Rapid Progression Of Osteoarthritis Research Articles

Development of a Novel Rat Knee Osteoarthritis Model Induced by Medial Meniscus Extrusion.

The medial meniscus extrusion (MME) is associated with increased stress on the knee joint, which leads to cartilage degeneration. To evaluate the etiology of knee osteoarthritis, it is extremely important to create animal models of the disease that more closely resemble actual clinical conditions in terms of symptomatology, molecular biology, and histology. This study aimed to create a clinically relevant model of MME in rats. Behavioral, molecular biological, and histological changes in the newly developed rat MME model were compared with those in sham and medial meniscus transection and medial collateral ligament transection (MMT) models to examine the characteristics of this model. In the MME rat model, behavioral evaluation shows abnormalities in gait compared with the other 2 groups, and molecular biological evaluation of the infrapatellar synovia of rats shows that gene expression of inflammatory cytokines, matrix-degrading enzymes, and pain-related nerve growth factor was increased compared with the sham group. Furthermore, histological evaluation reveals that cartilage degeneration was the most severe in the MME group. The newly developed MME model reproduced the characteristic pathology of MME in clinical practice, such as severe pain, inflammation, and rapid progression of osteoarthritis. The MME model, which might more closely mimic human knee osteoarthritis (OA), could be a useful model for elucidating the pathophysiology and considering therapeutic management for knee OA.

Terrible triad injuries

The complex injury pattern of aposterior elbow dislocation with concomitant radial head and coronoid fractures is usually referred to as a terrible triad injury. Due to the concomitant compromise of several osteoligamentous structures of the elbow joint relevant for stability, these injuries pose aparticularly major challenge to the treating trauma surgeons. For this reason, acareful preoperative analysis of all relevant injury components is mandatory in order to make an adequate treatment decision. In most cases, surgical treatment addressing all elements relevant for stability is necessary to achieve astable and congruent elbow joint. Only this enables early functional follow-up treatment and minimizes the complication rate. Delayed or even insufficient treatment with persistent (sub)dislocation must be avoided at all costs, otherwise there is ahigh risk of serious posttraumatic functional disorders of the elbow with rapid progression of osteoarthritis.

Meniscus Root Tears: A Clinical Review.

Meniscus root tears are important to recognize early given their potentially devastating consequences on joint health. This injury results in the lost ability of the meniscus to transfer axial loads into hoop stress; therefore, it is functionally equivalent to a complete meniscectomy. This causes rapid progression of osteoarthritis and increased need to total knee arthroplasty in a previously healthy joint. Despite these consequences, root tears have only been discussed in the orthopedic literature in the last 10 to 15 years and have not been routinely integrated into nonoperative sports medicine education. It is important for all nonoperative sports medicine providers to properly diagnose and triage this injury early in its course to maximize joint preservation efforts. The goal of this manuscript is to review the anatomy, presentation, natural history, imaging, and treatment options for meniscal root tears.

Superior capsular reconstruction for management of massive irreparable rotator cuff tears: current concepts

Irreparable massive rotator cuff tears in active middle-aged patients result in significant shoulder dysfunction and challenge surgeons in their treatment selection. Superior capsular reconstruction (SCR) is a joint-preserving surgical option that restores glenohumeral stability and prevents superior humeral head migration, thereby improving shoulder function, lessening pain, and limiting development of rotator cuff arthropathy. Indications for SCR are irreparable supraspinatus and/or infraspinatus tears with persistent shoulder pain and/or dysfunction for which conservative treatment has failed in a patient who is not an ideal candidate for arthroplasty because of age or activity level. Patients must have relatively preserved glenohumeral cartilage, an intact or repairable subscapularis tendon, and a fully functioning deltoid muscle to be an appropriate candidate for SCR. The procedure was originally described by Dr. Teruhisa Mihata using fascia lata autograft; however, in North America, dermal allograft has become the most common graft choice. The graft is secured medially to the superior glenoid with two or three suture anchors and laterally to the tuberosity commonly using four anchors in a double-row configuration. Preliminary clinical studies demonstrate significant improvement in pain, function, muscle strength, active shoulder range of motion with resolution of pseudoparalysis, normalization of the acromiohumeral interval, and no rapid progression of osteoarthritis. Superior capsular reconstruction is a viable, joint-sparing surgical option for irreparable massive rotator cuff tears.

