Björn Barenius

Increased Risk of Osteoarthritis After Anterior Cruciate Ligament Reconstruction A 14-Year Follow-up Study of a Randomized Controlled Trial

Background: The reported prevalence of radiological osteoarthritis (OA) after anterior cruciate ligament (ACL) reconstruction varies from 10% to 90%. Purpose/Hypothesis: To report the prevalence of OA after ACL reconstruction and to compare the OA prevalence between quadrupled semitendinosus tendon (ST) and bone–patellar tendon–bone (BPTB) grafts. The hypothesis was that there would be no difference in OA prevalence between the graft types. The secondary aim was to study whether patient characteristics and additional injuries were associated with long-term outcomes. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Radiological examination results, Tegner activity levels, and Knee injury and Osteoarthritis Outcome Score (KOOS) values were determined in 135 (82%) of 164 patients at a mean of 14 years after ACL reconstruction randomized to an ST or a BPTB graft. Osteoarthritis was defined according to a consensus by at least 2 of 3 radiologists of Kellgren-Lawrence grade ≥2. Using regression analysis, graft type, sex, age, overweight, time between injury and reconstruction, additional meniscus injury, and a number of other variables were assessed as risk factors for OA 14 years after ACL reconstruction. Results: Osteoarthritis of the medial compartment was most frequent, with 57% of OA cases in the ACL-reconstructed knee and 18% of OA cases in the contralateral knee (P < .001). There was no difference between the graft types: 49% of OA of the medial compartment for BPTB grafts and 65% for ST grafts (P = .073). The KOOS results were lower for patients with OA in all subscales, indicating that OA was symptomatic. No difference in the KOOS between the graft types was found. Meniscus resection was a strong risk factor for OA of the medial compartment (odds ratio, 3.6; 95% CI, 1.4-9.3) in the multivariable logistic regression analysis. Conclusion: A 3-fold increased prevalence of OA was found after an ACL injury treated with reconstruction compared with the contralateral healthy knee. No differences in the prevalence of OA between the BPTB and quadrupled ST reconstructions were found. An initial meniscus resection was a strong risk factor for OA; the time between injury and reconstruction was not.

Quality of Life and Clinical Outcome After Anterior Cruciate Ligament Reconstruction Using Patellar Tendon Graft or Quadrupled Semitendinosus Graft: An 8-Year Follow-up of a Randomized Controlled Trial

Background: Randomized controlled trials after anterior cruciate ligament reconstructions with long-term follow-up including assessment of health-related quality of life are rare. Purpose: To compare clinical outcome and health-related quality of life 8 years after anterior cruciate ligament reconstruction using 2 types of graft. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: Long-term follow-up of 164 patients with anterior cruciate ligament injury randomized to arthroscopic reconstruction with a quadrupled semitendinosus graft or a bone–patellar tendon–bone graft was undertaken. After a mean 8 years, 153 patients were available for follow-up, including instrumented laxity, 1-legged hop test, a knee-walking test, and assessment with International Knee Documentation Committee, Lysholm, Tegner, and patellofemoral pain score. Health-related quality of life was assessed with Knee Osteoarthritis Outcome Score and Short Form–36. Results: Patients in both graft groups retained the same stability, knee function, and health-related quality of life. The patellofemoral pain score was similar for both groups; the bone–patellar tendon–bone group had more donor site morbidity from kneeling and knee walking. In the bone–patellar tendon–bone group, 19 patients had no kneeling problems, 23 slight problems, 31 moderate problems, and 5 unable to kneel. Corresponding figures for the semitendinosus group were 25, 32, 16, and 2 (P < .001). Patients with early reconstructions (<5 months) had a lower risk for meniscal injuries (37%) than did later reconstructed (62%, P = .008). Health-related quality of life regarding physical functioning in Short Form–36 was better for the early-reconstructed patients than for the later reconstructed (92 vs 85; P = .014). Patients without medial meniscal surgery had higher Knee Osteoarthritis Outcome Scores for all subscales than did patients with medial meniscal surgery, with most significant difference for sport and recreation (63 vs 75, P = .008). Conclusion: In the long term, the semitendinosus graft provided similar stability, knee function, and health-related quality of life but with less kneeling morbidity than did the bone–patellar tendon–bone graft.

