Initial Tendon Retraction is Associated With Muscle Degeneration After Nonoperatively Treated Proximal Hamstring Avulsions

Initial Tendon Retraction is Associated With Muscle Degeneration After Nonoperatively Treated Proximal Hamstring Avulsions | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Initial Tendon Retraction is Associated With Muscle Degeneration After Nonoperatively Treated Proximal Hamstring Avulsions Sofia Laszlo, Anne-Mari Rosenlund, Elsa Pihl, Målfrid Holen Kristoffersen, and 6 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6386233/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract 1.1-Background and purpose Magnetic resonance imaging (MRI) is crucial for diagnosing proximal hamstring avulsions (PHA) by assessing tendon rupture and retraction, thereby guiding treatment decisions alongside clinical and patient data. However, the prognostic value of pre-treatment MRI for predicting muscle degeneration and clinical outcomes remains unclear. This study aimed to determine whether pre-treatment MRI findings—particularly tendon retraction—predict subsequent muscle degeneration and clinical outcomes in nonoperatively treated PHA patients. 1.2-Methods This study is a post hoc analysis of nonoperatively treated patients (n = 95) from the Proximal Hamstring Avulsion Clinical Trial (PHACT). Diagnostic MRIs were reassessed for tendon retraction, Wood classification, number of tendons avulsed, and hematoma size. The primary outcome was muscle degeneration, defined by the loss of lean muscle volume (LMV) and an increase in muscle fat fraction (MFF) quantified by DIXON MRI at 24 months. The secondary outcome was maximum hamstring muscle isometric force at 24 months. Outcome data was expressed as the limb symmetry index (LSI), which was the measurement of the injured hamstring expressed as a percentage of measurement of the uninjured hamstring. Linear regression was used to analyze the association between diagnostic MRI measurements, patient factors, and LSIs for LMV, MFF, and maximum isometric force. 1.3-Results The median LSIs of the LMV, MFF and maximum strength were 78%, 139%, and 84%, respectively, at 24-month follow-up. A multivariate linear regression model including tendon retraction, age, sex, hematoma size and whether the dominant limb was injured explained 48%, 48% and 23% of the variance in the LSIs of LMV, MFF and maximum force, respectively. Tendon retraction was the strongest explanatory factor for the variance of muscle degeneration observed in patients with nonoperatively treated PHA. 1.4-Interpretation Greater initial tendon retraction is associated with increased muscle atrophy and fat infiltration in the hamstring muscles in patients with nonoperatively treated PHA. ClinicalTrials.gov number, NCT03311997 Figures Figure 1 Figure 2 Figure 3 Key points Clinicians routinely rely on MRI findings, clinical examinations, and patient characteristics to guide treatment decisions and counsel patients; our study is the first to validate this integrated approach for predicting muscle degeneration in proximal hamstring avulsion injuries. Greater initial tendon retraction is significantly associated with increased muscle degeneration—including both muscle atrophy and fat infiltration—in nonoperatively treated proximal hamstring avulsions. A unified multivariate regression model including tendon retraction, BMI, sex, and whether the dominant limb was injured explained 48% of the variance in muscle degeneration outcomes, with tendon retraction emerging as the strongest independent predictor. Introduction Proximal hamstring avulsion (PHA) is a severe injury commonly associated with slip and fall incidents in daily activities and sports[ 1 – 3 ]. Magnetic Resonance Imaging (MRI) is the gold standard for the diagnosis of PHA[ 3 – 5 ]and for determining the number of avulsed tendons and degree of tendon retraction. In addition, edema, displacement of the sciatic nerve, and size of the hematoma is visualized. MRI findings, along with a clinical examination and patient characteristics, guide treatment decisions among clinicians[ 6 , 7 ]. Although the clinical significance of tendon retraction has not been thoroughly studied, retraction above 2 cm is typically considered to support surgical intervention[ 1 , 3 , 7 , 8 ]. Only one previous publication has explored the association of pre-treatment MRI findings with clinical outcomes after nonoperative treatment of PHA, finding a weak association between initial tendon retraction and patient outcomes[ 9 ]. Results from the only randomized controlled trial comparing operative and nonoperative treatment (PHACT)[ 10 ]demonstrated that nonoperative treatment is noninferior to operative treatment, as measured by patient-reported outcomes at 24-months. These results challenge the traditional preferences for operative treatment and are supported by recent cohort studies[ 11 – 13 ]. Data from PHACT indicate that some degree of hamstring muscle degeneration is inevitable. However, identifying patients at higher risk of excessive degeneration could help guide more individualized treatment decisions. The aim of this study was to assess whether diagnostic MRI findings at the time of injury are associated with muscle degeneration after 24 months in patients with acute PHA managed nonoperatively. Materials and methods 3.1-Trial design This is a post hoc analysis of nonoperatively treated individuals in PHACT[10]. PHACT was a multicenter, preference-tolerant, randomized controlled noninferiority trial carried out across ten hospitals in Sweden and Norway[10, 14]. Ethical approval was obtained from the Uppsala Regional Ethical Committee and the Regional Committee of Medical and Health Research Ethics in Norway. 3.2-Participants Patients, 30–70 years of age with a suspected PHA were screened for inclusion in PHACT[10]. Eligibility required an active lifestyle and MRI confirmation of an acute (within 4 weeks) proximal avulsion of at least two hamstring tendons. Exclusions encompassed patients with multiple injuries and an unacceptable surgical risk. Participants were randomly assigned to operative reattachment of the tendons or nonoperative treatment. In cases where either the patient or the surgeon exhibited a clear preference for a particular treatment, inclusion in an observational cohort was offered. Recruitment started October 2017 and concluded in July 2020. The current study focused on the nonoperatively treated patients within both the randomized trial and the observational cohort of PHACT, with a retrievable diagnostic MRI and 24-month follow-up. Patients with incomplete injuries and patients operated on prior to the follow-up MRI were excluded. Baseline data on age, sex, body mass index (BMI) and footedness were collected. The side of injury and footedness were combined into a single binary variable indicating if the dominant limb was injured. 3.3-Diagnostic MRI Patients underwent MRI scans following local clinical protocols at participating hospitals for diagnosing suspected hamstring avulsion injuries, in this study referred to as diagnostic MRIs. Imaging protocols varied, encompassing sequences such as proton-density (PD), PD fatsat, PD SPAIR (spectral attenuated inversion recovery), PD Dixon, T2 fatsat, T2 Dixon, STIR (short tau inversion recovery), TIRM (turbo inversion recovery magnitude), T2-weighted, and T1-weighted. The scans encompassed the origin of the hamstring muscles at the pelvis and extended through one or both thighs. The initial interpretation of the MRI images was conducted in accordance with local protocols. Diagnostic MRIs were independently re-evaluated by a musculoskeletal radiologist (Skorpil) and an orthopedic resident (Laszlo). Injuries were classified according to the Wood classification[1], and the number and identity of avulsed tendons were determined. Tendon retraction was measured using the method described by van der Made[15]. This involved identifying the center point of the proximal hamstring origin on the upper region of the ischial tuberosity on coronal images and measuring the shortest distance from this point to the most proximal part of the hypodense tendon stump. Hematoma size was quantified by examining all axial images to find the axial plane having the largest hematoma and then measuring the largest diameter. In cases of differing assessments between the two evaluators, the case was discussed until consensus was reached. 3.4-Outcome variables MRI AT 24-MONTH FOLLOW UP The primary outcome was muscle degeneration defined by the loss of lean muscle volume (LMV) and increase in muscle fat fraction (MFF) of the injured hamstrings in relation to the uninjured hamstrings, as measured on DIXON MRI at the 24-month follow-up. A detailed description of the MRI scan protocol and the subsequent analysis chain at AMRA (AMRA Medical, Linköping, Sweden), image processing, segmentation-methods, and quality control measures of the service have been previously published[10, 16–19]. In summary the hamstring muscles, including the semimembranosus, semitendinosus, and both the short and long heads of the biceps femoris, were fully segmented bilaterally. The total muscle volume (TMV), LMV and MFF of each individual muscle were calculated. The TMV was defined as the sum of all voxels included in a muscle segment, and MFF as the total volume of fat within the muscle segment divided by the total muscle volume. LMV was defined as TMV * (1-MFF). Strength measurements Maximum isometric force (Newton, N) was measured in both the injured and uninjured leg at 24 months. The patient was placed in supine position with the hip fixed on the examination table. A handheld isometric dynamometer (microFET 2, Hoggan health industries) was placed on a 15 cm block on the examination table. The heel of the tested leg was then placed on the dynamometer and the knee angle adjusted with a goniometer to approximately 15°. The patient was asked to perform a maximum contraction for 5 sec with the knee angle fixed at 15°. The maximum force, in Newtons (N), after three attempts was recorded. 