Risk Of Developing Osteoarthritis Research Articles

Long-Term Clinical and Radiographic Outcomes of Meniscus Allograft Transplant.

To reduce pain, improve function and possibly mitigate the risk for development of osteoarthritis in patients with functionally deficient meniscus pathology, meniscal allograft transplantation (MAT) can be used to restore native joint biomechanics and increase knee joint longevity. This review explores the senior author's preferred bridge-in-slot technique and recently published long-term clinical and radiographic outcomes following MAT. Recent literature demonstrates MAT to be a safe and largely successful procedure for patients with functional meniscus deficiency. A majority of patients reach established minimal clinically important difference (MCID) values. Graft survivorship is approximately 80% at 10years, significantly delaying and in some cases, preventing the need for future joint reconstruction procedures in these young patients. Return to sport rates are over 70%, revealing meniscal allografts can withstand high impact activities. Cartilage damage at the time of MAT increases the risk for graft and clinical failure, though this may be mitigated with a concomitant cartilage restoration procedure. Meniscal allograft transplantation can provide a durable and effective long-term solution to meniscal deficiency in symptomatic patients who wish to decrease the risk of symptomatic progression and possibly further osteoarthritis and continue activities of daily life and sports with less pain and more function. By restoring more normal joint biomechanics, MAT can mitigate the potential need for future knee arthroplasty in this young active patient population.

Dysregulated fibrinolysis and plasmin activation promote the pathogenesis of osteoarthritis.

Joint injury is associated with risk for development of osteoarthritis (OA). Increasing evidence suggests that activation of fibrinolysis is involved in OA pathogenesis. However, the role of the fibrinolytic pathway is not well understood. Here, we showed that the fibrinolytic pathway, which includes plasminogen/plasmin, tissue plasminogen activator, urokinase plasminogen activator (uPA), and the uPA receptor (uPAR), was dysregulated in human OA joints. Pharmacological inhibition of plasmin attenuated OA progression after a destabilization of the medial meniscus in a mouse model whereas genetic deficiency of plasmin activator inhibitor, or injection of plasmin, exacerbated OA. We detected increased uptake of uPA/uPAR in mouse OA joints by microPET/CT imaging. In vitro studies identified that plasmin promotes OA development through multiple mechanisms, including the degradation of lubricin and cartilage proteoglycans and induction of inflammatory and degradative mediators. We showed that uPA and uPAR produced inflammatory and degradative mediators by activating the PI3K, 3'-phosphoinositide-dependent kinase-1, AKT, and ERK signaling cascades and activated matrix metalloproteinases to degrade proteoglycan. Together, we demonstrated that fibrinolysis contributes to the development of OA through multiple mechanisms and suggested that therapeutic targeting of the fibrinolysis pathway can prevent or slow development of OA.

Is the Surface Anatomy of the Popliteal Crease Related to Lower Extremity Alignment or Knee Osseous Morphology? A Radiographic Study.

Background and objectives: The popliteal crease varies among individuals, and there has been no prior study on this aspect. We assumed that it may be associated with lower extremity alignment and osseous morphology. To demonstrate this, we conducted a radiographic analysis. Materials and Methods: The study was conducted on 121 knees of 63 patients, whose popliteal creases were well distinguished on clinical photographs. PCOA was defined as the angle between the longitudinal axis of the lower leg and the popliteal crease. Through the radiologic examinations performed, the HKA, MPTA, mLDFA, JLCA, MFCA/TEA, and PCA/TEA were measured. Pearson correlation analysis and multiple linear regression analysis were performed on the PCOA and the six radiologic measurements to analyze the relationship. Results: Pearson correlation analysis found HKA had the highest coefficient at 0.568. In multiple linear regression, only HKA was associated, excluding all other measurements. Conclusions: Popliteal crease obliquity is significantly associated with coronal plane lower extremity alignment and exhibits a stronger correlation than with underlying knee osseous morphology. If future research is conducted based on this, popliteal crease could serve as a valuable clue for predicting lower extremity alignment and the risk of osteoarthritis development.

