Increased hazard ratio of a second ACL injury after return to sport for each positive hypermobility test on the Beighton Score: a registry study.

Increased hazard ratio of a second ACL injury after return to sport for each positive hypermobility test on the Beighton Score: a registry study. | 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 Increased hazard ratio of a second ACL injury after return to sport for each positive hypermobility test on the Beighton Score: a registry study. Jakob Lindskog, Balint Zsidai, Axel Sundberg, Johan Högberg, Rebecca Hamrin Senorski, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8681152/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 6 You are reading this latest preprint version Abstract Background Generalized joint hypermobility increases the risk of second anterior cruciate ligament (ACL) injury. The clinical diagnosis of GJH relies on a binary threshold of positive joint hypermobility tests, based on age and patient sex, which may overlook the degree of hypermobility. Purpose To analyze the association between the number of positive joint hypermobility tests on the Beighton Score and the hazard ratio (HR) of second anterior cruciate ligament (ACL) injury in patients who return to sport (RTS) after primary ACL reconstruction, which included secondary, stratified analyses of graft rupture and contralateral ACL injury. Design: Registry study. Methods Data was extracted in January 2026 from an ACL-rehabilitation-specific registry, YYY. Included patients were 15–50 years who underwent primary ACL reconstruction with hamstring tendon or bone-patellar tendon-bone autograft, had a documented Beighton Score, participated in knee-strenuous sports before injury, had RTS, reported second ACL injury or had ≥ 1 year follow-up without second ACL injury after RTS. Multivariable Cox proportional hazard regression was used to estimate the HR of second ACL injury (measured from RTS) based on the Beighton Score, adjusted for age, return to pre-injury physical activity level or higher, graft choice, knee hyperextension (≥ 10° knee extension), and patient sex. Results The analysis included 935 patients (mean age 23.7 ± 7.8 years, 51.4% female), with median Beighton Score of 2 (interquartile range: 4). The median follow-up time was 54.4 months. Second ACL injury was reported in 122 (13.0%) patients. The adjusted HR of second ACL injury after RTS was 1.10 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.003–1.22, p = 0.044). Conclusion The HR of second ACL injury after RTS in patients who had undergone primary ACL reconstruction increased by 10% for each positive joint hypermobility test on the Beighton Score. Anterior cruciate ligament reconstruction RTS Postoperative complications graft rupture contralateral ACL injury joint instability Figures Figure 1 Figure 2 Figure 3 Key Points There was an increased hazard ratio of second ACL injury for each positive test on the Beighton Score after return to sport after primary ACL reconstruction. Clinicians should consider the number of hypermobile joints in conjunction with presence of generalized joint hypermobility when assessing risk for second ACL injury. Introduction Patients who sustain an anterior cruciate ligament (ACL) injury typically participate in cutting or pivoting sports.(1) For patients who aim to return to sport (RTS), the current standard of care for the ACL injury consist of ACL reconstruction,(2) typically performed with an autograft.(1) Despite ACL reconstruction, up to 20% of all patients, and 23% of patients younger than 25 years, sustain a second ACL injury after RTS.(3) A factor proposed to increase risk of second ACL injury is generalized joint hypermobility (GJH).(4) The GJH phenotype is a congenital condition characterized by an altered structural integrity of collagen fibrils, which consequently leads to joint hyperextensibility compared to individuals without GJH.(5) The current consensus for assessment of GJH recommends the Beighton Score, which relies on 9 joint mobility tests, where the number of positive tests confirms GJH based on age and patient sex-dependent cutoff thresholds.(6) , (7) Currently accepted thresholds for GJH based on the Beighton Score include ≥ 5/9 points for pre-pubertal males, and ≥ 4/9 points for post-pubertal males.(7) Females with pre- and post-puberal age criteria require an additional point to be assigned the GJH phenotype (≥ 6/9 and ≥ 5/9, respectively).(7) However, cautious interpretation of the Beighton Score is warranted, as joint mobility can be confounded by various factors, such as traumatically acquired joint hyper- or hypomobility(8, 9). The use of predetermined binary cutoff values to classify GJH could make accurate classification difficult, which could potentially lead to over- or underestimation of GJH prevalence, and incorrect second ACL injury risk-stratification. Given that joint hypermobility exists on a spectrum,(10) the associated risk of a second ACL injury is also likely to vary along a continuum. Accordingly, the total number of hypermobile joints may offer valuable insight into individual risk profiles. Despite this, the association between the number of positive joint hypermobility tests on the Beighton Score and the incidence of second ACL injury has been scarcely studied, but may provide a more informative alternative for second ACL injury risk assessment than relying on predetermined binary cutoffs. The purpose of this study was to analyze the association between the number of positive joint hypermobility tests on the Beighton Score and the hazard ratio (HR) of second ACL injury in patients who RTS after primary ACL reconstruction, which included secondary, stratified analyses of graft rupture and contralateral ACL injury. We hypothesized that there would be an increased HR based on the increased number of positive hypermobile joints on the Beighton Score. Methods Study design The present study was a registry-based retrospective cohort study performed in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.(11) Ethical approval has been obtained from the YYY (registration numbers: YYY, YYY), and the YYY, YYY (registration numbers: YYY, YYY). Setting Data was extracted from a rehabilitation specific registry (YYY), previously described in detail. yyy,yyy YYY was established in 2014 in YYY, YYY, with the aim to improve care for patients after ACL injury. Patients registered in YYY are invited to participate in supervised muscle function tests and answer web-based questionnaires at predefined follow-ups at 10 weeks, 4-, 8-, 12-, 18-, 24 months, 5 years and then every fifth year after ACL injury or reconstruction. Patients may register to YYY at any time after ACL injury or reconstruction. Upon registration in YYY, patients are required to provide demographic information, such as patient sex, date of birth, height, and weight. Joint hypermobility assessment is performed at the initial muscle function test and is conducted by a trained test supervisor. The Beighton Score was added to YYYs standardized assessment protocol in 2019. Patients Patients registered in YYY were checked for eligibility for inclusion by application of the following criteria: underwent primary ACL reconstruction performed with hamstring tendon- or bone-patellar tendon-bone autograft, were aged between 15 and 50 years at the time of primary ACL reconstruction, had registered Beighton Score with specific information on the presence of knee hyperextension, pre-injury participation in knee-strenuous sports, defined as ≥ 6 on the Tegner Activity Scale(12) (Tegner), RTS after primary ACL reconstruction, i.e., ≥ 6 on the Tegner, and sustained a second ACL injury (defined as graft rupture or contralateral ACL injury), or had ≥ 1 year follow-up after RTS without a second ACL injury. Patients with ≥ 3 ACL injuries were excluded. The rationale for the chosen inclusion criteria was to study patients who were active in sports prior to primary ACL injury, and to allow adequate exposure time to sustain a second ACL injury after RTS. Outcomes The primary outcome of interest was the HR of second ACL injury based on the number of positive hypermobility tests. The secondary outcomes were the HRs of isolated graft rupture and contralateral ACL injury based on the number of hypermobility tests. Patients were followed until the incidence of second ACL injury or the date of data extraction (January 2026). Variables Incidence of second ACL injury A second ACL injury (graft rupture or a contralateral ACL injury) can be reported by the responsible clinician or by the patient, after confirmation through clinical assessment or imaging. The occurrence of a second ACL injury is documented in the patient’s profile within the YYY database. Tests of hypermobility The Beighton Score assesses joint hypermobility on a 9-point scale,(6) and has been reported with a substantial to excellent inter- and intrarater reliability for raters, regardless of expertise.(13) The Beighton Score comprises 9 tests, where each positive test yields one point on the score, up to a maximum of 9 points. Eight of the tests are unilateral, and one is bilateral. The eight unilateral tests are performed bilaterally and consist of dorsiflexion of the metacarpal joints of the fifth finger beyond 90°, apposition of the thumbs to the flexor aspects of the forearms, hyperextension of the elbows and knees beyond 10°, and the one bilateral test is forward flexion of the trunk, with the knees straight, so that the palms of the hands can rest easily on the floor.(6) The Beighton Score is currently the most frequently used assessment tool for GJH.(7) In YYY, the unilateral tests are passively performed by a test supervisor. The trunk flexion test is performed actively by the patient. The assessment can be performed both prior and after ACL reconstruction, dependent on when the patients perform the first muscle function tests. To account for the potential altered joint mobility due to the ACL injury or reconstruction, the use of an injury allowance point is applied.