Osteoarthritis

doi:10.1016/j.addr.2006.01.006

Advanced Drug Delivery Reviews

Volume 58, Issue 2, 20 May 2006, Pages 150-167

https://doi.org/10.1016/j.addr.2006.01.006 Get rights and content

Abstract

Osteoarthritis (OA), the syndrome of joint pain and dysfunction caused by joint degeneration, affects more people than any other joint disease. In most instances joint degeneration develops in the absence of an identifiable cause, but increasing age, excessive joint loading, and joint abnormalities and insults increase the risk of OA. Articular surface contact stress that causes tissue damage and compromises that ability of chondrocytes to maintain and restore the tissue has an important role in the development of joint degeneration Current methods of attempting to restore an articular surface in osteoarthritic joints include penetrating subchondral bone, altering joint loading, osteotomies and insertion of soft tissue grafts. Dramatic advances in the prevention and treatment of OA are likely to stem from better understanding of the role of mechanical forces in the initiation and progression of joint degeneration.

Introduction

Osteoarthritis (OA), the most common joint disease, is among the most frequent and symptomatic health problems for middle aged and older people [1], [2], [3], [4], [5], [6], [7]. It is characterized by joint pain and dysfunction; and, in its advanced stages, joint contractures, muscle atrophy and limb deformity [8], [9], [10]. OA is caused by joint degeneration, a process that includes progressive loss of articular cartilage accompanied by attempted repair of articular cartilage, remodeling and sclerosis of subchondral bone, and osteophyte formation [9], [10]. Although increasing age and excessive articular surface contact stress increase the risk of degeneration in all joints, the pathophysiology of the joint degeneration that leads to the clinical syndrome of OA remains poorly understood. For this reason, efforts to prevent this disease or slow its progression are based more on speculation than science. Current treatments do not prevent or cure OA, and symptomatic treatments often fail to provide satisfactory pain relief. Once patients develop OA, they suffer from the disease for the remainder of their lives and the severity of pain and disability generally increase. The frequency and chronicity of OA and the lack of effective preventive measures or cures make this disease a substantial economic burden for patients, health care systems, businesses, and nations [2], [3], [5], [6], [11], [12], [13], [14].

Improving the prevention and treatment of OA will require finding methods of preventing and slowing the joint degeneration that causes OA and decreasing the joint pain and dysfunction. This manuscript was developed in part from the authors' previously published works [8], [9], [15], [16], [17], [18], [19]. It examines the clinical classification, incidence, prevalence, costs, distribution among joints, risk factors, and natural history of OA. The final section discusses approaches to restoring degenerated joint surfaces.

Section snippets

Diagnosis

Osteoarthritis results from degeneration of a synovial joint: a generally progressive loss of articular cartilage accompanied by attempted repair of articular cartilage, remodeling and sclerosis of subchondral bone, and in many instances the formation of subchondral bone cysts and marginal osteophytes [8], [9]. In addition to the changes in the synovial joint, usually demonstrated by plain radiographs, diagnosis of the clinical syndrome of osteoarthritis requires the presence of chronic joint

Classification

OA develops most commonly in the absence of a known cause of joint degeneration, a condition referred to as primary or idiopathic OA [9], [10]. Less frequently, it develops as a result of joint degeneration caused by injuries or a variety of hereditary, inflammatory, or developmental, metabolic, and neurologic disorders, a group of conditions referred to as secondary OA (Table 1) [9], [10]. Idiopathic OA rarely occurs in people younger than 40 years. Secondary OA, caused by joint insults or

Prevalence, incidence, and costs

To some extent, estimates of the prevalence, incidence and costs of OA depend on the criteria used to diagnose the disorder. Symptoms of persistent joint pain and stiffness and evidence of joint degeneration, typically radiographic evidence of articular cartilage loss, osteophytes, and in some instances increased subchondral bone density and cysts, establish the diagnosis of OA [8]. More severe joint degeneration is associated with increased prevalence of pain, but the prevalence of pain

Distribution among joints

Osteoarthritis can affect any synovial joint. Idiopathic OA rarely occurs in the ankle, wrist, elbow and shoulder, but it is common in the hand, foot, knee, spine and hip joints [5], [6], [21], [22], [27], [31], [39] In a study of 607 consecutive patients referred to the University of Iowa orthopaedic clinic for treatment of severe ankle, hip or knee OA, 7% of the patients with ankle OA, 69% of the patients with hip OA and 85% of the patients with knee OA had primary disease. Seventy-three