3.5-Data Analysis Data were analyzed using RStudio version 2023.12.0 + 369. Independent variables included patient characteristics (age, sex, BMI, dominant limb injured) and MRI findings at the time of injury (tendon retraction, Wood classification and diameter of the hematoma). Dependent variables were limb symmetry indices (LSIs) of LMV, MFF, and maximum force in the injured hamstring at 24 months. Values for the injured leg were divided by those of the uninjured hamstring and multiplied by 100 to calculate LSI. The LSI was assumed to represent the change in muscle quality and function induced by the injury. Bivariate correlations were calculated using Pearson’s correlation coefficient to assess relationships between various continuous variables. Correlation strength was categorized as follows: <0.1 (negligible), ≥ 0.1 to < 0.4 (weak), ≥ 0.4 to < 0.7(moderate), and ≥ 0.7 (strong)[20]. The association between baseline MRI findings and patient characteristics with outcomes of muscle degeneration and function was assessed using both univariate and multivariate linear regression analyses. Univariate linear regression analyses were first performed to assess the association between baseline MRI characteristics and patient factors with each outcome variable. For multivariate analysis, candidate models were generated using the Leaps R package, which systematically evaluated all possible subsets of predictor variables to identify models that optimized adjusted R². Based on this selection process, a unified linear regression model was constructed—including age, sex, BMI, injured dominant side, tendon retraction, and hematoma size—to examine their collective association with limb symmetry indices (LSIs) for LMV, MFF, and maximum muscle force. Model performance was quantified using the adjusted R², Akaike Information Criterion (AIC), and Root Mean Square Error (RMSE). Predictor variables with p-values < 0.05 were considered statistically significant. In addition, the relative importance of each predictor was assessed using the varImp function from the caret R package, which yielded results identical to ranking predictors by the absolute value of their t-statistics. Prior to modeling, missing data for the independent variables were imputed as follows: three missing BMI values were replaced with the cohort median BMI, one missing footedness value (used to determine the injured dominant side) was imputed as “injury to the dominant side”, and one missing muscle force measurement was replaced with the cohort’s median value. Results 4.1-Patients In PHACT, 118 out of 222 available patients received nonoperative treatment. Following exclusions due to incomplete follow-ups and other reasons, 95 patients remained for analysis (Fig. 1, Table 1). The median age was 53.9 years (range: 30 to 70, interquartile range [IQR]: 49 to 58) and 67% were female. Most cases were classified as Wood type 5 (complete injury with tendon retraction) (n = 87), with 8 cases classified as Wood type 4 (complete injury without retraction). The median tendon retraction was 4 cm, with an IQR of 2.5 to 6 cm. The median diameter of the hematoma was 4 cm (IQR: 2.5 to 6, [Table 1]). Table 1 Baseline characteristics Characteristic N = 95 1 Age (years) 54 (49, 58) Body Mass Index (kg/m^2) 25.9 (23.4, 28.4) Unknown 3 Retraction (cm) 4.0 (2.5, 6.0) Hematoma Size (cm) 4.0 (2.50 6.0) Sex female 64 (67%) male 31 (33%) Dominant leg injured 56 (60%) Unknown 1 Wood type (1–5) 4 8 (8.4%) 5 87 (92%) 1 Median (IQR); n (%) T able 1. Pretreatment characteristics of the study population. Data are presented with Median ± Inter Quartile Range (IQR) for continuous data, and with count and percentages for categorical data. Wood is the classification of injury according to Wood et al.[1] 4.2-MRI outcomes and maximum muscle force at 24 months Hamstring muscle degeneration and loss of strength were evident in the injured compared to the uninjured hamstrings at 24-month follow-up. The median LSI of the LMV was 78% (IQR: 67–87%). The median LSI of the MFF was 139% (IQR: 125–167%) and the median LSI of maximum muscle force was 84% (IQR: 75–94%, [Table 2]). Table 2 Outcome measures Muscle Quality N Uninjured Limb Injured Limb Limb Symmetry Index Lean Muscle Volume (L) 95 0.56 (0.49, 0.71) 0.44 (0.35, 0.57) 78.3 (67.2, 87.1) Muscle Fat Fraction 95 0.16 (0.13, 0.19) 0.22 (0.16, 0.29) 139.4 (124.5, 166.8) Maximum Muscle Force (N) 94 176.1 (140.1, 222.5) 142.0 (121.3, 179.7) 84.0 (75.4, 94.0) T able 2. MRI muscle quality outcome measurements and muscle maximum force of the study population. Limb Symmetry index was calculated: value of injured limb/ value of uninjured limb *100. Data are presented with Median ± Inter Quartile Range Table 3. Pairwise Correlations Variable 1 Variable 2 Correlation (95% CI) Lean Muscle Volume, uninjured side Maximum Muscle Force, uninjured side 0.78 (0.69, 0.85) Lean Muscle Volume, injured side Maximum Muscle Force, injured side 0.67 (0.54, 0.77) Muscle Fat Fraction, uninjured side Maximum Muscle Force, uninjured side -0.36 (-0.53, -0.17) Muscle Fat Fraction, injured side Maximum Muscle Force, injured side -0.34 (-0.51, -0.15) Lean Muscle Volume (LSI) Maximum Muscle Force (LSI) 0.54 (0.38, 0.67) Muscle Fat Fraction (LSI) Maximum Muscle Force (LSI) -0.47 (-0.62, -0.30) Age Lean Muscle Volume (LSI) -0.23 (-0.41, -0.03) BMI Lean Muscle Volume (LSI) -0.38 (-0.54, -0.19) Retraction Lean Muscle Volume (LSI) -0.56 (-0.69, -0.41) Age Muscle Fat Fraction (LSI) 0.21 (0.00, 0.39) BMI Muscle Fat Fraction (LSI) 0.44 (0.26, 0.59) Retraction Muscle Fat Fraction (LSI) 0.60 (0.45, 0.72) Age Maximum Muscle Force (LSI) -0.09 (-0.29, 0.11) BMI Maximum Muscle Force (LSI) -0.34 (-0.51, -0.14) Retraction Maximum Muscle Force (LSI) -0.35 (-0.51, -0.15) T able 3: Pairwise correlations of MRI muscle quality outcome measurements, pretreatment tendon retraction, patient age, Body Mass Index (BMI) and tendon retraction. First section shows correlations between MRI muscle quality outcome measurements and maximum muscle force of the uninjured and injured limb, respectively. Second section shows correlations between Limb Symmetry Indices (LSI) of MRI muscle quality outcome measurements and the LSI of Maximum Muscle Force. LSI was calculated: value of injured limb/ value of uninjured limb *100. The third section shows correlations of pretreatment characteristics and LSI of MRI muscle quality outcome measurements and maximum muscle force. Statistically significant correlations are highlighted by bold characters. 4.3-Bivariate correlations There were strong correlations between the absolute lean muscle volume and maximum muscle force at the 24-months follow-up (Table 3). This correlation was slightly stronger in the uninjured leg compared to the injured leg (Pearson correlation: r = 0.78 vs. 0.67). The loss of LMV, as measured by the limb symmetry index, showed a strong inverse correlation with an increase in muscle fat fraction (r = -0.86; data not in table). The loss of LMV and increase in MFF were moderately correlated with the loss of strength (r = 0.54 and − 0.47). Weaker but statistically significant correlations were seen between tendon retraction, patient age, BMI, and muscle degeneration. The correlations were even weaker when tendon retraction, BMI, and age were correlated to loss of maximum muscle force at 24 months (Table 3). Among the pretreatment factors, tendon retraction showed the strongest correlation to muscle degeneration and muscle strength. 4.4-Linear regression modelling Univariate linear regression using patient and pretreatment MRI data as independent variables and the loss of lean muscle volume as the dependent variable revealed statistically significant associations for several variables (Table S1). Similar results were observed when the dependent variables were increase in muscle fat fraction and loss of maximum muscle force. Among these, tendon retraction had the strongest explanatory value for both the loss of lean muscle volume and the increase in muscle fat fraction. However, for muscle force, BMI, hematoma size, and tendon retraction showed similar explanatory strength in their individual associations (Table S1). Multiple linear regression evaluated the association of pretreatment MRI data and patient factors with the outcomes; muscle degeneration and muscle force. A single, unified model—including age, BMI, sex, tendon retraction, hematoma size, and whether the dominant leg was injured—was applied to all outcomes (Table S2). This model explained 48% of the variance in the loss of LMV, 48% of the variance of the increase in muscle fat fraction, and 23% of the variance in the loss of muscle force (adjusted R-squared values: 0.48, 0.48, and 0.23, respectively; Fig. 2 and Table 4). Performance metrics (Table S3) indicate that the unified model performed best for lean muscle volume, as evidenced by the lowest Akaike Information Criterion (AIC) value. Although the model achieved a similar adjusted R² for muscle fat fraction, the substantially higher Root Mean Square Error (RMSE) for that outcome suggests larger absolute prediction errors. In contrast, for maximum muscle force, the model explained less variance but yielded a relatively low RMSE, indicating more precise predictions in absolute terms. Table 4 Multiple Linear Regression with Caret Rankings Term Estimate (95% CI) t - Statistic Rank LSI- Lean Muscle Volume: Adjusted R – squared = 0.48 Tendon Retraction -2.73 (-3.84, -1.62) -4.89 1 Body Mass Index -1 (-1.63, -0.38) -3.18 2 Age -0.38 (-0.66, -0.11) -2.76 3 Dominant Side