Osteoarthritis (OA) is the most common form of arthritis and a major cause of pain and disability in older adults (1) Often OA is referred to as degenerative joint disease “(DJD)” This is a misnomer because OA is not simply a process of wear and tear but rather abnormal remodeling of joint tissues driven by a host of inflammatory mediators within the affected joint The most common risk factors for OA include age, gender, prior joint injury, obesity, genetic predisposition, and mechanical factors, including malalignment and abnormal joint shape (2, 3) Despite the multifactorial nature of OA, the pathological changes seen in osteoarthritic joints have common features that affect the entire joint structure resulting in pain, deformity and loss of function

The pathologic changes seen in OA joints (Figures 1 and ​and2)2) include degradation of the articular cartilage, thickening of the subchondral bone, osteophyte formation, variable degrees of synovial inflammation, degeneration of ligaments and, in the knee, the menisci, and hypertrophy of the joint capsule There can also be changes in periarticular muscles, nerves, bursa, and local fat pads that may contribute to OA or the symptoms of OA The findings of pathological changes in all of the joint tissues are the impetus for considering OA as a disease of the joint as an organ resulting in “joint failure” In this review, we will summarize the key features of OA in the various joint tissues affected and provide an overview of the basic mechanisms currently thought to contribute to the pathological changes seen in these tissues






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Figure 1


Sagittal inversion recovery (A–C) and coronal fast spin echo (D–F) images illustrating the magnetic resonance imaging findings of osteoarthritis (A) reactive synovitis (thick white arrow), (B) subchondral cyst formation (white arrow), (C) bone marrow edema (thin white arrows), (D) partial thickness cartilage wear (thick black arrow), (E–F) full thickness cartilage wear (thin black arrows), subchondral sclerosis (arrowhead) and marginal osteophyte formation (double arrow) Image courtesy of Drs Hollis Potter and Catherine Hayter, Hospital for Special Surgery, New York, NY

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.34453

Osteoarthritis: A Disease of the Joint as an Organ

American association of clinical endocrinologists and american college of endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity.

Osteoarthritis (OA) has traditionally been classified as a noninflammatory arthritis; however, the dichotomy between inflammatory and degenerative arthritis is becoming less clear with the recognition of a plethora of ongoing immune processes within the OA joint and synovium. Synovitis is defined as inflammation of the synovial membrane and is characteristic of classical inflammatory arthritidies. Increasingly recognized is the presence of synovitis in a significant proportion of patients with primary OA, and based on this observation, further studies have gone on to implicate joint inflammation and synovitis in the pathogenesis of OA. However, clinical OA is not one disease but a final common pathway secondary to many predisposing factors, most notably age, joint trauma, altered biomechanics, and obesity. How such biochemical and mechanical processes contribute to the progressive joint failure characteristic of OA is tightly linked to the interplay of joint damage, the immune response to perceived damage, and the subsequent state of chronic inflammation resulting in propagation and progression toward the phenotype recognized as clinical OA. This review will discuss a wide range of evolving data leading to our current hypotheses regarding the role of immune activation and inflammation in OA onset and progression. Although OA can affect any joint, most commonly the knee, hip, spine, and hands, this review will focus primarily on OA of the knee as this is the joint most well characterized by epidemiologic, imaging, and translational studies investigating the association of inflammation with OA.

/pdf/role-of-inflammation-in-the-pathogenesis-of-osteoarthritis-2aaujdkp8y.pdf

Role of inflammation in the pathogenesis of osteoarthritis: latest findings and interpretations

http://www.engineering.union.edu/~curreyj/BNG-345_files/Kutzner%20et%20al%20JBiomech%202010.pdf

Loading of the knee joint during activities of daily living measured in vivo in five subjects.

