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Knee osteoarthritis

197 citationsUpdated Sep 2026

Overview

Knee osteoarthritis (OA) management requires recognizing the broader pathophysiological landscape of obesity to refine surgical indications, personalize treatments, and improve long-term outcomes [1]. While more than 50% of patients referred with mild-to-moderate knee OA may not need surgery at 7 years [13], patient preferences for treatment attributes vary significantly within this population [171]. A Malaysian Delphi consensus advocates an algorithmic approach to management [19], and the MultiKnee trial aims to contribute evidence-based personalized treatment recommendations for patients currently lacking effective options [210]. Although a high proportion of patients avoid surgery at 5 years, their outcomes show no improvement from baseline and are poorer than those who have undergone total knee arthroplasty (TKA) [156].

Arthroscopic débridement is indicated for mild to moderate arthritis with minimal malalignment and mechanical symptoms consistent with a loose body, meniscus tear, synovitis, or painful osteophytes [5]. This procedure allows assessment of the joint and removal of loose bodies, meniscal tears, and synovial impingement, potentially delaying the need for arthroplasty in properly selected early-stage patients [5]. However, arthroscopic procedures are contraindicated in advanced arthritis with varus or valgus malalignment [5]. Evidence does not support the effectiveness of arthroscopic knee surgery compared to conservative treatments [58], and randomized trials provide strong evidence that arthroscopic surgery provides no added benefit over non-surgical treatment [68].

Osteotomy is effective in treating arthritis caused by varus or valgus malalignment and can delay the need for TKA [254]. It is ideal for the young, active patient with isolated medial or lateral compartment disease, realigning the limb to reduce stresses on articular cartilage [254]. Medial compartment arthritis in a varus malaligned limb is treated with a valgus-producing high tibial osteotomy, while lateral compartment arthritis in a valgus malaligned limb is usually treated with a varus-producing distal femoral osteotomy [254]. Valgus-producing high tibial osteotomy has been successful in approximately 50% to 85% of patients at 10 years, and varus-producing distal femoral osteotomy has been successful in up to 87% of patients at 10 years [254]. TKA after osteotomy is technically challenging due to previous incisions, scar tissue, and retained hardware, though survivorship does not seem to be affected by prior osteotomy [254].

Anatomy & Pathophysiology

Bony Anatomy

The medial femoral condyle is larger and projects farther posteriorly and distally than the lateral femoral condyle [93]. Conversely, the lateral femoral condyle projects farther anteriorly and is wider in the medial-lateral direction [93]. The tibial articular surface slopes 7° to 10° in the sagittal plane [93]. The medial tibial plateau is larger than the lateral plateau and is concave in both its frontal and sagittal planes [93]. In contrast, the lateral tibial plateau is smaller and more circular, concave in the frontal plane, and convex in the sagittal plane [93]. The posterior slope of the medial tibial plateau averages 10.7°, while the lateral tibial plateau averages 7.2° [106].

The patella is the largest sesamoid bone in the body, with a mean thickness of 2.5 cm [93, 106]. Its articular surface features a vertical central ridge that separates the broader lateral facet from the medial facet, along with a smaller odd facet [93]. The fibular head is located a mean of 1.5 cm distal to the joint line, with a range of 6 to 32 mm [106].

Ligament Anatomy

The anterior cruciate ligament (ACL) is composed of 90% type I collagen and 10% type III collagen [93, 106]. It has a mean length of 33 mm and a mean midsubstance width of 11 mm [93, 106]. The ACL femoral attachment is a semicircular area on the posteromedial aspect of the lateral femoral condyle [93, 106], while the tibial attachment is a broad, irregular, oval-shaped area between the medial and lateral tibial spinous processes [93, 106]. The ACL anteromedial bundle is tight in knee flexion, whereas the posterolateral bundle is tight in knee extension [106].

The posterior cruciate ligament (PCL) has a mean length of 38 mm and a mean width of 13 mm [106, 114]. Its femoral attachment is a broad, crescent-shaped area on the anterolateral aspect of the medial femoral condyle [106]. The PCL tibial insertion is located 10 to 15 mm distal to the joint line of the knee [106, 114]. The PCL anterolateral bundle is tight in knee flexion, and the posteromedial bundle is tight in knee extension [106].

The medial collateral ligament (MCL) originates on the femoral sulcus approximately 3.2 cm proximal and 4.8 cm posterior to the articular surface of the femur [106]. The middle geniculate artery is the primary blood supply to both the ACL and PCL [93, 106]. Innervation to the ACL and PCL is provided by the posterior articular branch of the tibial nerve [93, 106].

Meniscal Anatomy

The menisci are C-shaped fibrocartilaginous disks that provide shock absorption, increase joint congruency, enhance stability, and aid in synovial fluid distribution [41]. They consist of type I collagen fibers arranged obliquely, radially, and vertically [106]. The medial meniscus is firmly attached to the joint capsule along its entire peripheral edge [41]. In contrast, the lateral meniscus is attached to the anterior and posterior capsule but has a region posterolaterally where it is not firmly attached [41].

The medial meniscus has less mobility than the lateral meniscus and is more susceptible to tearing when trapped between the femoral condyle and tibial plateau [41]. Specifically, the lateral meniscus has a mobility of 10 mm, while the medial meniscus has a mobility of 5 mm [106]. The lateral meniscus is larger than the medial meniscus and carries a greater share of the lateral compartment pressure [41]. Vascular supply to the menisci penetrates 20% to 30% of the peripheral medial meniscus and 10% to 25% of the peripheral lateral meniscus [106].