Risk factors

In addition to the disorders associated with the multiple forms of secondary OA (Table 1), genetic predisposition, obesity, female gender, greater bone density, and joint laxity have been identified as risk factors [21], [57], [58], [59], [60], [61]. Although these factors may increase the risk of OA in selected populations, the most important risk factor in all populations is age. Mechanical loading that exceeds the ability of a joint to repair or maintain itself is another universal risk

Natural history

Although physicians and patients commonly regard OA as relentlessly progressive, [62] the disease does not necessarily follow this course (Table 2) [89], [120], [121], [122], [123], [124], [125], [126], [127], [128]. The symptoms of OA may remain unchanged, slowly progress over many years, improve temporarily, or progress rapidly to the point that the patient is disabled within a few years of the onset of the disease [20], [39]. Most patients with OA have intervals of symptomatic improvement [9]

Restoring degenerated articular surfaces

For more than 250 years surgeons have been seeking ways to repair or regenerate degenerated articular surfaces. Repair refers to restoring a damaged articular surface with new tissue that resembles but does not duplicate the structure, composition and function of articular cartilage; regeneration refers to forming new tissue indistinguishable from normal articular cartilage [17], [130], [131], [132]. They made little progress for 200 years, but in the last 50 years use of surgical procedures to

Conclusions

Despite the great success of joint replacement and the proliferation of medical, nutritional, and physical treatments, the problem of OA has not been solved, and its adverse impacts on individuals, populations and economies will continue to increase. Replacing a severely degenerated joint with an implant is much like replacing a failing heart with a mechanical pump, both operations restore function, but neither treats the disease, the costs are high and the complications severe. None of the

Acknowledgement

The work reported in this manuscript was supported by award P50 AR48939 National Institutes of Health Specialized Center on Research for OA. http://poppy.obrl.uiowa.edu/Specialized Center of Research/SCOR.htm. This grant was awarded to the University of Iowa and the authors receive salary and research support from the grant.