Injured (Yes) 5.92 (1.19, 10.65) 2.49 4 Sex (Male) 5.76 (0.82, 10.69) 2.32 5 Hematoma Size -1.49 (-2.78, -0.2) -2.29 6 LSI-Muscle Fat Fraction: Adjusted R – squared = 0.48 Tendon Retraction 7.46 (4.57, 10.35) 5.14 1 Body Mass Index 2.9 (1.27, 4.53) 3.54 2 Age 0.86 (0.14, 1.58) 2.38 3 Dominant Side Injured (Yes) -7.1 (-19.41, 5.21) -1.15 5 Sex (Male) 0.01 (-12.83, 12.85) 0.00 6 Hematoma Size 3.14 (-0.22, 6.51) 1.86 4 LSI- Maximum Force: Adjusted R – squared = 0.23 Tendon Retraction -1.25 (-2.7, 0.2) -1.72 3 Body Mass Index -0.98 (-1.8, -0.16) -2.38 1 Age -0.19 (-0.55, 0.17) -1.04 5 Dominant Side Injured (Yes) 5.31 (-0.86, 11.49) 1.71 4 Sex (Male) -1.42 (-7.87, 5.02) -0.44 6 Hematoma Size -1.96 (-3.64, -0.27) -2.30 2 T able 4. Multiple linear regression modelling of the effect of initial tendon retraction and covariates on the injury induced loss of lean muscle volume, muscle fat fraction and maximum muscle force. LSI is Limb Symmetry Index and was calculated: value of injured limb/ value of uninjured limb *100. Rank is the order of highest contribution of the independent variable to the overall performance of the model and was calculated using the varImp function in the R caret library. Diagnostic tests confirmed that the model met the assumptions of linear regression. The Durbin-Watson test showed no significant autocorrelation, the Breusch-Pagan test supported homoscedasticity, and the Shapiro-Wilk test indicated that the residuals were normally distributed. Furthermore, multicollinearity was minimal (Variance Inflation Factor: 1.01–1.37; Table S4). Tendon retraction emerged as the strongest predictor of muscle degeneration, particularly for lean muscle volume and muscle fat fraction. In contrast, for the loss of maximum muscle force, BMI, hematoma size, and whether the dominant leg was injured contributed to a similar extent as tendon retraction. To illustrate these findings, Fig. 3 shows the marginal effect of initial tendon retraction (grouped into intervals commonly used in clinical practice) on muscle degeneration and maximum muscle force. Discussion Our findings demonstrate that initial tendon retraction is associated with muscle degeneration in patients with nonoperatively treated proximal hamstring avulsions (PHA). Multiple linear regression analyses showed that greater tendon retraction is significantly linked to lean muscle atrophy and increased fat infiltration. However, muscle degeneration was observed even at minimal retraction levels (< 2 cm), indicating that while retraction magnitude is predictive, lower degrees of retraction do not preclude degenerative changes. These results highlight the predictive value of pretreatment MRI assessments, which surgeons already use as a key factor in treatment decisions. As expected, we observed a strong correlation between lean muscle volume and muscle strength. However, the relationship between muscle degeneration and the loss of maximum isometric force was only moderate. In our multiple regression model, tendon retraction was not a significant predictor of maximum muscle force, suggesting that other factors influence strength loss. One possible explanation is compensatory activation of other muscles, which may vary among patients depending on rehabilitation intensity. Additionally, the method used to measure muscle force was not optimal. Handheld dynamometers present challenges in isolating hamstring power, and the absence of an isokinetic computerized dynamometer may have limited measurement precision. Among the other covariates investigated, body mass index was the strongest predictor of muscle degeneration in PHA and the most significant contributor to loss of maximum muscle force. This may reflect both biological factors and the reduced rehabilitative capacity of less fit patients. Age showed a similar trend, with older individuals at the time of injury experiencing more severe muscle degeneration. Interestingly, hematoma size on the initial MRI independently predicted both muscle degeneration and strength loss, even though it was moderately correlated with tendon retraction (r = 0.48). This suggests that the effect of hematoma size is not merely a surrogate for injury severity as reflected by tendon retraction. One possible explanation is that extensive bleeding may be associated with local nerve injury, which could further impair muscle function. Our previous randomized controlled trial (PHACT)[ 10 ]demonstrated a modest but significant protective effect of surgical reattachment on muscle degeneration. However, subgroup analysis did not show that surgery provided greater benefit for patients with more pronounced retraction when assessed by the PHAT score. Taken together, the current findings and PHACT data suggest that while tendon retraction strongly influences muscle degeneration, its impact on functional and patient-perceived outcomes is less straightforward. 5.2-Limitations of study Aside from the points mentioned above, our study has several limitations. The limited number of participants made it impractical to subset the data for model training and evaluation, potentially affecting the robustness and generalizability of our predictive models. Additionally, the patient population consisted of both patients randomized to nonoperative treatment and a parallel cohort of prospectively followed patients who actively chose nonoperative treatment. While females were generally overrepresented in PHACT, this imbalance was even greater in the current study due to a higher proportion of female patients in the parallel cohort opting for nonoperative treatment. Ideally, to maximize external validity, nonoperative treatment would be studied in a setting where all patients, regardless of sex, had no option but to be treated nonoperatively. However, sex was included in the predictive model to control for gender-related differences in muscle degeneration. 5.3-Strengths of study The prospective design and the relatively large cohort of nonoperatively treated patients enhance the reliability of our data, while the use of the DIXON MRI technique allowed for precise quantification of muscle degeneration and fat infiltration. These aspects contribute to a better understanding of the natural progression of muscle changes following PHA without surgical intervention. Conclusions In conclusion, initial tendon retraction is a crucial factor in determining the degree of muscle degeneration after nonoperatively treated proximal hamstring avulsions. While greater retraction is significantly associated with increased muscle atrophy and fat infiltration, its impact on functional outcomes and patient-reported measures appears to be limited. These insights underscore the importance of integrating detailed pretreatment MRI assessments and patient-specific characteristics into the decision-making process for managing PHA. Abbreviations MRI- Magnetic resonance imaging PHA- Proximal hamstrings avulsion PHACT- The proximal hamstring avulsion clinical trial LMV- Lean muscle volume MFF- Muscle fat fraction TMV- Total muscle volume LSI- Limb symmetry index PD- Proton density SPAIR- Spectral attenuated inversion recovery STIR- Short tau inversion recovery TIRM- turbo inversion recovery magnitude BMI- Body mass index RSME- Root Mean Square Error AIC- Akaike Information Criterion IQR- Inter quartile range Declarations Ethics Approval and Consent to Participate The study was approved by the Uppsala Regional Ethical Committee and the Regional Committee of Medical and Health Research Ethics in Norway. Informed consent was obtained from all participants Consent for publication Not applicable Data Availability The data and the analysis code that support the findings of this study are available from the corresponding author, upon reasonable request. Competing interests The authors declare that they have no competing interests. Funding Afa Försäkring was the main sponsor of the trial but had no role in protocol development, data analysis or manuscript preparation. Author Contributions All authors contributed to the planning and design of the study, as well as to patient recruitment and data collection. The first (SL) and last authors (KJ) performed the initial statistical analysis. All authors participated in drafting and critically revising the manuscript and approved the final version for submission. Acknowledgements Not applicable References Wood DG, Packham I, Trikha SP, Linklater J. Avulsion of the Proximal Hamstring Origin. J Bone Jt Surg. 2008;90:2365–74. Irger M, Willinger L, Lacheta L, Pogorzelski J, Imhoff AB, Feucht MJ. Proximal hamstring tendon avulsion injuries occur predominately in middle‐aged patients with distinct gender differences: epidemiologic analysis of 263 surgically treated cases. 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Karlsson A, Rosander J, Romu T, Tallberg J, Grönqvist A, Borga M, et al. Automatic and quantitative assessment of regional muscle volume by multi‐atlas segmentation using whole‐body water–fat MRI. J Magn Reson Imaging. 2015;41:1558–69. Schober P, Boer C, Schwarte LA. Correlation Coefficients. Anesthesia Analg. 2018;126:1763–8. Supplementary Files Appendix.