Relative Efficacy and Safety of Tanezumab for Osteoarthritis: A Systematic Review and Meta-analysis of Randomized-Controlled Trials.

The aim of this meta-analysis was to evaluate the efficacy and safety of tanezumab for the treatment of patients with knee or hip osteoarthritis (OA). PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were searched from inception to July 2020. Randomized-controlled trials comparing tanezumab with placebo or nonsteroidal anti-inflammatory drugs in patients with OA. Two investigators identified studies and independently extracted data, and conventional meta-analyses were conducted with Review Manager 5.3. The outcomes were pain relief, functional improvement, and risk of adverse events (AEs). A total of 8 articles, comprising 9 randomized-controlled trials, were included. Overall, tanezumab was superior to placebo for relieving pain and improving function, as well as in the patient's global assessment. Tanezumab also had significant advantages over nonsteroidal anti-inflammatory drugs for relieving pain and improving function, as well as in the patient's global assessment. Significantly more patients discontinued treatment because of AEs after treatment with tanezumab. However, the differences in serious AEs and total joint replacement were not significant. Moreover, tanezumab-treated patients experienced significantly more rapid progression of osteoarthritis. Tanezumab can alleviate pain and improve function for patients with OA of the hip or knee. Although tanezumab does not cause serious AEs, rapid progression of OA occurred in a small number of participants, so more clinical trials are needed to explore its safety.

Use of tanezumab for chronic pain treatment

The problem of chronic musculoskeletal pain, the cause of severe suffering and disability of hundreds of millions of people on our planet, is far from being solved. Pain control is particularly difficult in patients with severe forms of osteoarthritis (OA) and chronic non-specific low back pain (CLBP). Popular analgesics – nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids, demonstrate moderate effectiveness and a high risk of adverse events (AE). This leads to the search for new approaches for analgesic therapy. Tanezumab is a monoclonal antibody that specifically blocks nerve growth factor, which plays a key role in the development of chronic pain. A series of phase II and III studies showed that tanezumab was administered intravenously or subcutaneously at a dose of 2.5 mg to 20 mg once every 8 weeks. In patients with OA or CNSLBP, it has a pronounced and persistent analgesic effect that exceeds the effect of placebo, and is equal to or superior to the effect of many months of daily intake of naproxen, celecoxib, diclofenac, oxycodone and tramadol. Tanezumab can cause various AE, primarily rapid progression of OA (in 2.6–6.0%) and neurological disorders (paresthesia and hyposthesia, in ≈5%). At the same time, the progression of OA was significantly more often observed with the combined use of tanezumab and NSAIDs. Nevertheless, taking into account the characteristics of patients who used tanezumab (patients with pain refractory to standard treatment; severe forms of OA), the good analgesic potential of tanezumab allows us to consider it as a promising tool for the control of chronic musculoskeletal pain, which will be widely used in real clinical practice.

Patient Characteristics Independently Associated With Knee Osteoarthritis Symptom Severity at Initial Orthopedic Consultation.

The objective of this study was to identify patient and disease characteristics associated with the symptomatic severity of knee osteoarthritis (OA) at the time of initial knee OA diagnosis by an orthopedist. This medical records review included patients initially diagnosed with knee OA during 2016 to 2017 by a single orthopedic surgeon in a university-based tertiary care setting. All variables were assessed at first OA diagnosis. Main outcomes were subscales of the Knee Injury and Osteoarthritis Outcome Score-Pain, other Symptoms, knee-related quality of life, and function in daily living. Multivariable regression analyses examined the following predictors of main outcomes: sex, race, age, insurance type, body mass index, Charlson comorbidity index, and radiographic OA severity (Kellgren-Lawrence grade). Of the 559 patients included in the study, most were African American (52.1%), female (71.7%), and had severe radiographic OA (Kellgren-Lawrence grade, 4; 68.7%). Female sex, African American racial/ethnic group, Medicaid insurance, younger age, and severe radiographic OA were independently statistically significantly associated with worse symptoms, pain, and function (p < 0.05 for all). Body mass index and Charlson comorbidity index were not statistically significant predictors of any outcome. This study identified disparities in the perception of knee OA problems at initial orthopedist diagnosis based on sex, age, race, insurance, and radiographic OA severity. Because most of these variables are also associated with more rapid progression of OA, identifying their biopsychosocial underpinnings may help determine which interventions are most likely to redress these disparities and delay progression to end-stage knee OA.