(14) Application of an injury allowance point means to assign the result of the non-involved limb to the involved limb if the involved limb has altered joint mobility. In YYY the Beighton Score assessment is entered into the database as a total score, and a binary categorical variable (yes/no) is reported for the prevalence of knee hyperextension (≥ 10° knee extension). Measurement of knee-strenuous activity and RTS The Tegner is a self-reported questionnaire used to quantify the level of knee-strenuous activity performed before and after an injury.(12) The intraclass correlation coefficient for test-retest reliability for the Tegner was reported to be 0.8.(15) The original Tegner ranges from 0 to 10, where 10 represents highest knee demanding activity, such as professional football.(12) YYY utilizes a modified version of the Tegner that ranges between 1 to 10. Tegner level 6 was the cut-off used to determine RTS in the present study, as Tegner level 6 is the first level determined as knee-strenuous and only includes sport activities, such as ice-hockey, tennis, alpine skiing, or volleyball. Data collection Data was extracted from YYY for analysis on January 5, 2025. Data consisted of categorical data of patient sex, choice of autograft for primary ACL reconstruction, Beighton Score, presence of knee hyperextension, as well as incidence and time of second ACL injury. Furthermore, continuous demographic variables which include age, height, weight, body mass index, time between primary ACL injury and reconstruction, time between ACL reconstruction and RTS, follow-up time after RTS, and level of sport pre-injury and at RTS were extracted. Statistical analysis Continuous data was presented as mean with standard deviation (SD) for parametric data and median with interquartile range (IQR) for non-parametric data. Categorical data was presented as numbers with percentage. Follow-up time after RTS was analyzed with the Kruskal-Wallis test between patients with different numbers of positive joint hypermobility tests on the Beighton Score. The HR of second ACL injury was determined using multivariable cox proportional hazard regression models and was presented with a 95% confidence interval (CI). For the primary outcome, the dependent variable was the dichotomized incidence of second ACL injury after RTS (yes/no). For the secondary outcomes, the dependent variable was the dichotomized incidence of graft rupture or contralateral ACL injury, and in each analysis patients who sustained the alternative second ACL injury were censored at the time of injury. For the unadjusted and adjusted analysis, the independent variable was the continuous number of positive joint hypermobility tests assessed with the Beighton Score. For the adjusted analysis, the age at primary ACL reconstruction, return to pre-injury Tegner or higher (yes/no), autograft choice (hamstring tendon or bone-patellar tendon-bone), presence of knee hyperextension, and patient sex were added as confounders to the model based on their relevance in current literature.(16-25) For all outcomes, the adjusted models were checked for performance with the Grambsch and Thernaeu’s test for proportional hazards assumption, Harrell’s C-statistic for model discrimination, and likelihood ratio test for model fit. For model discrimination, Harrell’s C-statistic was used for the primary outcome, and interpreted as follows: < 0.60 poor discrimination; ≥ 0.6 to < 0.75 possibly helpful discrimination; and ≥ 0.75 useful discrimination.(26) For model fit, the likelihood ratio test assesses whether adding covariates to the model improves the ability to explain variation in hazard compared to a model without covariates, where a good fit is considered if p < 0.05. Alpha was set to p < 0.05. Statistical analyses were performed with the Statistical Product and Service Solutions (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp.). Results Data for a total of 4,933 patients were extracted from YYY’s database, of which 935 patients were included (Figure 1). Of the included patients, 481 (51.4%) were female and the mean age at the time of ACL reconstruction was 23.7 ± 7.8 years (Table 1). The median follow-up time from the time of RTS to the end point was 54.4 months (IQR: 47.5 months), which was significantly different between patients with different numbers of positive hypermobility tests on the Beighton Score (p < 0.001). Patients with 9 positive hypermobility tests on the Beighton Score had the shortest median follow-up time after RTS of 24.7 months (IQR: 29.7 months). Over the study period, a total of 122 patients (13.0%) sustained a second ACL injury, of which 69 (56.6%) were graft ruptures, and 53 (43.4%) were contralateral ACL injuries. The median Beighton Score for all included patients was 2 (IQR: 4). The highest proportion of second ACL injuries were observed in patients with Beighton Scores 9 (21.4%), 5 (21.1%), and 7 (18.4%) (Figure 2). Figure 3 displays the distribution of second ACL injuries, stratified by graft ruptures or contralateral ACL injuries, for each year after RTS until the study end point. Table 1 – Demographic data for included patients. Patient demographics Total , n = 935 Patient sex, females, n (%) 481 (51.4) Age, years mean ± SD 23.7 ± 7.8 Height, cm mean ± SD 174.8 ± 9.1 Weight, kg mean ± SD 71.9 ± 11.7 BMI, mean ± SD 23.4 ± 2.6 Knee hyperextension, n (%) 283 (30.3) Time from injury to ACL reconstruction, months median (IQR) 3.6 (4.0) Time from ACL reconstruction to RTS, months median (IQR) 11.8 (4.3) Follow-up time after RTS, months median (IQR) 54.4 (47.5) Level of sport pre-injury, Tegner median (IQR) 9.0 (1.0) Level of sport at RTS , Tegner median (IQR) 7.0 (2.0) Beighton Score, median (IQR) 2 (4) Distribution of patients across each Beighton Score , n (%) 0 370 (39.6) 1 78 (8.3) 2 147 (15.7) 3 65 (7.0) 4 101 (10.8) 5 57 (6.1) 6 47 (5.0) 7 38 (4.1) 8 18 (1.9) 9 14 (1.5) Graft choice , n (%) Hamstring tendon autograft Bone-Patellar Tendon-Bone autograft 732 (78.3) 203 (21.7) Second ACL injury over the study period , n (%) Graft rupture, n (%) Contralateral ACL injury, n (%) 122 (13.0) 69 (56.6) 53 (43.4) Time from RTS to second ACL injury, months median (IQR) 12.4 (25.1) Time from RTS to graft rupture, months median (IQR) 7.6 (12.2) Time from RTS to contralateral ACL injury, months median (IQR) 28.0 (36.6) BMI = Body mass index, cm = Centimeters, GJH = Generalized joint hypermobility, IQR = Interquartile range, kg = Kilogram, n = Number of patients, RTS = Return to Sport, SD = Standard deviation, Tegner = Tegner activity scale. Primary outcome Over the study period of median 54.4 months after RTS, the HR of second ACL injury was 1.10 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.003-1.22, p = 0.044) adjusted for age at primary ACL reconstruction, return to pre-injury level Tegner or higher, choice of autograft, presence of knee hyperextension, and patient sex (Table 2). The model demonstrated a possibly helpful discrimination (Harrell’s C = 0.621), the proportional hazards assumption was not violated (Grambsch and Thernaeu’s test p = 0.473), and the model showed good fit (χ² = 24.4, p < 0.001). Data availability throughout the study period is presented for respective 12-month period in Appendix Table 1. Table 2 – Unadjusted and adjusted cox regression model to estimate the hazard ratio of second ACL injury over the study period after return to sport dependent on Beighton Score a Unadjusted Adjusted Covariate Hazard ratio (95% CI) p-value Hazard ratio (95% CI) p-value Beighton Score 1.10 (1.03-1.18) 0.006 1.10 (1.003-1.22) 0.044 ACL = Anterior cruciate ligament, CI = Confidence interval, Tegner = Tegner activity scale. a Adjusted for age at primary ACL reconstruction, return to pre-injury level of Tegner or higher, choice of autograft for ACL reconstruction, presence of knee hyperextension, and patient sex. Number of second ACL injuries, i.e., graft rupture or contralateral ACL injury, n = 122. Secondary outcomes Over the study period, the adjusted HR of graft rupture was 1.15 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.01-1.30, p = 0.031) (Table 3). The model demonstrated a possibly helpful discrimination (Harrell’s C = 0.660), the proportional hazards assumption was not violated (Grambsch and Thernaeu’s test p = 0.466), and the model showed good fit (χ² = 22.9, p = 0.001). There was no difference in the adjusted HR of contralateral ACL injury based on the number of positive joint hypermobility tests on the Beighton Score (HR: 1.04, 95% CI: 0.89-1.21, p = 0.598). The model demonstrated a poor discrimination (Harrell’s C = 0.599), the proportional hazards assumption was not violated (Grambsch and Thernaeu’s test p = 0.962), and the model did not show good fit (χ² = 8.22, p = 0.222). Table 3 – Unadjusted and adjusted cox regression model to estimate the hazard ratio of graft rupture and contralateral ACL injury over the study period after return to sport dependent on Beighton Score a Unadjusted Adjusted Outcome/covariate Hazard ratio (95% CI) p-value Hazard ratio (95% CI) p-value Graft rupture Beighton Score 1.10 (1.002-1.20) 0.044 1.15 (1.01-1.30) 0.031 Contralateral ACL injury Beighton Score 1.10 (0.99-1.23) 0.065 1.04 (0.89-1.22) 0.598 ACL = Anterior cruciate ligament, CI = Confidence interval, Tegner = Tegner activity scale. a Adjusted age at primary ACL reconstruction, for return to pre-injury level of Tegner or higher, choice of autograft for ACL reconstruction, presence of knee hyperextension, and patient sex. Number of graft ruptures: n = 69; number of contralateral ACL injuries: n = 53. Discussion The main finding of this study was that for each unit increase in the number of positive joint hypermobility tests on the Beighton Score, the HR of second ACL injury after RTS increased by 10%, adjusted for age at primary ACL reconstruction, return to pre-injury Tegner level or higher at RTS, choice of autograft for primary ACL reconstruction, presence of knee hyperextension, and patient sex. The association between Beighton Score and the composite second ACL injury endpoint appeared primarily attributable to graft rupture (HR: 1.15, 95% CI: 1.01-1.30, p=0.031), whereas the estimate for contralateral ACL injury was smaller and inconclusive (HR: 1.04, 95% CI: 0.89-1.22, p=0.598). These findings suggest that clinicians should consider the number of positive joint hypermobility tests, rather than solely rely on a binary GJH classification when assessing and counseling patients on the risk of a second ACL injury after ACL reconstruction. Patients with GJH have previously been reported to be at greater risk for a second ACL injury compared with patients without GJH.