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major Revision 07 Oct, 2025 Reviewers agreed at journal 17 Jul, 2025 Reviewers invited by journal 15 Jul, 2025 Editor assigned by journal 09 Apr, 2025 First submitted to journal 08 Apr, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6386233","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":486033377,"identity":"8e760ed9-b86e-4a1a-8d38-3f8fc50a428e","order_by":0,"name":"Sofia Laszlo","email":"","orcid":"","institution":"Uppsala University","correspondingAuthor":false,"prefix":"","firstName":"Sofia","middleName":"","lastName":"Laszlo","suffix":""},{"id":486033378,"identity":"67a6b0e0-085d-474d-9c49-f21fb51f4d3e","order_by":1,"name":"Anne-Mari Rosenlund","email":"","orcid":"","institution":"University of Oslo","correspondingAuthor":false,"prefix":"","firstName":"Anne-Mari","middleName":"","lastName":"Rosenlund","suffix":""},{"id":486033379,"identity":"f5611e1c-0d86-4009-9751-8fb7e6cad22d","order_by":2,"name":"Elsa Pihl","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Elsa","middleName":"","lastName":"Pihl","suffix":""},{"id":486033380,"identity":"6fbb8df9-ebb2-4d5e-b9c0-4eb80e81a477","order_by":3,"name":"Målfrid Holen Kristoffersen","email":"","orcid":"","institution":"University of Bergen","correspondingAuthor":false,"prefix":"","firstName":"Målfrid","middleName":"Holen","lastName":"Kristoffersen","suffix":""},{"id":486033381,"identity":"3986bcac-cee1-457c-a30a-474b6a09a38d","order_by":4,"name":"Olof Sköldenberg","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Olof","middleName":"","lastName":"Sköldenberg","suffix":""},{"id":486033382,"identity":"74dda545-75ed-4a52-8737-8b65e678e8d3","order_by":5,"name":"Jörg Schilcher","email":"","orcid":"","institution":"Linköping University","correspondingAuthor":false,"prefix":"","firstName":"Jörg","middleName":"","lastName":"Schilcher","suffix":""},{"id":486033383,"identity":"8e182635-ebb3-414f-a783-28bbbd8794a6","order_by":6,"name":"Martin Eklund","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Martin","middleName":"","lastName":"Eklund","suffix":""},{"id":486033384,"identity":"bc8d6833-8308-4956-8c94-b81523c129c8","order_by":7,"name":"Frede Frihagen","email":"","orcid":"","institution":"University of Oslo","correspondingAuthor":false,"prefix":"","firstName":"Frede","middleName":"","lastName":"Frihagen","suffix":""},{"id":486033385,"identity":"5936d744-d162-4c42-a1dc-a0383036af89","order_by":8,"name":"Mikael Skorpil","email":"","orcid":"","institution":"Karolinska Institutet","correspondingAuthor":false,"prefix":"","firstName":"Mikael","middleName":"","lastName":"Skorpil","suffix":""},{"id":486033386,"identity":"489eb1d9-9402-4c61-b012-af54e3829b2e","order_by":9,"name":"Kenneth Jonsson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA50lEQVRIie3QPQrCMBiA4YSCU3ROCbRXsBQyeZiIYJe6O3Zql7jXW3gE4QO7BGcHB12cHFpcKjgYrD84GDsK5l2SIQ/5EoRsth+MNssS4aTZeS2JeJGwPXk0TL4RN5utdlW9RU42g6qebqPFRjhlaSCMrKMgFweE5XrMiDpMNOm4uYF4NOaMCEA4j7mDU7gRh5iIf+Ts0pCwOqcQ9fVgp4tpMEo4Qw3p024KQhPEjM+XMXflGAiWSk+oIJirfepKA6GF4rQegBdkMtQ/Bn6vGEFZm665R4LkucfJx2Nv+e2O2Ww22z92Bc5ST5G4e/E/AAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-2268-8008","institution":"Uppsala University","correspondingAuthor":true,"prefix":"","firstName":"Kenneth","middleName":"","lastName":"Jonsson","suffix":""}],"badges":[],"createdAt":"2025-04-06 10:54:49","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6386233/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6386233/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87360345,"identity":"7b40cda6-48c1-4f85-be20-54c7236ad054","added_by":"auto","created_at":"2025-07-23 05:46:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":125021,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flowchart. PHACT is the proximal hamstring avulsion clinical trial. Incomplete follow-ups were missing MRIs at 2 years. Delayed surgery were patients initially treated nonoperatively but operated on before the follow-up MRI.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6386233/v1/8ce6772f53842cdb02702a1b.png"},{"id":87360348,"identity":"57bdb7ac-f92b-4b3a-aa04-27c05eb39a46","added_by":"auto","created_at":"2025-07-23 05:46:37","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":275848,"visible":true,"origin":"","legend":"\u003cp\u003ePerformance of the multiple regression model across three outcomes.\u003cstrong\u003e \u003c/strong\u003eThe scatter plots depict the observed values against the predicted values for the three dependent variables: loss of lean muscle volume, increase in muscle fat fraction, and loss of maximum muscle force. The independent variables in the model were age, sex, tendon retraction, Body Mass Index (BMI), whether the dominant limb was injured, and hematoma size. The adjusted R² values (0.48 for lean muscle volume and muscle fat fraction, and 0.23 for muscle force) indicate the proportion of variance explained by the model for each outcome.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6386233/v1/b72b27aa82c338d78f5c0ad7.png"},{"id":87360346,"identity":"798f9cad-e10a-41d2-b59b-2b161559d77f","added_by":"auto","created_at":"2025-07-23 05:46:37","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":195536,"visible":true,"origin":"","legend":"\u003cp\u003eThe mean marginal effect of tendon retraction in increments of 2 cm on predicted outcomes: lean muscle volume (black bars), muscle fat fraction (dark grey bars), and maximum muscle force (light grey bars). Error bars represent the 95% confidence intervals. Data are adjusted for age, gender, BMI, dominant side, and hematoma size. An LSI value of 100% indicates no difference between the injured and uninjured hamstring.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6386233/v1/f98858513ea8c86e5dab9b15.png"},{"id":87364081,"identity":"5118840f-a5da-43be-a115-4b34d41e0d3a","added_by":"auto","created_at":"2025-07-23 06:10:37","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1498543,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6386233/v1/0151ab5b-c762-4d82-a083-8356103e3a5d.pdf"},{"id":87362150,"identity":"6271e289-9af8-4f5b-976a-7d00742932c4","added_by":"auto","created_at":"2025-07-23 05:54:37","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":28314,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-6386233/v1/717c3ed76eb9948f44ca1bd6.docx"}],"financialInterests":"","formattedTitle":"\u003cp\u003eInitial Tendon Retraction is Associated With Muscle Degeneration After Nonoperatively Treated Proximal Hamstring Avulsions\u003c/p\u003e","fulltext":[{"header":"Key points","content":"\u003cul\u003e\n \u003cli\u003eClinicians routinely rely on MRI findings, clinical examinations, and patient characteristics to guide treatment decisions and counsel patients; our study is the first to validate this integrated approach for predicting muscle degeneration in proximal hamstring avulsion injuries.\u003c/li\u003e\n \u003cli\u003eGreater initial tendon retraction is significantly associated with increased muscle degeneration\u0026mdash;including both muscle atrophy and fat infiltration\u0026mdash;in nonoperatively treated proximal hamstring avulsions.\u003c/li\u003e\n \u003cli\u003eA unified multivariate regression model including tendon retraction, BMI, sex, and whether the dominant limb was injured explained 48% of the variance in muscle degeneration outcomes, with tendon retraction emerging as the strongest independent predictor.\u003c/li\u003e\n\u003c/ul\u003e\n"},{"header":"Introduction","content":"\u003cp\u003eProximal hamstring avulsion (PHA) is a severe injury commonly associated with slip and fall incidents in daily activities and sports[\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Magnetic Resonance Imaging (MRI) is the gold standard for the diagnosis of PHA[\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]and for determining the number of avulsed tendons and degree of tendon retraction. In addition, edema, displacement of the sciatic nerve, and size of the hematoma is visualized. MRI findings, along with a clinical examination and patient characteristics, guide treatment decisions among clinicians[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Although the clinical significance of tendon retraction has not been thoroughly studied, retraction above 2 cm is typically considered to support surgical intervention[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Only one previous publication has explored the association of pre-treatment MRI findings with clinical outcomes after nonoperative treatment of PHA, finding a weak association between initial tendon retraction and patient outcomes[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eResults from the only randomized controlled trial comparing operative and nonoperative treatment (PHACT)[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]demonstrated that nonoperative treatment is noninferior to operative treatment, as measured by patient-reported outcomes at 24-months. These results challenge the traditional preferences for operative treatment and are supported by recent cohort studies[\u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Data from PHACT indicate that some degree of hamstring muscle degeneration is inevitable. However, identifying patients at higher risk of excessive degeneration could help guide more individualized treatment decisions.\u003c/p\u003e\u003cp\u003eThe aim of this study was to assess whether diagnostic MRI findings at the time of injury are associated with muscle degeneration after 24 months in patients with acute PHA managed nonoperatively.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003ch2\u003e3.1-Trial design\u003c/h2\u003e\n\u003cp\u003eThis is a post hoc analysis of nonoperatively treated individuals in PHACT[10]. PHACT was a multicenter, preference-tolerant, randomized controlled noninferiority trial carried out across ten hospitals in Sweden and Norway[10, 14]. Ethical approval was obtained from the Uppsala Regional Ethical Committee and the Regional Committee of Medical and Health Research Ethics in Norway.