New ideas about the pathogenesis of osteoarthritis, the role of metabolic disorders

The article highlights the current data on the prevalence and pathogenesis of osteoarthritis (OA), presents a new definition of the disease, research results on the heterogeneity of OA, its relationship with obesity and metabolic syndrome. Obesity is one of the main factors in the development and more rapid progression of OA, and the presence of metabolic syndrome not only increases the risk of developing the disease, but also determines its severity. It is noted that with an increase of the components of the metabolic syndrome, the severity of OA increases. Therefore, hyperuricemia is associated with the presence of osteophytes and the progression of osteoarthritis, hyperglycemia - with the severity of the clinical manifestations and radiological progression. Much attention is given to the treatment of patients with OA and The European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) recommendations for the treatment of knee joints OA updated in 2019. In which for the first time a symptomatic slow-acting drugs for osteoarthritis (SYSADOAs) are assigned as the basis in the treatment of OA. The data on the effectiveness of some drugs from this group are presented. The glycosaminoglycan-peptide complex, which contains pharmacologically high-quality chondroitin sulfate when administered intramuscularly, has a significant effect on the symptoms, and in case of continued use, slows the progression of OA. The multicenter open-label prospective study of diacerein in patients with knee-joint OA combined with metabolic syndrome showed that during therapy pain syndrome and stiffness are reduced, and functional condition of the joints and quality of life of patients improves quickly and significantly. In addition, the positive effect of the drug on some components of the metabolic syndrome was demonstrated: a significant decrease in body mass index, low density lipoproteins, triglycerides, glucose and uric acid.

When Is Osteonecrosis Not Osteonecrosis?: Adjudication of Reported Serious Adverse Joint Events in the Tanezumab Clinical Development Program.

Tanezumab, a monoclonal antibody against nerve growth factor, has demonstrated efficacy in clinical trials of chronic pain in osteoarthritis (OA) and chronic low back pain. Unexpected adverse events (AEs) described as osteonecrosis (ON) occurred during tanezumab development, leading the US Food and Drug Administration to impose a partial clinical hold for all indications except cancer pain. A blinded Adjudication Committee (AC) including orthopedic surgeons, rheumatologists, and an orthopedic pathologist reviewed and adjudicated joint-related AEs in the tanezumab clinical program. The AC adjudicated all reported cases of ON as well as cases of total joint replacements (TJRs) not reported as ON for which radiographs obtained within 9 months of the surgery were available. The AC prespecified categories for joint safety events including primary ON, worsening OA (rapid progression of OA [RPOA], normal progression of OA, insufficient information to distinguish between rapid and normal progression of OA), other, or insufficient information to distinguish between primary ON and worsening OA or another diagnosis. The AC reviewed events in 249 of 386 patients with an investigator-reported AE of ON and/or a TJR. Two events were adjudicated as primary ON, 200 events were adjudicated as worsening OA (68 of which were classified as RPOA), 29 events had another diagnosis, 11 had insufficient information to distinguish primary ON from worsening OA, and 7 did not have committee member consensus. Despite initial reports, tanezumab treatment was not associated with an increase in ON but was associated with an increase in RPOA. Higher doses of tanezumab, tanezumab administered with nonsteroidal antiinflammatory drugs, and preexisting subchondral insufficiency fractures were risk factors for RPOA in this cohort.

Serious joint-related adverse events in randomized controlled trials of anti-nerve growth factor monoclonal antibodies

Reports of serious joint adverse events (AEs) due to osteonecrosis were noted during randomized placebo-controlled clinical trials of monoclonal antibodies to nerve growth factor (NGF), including tanezumab and fulranumab. All available medical records from subjects with reported cases of osteonecrosis, as well as records of subjects who underwent joint replacement during these studies, were reviewed by an independent adjudication committee that was established by each company; the committees were different for each company and included distinct individual experts. Cases were categorized as having definite osteonecrosis, normal or rapid progression of osteoarthritis (OA), another diagnosis or unable to determine the underlying diagnosis. The vast majority of investigator reported cases of osteonecrosis were adjudicated as either normal or rapid progression of OA. Indeed, the syndrome of rapid progression of OA associated with chondrolysis and bone destruction appears to be a safety signal that is associated with not only increasing doses of anti-NGF antibodies but also concomitant therapy with nonsteroidal anti-inflammatory drugs. These results have implications for future clinical trials of anti-NGF agents in OA and other painful conditions.