(4, 21, 27) A previous study reported 4.24 times greater HR of second ACL injury in patients with GJH compared to those without GJH.(4) However, the binary classification of GJH through the cutoffs in Beighton Score may risk to either overestimate or underestimate the presence of GJH. The greater HR observed with increasing numbers of positive joint hypermobility tests on the Beighton Score, suggests that GJH exists on a spectrum rather than being dichotomous characterized by a clear threshold. Consequently, our findings of 10% exponential increase in second ACL injury HR after RTS may underscore the importance of more refined assessment of joint hypermobility. Specifically, our findings suggest that the number of positive joint hypermobility tests, rather than the mere presence of GJH, should be considered in individualized rehabilitation and risk-stratification after primary ACL reconstruction. The use of the traditional binary classification of GJH based on the Beighton Score, Larson et al.,(21) and Zsidai et al.,(4) reported that patients with GJH had a second ACL injury incidence of 34.1% (mean follow-up time: 72 months), and 38.2% (≤ 84 months follow-up time), respectively, in contrast to 7.7%, and 10.1%, respectively, in patients without GJH. In the present study, the overall incidence of second ACL injury over a median follow-up time of 48 months was 12.9% where no classification of GJH was made. Nonetheless, previous studies(4, 21) have used two different cut-off points for the classification of the GJH phenotype. According to the most recent consensus,(28) different cut-off points for GJH are advocated with increased threshold for females and younger individuals, since joint hypermobility is more common in females and in the younger population. The need for different cut-off points for GJH in different sub-populations is further highlighted in a study by Singh et al.,(24) which reported that only a minority of patients were correctly classified with GJH when a single cut-off point was utilized on the Beighton Score. Nevertheless, the risk of misclassification of GJH is still possible even if different cut-off points in different sub-populations are applied. The results of this study offer an alternative to binary classification of GJH since we show that the HR of second ACL injury increases exponentially with each positive joint hypermobility test on the Beighton Score. For example, based on the adjusted HR of 1.10 per point, patients with 1, 2, or 3 positive Beighton Score tests had an estimated 10%, 21%, or 33% higher HR of second ACL injury, respectively, compared to patients with a score of 0. Consequently, although GJH assessment using a standardized method, such as the Beighton Score, remains valuable for second ACL injury risk-stratification, interpretation should not only consider the possible presence of GJH, but also the degree and extent of joint hypermobility. Patients should be counseled and informed accordingly with regard to the potential increased HR of second ACL injury after RTS after primary ACL reconstruction. Future research should aim to identify rehabilitation and surgical factors that increase the likelihood of a RTS with minimal risk of re-injury for high-risk patients, and, if none are sufficient, explore the option of advising against RTS. The timing of second ACL injuries differed substantially between components: graft ruptures occurred earlier after RTS (median 7.6 months), whereas contralateral ACL injuries occurred later (median 28 months). This observed temporal separation was consistent with previous literature on graft rupture and contralateral injury,(29) which reflects partly distinct processes and may partly explain why the composite second ACL injury association was more apparent for graft rupture than for contralateral ACL injury. For clinicians, the results suggest to prioritize early post-RTS strategies aimed at reducing graft failure risk, while recognizing that contralateral injury risk may emerge later and warrants continued preventive efforts beyond the first year. Limitations The presented study has some limitations. First, the degree of hypermobility in the joint, i.e., joint angle was not accounted for, but only the threshold for a positive test in the Beighton Score was considered. Second, only the reported level of physical activity on the Tegner was analyzed in this study, and not the exact sport or exposure time the patients were undertaking in their sport. Greater and more intense exposure to knee demanding maneuvers would likely increase the risk for second ACL injury. Third, only 117 (12.5%) patients included in the study had Beighton Score ≥ 6, which may potentially limit the statistical precision of our analysis. Fourth, the results of our study could be affected by potential concomitant ligamentous or intraarticular injuries, which include medial collateral ligament injury(30) or lateral meniscus injury(31), which are not reported in YYY. Lastly, we could not account for additional surgical procedures, such as the lateral extra-articular tenodesis, performed in addition to the ACL reconstruction, which has been shown to reduce the risk of second ACL injury.(32) Conclusion The HR of second ACL injury after RTS in patients with primary ACL reconstruction increased by 10% for each positive joint hypermobility test on the Beighton Score. The presented findings should prompt clinicians to consider the number of positive joint hypermobility tests, and not solely rely on binary GJH classification, when assessing risk for second ACL injury after ACL reconstruction. Declarations Funding Partial financial support was granted from Research and development primary health care Gothenburg and Södra Bohuslän. Competing interests No competing interests to declare. Ethics approval The principles of the Helsinki declaration have been used as guidance in this study. Ethical approval has been obtained from the Swedish Ethical Review Authority (registration number: 2020-02501, 2024-08724-01), and the Regional Ethical Review Board in Gothenburg, Sweden (registration numbers: 265–13, T023–17). Consent Data for this study is based on a rehabilitation registry project (Project ACL), where all patients have received written information and have given their informed consent in the research project. Data and material availability The data that support the findings of this study are available on reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Clinical trial registration Not applicable. Permission to reproduce material from other sources Not applicable. Ai disclosure During the preparation of this work the authors used ChatGPT 4o and 5.2 in order to enhance readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article. Author contributions Jakob Lindskog drafted the initial version of the manuscript, performed analysis of data, has approved the final work for publication, and has agreed to be accountable for all aspects of the work. Axel Sundberg, Bálint Zsidai, Johan Högberg, Rebecca Hamrin Senorski, Behnam Liaghat, and Ramana Piussi have contributed majorly during the analysis and interpretation of data, has made important contributions during the drafting of the work, has approved the final work, and has agreed to be accountable for all aspects of the work. Kristian Samuelsson and Roland Thomeé have contributed during the interpretation of data, made meaningful contributions during the final stages of manuscript drafting, has approved the final work, and has agreed to be accountable for all aspects of the work. Eric Hamrin Senorski has contributed majorly during the drafting of the manuscript, analysis and interpretation of data, is responsible for the design concept, has approved the final work, and has agreed to be accountable for all aspects of the work. Acknowledgments Not Applicable Declaration of interests ☐ The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. ☒ The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: References Forssblad M. Svenska knäligamentsregistret (Eng: The Swedish knee ligament registry). Annual report 2024. XBase 2023 [Available from: https://aclregister.nu/media/uploads/Annual%20reports/rapport2024.pdf Meredith SJ, Rauer T, Chmielewski TL, Fink C, Diermeier T, Rothrauff BB et al. 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Larson CM, Bedi A, Dietrich ME, Swaringen JC, Wulf CA, Rowley DM, et al. Generalized Hypermobility, Knee Hyperextension, and Outcomes After Anterior Cruciate Ligament Reconstruction: Prospective, Case-Control Study With Mean 6 Years Follow-up. Arthroscopy. 2017;33(10):1852–8. Fares A, Horteur C, Abou Al Ezz M, Hardy A, Rubens-Duval B, Karam K, et al. Posterior tibial slope (PTS) ≥ 10 degrees is a risk factor for further anterior cruciate ligament (ACL) injury; BMI is not. Eur J Orthop Surg Traumatol. 2023;33(5):2091–9. Guimarães TM, Giglio PN, Sobrado MF, Bonadio MB, Gobbi RG, Pécora JR, et al. Knee Hyperextension Greater Than 5° Is a Risk Factor for Failure in ACL Reconstruction Using Hamstring Graft. Orthop J Sports Med. 2021;9(11):23259671211056325. Singh H, McKay M, Baldwin J, Nicholson L, Chan C, Burns J, et al. Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology (Oxford). 2017;56(11):1857–64. Hamrin Senorski E, Svantesson E, Baldari A, Ayeni OR, Engebretsen L, Franceschi F, et al. Factors that affect patient reported outcome after anterior cruciate ligament reconstruction-a systematic review of the Scandinavian knee ligament registers. Br J Sports Med. 2019;53(7):410–7. Foroutan F, Mayer M, Guyatt G, Riley RD, Mustafa R, Kreuzberger N, et al. GRADE concept paper 8: judging the certainty of discrimination performance estimates of prognostic models in a body of validation studies. J Clin Epidemiol. 