\u003c/p\u003e\n\u003ch2\u003e3.2-Participants\u003c/h2\u003e\n\u003cp\u003ePatients, 30\u0026ndash;70 years of age with a suspected PHA were screened for inclusion in PHACT[10]. Eligibility required an active lifestyle and MRI confirmation of an acute (within 4 weeks) proximal avulsion of at least two hamstring tendons. Exclusions encompassed patients with multiple injuries and an unacceptable surgical risk. Participants were randomly assigned to operative reattachment of the tendons or nonoperative treatment. In cases where either the patient or the surgeon exhibited a clear preference for a particular treatment, inclusion in an observational cohort was offered. Recruitment started October 2017 and concluded in July 2020. The current study focused on the nonoperatively treated patients within both the randomized trial and the observational cohort of PHACT, with a retrievable diagnostic MRI and 24-month follow-up. Patients with incomplete injuries and patients operated on prior to the follow-up MRI were excluded. Baseline data on age, sex, body mass index (BMI) and footedness were collected. The side of injury and footedness were combined into a single binary variable indicating if the dominant limb was injured.\u003c/p\u003e\n\u003ch2\u003e3.3-Diagnostic MRI\u003c/h2\u003e\n\u003cp\u003ePatients underwent MRI scans following local clinical protocols at participating hospitals for diagnosing suspected hamstring avulsion injuries, in this study referred to as diagnostic MRIs. Imaging protocols varied, encompassing sequences such as proton-density (PD), PD fatsat, PD SPAIR (spectral attenuated inversion recovery), PD Dixon, T2 fatsat, T2 Dixon, STIR (short tau inversion recovery), TIRM (turbo inversion recovery magnitude), T2-weighted, and T1-weighted. The scans encompassed the origin of the hamstring muscles at the pelvis and extended through one or both thighs. The initial interpretation of the MRI images was conducted in accordance with local protocols.\u003c/p\u003e\n\u003cp\u003eDiagnostic MRIs were independently re-evaluated by a musculoskeletal radiologist (Skorpil) and an orthopedic resident (Laszlo). Injuries were classified according to the Wood classification[1], and the number and identity of avulsed tendons were determined. Tendon retraction was measured using the method described by van der Made[15]. This involved identifying the center point of the proximal hamstring origin on the upper region of the ischial tuberosity on coronal images and measuring the shortest distance from this point to the most proximal part of the hypodense tendon stump. Hematoma size was quantified by examining all axial images to find the axial plane having the largest hematoma and then measuring the largest diameter. In cases of differing assessments between the two evaluators, the case was discussed until consensus was reached.\u003c/p\u003e\n\u003ch2\u003e3.4-Outcome variables\u003c/h2\u003e\n\u003cp\u003eMRI AT 24-MONTH FOLLOW UP\u003c/p\u003e\n\u003cp\u003eThe primary outcome was muscle degeneration defined by the loss of lean muscle volume (LMV) and increase in muscle fat fraction (MFF) of the injured hamstrings in relation to the uninjured hamstrings, as measured on DIXON MRI at the 24-month follow-up. A detailed description of the MRI scan protocol and the subsequent analysis chain at AMRA (AMRA Medical, Link\u0026ouml;ping, Sweden), image processing, segmentation-methods, and quality control measures of the service have been previously published[10, 16\u0026ndash;19]. In summary the hamstring muscles, including the semimembranosus, semitendinosus, and both the short and long heads of the biceps femoris, were fully segmented bilaterally. The total muscle volume (TMV), LMV and MFF of each individual muscle were calculated. The TMV was defined as the sum of all voxels included in a muscle segment, and MFF as the total volume of fat within the muscle segment divided by the total muscle volume. LMV was defined as TMV * (1-MFF).\u003c/p\u003e\n\u003cp\u003eStrength measurements\u003c/p\u003e\n\u003cp\u003eMaximum isometric force (Newton, N) was measured in both the injured and uninjured leg at 24 months. The patient was placed in supine position with the hip fixed on the examination table. A handheld isometric dynamometer (microFET 2, Hoggan health industries) was placed on a 15 cm block on the examination table. The heel of the tested leg was then placed on the dynamometer and the knee angle adjusted with a goniometer to approximately 15\u0026deg;. The patient was asked to perform a maximum contraction for 5 sec with the knee angle fixed at 15\u0026deg;. The maximum force, in Newtons (N), after three attempts was recorded.\u003c/p\u003e\n\u003ch2\u003e3.5-Data Analysis\u003c/h2\u003e\n\u003cp\u003eData were analyzed using RStudio version 2023.12.0\u0026thinsp;+\u0026thinsp;369. Independent variables included patient characteristics (age, sex, BMI, dominant limb injured) and MRI findings at the time of injury (tendon retraction, Wood classification and diameter of the hematoma). Dependent variables were limb symmetry indices (LSIs) of LMV, MFF, and maximum force in the injured hamstring at 24 months. Values for the injured leg were divided by those of the uninjured hamstring and multiplied by 100 to calculate LSI. The LSI was assumed to represent the change in muscle quality and function induced by the injury.\u003c/p\u003e\n\u003cp\u003eBivariate correlations were calculated using Pearson\u0026rsquo;s correlation coefficient to assess relationships between various continuous variables. Correlation strength was categorized as follows: \u0026lt;0.1 (negligible), \u0026ge; 0.1 to \u0026lt;\u0026thinsp;0.4 (weak), \u0026ge;\u0026thinsp;0.4 to \u0026lt;\u0026thinsp;0.7(moderate), and \u0026ge;\u0026thinsp;0.7 (strong)[20].\u003c/p\u003e\n\u003cp\u003eThe association between baseline MRI findings and patient characteristics with outcomes of muscle degeneration and function was assessed using both univariate and multivariate linear regression analyses. Univariate linear regression analyses were first performed to assess the association between baseline MRI characteristics and patient factors with each outcome variable. For multivariate analysis, candidate models were generated using the Leaps R package, which systematically evaluated all possible subsets of predictor variables to identify models that optimized adjusted R\u0026sup2;. Based on this selection process, a unified linear regression model was constructed\u0026mdash;including age, sex, BMI, injured dominant side, tendon retraction, and hematoma size\u0026mdash;to examine their collective association with limb symmetry indices (LSIs) for LMV, MFF, and maximum muscle force.\u003c/p\u003e\n\u003cp\u003eModel performance was quantified using the adjusted R\u0026sup2;, Akaike Information Criterion (AIC), and Root Mean Square Error (RMSE). Predictor variables with p-values\u0026thinsp;\u0026lt;\u0026thinsp;0.05 were considered statistically significant. In addition, the relative importance of each predictor was assessed using the varImp function from the caret R package, which yielded results identical to ranking predictors by the absolute value of their t-statistics.\u003c/p\u003e\n\u003cp\u003ePrior to modeling, missing data for the independent variables were imputed as follows: three missing BMI values were replaced with the cohort median BMI, one missing footedness value (used to determine the injured dominant side) was imputed as \u0026ldquo;injury to the dominant side\u0026rdquo;, and one missing muscle force measurement was replaced with the cohort\u0026rsquo;s median value.\u003c/p\u003e"},{"header":"Results","content":"\u003ch2\u003e4.1-Patients\u003c/h2\u003e\n\u003cp\u003eIn PHACT, 118 out of 222 available patients received nonoperative treatment. Following exclusions due to incomplete follow-ups and other reasons, 95 patients remained for analysis (Fig. 1, Table 1). The median age was 53.9 years (range: 30 to 70, interquartile range [IQR]: 49 to 58) and 67% were female. Most cases were classified as Wood type 5 (complete injury with tendon retraction) (n\u0026thinsp;=\u0026thinsp;87), with 8 cases classified as Wood type 4 (complete injury without retraction). The median tendon retraction was 4 cm, with an IQR of 2.5 to 6 cm. The median diameter of the hematoma was 4 cm (IQR: 2.5 to 6, [Table 1]).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 1\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eBaseline characteristics\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;95\u003csup\u003e1\u003c/sup\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e54 (49, 58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index (kg/m^2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e25.9 (23.4, 28.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetraction (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (2.5, 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematoma Size (cm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.0 (2.50 6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003efemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e64 (67%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e31 (33%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant leg injured\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56 (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWood type (1\u0026ndash;5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (8.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e87 (92%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003csup\u003e1\u003c/sup\u003eMedian (IQR); n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003eable 1. Pretreatment characteristics of the study population. Data are presented with Median \u0026plusmn; Inter Quartile Range (IQR) for continuous data, and with count and percentages for categorical data. Wood is the classification of injury according to Wood et al.[1]\u003c/p\u003e\n\u003ch2\u003e4.2-MRI outcomes and maximum muscle force at 24 months\u003c/h2\u003e\n\u003cp\u003eHamstring muscle degeneration and loss of strength were evident in the injured compared to the uninjured hamstrings at 24-month follow-up. The median LSI of the LMV was 78% (IQR: 67\u0026ndash;87%). The median LSI of the MFF was 139% (IQR: 125\u0026ndash;167%) and the median LSI of maximum muscle force was 84% (IQR: 75\u0026ndash;94%, [Table 2]).