Targeted deletion of Atg5 in chondrocytes promotes age-related osteoarthritis

Objectives It has been suggested that the lysosomal recycling process called macro-autophagy plays a role in osteoarthritis development. We thus decided to genetically ablate the autophagy-indispensable Atg5 gene specifically in chondrocytes and analyse the development of osteoarthritis upon aging and in a post-traumatic model. Methods Mice lacking the Atg5 gene in their chondrocytes (Atg5cKO) were generated by crossing Atg5-floxed mice with transgenic mice that expressed cre recombinase driven by the collagen type 2 promoter. Animals were analysed at the age of 2, 6 and 12 months for age-related osteoarthritis or underwent mini-open partial medial meniscectomy at 2 months of age and were analysed 1 or 2 months after surgery. We evaluated osteoarthritis using the Osteoarthritis Research Society International (OARSI) scoring on safranin-O-stained samples. Cell death was evaluated by terminal deoxy-nucleotidyl-transferase-mediated deoxy-UTP nick end labelling (TUNEL) and by immunostaining of cleaved caspases. Results We observed the development of osteoarthritis in Atg5cKO mice with aging including fibrillation and loss of proteoglycans, which was particularly severe in males. The ablation of Atg5 was associated with an increased cell death as assessed by TUNEL, cleaved caspase 3 and cleaved caspase 9. Surprisingly, no difference in the development of post-traumatic osteoarthritis was observed between Atg5cKO and control mice. Conclusions Autophagy protects from age-related osteoarthritis by facilitating chondrocyte survival.

Hamstring tendon anterior cruciate ligament reconstruction: does gracilis tendon harvest matter?

PurposeHamstring tendon grafts are a popular choice for anterior cruciate ligament (ACL) reconstruction. Typical morbidity reported after hamstring tendon harvest is muscle weakness in flexion, and whilst still a matter for debate, this morbidity may be greater if the gracilis tendon is harvested in addition to the semitendinosus.This study sought to comprehensively compare the outcome of ACL reconstructions in which the semitendinosus was harvested alone (ST group) or with the gracilis (ST/G group).MethodsTwenty patients (ten ST, ten ST/G) were assessed with a variety of measures that included subjective scores, function, strength and tibial rotation as measured by gait analysis during a pivoting task.ResultsResults showed that the graft diameter was significantly larger in the ST group, but there were no other differences between the groups for any other outcome measure.ConclusionHarvesting the gracilis in addition to semitendinosus does not appear to affect either the outcome or graft-related morbidity after hamstring ACL reconstruction.

Superficial cells are self-renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice.

Articular cartilage has little regenerative capacity. Recently, genetic lineage tracing experiments have revealed chondrocyte progenitors at the articular surface. We further characterized these progenitors by using in vivo genetic approaches. Histone H2B–green fluorescent protein retention revealed that superficial cells divide more slowly than underlying articular chondrocytes. Clonal genetic tracing combined with immunohistochemistry revealed that superficial cells renew their number by symmetric division, express mesenchymal stem cell markers, and generate chondrocytes via both asymmetric and symmetric differentiation. Quantitative analysis of cellular kinetics, in combination with phosphotungstic acid–enhanced micro–computed tomography, showed that superficial cells generate chondrocytes and contribute to the growth and reshaping of articular cartilage. Furthermore, we found that cartilage renewal occurs as the progeny of superficial cells fully replace fetal chondrocytes during early postnatal life. Thus, superficial cells are self‐renewing progenitors that are capable of maintaining their own population and fulfilling criteria of unipotent adult stem cells. Furthermore, the progeny of these cells reconstitute adult articular cartilage de novo, entirely substituting fetal chondrocytes.—Li, L., Newton, P. T., Bouderlique, T., Sejnohova, M., Zikmund, T., Kozhemyakina, E., Xie, M., Krivanek, J., Kaiser, J., Qian, H., Dyachuk, V., Lassar, A. B., Warman, M. L., Barenius, B., Adameyko, I., Chagin, A. S. Superficial cells are self‐renewing chondrocyte progenitors, which form the articular cartilage in juvenile mice. FASEB J. 31, 1067–1084 (2017). www.fasebj.org

Meniscal Sutures are Superior to Bioabsorbable Arrows: Results After 918 Consecutive Meniscal Repairs in a Dual Center Analysis