2024;170:111344. Sundemo D, Hamrin Senorski E, Karlsson L, Horvath A, Juul-Kristensen B, Karlsson J, et al. Generalised joint hypermobility increases ACL injury risk and is associated with inferior outcome after ACL reconstruction: a systematic review. BMJ Open Sport Exerc Med. 2019;5(1):e000620. Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26. Salmon L, Russell V, Musgrove T, Pinczewski L, Refshauge K. Incidence and risk factors for graft rupture and contralateral rupture after anterior cruciate ligament reconstruction. Arthroscopy. 2005;21(8):948–57. Zhao D, Pan JK, Lin FZ, Luo MH, Liang GH, Zeng LF, et al. Risk Factors for Revision or Rerupture After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis. Am J Sports Med. 2023;51(11):3053–75. Olsson Wållgren J, Oeding JF, Kaarre J, Hamrin Senorski E, Musahl V, Samuelsson K. Long-term Effects of Concomitant Lateral Meniscal Management on ACL Reconstruction Revision Rate and Secondary Meniscal and Cartilaginous Injuries. Orthop J Sports Med. 2025;13(5):23259671251330655. Rezansoff A, Firth AD, Bryant DM, Litchfield R, McCormack RG, Heard M et al. Anterior Cruciate Ligament Reconstruction Plus Lateral Extra-articular Tenodesis Has a Similar Return-to-Sport Rate to Anterior Cruciate Ligament Reconstruction Alone but a Lower Failure Rate. Arthroscopy. 2023. Supplementary Files Appendix.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major Revision 19 Apr, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers invited by journal 04 Feb, 2026 Editor invited by journal 03 Feb, 2026 Editor assigned by journal 27 Jan, 2026 First submitted to journal 25 Jan, 2026 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. We do this by developing innovative software and high quality services for the global research community. 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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-8681152","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":585922430,"identity":"f287632c-e727-419f-ac59-071dd3c63ed5","order_by":0,"name":"Jakob Lindskog","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA8ElEQVRIie3QPQrCMBiA4a8U2iU6VxS8QkrAH5D2Ki2BdnFwdOxkl2LX9hYeIVDQRXQVuigBXRw6ijgY0Q4u0VEw75CQ4SFfAqBS/WBaZIAOMEAAnthh9DWxahJ8c8+TwIsUn4EeL30+AavTN0OOq+vWWTDzsJcOlgQFycRgw+RM/Hxe0gVDBMvfEs7aSBC8G+tFIykpZsiwpCQ91STkgmwEMU8XKcmC5Yt4hKILczCDnkwIcqQkw4Ksz8TOI+q1CkSkg9lpYPPJdOTiVcit6ua4zVV8qKQkeqz1D2kz8CNdOhZA9/14A/cDUKlUqj/sDqUoSB6m+uroAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0009-0005-9146-0073","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och fysiologi","correspondingAuthor":true,"prefix":"","firstName":"Jakob","middleName":"","lastName":"Lindskog","suffix":""},{"id":585922431,"identity":"659cadec-5b4a-47db-a53d-8ce77227ca99","order_by":1,"name":"Balint Zsidai","email":"","orcid":"","institution":"University of Gothenburg Institute of Clinical Sciences: Goteborgs universitet Institutionen for kliniska vetenskaper","correspondingAuthor":false,"prefix":"","firstName":"Balint","middleName":"","lastName":"Zsidai","suffix":""},{"id":585922432,"identity":"f27d19ef-0cd8-4afd-8494-061a3802f19a","order_by":2,"name":"Axel Sundberg","email":"","orcid":"","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och fysiologi","correspondingAuthor":false,"prefix":"","firstName":"Axel","middleName":"","lastName":"Sundberg","suffix":""},{"id":585922433,"identity":"e19f262e-72af-4224-a732-8f88cc7d2d13","order_by":3,"name":"Johan Högberg","email":"","orcid":"","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och 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Institute of Clinical Sciences: Goteborgs universitet Institutionen for kliniska vetenskaper","correspondingAuthor":false,"prefix":"","firstName":"Kristian","middleName":"","lastName":"Samuelsson","suffix":""},{"id":585922437,"identity":"918e6296-f386-4781-bf9e-feb7c5fdfcf3","order_by":7,"name":"Roland Thomeé","email":"","orcid":"","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och fysiologi","correspondingAuthor":false,"prefix":"","firstName":"Roland","middleName":"","lastName":"Thomeé","suffix":""},{"id":585922438,"identity":"6757e86f-3d9b-41f3-8f59-61dfb8e70af1","order_by":8,"name":"Ramana Piussi","email":"","orcid":"","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och fysiologi","correspondingAuthor":false,"prefix":"","firstName":"Ramana","middleName":"","lastName":"Piussi","suffix":""},{"id":585922439,"identity":"6cc88981-a9fd-4e21-b5ce-1e1463247d67","order_by":9,"name":"Eric Hamrin Senorski","email":"","orcid":"","institution":"University of Gothenburg Institute of Neuroscience and Physiology: Goteborgs universitet Institutionen for neurovetenskap och fysiologi","correspondingAuthor":false,"prefix":"","firstName":"Eric","middleName":"Hamrin","lastName":"Senorski","suffix":""}],"badges":[],"createdAt":"2026-01-23 16:30:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8681152/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8681152/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":102212559,"identity":"14b93515-29ee-44b6-8a81-dfeb9b422004","added_by":"auto","created_at":"2026-02-09 12:34:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":6036,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eFlowchart representing patient selection, ACL = Anterior cruciate ligament, n = Number of patients.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-8681152/v1/cd39c2a5e998c133cbee89bd.png"},{"id":102212562,"identity":"6f468a48-2507-4d65-b577-a1260574b3d6","added_by":"auto","created_at":"2026-02-09 12:34:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":36190,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eProportion (black bars), and cumulative hazard ratio (gray line), of second ACL injuries, i.e., graft rupture or contralateral ACL injury, across patients based on the numbers of positive joint hypermobility tests on the Beighton Score at the longest available time after return to sport. ACL = Anterior cruciate ligament, n = Number of patients.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-8681152/v1/447d9215a3478d9cdacb31e2.png"},{"id":102212560,"identity":"ac539ab5-2bc1-4d77-aa22-7ba2ee8c8912","added_by":"auto","created_at":"2026-02-09 12:34:18","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":24130,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cem\u003eDistribution of second ACL injuries, graft ruptures (black bars) or contralateral ACL injuries (gray bars), for each year after RTS until date of data extraction. ACL = Anterior cruciate ligament, n = Number of patients, RTS = Return to sport.\u003c/em\u003e\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-8681152/v1/808ac5d0e3de6634728446a0.png"},{"id":105561974,"identity":"08495867-17ed-4659-a120-ce423e38df2a","added_by":"auto","created_at":"2026-03-27 12:20:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1027473,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8681152/v1/3f300e78-9b0a-49ee-8f0c-07541cc2dbaa.pdf"},{"id":102297102,"identity":"48181d21-96e4-4e28-a1ac-9986aa71f549","added_by":"auto","created_at":"2026-02-10 10:25:48","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":18033,"visible":true,"origin":"","legend":"","description":"","filename":"Appendix.docx","url":"https://assets-eu.researchsquare.com/files/rs-8681152/v1/c2e1399d27a4ff6f1e7d77cc.docx"}],"financialInterests":"","formattedTitle":"Increased hazard ratio of a second ACL injury after return to sport for each positive hypermobility test on the Beighton Score: a registry study.","fulltext":[{"header":"Key Points","content":"\u003cul\u003e\n \u003cli\u003eThere was an increased hazard ratio of second ACL injury for each positive test on the Beighton Score after return to sport after primary ACL reconstruction.\u003c/li\u003e\n \u003cli\u003eClinicians should consider the number of hypermobile joints in conjunction with presence of generalized joint hypermobility when assessing risk for second ACL injury.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Introduction","content":"\u003cp\u003ePatients who sustain an anterior cruciate ligament (ACL) injury typically participate in cutting or pivoting sports.(1) For patients who aim to return to sport (RTS), the current standard of care for the ACL injury consist of ACL reconstruction,(2) typically performed with an autograft.(1) Despite ACL reconstruction, up to 20% of all patients, and 23% of patients younger than 25 years, sustain a second ACL injury after RTS.(3) A factor proposed to increase risk of second ACL injury is generalized joint hypermobility (GJH).(4) The GJH phenotype is a congenital condition characterized by an altered structural integrity of collagen fibrils, which consequently leads to joint hyperextensibility compared to individuals without GJH.(5) The current consensus for assessment of GJH recommends the Beighton Score, which relies on 9 joint mobility tests, where the number of positive tests confirms GJH based on age and patient sex-dependent cutoff thresholds.(6)\u003csup\u003e,\u0026nbsp;\u003c/sup\u003e(7) Currently accepted thresholds for GJH based on the Beighton Score include ≥ 5/9 points for pre-pubertal males, and ≥ 4/9 points for post-pubertal males.(7) Females with pre- and post-puberal age criteria require an additional point to be assigned the GJH phenotype (≥ 6/9 and ≥ 5/9, respectively).(7) However, cautious interpretation of the Beighton Score is warranted, as joint mobility can be confounded by various factors, such as traumatically acquired joint hyper- or hypomobility(8, 9). The use of predetermined binary cutoff values to classify GJH could make accurate classification difficult, which could potentially lead to over- or underestimation of GJH prevalence, and incorrect second ACL injury risk-stratification. Given that joint hypermobility exists on a spectrum,(10) the associated risk of a second ACL injury is also likely to vary along a continuum. Accordingly, the total number of hypermobile joints may offer valuable insight into individual risk profiles. Despite this, the association between the number of positive joint hypermobility tests on the Beighton Score and the incidence of second ACL injury has been scarcely studied, but may provide a more informative alternative for second ACL injury risk assessment than relying on predetermined binary cutoffs.