Kinematics

The knee is a hinge joint that incorporates both gliding and rolling motions [94, 95]. The "screw-home" mechanism involves the tibia externally rotating 5 degrees in the final 15 degrees of extension [94, 95]. In full extension, the knee slightly hyperextends with slight tibial external rotation while collateral and cruciate ligaments tighten to lock the knee [122]. The popliteus muscle initiates flexion by pulling the lateral femoral condyle backward while the medial femoral condyle slides forward, resulting in tibial internal rotation [122].

The greatest range of motion in the knee occurs in the sagittal plane at approximately 160° [121]. Knee rotation ranges from 45° in external rotation to 30° in internal rotation [121]. The range of motion in the frontal plane for both abduction and adduction reaches a maximum of 10° [121]. During walking, knee range of motion reaches approximately 70° in the sagittal plane, 15° in the frontal plane, and 10° in the transverse plane [121].

The normal instant center of the knee joint follows a semicircular path related to the tibiofemoral surface and ligaments [121]. Rupture of the cruciate ligaments or disruption of the tibiofemoral surface causes a major change in the path of the instant center, leading to articular dysfunction [121].

Pathophysiology of Osteoarthritis

Primary changes of osteoarthritis include loss of articular cartilage, remodeling of subchondral bone, and formation of osteophytes [34]. The disease involves all tissues that form the synovial joint, including articular cartilage, subchondral bone, metaphyseal bone, synovium, ligaments, joint capsule, and muscles crossing the joint [34]. Osteoarthritis is the leading cause of disability and impaired quality of life in developed countries in patients older than 65 years [34]. The prevalence of osteoarthritis is expected to increase 66% to 100% by 2030 [34]. The knee is the most commonly affected joint, with 12% of adults older than 60 years diagnosed with knee osteoarthritis [34].

Advancing age is perhaps the most important risk factor for osteoarthritis [34]. Female sex and the loss of estrogen over time increase the risk of osteoarthritis [34]. Genetics and obesity are also risk factors [34]. Osteoarthritis is not simply the result of mechanical wear from joint use [34]. At a cellular level, osteoarthritis appears to be the result of deterioration in the ability of chondrocytes to maintain and restore articular cartilage [34]. Chondrocytes undergo age-related telomere erosion and increased expression of the senescence marker β-galactosidase, suggesting cell senescence is responsible for age-related loss of chondrocyte function [34]. Inflammation does not appear to be a major component of osteoarthritis in most patients [34].

The natural history of accelerated knee osteoarthritis can be conceptualized as three phases [2]. In the early phase, occurring at least 2 years in advance of radiographic onset, patients experience greater effusion-synovitis, thicker articular cartilage, diffuse meniscal pathology, and degenerative changes in cruciate ligaments and the extensor mechanism [2]. The subsequent 12-month phase is defined by a dramatic rate of worsening in effusion-synovitis, bone marrow lesions, and articular cartilage [2]. Within 12 months before radiographic onset, adults with accelerated knee osteoarthritis report more joint symptoms, frequent use of pain medication, frequent knee swelling, and daily knee pain compared with those who develop typical knee osteoarthritis [2]. Joint trauma, often characterized by a destabilizing meniscal tear, may be a triggering event in a joint with an impaired ability to heal, leading to joint failure [2].

Knee biomechanical markers are associated with patient-reported knee function to a greater extent than X-ray grading [8]. Patients with knee osteoarthritis are more likely to display a number of biomechanical characteristics [17]. In patients with knee osteoarthritis, 74.4% experienced pain consistent with a predominantly nociceptive mechanism [88]. In patients with knee osteoarthritis, 25.6% exhibited either neuropathic pain or central sensitization components [88]. Neuropathic pain and central sensitization in knee osteoarthritis were not associated with radiographic severity [88]. Higher pain at rest was associated with neuropathic pain and central sensitization in knee osteoarthritis [88].

Knee osteoarthritis management and prevention necessitate a paradigm shift from viewing it as a localized knee disease to recognizing related mechanical overloads of the human complex motion system [96]. The static alignment of the knee as assessed by the mechanical axis was the best single predictor of the peak external knee adduction moment in subjects with milder symptomatic knee osteoarthritis [134]. The association among the coronal inclination of the medial proximal tibia, lower extremity alignment, and external knee adduction moment is a key factor in understanding the etiology of knee osteoarthritis [189]. Alignment and tibial structural factors at baseline are useful in predicting the incidence of knee osteoarthritis [186]. The most relevant relation between the progression of knee osteoarthritis and the deformation of the meniscus was in the longitudinal direction [190].

Regular morphological changes take place in the lateral knee with varus osteoarthritis, including lateral dislocation of the tibial plateau, proximal fibula bending, and upward movement of the fibular head [222]. As the knee mechanical axis became more varus, the distal tibia plafond became more valgus, particularly in women [213]. Gait analysis provides critical information needed to understand the role of ambulatory biomechanics in osteoarthritis development [211]. Gait mechanics contribute to exercise-induced pain flares in knee osteoarthritis [145]. Early-stage knee osteoarthritis directly influences specific temporal and spatial gait characteristics during stair climbing [155].

Gender-specific analysis and rehabilitation protocols should be developed for knee osteoarthritis due to differences in gait kinematics [142]. Spatio-temporal differences between genders in knee osteoarthritis suggest underlying differences in gait strategies adopted to reduce pain and cope with joint loads [178]. Inter-limb asymmetries are prevalent in knee osteoarthritis patients, and restoring symmetry may mitigate contralateral osteoarthritis progression [193]. Walking in minimalistic footwear without sufficient accommodation affected kinetic and kinematic parameters and could increase the risk of early development of knee osteoarthritis [131]. Proper alignment and morphology of the patella might be associated with maintaining normal biomechanical function in knee osteoarthritis [150]. The dynamic evaluation of the medial meniscus is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee osteoarthritis [212]. Adding an objective functional spatiotemporal gait test may assist in the diagnostic process of knee pathologies by detecting differences between knee osteoarthritis, degenerative meniscal lesion, and spontaneous osteonecrosis of the knee [177]. No significant associations were observed between pain catastrophizing and objective knee function or knee biomechanics during gait in patients with severe knee osteoarthritis [163].

