Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

Atraumatic Spontaneous Achilles Tendon Rupture in Patients Receiving Oral Corticosteroids Treated With the Modified Side-Locking Loop Suture Technique.

Atraumatic spontaneous Achilles tendon ruptures sometimes occur in patients receiving oral corticosteroids. In general, these cases are treated surgically; however, delayed postoperative management can lead to impaired activities of daily living. The modified side-locking loop suture (SLLS) technique is a useful suture method for safe and early active mobilization. Three cases of spontaneous Achilles tendon ruptures were treated with the modified SLLS technique with good clinical results. The modified SLLS technique is a useful method with a short rehabilitation period for treating atraumatic spontaneous Achilles tendon rupture in patients undergoing corticosteroid therapy.

A genome-wide association study identifies a locus associated with knee extension strength in older Japanese individuals.

Sarcopenia is a common skeletal muscle disease in older people. Lower limb muscle strength is a good predictive value for sarcopenia; however, little is known about its genetic components. Here, we conducted a genome-wide association study (GWAS) for knee extension strength in a total of 3452 Japanese aged 60 years or older from two independent cohorts. We identified a significant locus, rs10749438 which is an intronic variant in TACC2 (transforming acidic coiled-coil-containing 2) (P = 4.2 × 10-8). TACC2, encoding a cytoskeleton-related protein, is highly expressed in skeletal muscle, and is reported as a target of myotonic dystrophy 1-associated splicing alterations. These suggest that changes in TACC2 expression are associated with variations in muscle strength in older people. The association was consistently observed in young and middle-aged subjects. Our findings would shed light on genetic components of lower limb muscle strength and indicate TACC2 as a potential therapeutic target for sarcopenia.

Meniscal Allograft Transplantation Concomitant With Cartilage Repair for Symptomatic Lateral Meniscus-Deficient Knees With Over Two Years of Follow-up.

Background and objective The treatment for symptomatic meniscus-deficient knees with cartilage defects remains challenging on account of insufficient meniscal substitutes. One solution for this might involve combining meniscal allograft transplantation (MAT) and cartilage repair. In this study, we aimed to analyze the effectiveness and safety of MAT concomitant with cartilage repair for symptomatic lateral meniscus-deficient knees in a setting with limited availability of meniscal transplants in Japan. Methods Nine patients who underwent MAT concomitant with osteochondral transplantation (five) and/or autologous chondrocyte implantations (seven) were followed up for at least two years (mean: 51.2 months, range: 24-84 months). Their demographic data and other characteristics were as follows - mean age: 51.7 years, range: 36-67 years; men/women: 4/5; cause: trauma/discoid meniscus: 8/1; cartilage defect size: mean: 6.7 cm2/knee, range: 1.0-11.3. The effectiveness and safety were evaluated clinically by using the Lysholm Knee Scoring Scale (LKSS) and Japanese Orthopaedic Association (JOA) knee score, physical examination, X-rays, and MRI preoperatively and at one, 12, and 24 months after the implantation. Differences between the variables were analyzed using the Friedman test and Scheffe's multiple comparisons. Results The median LKSS and JOA scores significantly improved from 70 points (range: 21-80) and 35 (25-45) preoperatively to 86.5 (65-98) and 87.5 (80-95) at 24 months after surgery, respectively (p<0.001, p=0.0013). The range of motion (ROM), femorotibial angle, and the lateral joint space showed no significant changes. However, lateral meniscal extrusions (LMEs) increased by 3.0 mm (range: 0-6.3 mm) at one month postoperatively and remained unchanged until two years postoperatively. Treatment failure occurred in one case, which was revised by total knee arthroplasty (TKA) at 18 months postoperatively. Additional surgeries were needed in some cases: lateral meniscal tear (three cases), contracture (two cases), and patellar instability (one case). However, neither infection nor allergic reaction was observed in the blood exams. Conclusions Although MAT concomitant with cartilage repair showed good clinical outcomes, half of the cases needed additional surgeries. Based on our findings, this technique should be adopted only in select cases and performed by a handful of highly experienced surgeons.

Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.

Total knee arthroplasty combined with medial patellofemoral ligament augmentation using a Leeds-Keio ligament for 'Windswept deformity' with ipsilateral valgus deformity and permanent patellar dislocation: A case report and a literature review.

We present a 'Windswept deformity' in patient who had osteoarthritis with a mild varus and very severe valgus with ipsilateral permanent patellar dislocation. An 83-year-old woman could not walk for the past a few years due to bilateral knee pain. The femorotibial angle was 196° in the right knee pre-operatively and 134° in the left knee with permanent patellar dislocation. She underwent a staged total knee arthroplasty (TKA) for the right knee, and a semi-constrained TKA for the left knee with medial patellofemoral ligament (MPFL) augmentation using a Leeds-Keio (LK) ligament. At the final follow-up three years after surgery, bilateral knee pain and the extension lag had disappeared and range of motion (ROM) was 0° in extension and 130° in flexion for both knees without patellar re-dislocation. This clinical case indicates that the unconstrained and semi-constrained type of TKA combined with the MPFL augmentation using an LK ligament is effective to treat a 'Windswept deformity'.

Fibromas arising from the posterior cruciate ligament tendon sheath in the bilateral knee joints: Case report.

Fibroma of tendon sheath in the intra-knee joint is a very rare and benign soft-tissue tumour which has been reported unilaterally in the various aged people. To help distinguish it from other similar kinds of lesions and symptoms including osteoarthritis, we report the oldest case of fibromas arising from the posterior cruciate ligament tendon sheath in the bilateral knee joints within one year of each other confirmed with magnetic resonance imaging (MRI) features, operative findings and histological examination.