\u003c/p\u003e\n\u003cp\u003eThe purpose of this study was to analyze the association between the number of positive joint hypermobility tests on the Beighton Score and the hazard ratio (HR) of second ACL injury in patients who RTS after primary ACL reconstruction, which included secondary, stratified analyses of graft rupture and contralateral ACL injury. We hypothesized that there would be an increased HR based on the increased number of positive hypermobile joints on the Beighton Score.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cem\u003eStudy design\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe present study was a registry-based retrospective cohort study performed in accordance with the REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement.(11) Ethical approval has been obtained from the YYY (registration numbers: YYY, YYY), and the YYY, YYY (registration numbers: YYY, YYY).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSetting\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData was extracted from a rehabilitation specific registry (YYY), previously described in detail.\u003csup\u003eyyy,yyy\u003c/sup\u003e YYY was established in 2014 in YYY, YYY, with the aim to improve care for patients after ACL injury. Patients registered in YYY are invited to participate in supervised muscle function tests and answer web-based questionnaires at predefined follow-ups at 10 weeks, 4-, 8-, 12-, 18-, 24 months, 5 years and then every fifth year after ACL injury or reconstruction. Patients may register to YYY at any time after ACL injury or reconstruction. Upon registration in YYY, patients are required to provide demographic information, such as patient sex, date of birth, height, and weight. Joint hypermobility assessment is performed at the initial muscle function test and is conducted by a trained test supervisor.\u0026nbsp;The Beighton Score was added to YYYs standardized assessment protocol in 2019.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003ePatients\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003ePatients registered in YYY were checked for eligibility for inclusion by application of the following criteria: underwent primary ACL reconstruction performed with hamstring tendon- or bone-patellar tendon-bone autograft, were aged between 15 and 50 years at the time of primary ACL reconstruction, had registered Beighton Score with specific information on the presence of knee hyperextension, pre-injury participation in knee-strenuous sports, defined as ≥ 6 on the Tegner Activity Scale(12) (Tegner), RTS after primary ACL reconstruction, i.e., ≥ 6 on the Tegner, and sustained a second ACL injury (defined as graft rupture or contralateral ACL injury), or had ≥ 1 year follow-up after RTS without a second ACL injury.\u003c/p\u003e\n\u003cp\u003ePatients with ≥ 3 ACL injuries were excluded. The rationale for the chosen inclusion criteria was to study patients who were active in sports prior to primary ACL injury, and to allow adequate exposure time to sustain a second ACL injury after RTS.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eOutcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe primary outcome of interest was the HR of second ACL injury based on the number of positive hypermobility tests. The secondary outcomes were the HRs of isolated graft rupture and contralateral ACL injury based on the number of hypermobility tests. Patients were followed until the incidence of second ACL injury or the date of data extraction (January 2026).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eVariables\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eIncidence of second ACL injury\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eA second ACL injury (graft rupture or a contralateral ACL injury) can be reported by the responsible clinician or by the patient, after confirmation through clinical assessment or imaging. The occurrence of a second ACL injury is documented in the patient’s profile within the YYY database.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eTests of hypermobility\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Beighton Score assesses joint hypermobility on a 9-point scale,(6) and has been reported with a substantial to excellent inter- and intrarater reliability for raters, regardless of expertise.(13) The Beighton Score comprises 9 tests, where each positive test yields one point on the score, up to a maximum of 9 points. Eight of the tests are unilateral, and one is bilateral. The eight unilateral tests are performed bilaterally and consist of dorsiflexion of the metacarpal joints of the fifth finger beyond 90°, apposition of the thumbs to the flexor aspects of the forearms, hyperextension of the elbows and knees beyond 10°, and the one bilateral test is forward flexion of the trunk, with the knees straight, so that the palms of the hands can rest easily on the floor.(6) The Beighton Score is currently the most frequently used assessment tool for GJH.(7)\u003c/p\u003e\n\u003cp\u003eIn YYY, the unilateral tests are passively performed by a test supervisor. The trunk flexion test is performed actively by the patient. The assessment can be performed both prior and after ACL reconstruction, dependent on when the patients perform the first muscle function tests. To account for the potential altered joint mobility due to the ACL injury or reconstruction, the use of an injury allowance point is applied.(14) Application of an injury allowance point means to assign the result of the non-involved limb to the involved limb if the involved limb has altered joint mobility. In YYY the Beighton Score assessment is entered into the database as a total score, and a binary categorical variable (yes/no) is reported for the prevalence of knee hyperextension (≥ 10° knee extension).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMeasurement of knee-strenuous activity and RTS\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe Tegner is a self-reported questionnaire used to quantify the level of knee-strenuous activity performed before and after an injury.(12) The intraclass correlation coefficient for test-retest reliability for the Tegner was reported to be 0.8.(15) The original Tegner ranges from 0 to 10, where 10 represents highest knee demanding activity, such as professional football.(12) YYY utilizes a modified version of the Tegner that ranges between 1 to 10. Tegner level 6 was the cut-off used to determine RTS in the present study, as Tegner level 6 is the first level determined as knee-strenuous and only includes sport activities, such as ice-hockey, tennis, alpine skiing, or volleyball.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData collection\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eData was extracted from YYY for analysis on January 5, 2025. Data consisted of categorical data of patient sex, choice of autograft for primary ACL reconstruction, Beighton Score, presence of knee hyperextension, as well as incidence and time of second ACL injury. Furthermore, continuous demographic variables which include age, height, weight, body mass index, time between primary ACL injury and reconstruction, time between ACL reconstruction and RTS, follow-up time after RTS, and level of sport pre-injury and at RTS were extracted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eContinuous data was presented as mean with standard deviation (SD) for parametric data and median with interquartile range (IQR) for non-parametric data. Categorical data was presented as numbers with percentage. Follow-up time after RTS was analyzed with the Kruskal-Wallis test between patients with different numbers of positive joint hypermobility tests on the Beighton Score. The HR of second ACL injury was determined using multivariable cox proportional hazard regression models and was presented with a 95% confidence interval (CI). For the primary outcome, the dependent variable was the dichotomized incidence of second ACL injury after RTS (yes/no). For the secondary outcomes, the dependent variable was the dichotomized incidence of graft rupture or contralateral ACL injury, and in each analysis patients who sustained the alternative second ACL injury were censored at the time of injury. For the unadjusted and adjusted analysis, the independent variable was the continuous number of positive joint hypermobility tests assessed with the Beighton Score. For the adjusted analysis, the age at primary ACL reconstruction, return to pre-injury Tegner or higher (yes/no), autograft choice (hamstring tendon or bone-patellar tendon-bone), presence of knee hyperextension, and patient sex were added as confounders to the model based on their relevance in current literature.(16-25) For all outcomes, the adjusted models were checked for performance with the Grambsch and Thernaeu’s test for proportional hazards assumption, Harrell’s C-statistic for model discrimination, and likelihood ratio test for model fit. For model discrimination, Harrell’s C-statistic was used for the primary outcome, and interpreted as follows: \u0026lt; 0.60 poor discrimination; ≥ 0.6 to \u0026lt; 0.75 possibly helpful discrimination; and ≥ 0.75 useful discrimination.(26) For model fit, the likelihood ratio test assesses whether adding covariates to the model improves the ability to explain variation in hazard compared to a model without covariates, where a good fit is considered if p \u0026lt; 0.05. Alpha was set to p \u0026lt; 0.05. Statistical analyses were performed with the Statistical Product and Service Solutions (IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 29.0. Armonk, NY: IBM Corp.).\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eData for a total of 4,933 patients were extracted from YYY\u0026rsquo;s database, of which 935 patients were included (Figure 1). Of the included patients, 481 (51.4%) were female and the mean age at the time of ACL reconstruction was 23.7 \u0026plusmn; 7.8 years (Table 1). The median follow-up time from the time of RTS to the end point was 54.4 months (IQR: 47.5 months), which was significantly different between patients with different numbers of positive hypermobility tests on the Beighton Score (p \u0026lt; 0.001). Patients with 9 positive hypermobility tests on the Beighton Score had the shortest median follow-up time after RTS of 24.7 months (IQR: 29.7 months).