The OA inflammatory process starts in the synovial membrane with the activation of the immune system, involving both humoral and cellular mediators [251]. Damage-associated molecular patterns (DAMPs) play a crucial role in the OA inflammatory process [251]. Knee osteoarthritis results from a multifactorial interplay of constitutional and mechanical factors affecting the entire joint, including joint integrity, mechanical forces, genetic predisposition, inflammation, and cellular and biochemical processes [247].

Posttraumatic Osteoarthritis

History of ACL injury is a well-recognized cause of posttraumatic osteoarthritis with >40% incidence 5 to 15 years after injury [246]. Patients with a concomitant meniscus tear at the time of ACL injury are at further increased risk for the development of posttraumatic osteoarthritis [246]. Accumulating evidence suggests that cartilage damage at the time of injury rather than persistent joint instability is the incipient cause of eventual joint degeneration in posttraumatic osteoarthritis [246]. There is little difference in the development of posttraumatic osteoarthritis in patients who have undergone ACL reconstruction and those treated conservatively [246].

The mechanism responsible for cartilage breakdown and progression to osteoarthritis following ACL injury is multifactorial and not completely understood [200]. Occult osteochondral lesions or bone bruises occur in 80%–90% of patients with an acute ACL injury, most commonly on the posterolateral tibial plateau and the anterolateral femoral condyle [200]. The lack of a functionally normal ACL leads to chronic changes in the static and dynamic loading of the knee and increased forces on the cartilage and other joint structures [200]. ACL reconstruction does not restore normal knee kinematics [200]. Clinical measures of knee function were most predictive of subsequent osteoarthritis development following an extended period of rehabilitation early after ACL injury [84]. Patients who had radiographic knee osteoarthritis 5 years after ACL reconstruction walked with lower knee adduction moments and medial compartment joint contact forces than did those patients without osteoarthritis early after injury and reconstruction [219].

The pathological sequence leading to post-traumatic osteoarthritis is engaged within days, not months, following traumatic joint instability [265]. Synovial macrophages and subchondral osteoclasts are primary, actionable cellular targets for early disease interception in post-traumatic osteoarthritis [265]. Meniscus injury or dysfunction results in altered joint loading, which is postulated to result in articular cartilage injury and early joint degeneration [246]. Total menisectomy has been calculated to increase the contact stress in the joint by 235% [246]. 48% of patients developed advanced radiographic changes (Kellgren Lawrence ≥ 2) 21 years following total menisectomy [246]. Intra-articular fractures of the knee will progress to posttraumatic osteoarthritis in 44% of cases 7.5 years after injury [246].

Osteonecrosis

Secondary osteonecrosis of the knee is much less common than osteonecrosis of the femoral head, accounting for approximately 10% of cases [31]. Secondary osteonecrosis typically involves more than one compartment of the knee or even the metaphyseal bone [31]. Approximately 80% of secondary osteonecrosis cases have bilateral involvement, and many cases are multifocal [31]. Patients with secondary osteonecrosis are typically women (3:1 ratio) and are usually younger than 55 years [31]. Osteonecrotic lesions can occur in the epiphysis, diaphysis, or metaphysis [31]. Secondary osteonecrosis progresses to advanced osteoarthritis in 80% of patients treated nonsurgically [31].

Spontaneous osteonecrosis of the knee (SPONK) is more common in women older than 55 years [31]. In 99% of patients, SPONK involves only one joint and only one condyle, typically the epiphysis of the medial femoral condyle [31]. Some evidence shows that SPONK lesions actually represent microfractures [31]. SPONK involves a single condyle, almost always the medial femoral condyle [40]. The etiology of SPONK is mechanical overload, with the Mikulicz line running through the medial compartment [40]. The pathomechanics of SPONK involve mechanical stress overload of bone, microfracture of subchondral bone, fluid build-up increasing intraosseous pressure, and remodeling of necrotic bone [40]. The collapse pattern in SPONK shows a sclerotic halo around a lucent area of collapse, in distinct contrast to secondary osteonecrosis [40]. SPONK presents with sudden onset of medial knee pain, often with a limp, and acute pain lasting 6 to 8 weeks [40].

Secondary osteonecrosis of the knee affects multiple condyles, with the lateral femoral condyle being the most common [250]. Secondary osteonecrosis involves diffuse/extensive areas including subchondral/epiphyseal, metaphyseal, and diaphyseal regions [250]. Approximately 80% of secondary osteonecrosis cases involve the opposite knee [250]. Approximately 70 to 90% of secondary osteonecrosis cases involve the hip [250].

Classification

Radiographic Grading Systems

Kellgren-Lawrence: The Kellgren-Lawrence (KL) radiological classification is the most commonly used system to grade the severity of knee osteoarthritis in clinical studies [51]. However, its subjective nature leads to its exclusion from some study designs that rely on objective structural metrics [51]. The definition of KL grade 2 varies between the original criteria ("definite osteophytes and possible narrowing of joint space") and newer versions ("definite osteophyte, unimpaired joint space" or "minimal osteophytes, possible narrowing, cysts, and sclerosis") [241]. When defined by OARSI atlas criteria, radiographic tibiofemoral osteoarthritis is almost twice as common compared to the Kellgren-Lawrence system [197].