\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eOutcome measures\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMuscle Quality\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUninjured Limb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eInjured Limb\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eLimb Symmetry Index\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume (L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.49, 0.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.35, 0.57)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78.3 (67.2, 87.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e95\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.16 (0.13, 0.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.22 (0.16, 0.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e139.4 (124.5, 166.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (N)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e94\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e176.1 (140.1, 222.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e142.0 (121.3, 179.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84.0 (75.4, 94.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003eable 2. MRI muscle quality outcome measurements and muscle maximum force of the study population. Limb Symmetry index was calculated: value of injured limb/ value of uninjured limb *100. Data are presented with Median \u0026plusmn; Inter Quartile Range\u0026nbsp;\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTable\u0026nbsp;3. Pairwise Correlations\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable 1\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariable 2\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCorrelation (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume, uninjured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force, uninjured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.78 (0.69, 0.85)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume, injured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force, injured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.67 (0.54, 0.77)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction, uninjured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force, uninjured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.36 (-0.53, -0.17)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction, injured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force, injured side\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.34 (-0.51, -0.15)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.54 (0.38, 0.67)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.47 (-0.62, -0.30)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.23 (-0.41, -0.03)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.38 (-0.54, -0.19)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLean Muscle Volume (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.56 (-0.69, -0.41)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.21 (0.00, 0.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.44 (0.26, 0.59)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMuscle Fat Fraction (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e0.60 (0.45, 0.72)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.09 (-0.29, 0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.34 (-0.51, -0.14)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRetraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaximum Muscle Force (LSI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e-0.35 (-0.51, -0.15)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003eable 3: Pairwise correlations of MRI muscle quality outcome measurements, pretreatment tendon retraction, patient age, Body Mass Index (BMI) and tendon retraction. First section shows correlations between MRI muscle quality outcome measurements and maximum muscle force of the uninjured and injured limb, respectively. Second section shows correlations between Limb Symmetry Indices (LSI) of MRI muscle quality outcome measurements and the LSI of Maximum Muscle Force. LSI was calculated: value of injured limb/ value of uninjured limb *100. The third section shows correlations of pretreatment characteristics and LSI of MRI muscle quality outcome measurements and maximum muscle force. Statistically significant correlations are highlighted by bold characters.\u003c/p\u003e\n\u003ch2\u003e4.3-Bivariate correlations\u003c/h2\u003e\n\u003cp\u003eThere were strong correlations between the absolute lean muscle volume and maximum muscle force at the 24-months follow-up (Table\u0026nbsp;3). This correlation was slightly stronger in the uninjured leg compared to the injured leg (Pearson correlation: r\u0026thinsp;=\u0026thinsp;0.78 vs. 0.67). The loss of LMV, as measured by the limb symmetry index, showed a strong inverse correlation with an increase in muscle fat fraction (r = -0.86; data not in table). The loss of LMV and increase in MFF were moderately correlated with the loss of strength (r\u0026thinsp;=\u0026thinsp;0.54 and \u0026minus;\u0026thinsp;0.47). Weaker but statistically significant correlations were seen between tendon retraction, patient age, BMI, and muscle degeneration. The correlations were even weaker when tendon retraction, BMI, and age were correlated to loss of maximum muscle force at 24 months (Table\u0026nbsp;3). Among the pretreatment factors, tendon retraction showed the strongest correlation to muscle degeneration and muscle strength.\u003c/p\u003e\n\u003ch2\u003e4.4-Linear regression modelling\u003c/h2\u003e\n\u003cp\u003eUnivariate linear regression using patient and pretreatment MRI data as independent variables and the loss of lean muscle volume as the dependent variable revealed statistically significant associations for several variables (Table S1). Similar results were observed when the dependent variables were increase in muscle fat fraction and loss of maximum muscle force. Among these, tendon retraction had the strongest explanatory value for both the loss of lean muscle volume and the increase in muscle fat fraction. However, for muscle force, BMI, hematoma size, and tendon retraction showed similar explanatory strength in their individual associations (Table S1).\u003c/p\u003e\n\u003cp\u003eMultiple linear regression evaluated the association of pretreatment MRI data and patient factors with the outcomes; muscle degeneration and muscle force. A single, unified model\u0026mdash;including age, BMI, sex, tendon retraction, hematoma size, and whether the dominant leg was injured\u0026mdash;was applied to all outcomes (Table S2). This model explained 48% of the variance in the loss of LMV, 48% of the variance of the increase in muscle fat fraction, and 23% of the variance in the loss of muscle force (adjusted R-squared values: 0.48, 0.48, and 0.23, respectively; Fig. 2 and Table 4). Performance metrics (Table S3) indicate that the unified model performed best for lean muscle volume, as evidenced by the lowest Akaike Information Criterion (AIC) value. Although the model achieved a similar adjusted R\u0026sup2; for muscle fat fraction, the substantially higher Root Mean Square Error (RMSE) for that outcome suggests larger absolute prediction errors. In contrast, for maximum muscle force, the model explained less variance but yielded a relatively low RMSE, indicating more precise predictions in absolute terms.\u003c/p\u003e\n\u003cdiv\u003e\n \u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 4\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eMultiple Linear Regression with Caret Rankings\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTerm\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eEstimate (95% CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003et - Statistic\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRank\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003eLSI- Lean Muscle Volume: Adjusted R \u0026ndash; squared\u0026thinsp;=\u0026thinsp;0.48\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTendon Retraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.73 (-3.84, -1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-4.89\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1 (-1.63, -0.38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-3.18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.38 (-0.66, -0.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant Side Injured (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.92 (1.19, 10.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.76 (0.82, 10.69)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematoma Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.49 (-2.78, -0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eLSI-Muscle Fat Fraction: Adjusted R \u0026ndash; squared\u0026thinsp;=\u0026thinsp;0.48\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTendon Retraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.46 (4.57, 10.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.9 (1.27, 4.53)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.86 (0.14, 1.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant Side Injured (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-7.1 (-19.41, 5.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.01 (-12.83, 12.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematoma Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.14 (-0.22, 6.