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOver the study period, a total of 122 patients (13.0%) sustained a second ACL injury, of which 69 (56.6%) were graft ruptures, and 53 (43.4%) were contralateral ACL injuries. The median Beighton Score for all included patients was 2 (IQR: 4). The highest proportion of second ACL injuries were observed in patients with Beighton Scores 9 (21.4%), 5 (21.1%), and 7 (18.4%) (Figure 2). Figure 3 displays the distribution of second ACL injuries, stratified by graft ruptures or contralateral ACL injuries, for each year after RTS until the study end point.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 \u0026ndash; Demographic data for included patients.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"586\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 586px;\"\u003e\n \u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePatient demographics\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e, n = 935\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003ePatient sex, females, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e481 (51.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eAge, years mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e23.7 \u0026plusmn; 7.8\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eHeight, cm mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e174.8 \u0026plusmn; 9.1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eWeight, kg mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e71.9 \u0026plusmn; 11.7\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eBMI, mean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e23.4 \u0026plusmn; 2.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eKnee hyperextension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e283 (30.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTime from injury to ACL reconstruction, months median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e3.6 (4.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTime from ACL reconstruction to RTS, months median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e11.8 (4.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eFollow-up time after RTS, months median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e54.4 (47.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eLevel of sport pre-injury, Tegner median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e9.0 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eLevel of sport at RTS\u003cstrong\u003e,\u0026nbsp;\u003c/strong\u003eTegner median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e7.0 (2.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eBeighton Score, median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e2 (4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDistribution of patients across each Beighton Score\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e370 (39.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e78 (8.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e147 (15.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e65 (7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e101 (10.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e57 (6.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e47 (5.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e38 (4.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e18 (1.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e14 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGraft choice\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003cp\u003eHamstring tendon autograft\u003c/p\u003e\n \u003cp\u003eBone-Patellar Tendon-Bone autograft\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e732 (78.3)\u003c/p\u003e\n \u003cp\u003e203 (21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond ACL injury over the study period\u003c/strong\u003e, n (%)\u003c/p\u003e\n \u003cp\u003eGraft rupture, n (%)\u003c/p\u003e\n \u003cp\u003eContralateral ACL injury, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e122 (13.0)\u003c/p\u003e\n \u003cp\u003e69 (56.6)\u003c/p\u003e\n \u003cp\u003e53 (43.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime from RTS to second ACL injury, months median (IQR)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e12.4 (25.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTime from RTS to graft rupture, months median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e7.6 (12.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 302px;\"\u003e\n \u003cp\u003eTime from RTS to contralateral ACL injury, months median (IQR)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 284px;\"\u003e\n \u003cp\u003e28.0 (36.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 586px;\"\u003e\n \u003cp\u003eBMI = Body mass index, cm = Centimeters, GJH = Generalized joint hypermobility, IQR = Interquartile range, kg = Kilogram, n = Number of patients, RTS = Return to Sport, SD = Standard deviation, Tegner = Tegner activity scale.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary outcome\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOver the study period of median 54.4 months after RTS, the HR of second ACL injury was 1.10 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.003-1.22, p = 0.044) adjusted for age at primary ACL reconstruction, return to pre-injury level Tegner or higher, choice of autograft, presence of knee hyperextension, and patient sex (Table 2). The model demonstrated a possibly helpful discrimination (Harrell\u0026rsquo;s C = 0.621), the proportional hazards assumption was not violated (Grambsch and Thernaeu\u0026rsquo;s test p = 0.473), and the model showed good fit (\u0026chi;\u0026sup2; = 24.4, p \u0026lt; 0.001). Data availability throughout the study period is presented for respective 12-month period in Appendix Table 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2 \u0026ndash; Unadjusted and adjusted cox regression model to estimate the hazard ratio of second ACL injury over the study period after return to sport dependent on Beighton Score\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 270px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCovariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard ratio\u0026nbsp;\u003c/strong\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard ratio\u0026nbsp;\u003c/strong\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 108px;\"\u003e\n \u003cp\u003eBeighton Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 176px;\"\u003e\n \u003cp\u003e1.10 (1.03-1.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.10 (1.003-1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 624px;\"\u003e\n \u003cp\u003eACL = Anterior cruciate ligament, CI = Confidence interval, Tegner = Tegner activity scale.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003eAdjusted for age at primary ACL reconstruction, return to pre-injury level of Tegner or higher, choice of autograft for ACL reconstruction, presence of knee hyperextension, and patient sex.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNumber of second ACL injuries, i.e., graft rupture or contralateral ACL injury, n = 122.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary outcomes\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOver the study period, the adjusted HR of graft rupture was 1.15 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.01-1.30, p = 0.031) (Table 3). The model demonstrated a possibly helpful discrimination (Harrell\u0026rsquo;s C = 0.660), the proportional hazards assumption was not violated (Grambsch and Thernaeu\u0026rsquo;s test p = 0.466), and the model showed good fit (\u0026chi;\u0026sup2; = 22.9, p = 0.001). There was no difference in the adjusted HR of contralateral ACL injury based on the number of positive joint hypermobility tests on the Beighton Score (HR: 1.04, 95% CI: 0.89-1.21, p = 0.598). The model demonstrated a poor discrimination (Harrell\u0026rsquo;s C = 0.599), the proportional hazards assumption was not violated (Grambsch and Thernaeu\u0026rsquo;s test p = 0.962), and the model did not show good fit (\u0026chi;\u0026sup2; = 8.22, p = 0.222).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTable 3 \u0026ndash; Unadjusted and adjusted cox regression model to estimate the hazard ratio of graft rupture and contralateral ACL injury over the study period after return to sport dependent on Beighton Score\u003csup\u003ea\u003c/sup\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"624\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 236px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnadjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\" style=\"width: 246px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjusted\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOutcome/covariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard ratio\u0026nbsp;\u003c/strong\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eHazard ratio\u0026nbsp;\u003c/strong\u003e(95% CI)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ep-value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eGraft rupture\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBeighton Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.10 (1.002-1.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.044\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.15 (1.01-1.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eContralateral ACL injury\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 142px;\"\u003e\n \u003cp\u003eBeighton Score\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 142px;\"\u003e\n \u003cp\u003e1.10 (0.99-1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 94px;\"\u003e\n \u003cp\u003e0.065\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 151px;\"\u003e\n \u003cp\u003e1.04 (0.89-1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.598\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" valign=\"top\" style=\"width: 624px;\"\u003e\n \u003cp\u003eACL = Anterior cruciate ligament, CI = Confidence interval, Tegner = Tegner activity scale.