Ahlbäck: The Ahlbäck classification system emphasizes joint space narrowing (JSN) and does not include osteophyte formation for defining knee osteoarthritis [241].

IKDC: The IKDC radiographic evaluation rating system uses different cutoff grades for defining knee osteoarthritis compared to the Kellgren-Lawrence system [241].

KOGS: The KOGS classification provides a reliable and accurate tool to assess the suitability of an individual patient for undergoing patellofemoral knee arthroplasty (PKA) or total knee arthroplasty (TKA) [165].

Disease Definitions and Phenotypes

Osteoarthritis is considered an active process involving the entire synovial joint with both degenerative and repair processes [18]. It may comprise several distinct disease entities, such as tibiofemoral versus patellofemoral involvement or isolated knee versus generalized osteoarthritis [18]. "Symptomatic knee osteoarthritis" is defined as a combination of the pathology of disease with pain that occurs with joint use [18]. This condition affects an estimated 10–12% of the adult population aged 55 years and over [18]. The annual rate of radiographic progression for symptomatic knee osteoarthritis is approximately 3–4% [18]. Knee osteoarthritis may include different inflammatory subtypes according to the affected joints [235].

Patients with end-stage knee osteoarthritis can be classified into four clinical phenotypes: 'isolated end-stage knee osteoarthritis', 'obesity + hypertension', 'depression + anxiety', and 'rheumatoid arthritis' [66]. Neuropathic pain and central sensitization in knee osteoarthritis are not associated with radiographic severity [88]. However, higher pain at rest is associated with neuropathic pain and central sensitization in knee osteoarthritis [88].

Accelerated Knee Osteoarthritis (AKOA)

Accelerated knee osteoarthritis is defined as a knee with no radiographic osteoarthritis at baseline (Kellgren-Lawrence grade < 2) that develops advanced-stage knee osteoarthritis (Kellgren-Lawrence grade 3 or 4) within 48 months [45, 89]. Typical knee osteoarthritis progression is defined as a knee with no radiographic osteoarthritis at baseline (Kellgren-Lawrence grade < 2) that increases in radiographic scoring within 48 months, excluding those with accelerated progression [45, 89].

The natural history of incident accelerated knee osteoarthritis can be conceptualized as three phases [2]. In the phase more than 2 years in advance of radiographic onset, adults with accelerated knee osteoarthritis experience greater effusion-synovitis, thicker articular cartilage, diffuse meniscal pathology, and degenerative changes in the cruciate ligaments and extensor mechanism [2]. During the 12-month phase preceding radiographic onset, there is a dramatic rate of worsening in effusion-synovitis, bone marrow lesions, and articular cartilage [2]. Within 12 months before radiographic onset, adults with accelerated knee osteoarthritis report more joint symptoms, frequent use of pain medication, frequent knee swelling, and daily knee pain compared to those who develop typical knee osteoarthritis [2]. A lack of association between MRI and clinical definitions of early-stage knee osteoarthritis suggests a possible symptom-structure discordance in the early stages of post-traumatic osteoarthritis [15].

Epidemiology and Demographics

Bilateral knee osteoarthritis is very common, with the majority of sufferers eventually developing radiographic disease in both knees [3]. The highest early knee osteoarthritis prevalence was observed in middle-aged adult females aged 50–59 years [12]. The incidence of knee osteoarthritis is significantly different across regions, age groups, and sexes [181]. Osteoarthritis is more prevalent among females [236]. Hip and knee osteoarthritis are common in Europe, though prevalence varies widely across studies and diagnostic approaches [52].

Diagnostic Assessment and Technology

Biomechanical markers and X-ray grading provide complementary information in the assessment of osteoarthritis patients [8]. Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis [60]. The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee osteoarthritis diagnosis among board-certified orthopaedic surgeons [63]. ChatGPT-4o has the potential to rapidly identify and binary classify knee osteoarthritis on radiographs [82]. A convolutional neural network (CNN) can identify and classify knee osteoarthritis as accurately as a fellowship-trained arthroplasty surgeon [188]. The DMS model presents a significant advancement in predicting and grading knee osteoarthritis [196].

Clinical Presentation

History and Symptoms

Knee osteoarthritis (OA) is the leading cause of disability and impaired quality of life in developed countries for patients older than 65 years, with the knee being the most commonly affected joint [34]. The disease process involves all tissues of the synovial joint, including articular cartilage, subchondral bone, metaphyseal bone, synovium, ligaments, joint capsule, and muscles crossing the joint [34]. Pain is typically deep and aching, exacerbated by activity and relieved by rest [34]. Specific aggravating factors include stairs, inclines, and the transition from sitting to standing [27]. Symptoms tend to worsen when joint space narrowing is underway [54], and clinical symptoms may also be caused by meniscal tears [143].

Radiographic findings are an imprecise guide to the likelihood of pain or disability [43]. MRI-detected OA features are common in asymptomatic individuals and may not be the source of pain in symptomatic patients [47]. A lack of association between MRI and clinical definitions of early-stage knee OA suggests a possible symptom-structure discordance in early post-traumatic OA [15]. In the natural history of incident accelerated knee OA, adults may experience greater effusion-synovitis, thicker articular cartilage, diffuse meniscal pathology, and degenerative changes in the cruciate ligaments and extensor mechanism starting at least 2 years before radiographic onset [2]. This greater preradiographic disease burden explains why these patients report more prodromal symptoms than those with typical knee OA [2].