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"4\"\u003e\n \u003cp\u003e\u003cstrong\u003eLSI- Maximum Force: Adjusted R \u0026ndash; squared\u0026thinsp;=\u0026thinsp;0.23\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTendon Retraction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.25 (-2.7, 0.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.98 (-1.8, -0.16)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.19 (-0.55, 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDominant Side Injured (Yes)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.31 (-0.86, 11.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSex (Male)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.42 (-7.87, 5.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHematoma Size\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.96 (-3.64, -0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-2.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003e\u003cstrong\u003eT\u003c/strong\u003eable 4. Multiple linear regression modelling of the effect of initial tendon retraction and covariates on the injury induced loss of lean muscle volume, muscle fat fraction and maximum muscle force. LSI is Limb Symmetry Index and was calculated: value of injured limb/ value of uninjured limb *100. Rank is the order of highest contribution of the independent variable to the overall performance of the model and was calculated using the varImp function in the R caret library.\u003c/p\u003e\n\u003cp\u003eDiagnostic tests confirmed that the model met the assumptions of linear regression. The Durbin-Watson test showed no significant autocorrelation, the Breusch-Pagan test supported homoscedasticity, and the Shapiro-Wilk test indicated that the residuals were normally distributed. Furthermore, multicollinearity was minimal (Variance Inflation Factor: 1.01\u0026ndash;1.37; Table S4).\u003c/p\u003e\n\u003cp\u003eTendon retraction emerged as the strongest predictor of muscle degeneration, particularly for lean muscle volume and muscle fat fraction. In contrast, for the loss of maximum muscle force, BMI, hematoma size, and whether the dominant leg was injured contributed to a similar extent as tendon retraction.\u003c/p\u003e\n\u003cp\u003eTo illustrate these findings, Fig. 3 shows the marginal effect of initial tendon retraction (grouped into intervals commonly used in clinical practice) on muscle degeneration and maximum muscle force.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur findings demonstrate that initial tendon retraction is associated with muscle degeneration in patients with nonoperatively treated proximal hamstring avulsions (PHA). Multiple linear regression analyses showed that greater tendon retraction is significantly linked to lean muscle atrophy and increased fat infiltration. However, muscle degeneration was observed even at minimal retraction levels (\u0026lt; 2 cm), indicating that while retraction magnitude is predictive, lower degrees of retraction do not preclude degenerative changes. These results highlight the predictive value of pretreatment MRI assessments, which surgeons already use as a key factor in treatment decisions.\u003c/p\u003e\n\u003cp\u003eAs expected, we observed a strong correlation between lean muscle volume and muscle strength. However, the relationship between muscle degeneration and the loss of maximum isometric force was only moderate. In our multiple regression model, tendon retraction was not a significant predictor of maximum muscle force, suggesting that other factors influence strength loss. One possible explanation is compensatory activation of other muscles, which may vary among patients depending on rehabilitation intensity. Additionally, the method used to measure muscle force was not optimal. Handheld dynamometers present challenges in isolating hamstring power, and the absence of an isokinetic computerized dynamometer may have limited measurement precision.\u003c/p\u003e\n\u003cp\u003eAmong the other covariates investigated, body mass index was the strongest predictor of muscle degeneration in PHA and the most significant contributor to loss of maximum muscle force. This may reflect both biological factors and the reduced rehabilitative capacity of less fit patients. Age showed a similar trend, with older individuals at the time of injury experiencing more severe muscle degeneration. Interestingly, hematoma size on the initial MRI independently predicted both muscle degeneration and strength loss, even though it was moderately correlated with tendon retraction (r = 0.48). This suggests that the effect of hematoma size is not merely a surrogate for injury severity as reflected by tendon retraction. One possible explanation is that extensive bleeding may be associated with local nerve injury, which could further impair muscle function.\u003c/p\u003e\n\u003cp\u003eOur previous randomized controlled trial (PHACT)[\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e]demonstrated a modest but significant protective effect of surgical reattachment on muscle degeneration. However, subgroup analysis did not show that surgery provided greater benefit for patients with more pronounced retraction when assessed by the PHAT score. Taken together, the current findings and PHACT data suggest that while tendon retraction strongly influences muscle degeneration, its impact on functional and patient-perceived outcomes is less straightforward.\u003c/p\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e5.2-Limitations of study\u003c/h2\u003e\n \u003cp\u003eAside from the points mentioned above, our study has several limitations. The limited number of participants made it impractical to subset the data for model training and evaluation, potentially affecting the robustness and generalizability of our predictive models. Additionally, the patient population consisted of both patients randomized to nonoperative treatment and a parallel cohort of prospectively followed patients who actively chose nonoperative treatment. While females were generally overrepresented in PHACT, this imbalance was even greater in the current study due to a higher proportion of female patients in the parallel cohort opting for nonoperative treatment. Ideally, to maximize external validity, nonoperative treatment would be studied in a setting where all patients, regardless of sex, had no option but to be treated nonoperatively. However, sex was included in the predictive model to control for gender-related differences in muscle degeneration.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\n \u003ch2\u003e5.3-Strengths of study\u003c/h2\u003e\n \u003cp\u003eThe prospective design and the relatively large cohort of nonoperatively treated patients enhance the reliability of our data, while the use of the DIXON MRI technique allowed for precise quantification of muscle degeneration and fat infiltration. These aspects contribute to a better understanding of the natural progression of muscle changes following PHA without surgical intervention.\u003c/p\u003e\n\u003c/div\u003e\n"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, initial tendon retraction is a crucial factor in determining the degree of muscle degeneration after nonoperatively treated proximal hamstring avulsions. While greater retraction is significantly associated with increased muscle atrophy and fat infiltration, its impact on functional outcomes and patient-reported measures appears to be limited. These insights underscore the importance of integrating detailed pretreatment MRI assessments and patient-specific characteristics into the decision-making process for managing PHA.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMRI- Magnetic resonance imaging\u003c/p\u003e\n\u003cp\u003ePHA- Proximal hamstrings avulsion\u003c/p\u003e\n\u003cp\u003ePHACT- The proximal hamstring avulsion clinical trial\u003c/p\u003e\n\u003cp\u003eLMV- Lean muscle volume\u003c/p\u003e\n\u003cp\u003eMFF- Muscle fat fraction\u003c/p\u003e\n\u003cp\u003eTMV- Total muscle volume\u003c/p\u003e\n\u003cp\u003eLSI- Limb symmetry index\u003c/p\u003e\n\u003cp\u003ePD- Proton density\u003c/p\u003e\n\u003cp\u003eSPAIR- Spectral attenuated inversion recovery\u003c/p\u003e\n\u003cp\u003eSTIR- Short tau inversion recovery\u003c/p\u003e\n\u003cp\u003eTIRM- turbo inversion recovery magnitude\u003c/p\u003e\n\u003cp\u003eBMI- Body mass index\u003c/p\u003e\n\u003cp\u003eRSME- Root Mean Square Error\u003c/p\u003e\n\u003cp\u003eAIC- Akaike Information Criterion\u003c/p\u003e\n\u003cp\u003eIQR- Inter quartile range\u003c/p\u003e\n"},{"header":"Declarations","content":"\u003cp\u003eEthics Approval and Consent to Participate\u003cbr\u003e\u0026nbsp;The study was approved by the Uppsala Regional Ethical Committee and the Regional Committee of Medical and Health Research Ethics in Norway. Informed consent was obtained from all participants\u003c/p\u003e\n\u003ch3\u003eConsent for publication\u003c/h3\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003ch3\u003eData Availability\u003c/h3\u003e\n\u003cp\u003eThe data and the analysis code that support the findings of this study are available from the corresponding author, \u0026nbsp;upon reasonable request.\u003c/p\u003e\n\u003ch3\u003eCompeting interests\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eAfa F\u0026ouml;rs\u0026auml;kring was the main sponsor of the trial but had no role in protocol development, data analysis or manuscript preparation.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the planning and design of the study, as well as to patient recruitment and data collection. The first (SL) and last authors (KJ) performed the initial statistical analysis. All authors participated in drafting and critically revising the manuscript and approved the final version for submission.