Objectives: It has been long known that removal of the meniscus can lead to degenerative changes, and preserving surgery rather than meniscal resection is likely to have better long-term outcomes. Success rates after meniscal repair ranges from 60- 95%, but with most studies having small number of patients. The purpose of this study was to review all meniscal repairs, and potential predictors for failure, during a 12-year period. Methods: A dual center retrospective analysis was performed on two consecutive cohorts of meniscal repairs, during the period 1999-2011 and 1999-2010 respectively. Data from surgical protocols and follow up charts were reviewed including type of tear, location, associated injury to the knee, and surgery. Study endpoint was failure of repair, which was defined as a need for reoperation and secondary partial or total meniscal resection, within 3 years. Kaplan-Meier was used to assess repair device survival. Results were expressed as hazard ratios (HR) with 95% confidence intervals (CI) and were adjusted for confounding factors using cox regression. results: 954 meniscal repairs were performed on 918 patients (n = 536 males [58%] and 382 females [42%]) with a mean age of 23 years (12-60). 64% underwent medial meniscal repair and 36% underwent lateral meniscal repair. 4% were repaired both medially and laterally. 75% of the repairs were performed using meniscal sutures (predominantly Fast-Fix), and 25% of the meniscal tears were repaired using bioabsorbable arrows (Biofix). The median time from injury to surgery was 23 days (0-360). The reoperation rate in the whole cohort was 29%. 35% of the medial meniscal repairs failed and 17% failures were noted on the lateral side.
Repair with bioabsorbable arrows on the medial meniscus resulted in reoperation in 44% of the cases, whereas the reoperation rate for meniscal sutures was 32% on the medial side. On the lateral side 18% failures were noticed when using arrows, and 17% when sutures were used.
62% of the patients had a simultaneous anterior cruciate ligament (ACL) injury. When medial meniscal repair was preformed with simultaneous ACL-reconstruction 26% of the meniscal repairs failed, when no simultaneous ACL- reconstruction was performed 37% of the meniscal repairs failed and with no associated ACL-injury 41% of the meniscal repairs failed.
Analyzing failure in a multivariate cox regression, adjusted according to age, gender, meniscus, ACL-pathology and days- to-surgery, revealed a higher failure rate for medial meniscal repairs (HR 3.006 [2.074-4.355; p = 0.000). Bioabsorbable arrows had significantly more failures than meniscal sutures (HR 1.656 [1.207-2.273]; p = 0.002). With reference to no ACL injury, meniscal repairs performed with a simultaneous ACL-reconstruction resulted in less failure than when no simultaneous ACL-reconstruction was performed (HR 0.605 [0.413-0.885]; p = 0.010). Conclusion: The failure rate was significantly higher on the medial side, especially when using Biofix-arrows. Patients who underwent a simultaneous ACL-reconstruction had a significantly better healing than conservatively treated ACL-ruptures, and patients with no ACL-injury. Age and days-to-surgery were not significant factors for failure.

Acute Vs Delayed ACL Reconstruction. Early Differences and Preliminary Two Year Results A Randomized Controlled Trial

Objectives: Historically acute ACL reconstruction has been avoided due to reports of early rehabilitation problems with stiffness. Are these reports still valid today with modern arthroscopic techniques? Methods: 70 patients with a high recreational activity level (Tegner ≥6) who presented with a acute ACL injury were randomized to an acute reconstruction within 8 days from the injury or delayed reconstruction after 6-10 weeks. Four surgeons performed the ACL reconstructions with quadrupled semitendinosus tendon grafts and endobutton and metallic interference screw fixation. The rehabilitation training was performed at the same physiotherapy center for all patients. The follow up at 6 and 24 months included ROM, Lachman, Rolimeter, pivot shift, one leg hop, IKDC, KOOS, Lysholm and Tegner activity level. Results: There were no differences between the groups in ROM, IKDC, activity level or laxity at 6 months. Four patients had a combined extension and flexion deficit of more than 15 degrees, two from each group. In the acute group 79% had an objective IKDC grade A or B compared with 73% in the delayed group. The one leg hop index above 90% was found in 50% in the acute group and 24% in the delayed group (p=0.04). Functional data for the 2-year follow up are not available at the time of abstract writing. The median activity level according to Tegner was restored to pre-injury levels in both groups after one year, and was stationary at 2 years. The visual analogue scale (VAS) response to the question “How is your knee working on a scale from 0-100? (100 = best)” revealed 81 in the acute and 71 in the delayed group (p=0.1). To the question “How does your knee affect your activity level on a scale from 0-100? (100 = no affection)” the mean score was 75 in the acute group and 67 in the delayed group (p=0.3). At one and two years the KOOS was statistically similar between the groups but with slightly higher subscale “Sport and recreation” scores, 85 in the acute group at 2 years compared to 78 in the delayed group (p=0.2). At the meeting preliminary results regarding functional tests and additional procedures for the groups will be presented. Conclusion: No negative effects of an acute ACL reconstruction were found at 6 months follow up. Preliminary 2 year results point in the same direction. Acute reconstruction of the ACL seems to be safe and a potential benefit might be decreased loss of muscle function. Further analysis of the 2 year results is needed before final conclusions can be drawn.