GLYCOSAMINOGLYCAN SULFATION AS NICHE INSTRUCTION FEATURE TO DIRECT CHONDRAL VERSUS ENDOCHONDRAL IN VIVO DIFFERENTIATION OF MESENCHYMAL STROMA CELLS

Purpose: Articular cartilage has a low regeneration capacity and frequently fails to repair after injury, posing a severe risk for development of osteoarthritis (OA). OA is an age-associated disease and, in view of an expanding aging population, there is an increasing demand for regenerative therapies to meet this clinical need. Harnessing human mesenchymal stroma cells (MSC) for articular cartilage regeneration is still hampered by an inability to steer cells into the chondral developmental pathway to obtain articular chondrocytes (AC) with a stable phenotype.

Monocytes, Macrophages, and Their Potential Niches in Synovial Joints - Therapeutic Targets in Post-Traumatic Osteoarthritis?

Synovial joints are complex structures that enable normal locomotion. Following injury, they undergo a series of changes, including a prevalent inflammatory response. This increases the risk for development of osteoarthritis (OA), the most common joint disorder. In healthy joints, macrophages are the predominant immune cells. They regulate bone turnover, constantly scavenge debris from the joint cavity and, together with synovial fibroblasts, form a protective barrier. Macrophages thus work in concert with the non-hematopoietic stroma. In turn, the stroma provides a scaffold as well as molecular signals for macrophage survival and functional imprinting: “a macrophage niche”. These intricate cellular interactions are susceptible to perturbations like those induced by joint injury. With this review, we explore how the concepts of local tissue niches apply to synovial joints. We introduce the joint micro-anatomy and cellular players, and discuss their potential interactions in healthy joints, with an emphasis on molecular cues underlying their crosstalk and relevance to joint functionality. We then consider how these interactions are perturbed by joint injury and how they may contribute to OA pathogenesis. We conclude by discussing how understanding these changes might help identify novel therapeutic avenues with the potential of restoring joint function and reducing post-traumatic OA risk.

Long wait times for knee and hip total joint replacement in Canada: An isolated health system problem, or a symptom of a larger problem?

IntroductionThe wait times crisis for hip and knee total joint replacement surgery has been a significant health care issue in Alberta and across Canada. Significant resource and financial efforts have been put forward to reduce wait times for surgery as a means of treating patients with osteoarthritis (OA), but the gains achieved were not sustained. ObjectiveTo effectively address wait time issues, an alternative perspective on this problem is presented – that the wait times are an immediate problem for those needing surgery, but are also a symptom of the bigger issue of an inability of health care systems in Canada to address the needs of individuals with early OA with first-line treatment protocols. DiscussionIn considering this more comprehensive understanding of the overall OA management problem, encapsulated by the concept of an “osteoarthritis funnel”, we outline potential approaches for a solution on a systemic level that integrates services delivery, health care resource allocation and conceptualization of OA in research activities. It also emphasizes the need for a more effective and relevant program of research to address this complex problem that requires unique solutions. ConclusionsNew approaches and understanding are needed to address integrated implementation of effective first-line treatments for newly diagnosed osteoarthritis to prevent the expanding demand for joint replacement surgery. While the focus here is on the Canadian perspective, the need to develop and implement better first-line treatments for those with early OA and those at risk for development of OA is not unique to Canada.

FAI morphology increases the risk for osteoarthritis in young people with a minimum follow-up of 25years.

