa, and MGF in muscle and Achilles' tendon were measured by real-time RT-PCR. Muscle myostatin mRNA decreased in response to all types of training (2- to 8-fold) (P < 0.05), but the effect of eccentric training was greater than concentric and isometric training (P < 0.05). In tendon, myostatin mRNA was detected, but no changes were seen after exercise. IGF-IEa and MGF increased in muscle (up to 15-fold) and tendon (up to 4-fold) in response to training (P < 0.01). In tendon no difference was seen between training types, but in muscle the effect of eccentric training was greater than concentric training for both IGF-IEa and MGF (P < 0.05), and for IGF-IEa isometric training had greater effect than concentric (P < 0.05). The results indicate a possible role for IGF-IEa and MGF in adaptation of tendon to training, and the combined changes in myostatin and IGF-IEa/MGF expression could explain the important effect of eccentric actions for muscle hypertrophy.

Metabolic activity and collagen turnover in human tendon in response to physical activity.

Connective tissue of the human tendon plays an important role in force transmission. The extracellular matrix turnover of tendon is influenced by physical activity. Blood flow, oxygen demand, and the level of collagen synthesis and matrix metalloproteinases increase with mechanical loading. Gene transcription and especially post-translational modifications of proteins of the extracellular matrix are enhanced following exercise. Conversely, inactivity markedly decreases collagen turnover. Training leads to a chronically increased collagen turnover, and dependent on the type of collagen also to some degree of net collagen synthesis. These changes modify the biomechanical properties of the tissue (for example, viscoelastic characteristics) as well as the structural properties of the in collagen (for example, cross-sectional area). Mechanical loading of human tendon does result in a marked interstitial increase in growth factors that are known potentially to stimulate synthesis of collagen and other extracellular matrix proteins. Taken together, human tendon tissue mounts a vigorous acute and chronic response to mechanical loading in terms of metabolic-circulatory changes as well as of extracellular matrix formation. These changes may contribute to training-induced adaptation of biomechanical properties consisting of altered resistance to loading and enhanced tolerance to strenuous exercise. Understanding of such changes is a pre-requisite in the development of measures aimed at prevention of overuse tendon injuries occurring during sport, work or leisure-related activities.

Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue.

Microdialysis studies indicate that mechanical loading of human tendon tissue during exercise or training can affect local synthesis and degradation of type I collagen. Degradation of collagen and other extracellular matrix proteins is controlled by an interplay between matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). However, it is unknown whether local levels of MMPs and TIMPs are affected by tendon loading in humans in vivo. In the present experiment, six healthy young men performed 1 h of uphill (3%) treadmill running. Dialysate was collected from microdialysis probes (placed in the peritendinous tissue immediately anterior to the Achilles tendon) before, immediately after, 1 day after, and 3 days after an exercise bout. MMP-2 and MMP-9 were measured in dialysate by gelatin zymography, and amounts were quantified by densitometry in relation to total protein in the dialysate. TIMP-1 and TIMP-2 were analyzed by reverse gelatin zymography and semiquantitated visually. Pro-MMP-9 increased markedly after exercise and remained high for 3 days after exercise. Pro-MMP-2 dropped from the basal level immediately after exercise and remained low 1 day after exercise but was slightly elevated 3 days after exercise. The MMP-2 inhibitory activity of TIMP-1 was clearly elevated 1 and 3 days after exercise, and the MMP-2 inhibitory activity of TIMP-2 rose 1 day after loading. The present findings demonstrate enhanced interstitial amounts of MMPs and TIMPs after exercise in the human peritendinous tissue in vivo, and the magnitude and time pattern of these changes may well indicate that MMPs and TIMPs are playing a role in extracellular matrix adaptation to exercise in tendon tissue.

Non-linear analysis of the structure of variability in midfoot kinematics.

INTRODUCTION: Evaluation of structural variability in biological time series through measures such as sample entropy (SaEn) has provided important information in neurology and cardiology. This has contributed to the development of the "loss of complexity hypothesis" where high variability has been described as healthy flexibility and low variability associated with pathology. The purpose of this study was to calculate sample entropy (SaEn) to establish normal values of non-linear variability and to examine which factors are associated with SaEn in midfoot kinematics. METHOD: Static foot posture was measured using Foot Posture Index. A video sequence analysis system was used to quantify midfoot kinematics during walking in the sagittal plane. SaEn was calculated for navicular drop during stand phase as an expression of the dynamic complexity. RESULTS: A significant difference was observed between the three major foot types and between genders (p<0.001). Mean SaEn in women were 1.10+/-0.19 (supinated foot posture), 0.96+/-0.17 (neutral foot posture) and 0.77+/-0.16 (pronated foot posture) and 1.25+/-0.24 (supinated foot posture), 1.06+/-0.23 (neutral foot posture) and 0.86+/-0.19 (pronated foot posture) in males. The regression model showed that foot posture and dynamic navicular drop (dND) were both associated with SaEn. CONCLUSION: This study confirmed that non-linear analysis is of relevance in the interpretation of kinematic data. Pronated foot posture, large navicular drop and women were characterized by low values of non-linear variability. Future studies should investigate if measurements of SaEn are capable of identifying subjects with an increased risk of injury.

Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types.

Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle-tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-beta-1 (TGF-beta-1)), as well as enzymes related to collagen processing, are not clear. Furthermore, possible differential effects of specific contraction types on collagen regulation have not been investigated. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time PCR. In tendon, expression of TGF-beta-1 and collagens I and III (but not CTGF) increased in response to all types of training. Similarly, enzymes/factors involved in collagen processing were induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly greater than the effect of concentric training on the expression of several transcripts. In conclusion, the study supports an involvement of TGF-beta-1 in loading-induced collagen synthesis in the muscle-tendon unit and importantly, it indicates that muscle tissue is more sensitive than tendon to the specific mechanical stimulus.

Determination of markers for collagen type I turnover in peritendinous human tissue by microdialysis: effect of catheter types and insertion trauma.

OBJECTIVES: Previous results from our group have shown that loading of human tendon elevates tendinous type I collagen production measured by microdialysis. However, exclusion of the observed elevation as a response to trauma from inserting the microdialysis catheters or a possible influence from the collagen production in skin was not determined. METHODS: Using the microdialysis method we measured the tissue levels of type I collagen metabolism markers [procollagen I COOH-terminal propeptide (PICP) and COOH-terminal telopeptide of type I collagen (ICTP)] in peritendinous tissue of the Achilles tendon in volunteers at two time points, 0 and 72 h. Using two different catheter types, an investigation of the contribution from the skin in the collagen results obtained was also examined. RESULTS: The data showed no significant changes in the dialysate levels for PICP or ICTP (p>0.05) in either of the catheters. CONCLUSION: Inserting microdialysis fibres around the Achilles tendon twice does not increase the collagen type I metabolism determined 3 days after the initial trauma, and when using microdialysis for measuring peritendinous collagen turnover the skin contribution can be regarded as negligible. These findings support microdialysis as a valid method for the determination of collagen metabolism in peritendinous tissue.