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u003csup\u003ea\u0026nbsp;\u003c/sup\u003e\u003c/strong\u003eAdjusted age at primary ACL reconstruction, for return to pre-injury level of Tegner or higher, choice of autograft for ACL reconstruction, presence of knee hyperextension, and patient sex.\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eNumber of graft ruptures: n = 69; number of contralateral ACL injuries: n = 53.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main finding of this study was that for each unit increase in the number of positive joint hypermobility tests on the Beighton Score, the HR of second ACL injury after RTS increased by 10%, adjusted for age at primary ACL reconstruction, return to pre-injury Tegner level or higher at RTS, choice of autograft for primary ACL reconstruction, presence of knee hyperextension, and patient sex. The association between Beighton Score and the composite second ACL injury endpoint appeared primarily attributable to graft rupture (HR: 1.15, 95% CI: 1.01-1.30, p=0.031), whereas the estimate for contralateral ACL injury was smaller and inconclusive (HR: 1.04, 95% CI: 0.89-1.22, p=0.598). These findings suggest that clinicians should consider the number of positive joint hypermobility tests, rather than solely rely on a binary GJH classification when assessing and counseling patients on the risk of a second ACL injury after ACL reconstruction.\u003c/p\u003e\n\u003cp\u003ePatients with GJH have previously been reported to be at greater risk for a second ACL injury compared with patients without GJH.(4, 21, 27) A previous study reported 4.24 times greater HR of second ACL injury in patients with GJH compared to those without GJH.(4) However, the binary classification of GJH through the cutoffs in Beighton Score may risk to either overestimate or underestimate the presence of GJH. The greater HR observed with increasing numbers of positive joint hypermobility tests on the Beighton Score, suggests that GJH exists on a spectrum rather than being dichotomous characterized by a clear threshold. Consequently, our findings of 10% exponential increase in second ACL injury HR after RTS may underscore the importance of more refined assessment of joint hypermobility. Specifically, our findings suggest that the number of positive joint hypermobility tests, rather than the mere presence of GJH, should be considered in individualized rehabilitation and risk-stratification after primary ACL reconstruction.\u003c/p\u003e\n\u003cp\u003eThe use of the traditional binary classification of GJH based on the Beighton Score, Larson et al.,(21) and Zsidai et al.,(4) reported that patients with GJH had a second ACL injury incidence of 34.1% (mean follow-up time: 72 months), and 38.2% (≤ 84 months follow-up time), respectively, in contrast to 7.7%, and 10.1%, respectively, in patients without GJH. In the present study, the overall incidence of second ACL injury over a median follow-up time of 48 months was 12.9% where no classification of GJH was made. Nonetheless, previous studies(4, 21) have used two different cut-off points for the classification of the GJH phenotype. According to the most recent consensus,(28) different cut-off points for GJH are advocated with increased threshold for females and younger individuals, since joint hypermobility is more common in females and in the younger population. The need for different cut-off points for GJH in different sub-populations is further highlighted in a study by Singh et al.,(24) which reported that only a minority of patients were correctly classified with GJH when a single cut-off point was utilized on the Beighton Score. Nevertheless, the risk of misclassification of GJH is still possible even if different cut-off points in different sub-populations are applied. The results of this study offer an alternative to binary classification of GJH since we show that the HR of second ACL injury increases exponentially with each positive joint hypermobility test on the Beighton Score. For example, based on the adjusted HR of 1.10 per point, patients with 1, 2, or 3 positive Beighton Score tests had an estimated 10%, 21%, or 33% higher HR of second ACL injury, respectively, compared to patients with a score of 0. Consequently, although GJH assessment using a standardized method, such as the Beighton Score, remains valuable for second ACL injury risk-stratification, interpretation should not only consider the possible presence of GJH, but also the degree and extent of joint hypermobility. Patients should be counseled and informed accordingly with regard to the potential increased HR of second ACL injury after RTS after primary ACL reconstruction. Future research should aim to identify rehabilitation and surgical factors that increase the likelihood of a RTS with minimal risk of re-injury for high-risk patients, and, if none are sufficient, explore the option of advising against RTS.\u003c/p\u003e\n\u003cp\u003eThe timing of second ACL injuries differed substantially between components: graft ruptures occurred earlier after RTS (median 7.6 months), whereas contralateral ACL injuries occurred later (median 28 months). This observed temporal separation was consistent with previous literature on graft rupture and contralateral injury,(29) which reflects partly distinct processes and may partly explain why the composite second ACL injury association was more apparent for graft rupture than for contralateral ACL injury. For clinicians, the results suggest to prioritize early post-RTS strategies aimed at reducing graft failure risk, while recognizing that contralateral injury risk may emerge later and warrants continued preventive efforts beyond the first year.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLimitations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThe presented study has some limitations. First, the degree of hypermobility in the joint, i.e., joint angle was not accounted for, but only the threshold for a positive test in the Beighton Score was considered. Second, only the reported level of physical activity on the Tegner was analyzed in this study, and not the exact sport or exposure time the patients were undertaking in their sport. Greater and more intense exposure to knee demanding maneuvers would likely increase the risk for second ACL injury. Third, only 117 (12.5%) patients included in the study had Beighton Score ≥ 6, which may potentially limit the statistical precision of our analysis. Fourth, the results of our study could be affected by potential concomitant ligamentous or intraarticular injuries, which include medial collateral ligament injury(30) or lateral meniscus injury(31), which are not reported in YYY. Lastly, we could not account for additional surgical procedures, such as the lateral extra-articular tenodesis, performed in addition to the ACL reconstruction, which has been shown to reduce the risk of second ACL injury.(32)\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe HR of second ACL injury after RTS in patients with primary ACL reconstruction increased by 10% for each positive joint hypermobility test on the Beighton Score. The presented findings should prompt clinicians to consider the number of positive joint hypermobility tests, and not solely rely on binary GJH classification, when assessing risk for second ACL injury after ACL reconstruction.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePartial financial support was granted from Research and development primary health care Gothenburg and Södra Bohuslän.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo competing interests to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe principles of the Helsinki declaration have been used as guidance in this study. Ethical approval has been obtained from the Swedish Ethical Review Authority (registration number: 2020-02501, 2024-08724-01), and the Regional Ethical Review Board in Gothenburg, Sweden (registration numbers: 265–13, T023–17).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData for this study is based on a rehabilitation registry project (Project ACL), where all patients have received written information and have given their\u0026nbsp;informed consent in the research project.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData and material availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available on reasonable request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePermission to reproduce material from other sources\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAi disclosure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring the preparation of this work the authors used ChatGPT 4o and 5.2 in order to enhance readability. After using this tool/service, the authors reviewed and edited the content as needed and take full responsibility for the content of the published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJakob Lindskog drafted the initial version of the manuscript, performed analysis of data, has approved the final work for publication, and has agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eAxel Sundberg, Bálint Zsidai, Johan Högberg, Rebecca Hamrin Senorski, Behnam Liaghat, and Ramana Piussi have contributed majorly during the analysis and interpretation of data, has made important contributions during the drafting of the work, has approved the final work, and has agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eKristian Samuelsson and Roland Thomeé have contributed during the interpretation of data, made meaningful contributions during the final stages of manuscript drafting, has approved the final work, and has agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003eEric Hamrin Senorski has contributed majorly during the drafting of the manuscript, analysis and interpretation of data, is responsible for the design concept, has approved the final work, and has agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot Applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration of interests\u003c/strong\u003e\u003cbr\u003e\u0026nbsp;\u0026nbsp;\u003cbr\u003e\u0026nbsp;☐\u0026nbsp;The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.