The mechanical conflict in symptomatic femoroacetabular impingement can lead to early osteoarthritis. However, radiographic impingement morphology is often seen in asymptomatic individuals. Long-term observation regarding the risk of developing osteoarthritis in these individuals is lacking. Our study addressed the following questions: Does femoroacetabular impingement morphology increase the risk for development of osteoarthritis after at least 25years? If yes, which radiographic parameter is the most predictive? Does the level of activity influence the risk for development of osteoarthritis? Are PROM influenced by the grade of osteoarthritis in this population? We investigated 51 (32 male, 19 female) patients for whom AP pelvis and Dunn view radiographs were available with a minimum follow-up of 25years. Alpha angle in AP pelvis and Dunn view radiographs, femoral torsion in Dunn view, lateral center edge angle, cross-over sign, posterior wall sign and prominence of ischial spine sign in AP pelvis radiographs were determined. On the follow-up radiographs, osteoarthritis was graded. Tegner Score for the time of the index radiograph was evaluated. Harris Hip Score and Western Ontario and McMaster Universities Osteoarthritis Index were assessed at latest follow-up. The mean follow-up was 43years (range 25-58). Cam impingement morphology showed to increase the risk for development of osteoarthritis: Alpha angles of ≥ 55° on AP pelvis and Dunn view radiographs were associated risk factors and showed an OR of 1.05 (p = 0.002) and 1.10 (p = 0.001), respectively. Abnormal femoral torsion and acetabular retroversion were not risk factors for osteoarthritis. Tegner Score at index presentation, HHS and WOMAC Score did not correlate with the grade of osteoarthritis. This study showed that cam impingement morphology in young patients raises the risk for development of hip osteoarthritis by 5-10% in a long-term follow-up with a minimum of 25years, thus its contribution was small.

Взгляд на остеоартрит коленных суставов и бег через призму МРТ-исследований

The number of women and the elderly has now increased among marathon runners. This cohort has a high risk of osteoarthritis development. The hypothesis, based on little scientific evidence, is that the additional stress on knee joints that occurs during long running can potentially lead to damage to joint structures and osteoarthritis development. The review presents modern generalized data on magnetic resonance imaging (MRI) of knee joints in long-distance runners. Special attention is paid to the syndrome of fluid increase in subchondral bone, which is determined by increasing the signal intensity in T2-weighted images (decrease in T1-weighted images), called bone marrow oedema (BMO). Classification and pathogenetic variants of BMO development (theory of intrusion and contusion) are presented. Particular cases of BMO development in marathon runners are considered. The dynamics of BMO in different time intervals after the races in beginners and professional marathon runners is described. Changes in MRI images of knee cartilage after running on the treadmill in healthy women and in women suffering from osteoarthritis are shown. A comparison of the frequency of osteoarthritis of knee joints in runners compared to footballers and weightlifters was made. The conclusion was made on the preventive effect of long walking and running (at least 12.5 km/week), including marathon distances, on the development and progression of osteoarthritis of knee joints.

Dynamic Varus and the Development of Iliotibial Band Syndrome.

Although the risk of osteoarthritis development after acute knee injury has been widely studied, the long-term consequences of knee overuse injury are not well understood. To identify the relationship between gait-related risk factors associated with osteoarthritis and the development of iliotibial band syndrome (ITBS) in members of a single University Army Reserve Officers' Training Corps unit. Prospective cohort study. Biomechanics laboratory. Sixty-eight cadets undergoing standardized physical fitness training. Three-dimensional lower extremity kinematics (240 Hz) and kinetics (960 Hz) were collected for 3 bilateral trials during shod running at 4.0 m/s ± 10%. Injury tracking was conducted for 7 months of training. Biomechanical variables, including varus thrust and knee-adduction moment, were compared between the injured and control groups. Twenty-six cadets with no history of overuse injury served as the control group, whereas 6 cadets (7 limbs) who developed ITBS that required them to modify their training program or seek medical care (or both) served as the injured group. Maximum varus velocity was higher ( P = .006) and occurred sooner during stance ( P = .04) in the injured group than in the control group, indicating greater varus thrust. Maximum knee-varus angle and maximum knee-adduction moment were higher ( P = .02 and P = .002, respectively) and vertical stiffness was lower ( P = .03) in the injured group. Measures of dynamic varus stability appeared to be altered in individuals who developed ITBS. Biomechanical knee variables previously identified as increasing the risk for knee osteoarthritis were also associated with the development of ITBS in healthy adults.