Risk factors include age, obesity, and female sex [34]. While a strong association exists between age and OA, the disease is not simply the result of mechanical wear [34]. On a cellular level, OA results from chondrocyte deterioration in maintaining articular cartilage, potentially driven by age-related telomere erosion and cell senescence [34]. OA is more common in women than men, although men younger than 55 years are diagnosed at a higher rate than women [34]. The highest early prevalence is observed in middle-aged adult females aged 50–59 years [12]. Bilateral knee OA is very common, with the majority of sufferers eventually developing radiographic disease in both knees [3]. Patients with bilateral involvement experience greater progression of osteoarthritis [11].

Metabolic factors are associated with radiographic knee OA in individuals with knee pain, even in those with normal BMI [25]. Regarding activity, short-term running is not associated with worsening patient-reported outcomes or radiological signs of knee OA and may be protective against generalized knee pain [26]. Moderate- to low-quality evidence suggests no association, a positive association, and a negative association with knee OA surgery regarding running [48].

Psychosocial comorbidities are significant. Specific knee OA-related manifestations predict depression and anxiety cross-sectionally, 3 years in the future, and for depression, 7 years in the future [105]. Nearly one-third of patients with symptomatic knee OA have clinically significant depressive symptoms, with a higher proportion among women [146]. Knee OA risk factors, joint symptoms, and co-existing multi-site pain are associated with the presence and development of depression [53]. Patients with end-stage knee OA may be classified into four clinical phenotypes: 'isolated end-stage knee osteoarthritis', 'obesity + hypertension', 'depression + anxiety', and 'rheumatoid arthritis' [66].

Physical Examination

The evaluation of symptomatic knee OA begins with a detailed patient history and physical examination [78]. The history must include onset, quality, duration, tempo, and location of symptoms, modifying factors, ability to bear weight, and history of trauma [159]. Key historical information includes current medications, history of injury or prior surgery, instability, mechanical symptoms, medical comorbidities, response to previous treatments, swelling, symptom duration, temporal nature of pain, and distance able to ambulate [78]. The patient’s symptoms and response to previous therapy guide future treatment and prognosis [78]. The specific type of intra-articular knee injection and response should be noted; a patient who does not have temporary relief from an intra-articular injection should be evaluated for other pathology external to the knee joint [78].

Inspection of the knee reveals skin abnormalities, evidence of trauma, malalignment, and swelling [159]. Gait assessment may reveal abnormalities suggesting intra- or extra-articular causes [159]. Patients with OA have an altered gait and increased energy cost [34]. Palpation focuses on points of tenderness to identify focal pathologies such as joint line tenderness, patellar tendon tenderness, or pes anserine bursitis [159]. Palpation of peripatellar tissue reveals effusion and/or synovitis [159].

Range of motion (ROM) testing is divided into active and passive components [159]. Active ROM refers to the patient’s ability to move their own knee, while passive ROM refers to the examiner’s ability to move the patient’s knee [159]. Flexion contractures and hyperextension should be noted [159]. Blocks to motion can be pain-related or mechanical; when active and passive ROM differ, the diagnostician must differentiate between pain-related, mechanical, or neuromuscular causes [159]. Hip ROM should be examined, as intra-articular hip pathology can present as referred knee pain [159]. The lumbar spine and hips should be examined because pathology in these locations can present as referred pain to the knee [78].

Stability testing reveals ligamentous competency or deficiency [159]. Basic varus and valgus stability testing is performed at 0° and 30° of flexion [159]. Firm end points indicate ligament competence, while pronounced laxity indicates ligament deficiency [159]. Testing at 30° of flexion isolates the medial collateral ligament (MCL) and lateral collateral ligament (LCL) best, as testing in full extension also engages secondary stabilizers [159]. Anterior cruciate ligament (ACL) and posterior cruciate ligament (PCL) competence can be tested using special tests [159]. Patellar tracking and ligament stability should be assessed [34]. Varus or valgus alignment should be noted, as well as any gait abnormality [34]. Knee alignment should be assessed in both supine and standing positions, as bearing weight may change alignment dynamically [159].

Bowing deformity and instability are seen later in the clinical presentation [27]. Knee thrust is seen later and indicates ligament stretch-out on the convex side of the thrust [27]. A varus thrust occurs when the knee pushes outward during stance phase, overloading the medial compartment and accelerating medial cartilage degeneration [27]. A valgus thrust occurs when the knee pushes inward during stance phase, overloading the lateral compartment and accelerating lateral cartilage degeneration [27]. Atrophy in muscles crossing the affected joint is often present in chronic disease [34]. The lower extremities should be examined for muscular atrophy or weakness, with particular attention to hip abductor and quadriceps strength [78]. Distal sensation and vascular perfusion (peripheral pulses) should be assessed in all patients, and any abnormalities should be documented [78].

Catching or locking, instability in the coronal and/or sagittal plane, or an effusion can signal the presence of a mechanical pathology warranting surgical treatment [78]. Patients with spontaneous osteonecrosis of the knee frequently present with a limp and acute pain lasting 6 to 8 weeks located over the femoral condyle [40]. The archetypal case is an overweight, elderly female with osteoporosis presenting with acute onset of medial knee pain and limp, reporting no prior history of knee injury [40]. These patients present with mild to moderate effusion and loss of knee range [40].

Diagnostic Criteria and Prognostic Factors

Current guidelines discourage the routine ordering of x-rays to confirm a diagnosis of OA [18]. Although plain x-rays may be ordered by primary care clinicians, the decision is often determined by factors other than diagnostic necessity [18]. Using a clinical diagnosis is consistent with primary care where x-rays should not be routinely ordered [49]. The American College of Rheumatology (ACR) criteria for a clinical diagnosis of knee OA include any three of the following: age 50 years or older, stiffness lasting less than 30 minutes, crepitus felt on passive or active movement of the knee, bony tenderness, bony enlargement, and no warmth to touch [49].