Results Are Similar Two Years After Acute or Delayed Anterior Cruciate Ligament Reconstruction. A Randomized Controlled Trial

Objectives: Acute ACLR has been avoided since the 1990’s due to reports of postoperative stiffness. But are these risks still valid with modern arthroscopic techniques? The aim of this randomized controlled trial was to assess the impact of the time between injury and reconstruction on the outcome after ACLR. Our hypothesis was that acute ACLR with semitendinosus graft can be performed safely. Methods: The primary endpoint was ROM at three months after surgery. A power calculation revealed the need for 64 patients to detect a ROM difference of 5 degrees between the groups (5% significance level). 70 patients with a high recreational activity level (Tegner ≥6) who presented with an acute ACL injury were randomized to an acute reconstruction within 8 days from the injury or delayed reconstruction (after normalized ROM) 6-10 weeks after the injury. Fixation was with Endobutton in femur and a metallic interference screw in tibia. The rehabilitation was performed at the same physiotherapy center for all patients. Follow up assessment was performed by a physiotherapist not involved with the rehabilitation. The follow up at 24 months included ROM, Lachman, instrumented laxity with Rolimeter, pivot shift, one leg hop index, Biodex, IKDC, KOOS, Lysholm and Tegner Activity level, and a VAS question regarding knee function and the knee function’s effect on activity level. Results: Seventy percent of the patients were males, mean age at the time of surgery was 27 years (18 -41) and the median pre-injury Tegner level was 9 (6-10) with no differences between the groups. 64 (91%) patients were assessed at three months with no difference according to the primary endpoint. Median Tegner level was restored to pre-injury levels in both groups after one year, and did not change between one and two years. 63 (90%) patients were available for the 2-year follow up. There was one graft rupture and one contralateral ACL injury in both groups. There was additional surgery in 15% of the acute patients and in 31% in the delayed (n.s.). The mean instrumented laxity was 1.8 mm in the acute and 2.0 in the delayed group. There were no positive pivot shift in the acute group and 6 patients with grade 1 or not possible to perform in the delayed group (p=0.039). IKDC revealed no significant differences between the groups. Lysholm score was 87 in both groups. KOOS values showed no significant difference between the groups. VAS response to the question “How is your knee working on a scale from 0-100? (100 = best)” was 81 in the acute and 71 in the delayed group (p=0.1) and “How does your knee affect your activity level? (100 = no affection)” the mean score was 75 in the acute and 67 in the delayed group (p=0.3). Functional strength (one leg hop index >90%) was 85% in the acute and 67% in the delayed group (n.s). Conclusion: We found no increased risk of arthrofibrosis after acute ACLR. Good results can be achieved at two years regardless of ROM and swelling in the acute stage.

Acute ACL Surgery Decreases First Year Socio Economic Costs Compared to Delayed Reconstruction: A Randomized Controlled Trial

Objectives: Clinical practice has been to avoid acute ACL reconstruction due to the risk of complications, especially arthrofibrosis. Thus, a general rule has been to wait with reconstruction until he knee is “calm” which usually means 4-8 weeks following injury. Furthermore there is often also a prolonged waiting time due to operating space and other logistic factors. Since most of the patients undergoing ACL reconstruction are of working age, there is a potentially large socio-economic loss due to the fact that many of these patients are unable to work from the time of injury to the time of reconstruction. The aim of this study was to assess and compare the total number of sick leave days caused by the knee injury from the day of injury and over the first year between sub acute and delayed reconstruction. Methods: 70 patients with high recreational activity level, Tegner level of 6 or more, who presented with an acute ACL injury were randomized to acute reconstruction within 8 days from the injury or delayed reconstruction 6-10 weeks post injury. Four surgeons performed the ACL reconstructions with quadrupled semitendinosus tendon grafts. Patients were assessed at 6,12 and 24 months and these follow ups included Biodex strength test, Lachman, Rolimeter, pivot shift, one leg hop, IKDC, KOOS, Lysholm and Tegner activity level. With data from the Swedish Social Insurance Agency (Försäkringskassan) information about the number of sick leave days from the day of the knee injury and over the following twelve months was collected. The data was recalled based on diagnostic numbers related to the specific knee-injury and compared between the two groups. Results: Seventy percent of the patients were males, mean age at the time of inclusion was 27 years (18 -41) and the pre-injury median Tegner level was 9 (5-10), with no differences between the groups. 15/70 patients were students without registered compensation for sick leave, 5 in the acute and 10 in the delayed group. 4 patients in the acute group and 1 in the delayed group were neither students nor registered for any compensation for sick leave from work. One patient from the delayed group resigned from the study before surgery. The remaining 49 patients, 26 patients in the acute and 23 in the delayed group received compensation for sick leave due to the injury. The number of sick leave days for the acute group was significantly lower, mean 57 (median 53) days compared to the delayed group, mean 99 (median 66) days (p<0.05). Conclusion: Acute ACL reconstruction seems to significantly reduce socio economic costs (compensation for sick leave) compared to delayed reconstruction. From a nation based perspective this could have major implications in health care spending.