Radiographic subchondral bone trabecular integrity predicts osteoarthritis structural outcomes after anterior cruciate ligament rupture

Purpose: The course of post-traumatic osteoarthritis (OA) is an invaluable paradigm for discovery of markers of the very earliest stages of the OA disease process. Subchondral bone trabecular integrity (BTI) predicts structural progression of radiographic knee OA based on radiographic and MRI outcomes. The goal of this study was to determine if the BTI in a knee injury cohort, measured within 5 weeks after an anterior cruciate ligament (ACL) tear, is an early indicator of risk for development of OA over the subsequent 5 years. We hypothesized that thinning and loss of the subchondral vertical bone trabeculae, detected by BTI, would predict joint space width and joint space area loss. Methods: Bone trabecular integrity (BTI) of the medial tibial plateau was determined from analysis of knee radiographs from the completed randomized controlled KANON clinical trial (http://www.controlled-trials.com; ISRCTN 84752559), designed to compare rehabilitation plus early ACL reconstruction (ACLR, n = 61) versus rehabilitation plus optional delayed ACLR (n = 60) with follow-up out to 5 years. The KANON study enrolled 121 young active adults (aged 18–35 yrs) with acute ACL rupture within the prior 5 weeks to a previously uninjured knee. There was no loss to follow-up at 2 years and only 1 individual lost to follow-up at 5 years; none of the index knees had radiographic OA at baseline. Weight bearing knee radiographs, obtained at baseline (at time of enrollment), 2 years and 5 years using a modified Lyon-Schuss protocol, were analyzed using KneeAnalyzer software (Optasia Medical Ltd, Manchester, UK) to obtain fractal dimensions for computing BTI, minimum medial joint space width (mJSW), and medial joint space area (JSA). Multivariable regression models, adjusted for age, gender and body mass index, were used to evaluate the ability of baseline (BL) BTI parameters of index knees to predict the change in mJSW and JSA between BL and 2 y and 5 y after injury. Results: Based on BTI profiles injured knees on average showed thinning of vertical trabeculae over 2 years with further thinning between 2 and 5 years. Horizontal trabeculae showed thickening over 2 years with little further change to 5 years. Baseline BTI parameters were statistically significantly associated with change in mJSW over 2 (R2 0.19, p = 0.036) and 5 (R2 0.16, p = 0.04) years, and change in JSA over 5 (R2 0.22, p = 0.004), but not 2 (R2 0.13, p = 0.16) years. Conclusions: The qualitative changes in BTI parameters over time after injury, reflecting vertical and horizontal trabecular structure, were similar to changes earlier reported over similar time intervals in knee OA progressors. The remarkable finding that baseline BTI predicted subsequent changes in mJSW and JSA suggests that acute injury leads to dramatic acute alterations in bone structure, and/or, that pre-injury BTI identifies and perhaps contributes to, risk of knee injury. Longitudinal surveillance, initiated prior to injury, is needed to determine if BTI might identify individuals at high-risk for post-injury OA and who could be targeted with interventions to prevent subsequent development of OA.

Secreted 14-3-3ε: discovery by proteomics of a novel biomarker and/or therapeutical target in osteoarthritis

Secreted 14-3-3ε: discovery by proteomics of a novel biomarker and/or therapeutical target in osteoarthritis

Characterization of cell metabolic changes in osteoarthritic labrum cells

Characterization of cell metabolic changes in osteoarthritic labrum cells

Potent inhibition of cartilage biosynthesis by coincubation with joint capsule through an IL‐1‐independent pathway

The reason for the increased risk for development of osteoarthritis (OA) after acute joint trauma is not well understood, but the mechanically injured cartilage may be more susceptible to degradative mediators secreted by other tissues in the joint. To establish a model for such interactions, we coincubated bovine cartilage tissue explants together with normal joint capsule and found a profound ( approximately 70%) reduction in cartilage proteoglycan biosynthesis. This reduction is due to release by the joint capsule of a heat-labile and non-toxic factor. Surprisingly, while cultured synovium is a canonical source of interleukin-1 (IL-1), blockade either by soluble IL-1 type II receptor (sIL-1r) or IL-1 receptor antagonist (IL-1RA) had no effect. Combined blockade of IL-1 and tumor necrosis factor alpha (TNF-alpha) also had no effect. To support the clinical relevance of the findings, we harvested joint capsule from post-mortem human knees. Human joint capsule from a normal adult knee also released a substance that caused an approximately 40% decrease in cartilage proteoglycan biosynthesis. Furthermore, this inhibition was not affected by IL-1 blockade with either sIL-1r or IL-1RA. These results suggest that joint capsule tissue from a normal knee joint can release an uncharacterized cytokine that potently inhibits cartilage biosynthetic activity by an IL-1- and TNF-independent pathway.