\u003c/p\u003e\n\u003ch3\u003eAcknowledgements\u003c/h3\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eWood DG, Packham I, Trikha SP, Linklater J. Avulsion of the Proximal Hamstring Origin. J Bone Jt Surg. 2008;90:2365\u0026ndash;74. \u003c/li\u003e\n\u003cli\u003eIrger M, Willinger L, Lacheta L, Pogorzelski J, Imhoff AB, Feucht MJ. Proximal hamstring tendon avulsion injuries occur predominately in middle‐aged patients with distinct gender differences: epidemiologic analysis of 263 surgically treated cases. Knee Surg, Sports Traumatol, Arthrosc. 2020;28:1221\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eAllahabadi S, Salazar LM, Obioha OA, Fenn TW, Chahla J, Nho SJ. Hamstring Injuries: A Current Concepts Review: Evaluation, Nonoperative Treatment, and Surgical Decision Making. Am J Sports Med. 2023;52:832\u0026ndash;44. \u003c/li\u003e\n\u003cli\u003eAskling CM, Koulouris G, Saartok T, Werner S, Best TM. Total proximal hamstring ruptures: clinical and MRI aspects including guidelines for postoperative rehabilitation. Knee Surg, Sports Traumatol, Arthrosc. 2013;21:515\u0026ndash;33. \u003c/li\u003e\n\u003cli\u003eKoulouris G, Connell D. Hamstring Muscle Complex: An Imaging Review. Radiographics. 2005;25:571\u0026ndash;86. \u003c/li\u003e\n\u003cli\u003eMade AD van der, H\u0026ouml;lmich P, Kerkhoffs GMMJ, Gouttebarge V, D\u0026rsquo;Hooghe P, Tol JL. Proximal hamstring tendon avulsion treatment choice depends on a combination of clinical and imaging-related factors: a worldwide survey on current clinical practice and decision-making. J Isakos Jt Disord Orthop Sports Medicine [Internet]. 2019;4:175. Available from: http://jisakos.bmj.com/content/4/4/175.abstract\u003c/li\u003e\n\u003cli\u003eLaszlo S, Nilsson M, Pihl E, Mattila VM, Schilcher J, Sk\u0026ouml;ldenberg O, et al. Proximal Hamstring Tendon Avulsions: A Survey of Orthopaedic Surgeons\u0026rsquo; Current Practices in the Nordic Countries. Sports Medicine - Open. 2022;8:49. \u003c/li\u003e\n\u003cli\u003eOpar DA, Williams MD, Shield AJ. Hamstring strain injuries: factors that lead to injury and re-injury. Sports medicine (Auckland, NZ). 2012;42:209\u0026ndash;26. \u003c/li\u003e\n\u003cli\u003edeMeireles AJ, Kent RN, Bedi A, Crawford EA. Degree of Tendon Retraction and Younger Age Are Associated With Functional Decline Following Nonoperative Management of Complete Proximal Hamstring Ruptures. Arthrosc, Sports Med, Rehabilitation. 2023;5:e389\u0026ndash;94. \u003c/li\u003e\n\u003cli\u003ePihl E, Laszlo S, Rosenlund A-M, Kristoffersen MH, Schilcher J, Hedbeck CJ, et al. Operative versus Nonoperative Treatment of Proximal Hamstring Avulsions. NEJM Évid. 2024;3:EVIDoa2400056. \u003c/li\u003e\n\u003cli\u003eMade AD van der, Peters RW, Verheul C, Smithuis FF, Reurink G, Moen MH, et al. Proximal hamstring tendon avulsions: comparable clinical outcomes of operative and non-operative treatment at 1-year follow-up using a shared decision-making model. Brit J Sport Med. 2022;bjsports-2021-104588. \u003c/li\u003e\n\u003cli\u003ePihl E, Skoldenberg O, Nasell H, Jonhagen S, Pettersson PK, Hedbeck CJ. Patient-reported outcomes after surgical and non-surgical treatment of proximal hamstring avulsions in middle-aged patients. BMJ Open Sport Exerc Med. 2019;5:e000511. \u003c/li\u003e\n\u003cli\u003eMaffulli N, Hassan R, Poku D, Chan O, Oliva F. Non‐surgical management of acute proximal hamstring avulsions can produce clinically acceptable results. Knee Surg, Sports Traumatol, Arthrosc. 2024;32:2386\u0026ndash;94. \u003c/li\u003e\n\u003cli\u003ePihl E, Kristoffersen MH, Rosenlund A-M, Laszlo S, Bergl\u0026ouml;f M, Ribom E, et al. The proximal hamstring avulsion clinical trial (PHACT)\u0026mdash;a randomised controlled non-inferiority trial of operative versus non-operative treatment of proximal hamstrings avulsions: study protocol. BMJ Open. 2019;9:e031607. \u003c/li\u003e\n\u003cli\u003eMade AD van der, Smithuis FF, Buckens CF, Tol JL, Six WR, Lauf K, et al. Good Interrater Reliability for Standardized MRI Assessment of Tendon Discontinuity and Tendon Retraction in Acute Proximal Full-Thickness Hamstring Tendon Injury. Am J Sports Medicine. 2021;49:2475\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eWidholm P, Ahlgren A, Karlsson M, Romu T, Tawil R, Wagner KR, et al. Quantitative muscle analysis in facioscapulohumeral muscular dystrophy using whole‐body fat‐referenced MRI: Protocol development, multicenter feasibility, and repeatability. Muscle Nerve. 2022;66:183\u0026ndash;92. \u003c/li\u003e\n\u003cli\u003eKarlsson A, Peolsson A, Romu T, Leinhard OD, Holm AS, Thorell S, et al. The effect on precision and T1 bias comparing two flip angles when estimating muscle fat infiltration using fat‐referenced chemical shift‐encoded imaging. NMR Biomed. 2021;34:e4581. \u003c/li\u003e\n\u003cli\u003eBorga M, Ahlgren A, Romu T, Widholm P, Leinhard OD, West J. Reproducibility and repeatability of MRI‐based body composition analysis. Magn Reson Med. 2020;84:3146\u0026ndash;56. \u003c/li\u003e\n\u003cli\u003eKarlsson A, Rosander J, Romu T, Tallberg J, Gr\u0026ouml;nqvist A, Borga M, et al. Automatic and quantitative assessment of regional muscle volume by multi‐atlas segmentation using whole‐body water\u0026ndash;fat MRI. J Magn Reson Imaging. 2015;41:1558\u0026ndash;69. \u003c/li\u003e\n\u003cli\u003eSchober P, Boer C, Schwarte LA. Correlation Coefficients. Anesthesia Analg. 2018;126:1763\u0026ndash;8. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"sports-medicine-open","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"smoa","sideBox":"Learn more about [Sports Medicine-Open](http://sportsmedicine-open.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/smoa/default.aspx","title":"Sports Medicine-Open","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6386233/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6386233/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003e1.1-Background and purpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMagnetic resonance imaging (MRI) is crucial for diagnosing proximal hamstring avulsions (PHA) by assessing tendon rupture and retraction, thereby guiding treatment decisions alongside clinical and patient data. However, the prognostic value of pre-treatment MRI for predicting muscle degeneration and clinical outcomes remains unclear. This study aimed to determine whether pre-treatment MRI findings—particularly tendon retraction—predict subsequent muscle degeneration and clinical outcomes in nonoperatively treated PHA patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.2-Methods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is a post hoc analysis of nonoperatively treated patients (n = 95) from the Proximal Hamstring Avulsion Clinical Trial (PHACT). Diagnostic MRIs were reassessed for tendon retraction, Wood classification, number of tendons avulsed, and hematoma size. The primary outcome was muscle degeneration, defined by the loss of lean muscle volume (LMV) and an increase in muscle fat fraction (MFF) quantified by DIXON MRI at 24 months. The secondary outcome was maximum hamstring muscle isometric force at 24 months. Outcome data was expressed as the limb symmetry index (LSI), which was the measurement of the injured hamstring expressed as a percentage of measurement of the uninjured hamstring. Linear regression was used to analyze the association between diagnostic MRI measurements, patient factors, and LSIs for LMV, MFF, and maximum isometric force.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.3-Results\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe median LSIs of the LMV, MFF and maximum strength were 78%, 139%, and 84%, respectively, at 24-month follow-up. A multivariate linear regression model including tendon retraction, age, sex, hematoma size and whether the dominant limb was injured explained 48%, 48% and 23% of the variance in the LSIs of LMV, MFF and maximum force, respectively. Tendon retraction was the strongest explanatory factor for the variance of muscle degeneration observed in patients with nonoperatively treated PHA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e1.4-Interpretation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGreater initial tendon retraction is associated with increased muscle atrophy and fat infiltration in the hamstring muscles in patients with nonoperatively treated PHA. \u003cem\u003eClinicalTrials.gov number, NCT03311997\u003c/em\u003e\u003c/p\u003e","manuscriptTitle":"Initial Tendon Retraction is Associated With Muscle Degeneration After Nonoperatively Treated Proximal Hamstring Avulsions","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-23 05:46:32","doi":"10.21203/rs.3.rs-6386233/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2025-10-08T01:04:57+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2025-07-17T11:27:15+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-07-16T02:18:53+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-10T02:08:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Sports Medicine-Open","date":"2025-04-09T02:47:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sports-medicine-open","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"smoa","sideBox":"Learn more about [Sports Medicine-Open](http://sportsmedicine-open.springeropen.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/smoa/default.aspx","title":"Sports Medicine-Open","twitterHandle":"@SpringerOpen","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"33b58171-762f-4882-9067-2c76ab581cdb","owner":[],"postedDate":"July 23rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-16T23:44:30+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-23 05:46:32","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6386233","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6386233","identity":"rs-6386233","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}