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This study aimed to investigate the prevalence of radiographic ankle osteoarthritis (AOA) in Japan and identify its risk factors.
The analysis included data from the population-based cohort study, radiographs of the knees and ankles, ultrasonography of the ankle to examine chronic ankle instability (CAI), and questionnaires on ankle pain, job history, height, and body weight. A total of 597 individuals aged > 50 years were included in the study. The risk factors for AOA were calculated using multivariate logistic regression analysis.
The study revealed a 13.9% prevalence of radiographic AOA among the participants, with 1.2% reporting painful AOA. Female sex, aging, history of ankle fractures, and CAI were identified as the risk factors associated with AOA.
This cross-sectional study highlights the significant prevalence of radiographic AOA in a rural Japanese population, emphasizing the importance of considering ankle fractures and CAI as potential risk factors for AOA development.
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MAGL inhibition relieves synovial inflammation and pain via regulating NOX4-Nrf2 redox balance in osteoarthritis
2023, Free Radical Biology and Medicine
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage injury, hyperplasia of bone and inflammatory lesions of synovium. Monoacylglycerol lipase (MAGL), a member of the α/β hydrolase superfamily, is involved in regulation of injury protection and immune-inflammation response. Autoinflammatory response of the synovium and the release of inflammatory mediators play critical roles in occurrence of early-stage OA. Fibroblast-like synoviocytes (FLSs) are resident mesenchymal cells of the synovial tissue. Considering that MAGL inhibition regulates the inflammatory signaling cascade, it is crucial to ascertain the biological effects and specific mechanisms of MAGL in alleviating inflammatory infiltration of OA FLSs. The aim of this study was to investigate the effect of MAGL on biological function in OA FLSs. Results from in vitro experiments showed that MAGL blockade not only effectively inhibited proliferation, invasion and migration of FLSs, but also downregulated expression of inflammatory-associated proteins. Sequencing results indicated that MAGL inhibition significantly suppressed NOX4-mediated oxidative stress, thus promoting Nrf2 nuclear accumulation and inhibiting generation of intracellular reactive oxygen species (ROS). Attenuation of NOX4 further alleviated redox dysplasia and ultimately improved tumor-like phenotypes, such as abnormal proliferation, migration and migration of FLSs. In vivo results corroborated this finding, with MAGL inhibition found to modulate pain and disease progression in an OA rat model. Collectively, these results indicate that MAGL administration is an ideal therapy treating OA.
Effect of lorecivivint on osteoarthritis: A systematic review and meta-analysis
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To comprehensively evaluate the effectiveness and safety of lorecivivint inhibitors in the treatment of osteoarthritis through meta-analysis.
A comprehensive literature search on lorecivivint inhibitors in osteoarthritis was performed using electronic databases such as PubMed, Embase, Web of Science, and CochraneLibrary up to July 30, 2022. Two reviewers independently screened, evaluated, and reviewed the eligible studies. Data analysis and processing were carried out using RevMan 5.4 software.
A total of six studies involving 3056 participants were included. Meta-analysis showed that compared with the control group, lorecivivint significantly increased WOMAC discomfort (0.03 mg Week 12) (MD = −0.21, 95% CI [-1.94 – 1.53]; P = 0.81), WOMAC function (0.07 mg Week 24) (MD = −1.81, 95% CI [-4.74 – 1.12]; P = 0.23) and Joint space width (0.23 mg Week 24) (MD = −1.16, 95% CI [-3.69 – 1.38]; P = 0.37).
A new treatment method combining Wnt pathway modulators with intra-articular CLK2/DYRK1A inhibitors could be a promising therapy for treating osteoarthritis. Lorecivivint was found to significantly improve WOMAC discomfort, WOMAC function, and joint space width in osteoarthritis patients. It is anticipated to be a reliable, safe, and effective treatment option for osteoarthritis with significant therapeutic utility and potential applications.
“It's like a nail being driven in the ankle”: A qualitative study of individuals' lived experiences to inform a core domain set for ankle osteoarthritis
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Explore individuals' lived experience with ankle osteoarthritis and to identify health-related domains for ankle osteoarthritis based on the perspectives of people living with the condition, as an initial step to address the International Foot and Ankle Osteoarthritis Consortium's recommendation to develop a core domain set for ankle osteoarthritis.
A qualitative study using semi-structured interviews was conducted. Interviews were undertaken with individuals with symptomatic ankle osteoarthritis who were aged ≥35 years. Interviews were recorded, transcribed verbatim and thematically analysed.
Twenty-three individuals (16 females; mean (range) age 62 (42–80) years) were interviewed. Five themes were identified: pain, often severe, is a central feature of living with ankle osteoarthritis; stiffness and swelling are key symptoms; ankle osteoarthritis induced mobility impairments compromise enjoyment in life; ankle osteoarthritis instability and balance impairments lead to concerns about falling; there are financial implications of living with ankle osteoarthritis. We propose 17 domains based on individuals’ experiences.
Study findings indicate that individuals with ankle osteoarthritis live with chronic ankle pain, stiffness and swelling which affect their ability to participate in physical, and social activities, maintain an active lifestyle, and work in physical occupations. From the data, we propose 17 domains that are important to people with ankle osteoarthritis. These domains require further evaluation to ascertain their inclusion in a core domain set for ankle osteoarthritis.
High tibiofemoral contact and muscle forces during gait are associated with radiographic knee OA progression over 3 years
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The objective of this study was to investigate differences in tibiofemoral joint contact forces between individuals with moderate medial OA who exhibit radiographic knee OA progression within 3 years versus those who do not, and to understand the relationship between model-predicted contact forces and net external moments for this population.
27 individuals with moderate medial compartment knee OA underwent baseline instrumented gait analysis. OA progressors were defined as those who experienced at least a one grade increase in medial joint space narrowing at three years. An electromyography-driven musculoskeletal model was used to estimate muscle and tibiofemoral contact forces at baseline, which were compared between progressors and non-progressors using t-tests.
Seven individuals experienced radiographic OA progression by 3 years. Progressors walked with significantly higher peaks of medial and total tibiofemoral contact forces, and higher impulse of medial contact forces. Significant and high correlations were found between: first peaks of medial and total contact forces with first peak of the knee adduction moment (R² = 0.74; R² = 0.59); second peaks of medial and total knee contact forces with second peaks of knee adduction and flexion moments (R² = 0.71; R² = 0.68); medial knee contact force impulse with knee adduction moment impulse (R² = 0.76).
Higher tibiofemoral joint contact forces during walking were associated with three-year radiographic knee OA progression based on medial joint space narrowing. These results support the need for strategies that reduce compressive knee contact forces through the reduction of adduction and flexion moments during walking.
Biotribology of synovial cartilage: Role of albumin in adsorbed film formation
2022, Engineering Science and Technology, an International Journal
A properly lubricated natural synovial joint is the basis of the proper function of the natural musculoskeletal system to lead an active and painless life. A properly lubricated natural synovial joint is the basis of the proper function of the natural movement system to lead an active and painless life. Well lubricated synovial joints are expressed, in particular, by an extremely low coefficient of friction and wear between cartilage surfaces. The presented manuscript is focused on the impact of albumin protein on the formation of adsorbed boundary layer in the contact of cartilage – a simplified model of synovial joint. This can contribute to better understanding of the lubrication in synovial joints. All presented experimental tasks were performed using a reciprocating tribometer along with fluorescence microscopy – friction forces were measured simultaneously with fluorescence records of contact. This unique experimental approach used a newly designed evaluating procedure based on image processing. The experimental results show a great impact of hyaluronic acid; adding of hyaluronic acid leads to a reduction in friction and a larger area of albumin adsorbed boundary layer; however, the phospholipids show the opposite effect. A combination of the individual protein solutions, albumin and γ-globulin, has no significant effect on the particles count of albumin clusters adsorbed in the contact; however, the area of albumin adsorbed boundary layer with simple albumin solution was much larger than the solution combining both proteins. The conclusions and discussion of this study describe the role of albumin protein in the lubricating process prevailing in a simplified model of synovial joint under conditions corresponding to slow human gait.