Male and female participants with painful knee OA are defined according to ACR clinical and radiographic criteria, with pain of > 30 mm on a 100 mm visual analogue scale (VAS) and age 40–75 years [44]. People are eligible for knee OA studies if they report average knee pain over the past week ≥ 4 on an 11-point numeric rating scale and meet ACR criteria for a clinical diagnosis of knee OA [49]. Participants must meet criteria for at least one knee including a diagnosis of Knee OA and current joint symptoms such as pain, aching, or stiffness in one or both knees on most days of the week [97]. To be enrolled in specific trials, participants must meet all of the following criteria: a confirmed diagnosis of unilateral or bilateral knee osteoarthritis by an orthopedic specialist; morning joint stiffness lasting less than 30 min; a history of knee pain on most days of the past month; radiographic evidence of osteophytes; postmenopausal status; and the presence [97].

The annual rate of radiographic progression of symptomatic knee OA is approximately 3–4% [18]. The current consensus is that it is important to separate conceptually the disease process of osteoarthritis and the syndrome of musculoskeletal pain and disability [18]. The disease of osteoarthritis is considered an active process involving the entire synovial joint with both degenerative and repair processes [18]. From a clinical perspective, the most compelling definition of the disease combines the pathology of disease with pain that occurs with joint use [18].

Prognostic factors include pain localization, which serves as a prognostic tool for patient selection in advanced knee OA [116]. Weight examination and management are important for healthcare providers in outpatients with knee OA [133]. A patient who is overweight should be asked about recent weight gain or loss and current weight-maintenance strategy [78]. Recognizing and addressing the broader pathophysiological landscape of obesity in knee OA enables clinicians to refine surgical indications, personalize treatments, and improve long-term outcomes [1]. Comorbidities such as renal or peptic ulcer disease may preclude oral anti-inflammatory medication use [78]. Social factors such as occupation or residence in a nursing home could affect the treatment strategy [78].

Symptoms and difficulties experienced by patients with knee OA should be managed by evidence-based information integrating their perceptions and beliefs toward knee OA [135]. A consensus presents nine recommendations that advocate an algorithmic approach in the management of patients living with knee OA [19]. Experts identified a large number of characteristics for describing patients with knee osteoarthritis [20]. The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons [63]. A study identified speciality-related variability in some aspects of the management of knee OA [65]. Findings highlight the value of a novel clinical assessment strategy for patients with knee OA [61]. A combination of platelet-rich plasma with non-crosslinked hyaluronic acid versus a crosslinked hyaluronic acid demonstrated a good safety profile in symptomatic knee osteoarthritis [9].

Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period [14]. This finding suggests that oral NSAID therapy early after the initial diagnosis is associated with a reduced risk of knee replacement in patients with symptomatic knee osteoarthritis [137]. More than half of the patients (55.3%) had a previous diagnosis of OA within 12 months of surgery and 27.0% received a new diagnosis of knee OA within one year of surgery despite evidence against arthroscopic partial meniscectomy in patients with knee OA [56]. Radiographic signs of osteoarthritis are significant at 8 to 16 years' follow-up after knee arthroscopic partial meniscectomy, but clinical symptoms of knee arthritis are not significant [10]. Obesity, female sex, and preexisting early-stage OA are features associated with poor self-reported and radiographic outcome fifteen to twenty-two years after meniscectomy [32]. Patients reported improved knee function and minimal-to-moderate pain at a minimum 10-year follow-up after knee dislocation surgery, with age at surgery being a predictor of OA development [29]. Joint trauma may be a triggering event in a joint with an impaired ability to heal, which ultimately leads to joint failure [2]. The greater knee pain in accelerated knee OA could contribute to a new knee injury, which is often characterized by a destabilizing meniscal tear [2].

Investigations

Plain radiography: Plain radiographs serve as the standard initial imaging modality for most knee conditions, including traumatic injury, arthritis, patellofemoral alignment, osteochondral injury, bone neoplasm, and surgical implants [24]. They remain the standard for the initial evaluation of knee arthritis [27]. Weight-bearing AP radiographs in extension assess cartilage loss from the distal femur and tibial plateau [24], while weight-bearing PA (Rosenberg) radiographs in flexion assess cartilage loss from the posterior femur and tibial plateau [24]. Patellofemoral views evaluate patellofemoral alignment, patellar and trochlear morphology, osteochondral injury, and patellofemoral arthritis [24]. The notch view assesses posterior femoral cartilage, notch width, and osteophytes [24]. Radiography identifies subchondral sclerosis, joint space narrowing, subchondral cysts, osteophytes, and joint subluxation in osteoarthritis [24].

The Kellgren-Lawrence (KL) rating grades the extent of osteoarthritis based on the AP knee radiograph [27]. Primary features include osteophytes, joint space narrowing, subchondral sclerosis with or without subchondral cysts, and altered shape of periarticular bones [27]. KL Grade 0 indicates normal features [27]; Grade 1 indicates possibly present osteoarthritis [27]; Grade 2 indicates minimal severity [27]; Grade 3 indicates moderate severity [27]; and Grade 4 indicates severe osteoarthritis [27]. Knee arthroplasty is recommended when KL Grade 4 findings are present [27].