\u003cbr\u003e\u0026nbsp;\u0026nbsp;\u003cbr\u003e\u0026nbsp;☒\u0026nbsp;The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eForssblad M. Svenska kn\u0026auml;ligamentsregistret (Eng: The Swedish knee ligament registry). Annual report 2024. XBase 2023 [Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://aclregister.nu/media/uploads/Annual%20reports/rapport2024.pdf\u003c/span\u003e\u003cspan address=\"https://aclregister.nu/media/uploads/Annual%20reports/rapport2024.pdf\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeredith SJ, Rauer T, Chmielewski TL, Fink C, Diermeier T, Rothrauff BB et al. Return to sport after anterior cruciate ligament injury: Panther Symposium ACL Injury Return to Sport Consensus Group. J Isakos. 2021;6(3):138\u0026thinsp;\u0026ndash;\u0026thinsp;46.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWiggins AJ, Grandhi RK, Schneider DK, Stanfield D, Webster KE, Myer GD. Risk of Secondary Injury in Younger Athletes After Anterior Cruciate Ligament Reconstruction: A Systematic Review and Meta-analysis. Am J Sports Med. 2016;44(7):1861\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZsidai B, Piussi R, Thome\u0026eacute; R, Sundemo D, Musahl V, Samuelsson K et al. Generalised joint hypermobility leads to increased odds of sustaining a second ACL injury within 12 months of return to sport after ACL reconstruction. Br J Sports Med. 2023.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRemvig L, Jensen DV, Ward RC. Are diagnostic criteria for general joint hypermobility and benign joint hypermobility syndrome based on reproducible and valid tests? A review of the literature. J Rheumatol. 2007;34(4):798\u0026ndash;803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis. 1973;32(5):413\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148\u0026ndash;57.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNicholson LL, Simmonds J, Pacey V, De Wandele I, Rombaut L, Williams CM, et al. International Perspectives on Joint Hypermobility: A Synthesis of Current Science to Guide Clinical and Research Directions. J Clin Rheumatol. 2022;28(6):314\u0026ndash;20.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKeays SL, Mason M, Newcombe PA. Individualized physiotherapy in the treatment of patellofemoral pain. Physiother Res Int. 2015;20(1):22\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarroll MB. Hypermobility spectrum disorders: A review. Rheumatol Immunol Res. 2023;4(2):60\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBenchimol EI, Smeeth L, Guttmann A, Harron K, Moher D, Petersen I, et al. The REporting of studies Conducted using Observational Routinely-collected health Data (RECORD) statement. PLoS Med. 2015;12(10):e1001885.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTegner Y, Lysholm J. Rating systems in the evaluation of knee ligament injuries. Clin Orthop Relat Res. 1985(198):43\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBockhorn LN, Vera AM, Dong D, Delgado DA, Varner KE, Harris JD. Interrater and Intrarater Reliability of the Beighton Score: A Systematic Review. Orthop J Sports Med. 2021;9(1):2325967120968099.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStewart DR, Burden SB. Does generalised ligamentous laxity increase seasonal incidence of injuries in male first division club rugby players? Br J Sports Med. 2004;38(4):457\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eThome\u0026eacute; P, W\u0026auml;hrborg P, B\u0026ouml;rjesson M, Thome\u0026eacute; R, Eriksson BI, Karlsson J. Self-efficacy, symptoms and physical activity in patients with an anterior cruciate ligament injury: a prospective study. Scand J Med Sci Sports. 2007;17(3):238\u0026ndash;45.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWebster KE, Feller JA, Leigh WB, Richmond AK. Younger patients are at increased risk for graft rupture and contralateral injury after anterior cruciate ligament reconstruction. Am J Sports Med. 2014;42(3):641\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGrindem H, Snyder-Mackler L, Moksnes H, Engebretsen L, Risberg MA. Simple decision rules can reduce reinjury risk by 84% after ACL reconstruction: the Delaware-Oslo ACL cohort study. Br J Sports Med. 2016;50(13):804\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eF\u0026auml;ltstr\u0026ouml;m A, Kvist J, H\u0026auml;gglund M. High Risk of New Knee Injuries in Female Soccer Players After Primary Anterior Cruciate Ligament Reconstruction at 5- to 10-Year Follow-up. Am J Sports Med. 2021;49(13):3479\u0026ndash;87.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKrebs NM, Barber-Westin S, Noyes FR. Generalized Joint Laxity Is Associated With Increased Failure Rates of Primary Anterior Cruciate Ligament Reconstructions: A Systematic Review. Arthroscopy. 2021;37(7):2337\u0026ndash;47.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLindskog J, H\u0026ouml;gberg J, Simonsson R, Piussi R, Zsidai B, Samuelsson K et al. Primary Anterior Cruciate Ligament reconstruction performed with hamstring tendon autograft leads to an over four times greater rate of second ACL rupture after return to sport in patients with generalized joint hypermobility compared to bone-patellar tendon-bone autograft. Arthroscopy. 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarson CM, Bedi A, Dietrich ME, Swaringen JC, Wulf CA, Rowley DM, et al. Generalized Hypermobility, Knee Hyperextension, and Outcomes After Anterior Cruciate Ligament Reconstruction: Prospective, Case-Control Study With Mean 6 Years Follow-up. Arthroscopy. 2017;33(10):1852\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFares A, Horteur C, Abou Al Ezz M, Hardy A, Rubens-Duval B, Karam K, et al. Posterior tibial slope (PTS)\u0026thinsp;\u0026ge;\u0026thinsp;10 degrees is a risk factor for further anterior cruciate ligament (ACL) injury; BMI is not. 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Orthop J Sports Med. 2025;13(5):23259671251330655.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRezansoff A, Firth AD, Bryant DM, Litchfield R, McCormack RG, Heard M et al. Anterior Cruciate Ligament Reconstruction Plus Lateral Extra-articular Tenodesis Has a Similar Return-to-Sport Rate to Anterior Cruciate Ligament Reconstruction Alone but a Lower Failure Rate. Arthroscopy. 2023.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Anterior cruciate ligament reconstruction, RTS, Postoperative complications, graft rupture, contralateral ACL injury, joint instability","lastPublishedDoi":"10.21203/rs.3.rs-8681152/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8681152/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eGeneralized joint hypermobility increases the risk of second anterior cruciate ligament (ACL) injury. The clinical diagnosis of GJH relies on a binary threshold of positive joint hypermobility tests, based on age and patient sex, which may overlook the degree of hypermobility.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePurpose\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo analyze the association between the number of positive joint hypermobility tests on the Beighton Score and the hazard ratio (HR) of second anterior cruciate ligament (ACL) injury in patients who return to sport (RTS) after primary ACL reconstruction, which included secondary, stratified analyses of graft rupture and contralateral ACL injury.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDesign:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eRegistry study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData was extracted in January 2026 from an ACL-rehabilitation-specific registry, YYY. Included patients were 15–50 years who underwent primary ACL reconstruction with hamstring tendon or bone-patellar tendon-bone autograft, had a documented Beighton Score, participated in knee-strenuous sports before injury, had RTS, reported second ACL injury or had ≥ 1 year follow-up without second ACL injury after RTS. Multivariable Cox proportional hazard regression was used to estimate the HR of second ACL injury (measured from RTS) based on the Beighton Score, adjusted for age, return to pre-injury physical activity level or higher, graft choice, knee hyperextension (≥ 10° knee extension), and patient sex.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe analysis included 935 patients (mean age 23.7 ± 7.8 years, 51.4% female), with median Beighton Score of 2 (interquartile range: 4). The median follow-up time was 54.4 months. Second ACL injury was reported in 122 (13.0%) patients. The adjusted HR of second ACL injury after RTS was 1.10 times greater for each positive joint hypermobility test on the Beighton Score (95% CI: 1.003–1.22, p = 0.044).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe HR of second ACL injury after RTS in patients who had undergone primary ACL reconstruction increased by 10% for each positive joint hypermobility test on the Beighton Score.\u003c/p\u003e","manuscriptTitle":"Increased hazard ratio of a second ACL injury after return to sport for each positive hypermobility test on the Beighton Score: a registry study.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 12:34:13","doi":"10.21203/rs.3.rs-8681152/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major Revision","date":"2026-04-19T18:26:35+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"","date":"2026-02-05T04:59:51+00:00","index":0,"fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-04T19:50:40+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"Sports Medicine-Open","date":"2026-02-03T21:49:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T06:01:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Sports Medicine-Open","date":"2026-01-26T01:09:07+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":"e1b4a6c6-491c-4216-af7b-5ae594aaf818","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-05T21:10:33+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-09 12:34:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8681152","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8681152","identity":"rs-8681152","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}