Longitudinal Change of Medial and Lateral Patellar Stiffness After Reconstruction of the Medial Patellofemoral Ligament for Patients with Recurrent Patellar Dislocation.

BACKGROUND: Longitudinal changes in patellar stiffness following reconstruction of the medial patellofemoral ligament for recurrent patellar dislocation at full extension are unknown. METHODS: Fifteen consecutive patients (three men and twelve women, with a mean age of twenty-two years) with seventeen knees were matched by sex and age to thirty-two reference subjects in this prospective study. The follow-up period was a minimum of twenty-four months. The medial patellofemoral ligament reconstruction used an autograft semitendinosus tendon and an interference screw system with or without lateral release under 10 N of laterally directed force. The medial patellar stiffness and lateral patellar stiffness were measured in 0° of knee extension using the Patella Stability Tester preoperatively; postoperatively at three, six, twelve, and eighteen months; and at the time of the latest follow-up. Before and after the surgical procedure, patients were evaluated for apprehension and Kujala and Lysholm scores; radiographic examinations were performed to evaluate changes, including osteoarthritic changes. RESULTS: The medial stiffness of the affected side before the surgical procedure was significantly lower than the lateral stiffness (p = 0.004) and the stiffness for healthy reference knees (p = 0.004). Medial stiffness three months after the surgical procedure was significantly elevated compared with lateral values (p = 0.027), preoperative values (p < 0.001), and reference group values (p = 0.002); reached the reference level by six months; and was maintained for up to two years. Furthermore, medial stiffness and lateral stiffness were well balanced after six months and this balance was sustained for up to two years postoperatively. No recurrent dislocation occurred during the follow-up period; one patient experienced apprehension. Postoperative radiographic findings and clinical scores were significantly improved at the time of the latest follow-up (p < 0.05). One knee progressed to patellofemoral osteoarthritis. CONCLUSIONS: The value for medial stiffness was significantly improved three months after medial patellofemoral ligament reconstruction compared with the preoperative and lateral values and returned to the reference level by six months. Medial stiffness and lateral stiffness of the patella were well balanced by six months and retained that balance for up to two years, with good clinical results. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Simultaneous anterior cruciate ligament reconstruction and dome-shaped high tibial osteotomy for severe medial compartment osteoarthritis of the knee.

BACKGROUND: The optimal surgical procedure to address both anterior cruciate ligament (ACL) deficiency and medial compartment osteoarthritis (OA) has been controversial. CASE REPORT: A 49-year-old woman with a 30-year history of chronic anterior cruciate ligament (ACL) deficiency, medial compartment osteoarthritis, and varus deformity presented with medial knee pain and apprehension with walking and playing soccer. Her preoperative range of motion was from 0° of extension to 135° of flexion. The anterior drawer sign (1+), Lachman test (1+), and pivot shift test (glide) were positive before surgery, as measured by the International Knee Documentation Committee knee examination form. The patient underwent simultaneous arthroscopic ACL single-socket and single-bundle reconstruction using hamstring tendons, dome-shaped high tibial osteotomy using the TomoFix fixation device, and mosaicplasty to the medial condyle. The standing femorotibial angle changed from 185° preoperatively to 172° postoperatively. Range of motion exercises were started 1 week after surgery, and partial weight bearing was allowed 2 weeks after surgery. The patient returned to her baseline physical level 2 years after the operation. Range of motion was -10° of extension and 130° of flexion, and the anterior drawer sign, Lachman test, and pivot shift test were all negative at the final 3-year follow-up. CONCLUSION: An ACL reconstruction combined with a dome-shaped high tibial osteotomy using a locking plate is one option for treating an aged athlete with ACL deficiency and severe medial compartment osteoarthritis, and can allow the athlete to return to sports activity.

A comparison of patient-reported outcomes and arthroscopic findings between drilling and autologous osteochondral grafting for the treatment of articular cartilage defects combined with anterior cruciate ligament injury.

BACKGROUND: To compare the patient-reported outcomes and arthroscopic findings between drilling and autologous osteochondral grafting (AOG) for the treatment of articular cartilage defects combined with anterior cruciate ligament (ACL) injuries. METHODS: The subjects were 40 patients who had articular cartilage defects in the weight-bearing part of the medial and lateral femur condyle combined with ACL injuries that were treated by drilling (20 patients) or AOG (20 patients) at the same time as ACL reconstruction was performed. In the drilling group patients, lesions were penetrated with multiple 1.2-mm Kirschner wires, and in the AOG group patients, grafts were made to cartilage defects from one to three osteochondral pegs harvested from the less-weight-bearing periphery of the articular surface of the femoral condyle. The patient-reported outcomes were assessed using the International Knee Documentation Committee (IKDC) subjective knee examination score. Second-look arthroscopy was performed to evaluate the repaired cartilage macroscopically. RESULTS: The median follow-up duration was 25 (range, 12-42) months. The IKDC scores were significantly improved from 64.4 to 95.4 points in the drilling group and from 52.3 to 94.3 points in the AOG group, with no difference between the two groups, although there was a difference in the repaired cartilage findings of arthroscopy. CONCLUSION: In this study, no differences in IKDC scores were found in patients with a concomitant ACL rupture and an osteochondral lesion treated by drilling or AOG at a minimum follow-up of 1year, regardless of the differences at arthroscopic grading of the ICRS classification. LEVEL OF EVIDENCE: Case-control study (LEVEL III).