Although changes associated with ageing promote the development of osteoarthritis (OA), ageing and OA are independent processes. In this Review, the authors discuss the mechanisms by which age-related factors contribute to OA through effects on articular cartilage and propose that future improvements in our understanding of these mechanisms will inform new therapies to slow or stop the progression of OA. Ageing-associated changes that affect articular tissues promote the development of osteoarthritis (OA). Although ageing and OA are closely linked, they are independent processes. Several potential mechanisms by which ageing contributes to OA have been elucidated. This Review focuses on the contributions of the following factors: age-related inflammation (also referred to as 'inflammaging'); cellular senescence (including the senescence-associated secretory phenotype (SASP)); mitochondrial dysfunction and oxidative stress; dysfunction in energy metabolism due to reduced activity of 5′-AMP-activated protein kinase (AMPK), which is associated with reduced autophagy; and alterations in cell signalling due to age-related changes in the extracellular matrix. These various processes contribute to the development of OA by promoting a proinflammatory, catabolic state accompanied by increased susceptibility to cell death that together lead to increased joint tissue destruction and defective repair of damaged matrix. The majority of studies to date have focused on articular cartilage, and it will be important to determine whether similar mechanisms occur in other joint tissues. Improved understanding of ageing-related mechanisms that promote OA could lead to the discovery of new targets for therapies that aim to slow or stop the progression of this chronic and disabling condition.

/pdf/ageing-and-the-pathogenesis-of-osteoarthritis-2hwrgzqoa4.pdf

Ageing and the pathogenesis of osteoarthritis

Background: Polyethylene wear contributes substantially to both periprosthetic osteolysis and aseptic loosening after total hip arthroplasty. Acetabular component orientation has been shown to affect the range of motion of the hip as well as contact stresses. A series of studies was designed to test the hypothesis that acetabular component orientation can affect the magnitude and direction of polyethylene wear.

Methods: A finite-element model was used to compute contact stresses during a normal gait cycle. Wear at the end of each gait cycle was calculated with use of the sliding-distance-coupled finite-element formulation. The wear that was calculated with use of finite-element analysis was validated by comparison with the findings of hip wear simulator studies with the acetabular liner oriented to simulate 45° and 55° of abduction. In a clinical study, fifty-six patients who underwent sixty hip arthroplasties with use of a single prosthetic design were followed for as long as five years. Radiographs were analyzed to measure the abduction angle of the acetabular component and polyethylene wear.

Results: The finite-element analysis predicted increased peak contact stresses with an increased abduction angle and reduced peak contact stresses with an increased anteversion angle. Linear wear rates ranging from 0.036 to 0.045 mm/million cycles were also predicted, and increased acetabular abduction angles were predicted to be associated with higher linear wear rates. In the hip wear simulator studies, significantly different wear rates were found between the cups with acetabular abduction angles of 45° and 55° (mean, 17.2 compared with 21.7 mg/million cycles; p < 0.01). In the clinical study, radiographic analysis revealed significant correlation between the acetabular abduction angle and the linear polyethylene wear rate. A 40% increase in mean linear polyethylene wear was seen in cups with an abduction angle of ≥45°. The direction of wear was more medial (by 9.4°) in cups with an abduction angle of <45°.

Conclusion: All three studies presented here underlined the importance of optimizing the position of the acetabular component. Careful attention to acetabular position may help to minimize wear.

Polyethylene wear and acetabular component orientation.

https://www.oarsijournal.com/article/S1063-4584(11)00157-9/pdf

Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis

An instrumented tibial prosthesis was developed to measure forces in vivo after total tibial arthroplasty. This prosthesis was implanted in a 67-kg, 80-year-old man. The prosthesis measured forces at the 4 quadrants of the tibial tray. Tibial forces were measured postoperatively during rehabilitation, rising from a chair, standing, walking, and climbing stairs. By the sixth postoperative week, the peak tibial forces during walking averaged 2.2 times body weight (BW). Stair climbing increased from 1.9 times BW on day 6 to 2.5 times BW at 6 weeks. This represents the first direct in vivo measurement of tibial forces, which should lead to refined surgical techniques and enhanced prosthetic designs. Technical design improvements will enhance function, quality of life, and longevity of total knee arthroplasty.

Tibial forces measured in vivo after total knee arthroplasty.

Background: Unicompartmental replacement can be an alternative to tibial osteotomy in younger, active patients with unicompartmental knee disease. In unicompartmental replacement, the other compartments and knee ligaments are largely untouched. Therefore, it was hypothesized that the knee kinematics

Shantanu Patil

Papers

Polyethylene wear and acetabular component orientation.

Macroscopic and histopathologic analysis of human knee menisci in aging and osteoarthritis

Tibial forces measured in vivo after total knee arthroplasty.

Can normal knee kinematics be restored with unicompartmental knee replacement

In vivo knee moments and shear after total knee arthroplasty.