Supine AP knee radiographs do not adequately estimate joint space width needed to estimate the degree of osteoarthritis progression [128]. Plain frontal radiographs may not accurately display the actual joint space due to different cartilage wear patterns, meniscal integrity, or variances in tibial slopes [128]. A 45° standing flexion view was introduced to improve joint space evaluation [128]. The fixed flexion view (FFV) technique uses a fixed 10° caudal irradiation angle and fixed limb position relative to the cassette for improved reproducibility and joint space evaluation [128]. The Lyon Schuss view (LSV) uses the same posture as the FFV but requires fluoroscopic adjustment of the irradiation angle relative to the medial tibial plateau for more accurate measurement of actual joint space width [128]. Goniometer readings of long limb alignment or measured on an FFV correlate well with angles measured on long limb radiographs, providing an alternative if long limb radiographs are not available [128]. One in 3 patients considered to have mild to moderate knee OA on extension AP radiography is upgraded to severe knee OA (KL grade 4) on flexion PA radiography [35].

Radiographic findings including joint space narrowing are significantly associated with the long-term risk of total knee arthroplasty in persons with knee osteoarthritis [253]. A low radiological severity of osteoarthritis was not associated with pain 12 months postoperatively after total knee replacement [198]. Moderate osteoarthritis with a joint space of at least 2 mm on AP radiographs was not a predictor for poor outcome after total knee arthroplasty [269]. Radiographic signs of osteoarthritis are significant at 8 to 16 years' follow-up after knee arthroscopic partial meniscectomy [10]. The incidence of knee radiographic osteoarthritis in a Chinese suburban area was high [91]. There were clear associations between metabolic factors and radiographic knee osteoarthritis in individuals with knee pain, including those with normal BMI [25]. Stage of joint destruction assessed on radiographs does not preclude symptom relief following a clinically relevant weight loss in elderly obese female patients with knee osteoarthritis [208]. ChatGPT-4o has the potential to rapidly identify and binary classify knee OA on radiographs [82].

MRI: MRI may identify the degree of articular cartilage injury, including chondrosis and full-thickness cartilage loss, as well as associated bone marrow edema and location [24]. It is the most useful study for differentiating osteonecrosis from other conditions such as osteochondritis dissecans, transient osteoporosis, bone bruises, or occult fractures [31]. Serpentine lesions within a well-demarcated border are a specific finding on MRI for osteonecrosis [31]. MRI is grossly overused in the arthritic patient population [27]. If the joint space is significantly narrowed on radiograph, MRI is not indicated [27]. MRI is used when osteonecrosis is suspected [27].

There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration [207]. A lack of association between MRI and clinical definitions of early-stage knee OA suggests a possible symptom-structure discordance in the early stages of post-traumatic OA disease [15]. MRI contributes less than expected to the understanding of pain and function in knee OA and possibly offers little opportunity to develop structure-modifying treatments that could influence the patient's pain and function [191]. Meniscal extrusion is the strongest predictor of OA progression, highlighting the importance of MRI in identifying early changes and guiding personalised management [252]. MRI detected bone marrow lesions, synovitis, and effusion were all significantly associated with the long-term risk of total knee arthroplasty in persons with knee osteoarthritis [253].

Higher ultrasonographic echo intensity in the medial femoral cartilage is a feature of early cartilage degeneration in mild knee OA [256]. The MRI radiomics analysis represented promising performance in noninvasive and preoperative KOA diagnosis, especially when considering all available planes of all three compartments of knee joints [232]. An MRI radiomics framework integrating cartilage and subchondral bone features effectively predicts KOA incidence and progression, enhances individualized risk stratification, and facilitates timely clinical decisions [264]. In patients with moderate knee osteoarthritis treated within a standardized SVF-based arthroscopic pathway, adding microfracture was associated with more favourable MRI-based cartilage morphology compared with SVF without microfracture [244]. Micro-fragmented adipose tissue (mFAT) associated with arthroscopic debridement improves MRI appearance in the treatment of knee OA [259]. The study demonstrates previously undescribed subchondral vascular marks on axial MRI scans of the tibia and their inverse correlation with the presence and severity of early knee osteoarthritis [262]. In patients with KOA, the diagnostic value of single radiographic or MRI parameter in assessing the functional integrity of the ACL are equivalent [268]. In a population-based cohort of predominantly pre-radiographic knee OA, statins did not affect MRI incidence or progression of cartilage damage, bone marrow lesions, osteophytes, or effusion [266]. Composite quantitative knee structure metrics predict the development of accelerated knee osteoarthritis [16]. Knee biomechanical markers are associated with patient-reported knee function to a greater extent than X-ray grading, but both provide complementary information in the assessment of OA patients [8].

CT: Three-dimensional CT with remodeling is used for preoperative planning for reconstruction associated with dysplasia, post-trauma planning, and complex total knee arthroplasty planning [27]. Three-dimensional CT reconstructions may help with preoperative planning for complex intra-articular fractures, multiplanar osteotomy for limb malalignment, and reconstitution of bone loss in joint arthroplasty [24].

Bone scan: Technetium-99 (Tc-99) is a radionuclide that may help identify infection, neoplasia, occult fracture, bone healing, active phases of heterotopic ossification, implant loosening, or failure of osseointegration [24]. Gallium-67 (Ga-67) is a radionuclide that may help differentiate between aseptic and septic prosthetic loosening [24].

Other Considerations: Physical examination along with radiographic or advanced imaging findings must be used concomitantly to determine the source of each patient’s symptoms and to determine appropriate surgical intervention when nonsurgical measures have failed [4]. Assessment of the joint must combine physical examination along with radiographic (including full-length alignment views) and MRI findings [59]. Radiographic studies help confirm the clinical diagnosis of a joint disorder determined using the patient’s history and physical examination [24]. Patient assessment of knee pain includes a physical examination and diagnostic radiographic modalities [27]. Obesity, female sex, and preexisting early-stage OA are features associated with poor self-reported and radiographic outcome after meniscectomy [32]. Recognizing and addressing the broader pathophysiological landscape of obesity in knee OA will enable clinicians to refine surgical indications, personalize treatments, and improve long-term outcomes [1]. Alterations in the gut and joint microbiome are associated with perturbations of metabolic and inflammatory pathways, imaging findings, OA-related pain, and patient-reported outcome measure performance [263].