Joint injury causes knee osteoarthritis in young adults

This review presents recent data on joint injury as the cause of osteoarthritis development in young adults and proposes and discusses a model that highlights how joint injury and other risk factors may contribute to osteoarthritis development through two different pathways: joint-related mechanisms and deconditioning of the musculoskeletal system. Knee osteoarthritis in young adults is common after knee injury. In women who sustained an anterior cruciate ligament injury in soccer, 51% (mean age 31) had radiographic changes after 12 years. Men, 41% (mean age 36) had osteoarthritis after 14 years. An injury to the menisci during middle age resulting in a horizontal tear is more probably the first signal of an already ongoing osteoarthritis process of the knee. Known risk factors seem to contribute to osteoarthritis through pathways related to (1) mechanical aspects of the joint and (2) the musculoskeletal system. Osteoarthritis in young adults is most commonly a result of a previous injury to the knee. Deconditioning of the musculoskeletal system is seen with joint injury, obesity, and aging, all known risk factors for osteoarthritis. Muscular deconditioning contributes to increased joint loads and knee osteoarthritis development and progression. So far, it is unclear whether surgery reduces the development or progression of osteoarthritis. The risk for osteoarthritis development seems to increase as the amount of meniscal tissue removed increases. Knee injury prevention, rehabilitation after knee injuries, regular exercise, maintaining body weight, and a changed locomotion pattern may prevent osteoarthritis initiation and progression in young adults.

Higher grip strength increases the risk of incident radiographic osteoarthritis in proximal hand joints

Quadriceps strength may protect against knee osteoarthritis (OA), but muscle activity is a major determinant of forces at the hand joints. Gripping objects is a common task during which high muscular forces are sustained, particularly at the proximal hand joints (metacarpophalangeal (MCP) joints and thumb base). The association between maximal grip strength and incident OA at different hand joints was examined in a longitudinal study of radiographic hand OA. Subjects with higher maximal grip strength were at increased risk for development of OA in the proximal interphalangeal (PIP) joints, MCP and thumb base joints in men; and in the MCP in women. No association was found between maximal grip strength and incident distal interphalangeal (DIP) joints OA in men or women. The conclusion is that increased grip strength, which is the major force of loading across proximal hand joints, increases the risk of OA in those joints.

Site-specific variation in femoral head cartilage composition in dogs at high and low risk for development of osteoarthritis: insights into cartilage degeneration

Objective To determine which characteristics of cartilage lesion pathology are detected in dogs at high risk to develop osteoarthritis prior to diagnosis by standard radiographs or macroscopic cartilage abnormality on necropsy.Methods Fourteen disease-free dogs were assigned to risk groups based on hip distraction index. For seven dogs, three dimensional images of hip joints from computed tomography were available. At necropsy, ligamentum capitis femoris volumes were measured and articular cartilage was harvested and analyzed for percent water, swelling, glycosaminoglycan, and fibronectin. Comparisons were made with nine dogs with macroscopic cartilage lesions (OA group).Results Ligament volumes were greater in the high distraction index group (P=0.000). Water content was elevated in the lesion area in both low and high risk dogs (P=0.000); no additional increase was noted in the high risk group. Glycosaminoglycan content was slightly elevated in the surrounding area in both groups (P< 0.02) but loss was noted histologically in the lesion area of the high risk group. Fibronectin was increased in the lesion area and in the high risk group (P=0.000). The magnitude of this increase was greatest in the lesion area (P=0.000) in explants. Computed tomography indicated dorsal acetabular rim impingement on the lesion area in high risk dogs.Conclusions Water content and swelling suggest matrix structure is weaker at the site of lesion predilection in all dogs regardless of risk status. Computed tomography imaging is consistent with site specific initiation of lesions by mechanical factors.{copy}