View all citing articles on Scopus

^☆: This review is part of the Advanced Drug Delivery Reviews theme issue on “Drug Delivery in Degenerative Joint Disease”, Vol. 58/2, 2006.

View full text

Osteoarthritis☆

Abstract

Introduction

Section snippets

Diagnosis

Classification

Prevalence, incidence, and costs

Distribution among joints

Risk factors

Natural history

Restoring degenerated articular surfaces

Conclusions

Acknowledgement

Clin. Cornerstone

Osteoarthr. Cartil.

J. Shoulder Elbow Surg.

J. Orthop. Res.

Osteoarthritis Cartilage

Impact of osteoarthritis on individuals and society: how much disability? Social consequences and health economic implications

Curr. Opin. Rheumatol.

The prevalence and burden of arthritis

Rheumatology (Oxford)

Estimating the costs of job related arthritis

J. Rheumatol.

The disproportionate impact of chronic arthralgia and arthritis among women

Clin. Orthop.

Synovial joint degeneration and the syndrome of osteoarthritis

Instr. Course Lect.

Articular cartilage II. Degeneration and osteoarthritis, repair, regeneration and transplantation

J. Bone Jt. Surg.

Degenerative Joint Disease

Living with osteoarthritis: patient expenditures, health status, and social impact

Arthritis Rheum.

The increasing impact of arthritis on public health

J. Rheumatol., Suppl.

Costs of osteoarthritis: estimates from a geographically defined population

J. Rheumatol., Suppl.

Costs attributable to osteoarthritis

J. Rheumatol.

The impact of osteoarthritis: implications for research

Clin. Orthop. Relat. Res.

Joint injury, repair, and remodeling: roles in post-traumatic osteoarthritis

Clin. Orthop. Relat. Res.

Restoration of injured or degenerated articular surfaces

J. Am. Acad. Ortho. Surg.

Post-traumatic osteoarthritis: the role of accelerated chondrocyte senescence

Biorheology

Chondrocyte senescence, joint loading and osteoarthritis

Clin. Orthop. Relat. Res.

The Natural History and Prognosis of Osteoarthritis

Osteoarthritis: epidemiology and classification

The classification and diagnosis of osteoarthritis

Osteoarthritis and related disorders: clinical features and diagnostic problems

Legg–Calve–Perthes disease. Histochemical and ultrastructural observations of the epiphyseal cartilage and physis

J. Bone Jt. Surg.

Epidemiology of osteoarthritis

Ankle osteoarthritis: distinctive characteristics

Instr. Course Lect.

The epidemiology of osteoarthritis: prevalence and risk factors

Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States

Arthritis Rheum.

Epidemiological profile of symptomatic osteoarthritis in older adults: a population based study in Dicomano, Italy

Ann. Rheum. Dis.

The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study

Arthritis Rheum.

Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization

Arthritis Rheum.

Aging of the North American population: new challenges for orthopaedics

J. Bone Jt. Surg.

The economics of osteoarthritis

Direct and indirect costs of osteoarthritis of the knee

Clin. Exp. Rheumatol.

Symptomatic articular cartilage degeneration: the impact in the new millennium

Clin. Orthop.

Osteoarthritis and related disorders

Unicondylar fractures of the distal humerus: an operative approach

J. Orthop. Trauma

Displaced ankle fractures in patients over 50 years of age

J. Bone Jt. Surg.

The elbow