Importance of osteotomy around to the knee for medial gonarthritis. Indications, technique and results

Frontal plane deformities result in significant overload of the (ipsilateral) affected compartment of the knee and in rapid progression of osteoarthritis. The indication for osteotomy around the knee is related mainly to the constitutional metaphyseal deformity in the frontal plane. Exact analysis and planning based on a long-leg standing radiograph is mandatory. Valgus high tibial osteotomy can be performed safely and atraumatically by biplanar open-wedge osteotomy from medial using a specific plate-fixator. A new technique of closed wedge biplanar distal femur osteotomy with fixation by a new plate fixator is also presented. Our multicenter follow-up study with 533patients revealed good functional outcome scores with a small complication rate. The subjective ratings were better than in comparable groups with unicondylar knee replacement and with total knee arthroplasty. Metaanalysis from the literature have proven good long-term results of osteotomy around the knee. Osteotomy around the knee results in good middle-term and long-term results if the indication criteria are respected and a specific surgical technique is used.

Arthroscopic Partial Limbectomy in Hip Joints With Acetabular Hypoplasia

The purpose of this study was to clarify whether arthroscopic partial excision of a torn labrum in acetabular hypoplasia leads to rapid progression of osteoarthritis. Clinical case study. We performed arthroscopic partial limbectomy in 10 hips with pre- or early osteoarthritis secondary to acetabular hypoplasia. All the patients were females with mechanical symptoms such as giving way, catching, locking, or clicking sound. Their ages at the time of surgery ranged from 14 to 62 years (mean, 33.7 y). The follow-up period ranged from 2 to 14 years (mean, 8 y). None of the hips had subluxation. Arthroscopic surgery was performed in the supine position on a traction table, using a simultaneous 3-directional approach. The preoperative center-edge (CE) angle ranged from 0 degrees to 20 degrees (mean, 12.4 degrees). In all patients, preoperative radiographs and magnetic resonance imaging (MRI) depicted no tear of the acetabular labrum, whereas arthroscopic examinations revealed tears incarcerated in the joint space. Coxalgia improved within 4 or 5 days after surgery in all patients, showing that the torn labrum had caused the pain. The tears were classified as bucket-handle type in 6 hips, degenerative type in 3 hips, and flap type in 1 hip. Mechanical symptoms had subsided or disappeared in all hips postoperatively for a mean follow-up of 8 years. Radiographs revealed no evidence of osteoarthritis progression, although one case with a preoperative CE angle of 0 degrees showed lateralization of the femoral head. Labral tears in acetabular hypoplasia or dysplastic hip are mostly the bucket-handle type, located at the anterosuperior part of the acetabulum. Incarceration of the torn labrum in the joint space causes coxalgia. Rapid progression of osteoarthritis after limbectomy was not observed up to 8 years after surgery in this series. Level IV.

Anterior cruciate reconstruction combined with valgus upper tibial osteotomy: 12 years follow-up

A retrospective review of 29 patients (30 knees) was carried out who had previously undergone a single-stage combined ACL reconstruction with valgus upper tibial osteotomy for chronic ACL rupture coupled with early medial tibio-femoral arthritis. Of the 30 knees, 19 (63%) had had a previous medial meniscectomy. Major complications occurred in two knees resulting in stiffness. At a mean of 12 years follow-up (6–16 years) only five knees (17%) had progressed one arthritis grade. Fourteen patients (47%) returned to intensive sports, and a further 11 (37%) played moderate sports. The mean difference in anterior tibial translation with the opposite normal knee was 3 mm at review. It was concluded that the combined operation has a low morbidity, controls anterior laxity, allows many patients to return to sports, and does not result in a rapid progression of osteoarthritis.