Treatment

Non-Operative Management

A stepwise approach with graduated interventional treatment is recommended as pain and functional disability progress in knee osteoarthritis [79]. Patient education programs, exercise (including supervised, unsupervised, and aquatic modalities), and self-management programs are strong recommendations for management [79]. Pharmacologic management includes strong recommendations for topical NSAIDs, oral NSAIDs, and oral acetaminophen [79]. Oral narcotics, including tramadol, are not recommended [79]. Canes and brace treatment are moderate recommendations, as are neuromuscular training in combination with traditional exercise and sustained weight loss [79]. Intra-articular corticosteroids are a moderate recommendation for short-term relief [79]. Arthroscopic partial meniscectomy is a moderate recommendation for meniscal tears in patients with concomitant mild to moderate knee osteoarthritis [79]. Lateral wedge insoles, hyaluronic acid intra-articular injections, and arthroscopy with lavage and/or débridement are not recommended [79].

Supplements including turmeric, ginger extract, glucosamine, chondroitin, and vitamin D may be helpful [79]. Manual therapy in addition to an exercise program, massage in addition to usual care, FDA-approved laser treatment, acupuncture, transcutaneous electrical nerve stimulation, percutaneous electrical nerve stimulation, electromagnetic field therapy, and extracorporeal shockwave therapy may be used or may improve pain and function [79]. Platelet-rich plasma may reduce pain and improve function [79]. Denervation therapy may reduce pain and improve function [79]. High tibial osteotomy may improve pain and function in properly indicated patients with unicompartmental knee osteoarthritis [79]. Dry needling has unclear utility and efficacy [79]. Free-floating interpositional devices, such as the unispacer, are not recommended [79].

Maintenance of a healthy body weight is effective for decreasing the severity of symptoms and slowing the progression of knee osteoarthritis [172]. Obesity increases the likelihood of symptomatic knee osteoarthritis as much as threefold [172]. Forces at the knee are magnified to three to seven times the actual body weight [172]. Patients with a body mass index above 25 kg/m² should strive to lose at least 5% of their current body weight and maintain it with diet and exercise [172]. Weight loss for patients with a body mass index above 25 kg/m² is effective in decreasing pain and minimizing the progression of symptomatic knee osteoarthritis [55]. More than 50% of patients referred with mild-moderate knee osteoarthritis may not need surgery at 7 years [13].

Low-intensity long-duration ultrasound may be used as a conservative non-pharmaceutical and non-invasive treatment option [23]. Cooled radiofrequency ablation may have a role in delaying the need for knee replacement in some patients or may benefit patients who are not candidates for knee replacement [76]. Radiofrequency treatment is an efficacious and safe treatment for relieving knee pain and improving knee function [132]. A six-week physiotherapist-led exercise and education intervention resulted in sustained significant improvements in pain severity and interference in patients with hip or knee osteoarthritis awaiting arthroplasty [192]. Physical therapy programs for knee osteoarthritis should be comprehensive and functional, focusing on core and lower body function [195]. Home exercise programs should include strengthening exercises performed 2-3 times per week, daily range of motion exercises, and aerobic activity with a long-term goal of 150 minutes per week [195]. Modalities for pain management in physical therapy should be used conservatively, taking no more than 25% of the time of each clinic visit [195].

Oral supplementation with glucosamine and/or chondroitin sulfate has no benefit for the management of symptomatic knee osteoarthritis [55]. Intra-articular corticosteroid injections are effective for symptomatic management [55]. The 10 mg dose of triamcinolone acetonide is non-inferior to the 40 mg dose in improving pain in patients with symptomatic knee osteoarthritis [199]. Ultrasound-guided dextrose 25% hypertonic prolotherapy and intra-articular normal saline injection are both effective and well tolerated [138]. Amniotic suspension allograft injection is an effective treatment for the nonoperative management of symptomatic knee osteoarthritis [184]. Crespine Gel Plus may be considered a non-surgical option providing year-long symptomatic relief [164]. One-shot hyaluronic acid is an effective and safe treatment for advanced knee osteoarthritis, providing significant improvements in pain, stiffness, and function over six months [136]. Comparing short-term outcomes of hyaluronic acid injections with oral NSAIDs, hyaluronic acid injections provided statistically significant but not clinically important improvements in knee pain and function, along with a lower overall risk of adverse events [28].

Intra-articular injection of stromal vascular fraction is safe and effective to ameliorate clinical and functional scores in patients with early knee osteoarthritis for 6 months [120]. Micro-fragmented aspirated tissue injection therapy is effective and improves pain and functional outcomes [154]. Bone marrow aspirate concentrate injections demonstrated effectiveness in providing pain relief and functional improvement [152]. Bone marrow aspirate concentrate injection is effective in improving pain and patient-reported outcomes at short-to midterm follow-up [70]. Both platelet-rich plasma and bone marrow aspirate concentrate were effective in improving patient-reported outcomes in patients with mild to moderate knee osteoarthritis for at least 12 months, with neither treatment providing a superior clinical benefit [139]. Platelet-rich plasma demonstrated significantly improved pain and function compared with placebo at a minimum 6-month follow-up [30]. Patients undergoing treatment with platelet-rich plasma can be expected to experience improved clinical outcomes when compared with hyaluronic acid [64]. Platelet-rich plasma, particularly when combined with hyaluronic acid, provides superior long-term pain relief and functional improvement compared to other intra-articular injectables [67]. The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis [153]. Platelet-rich plasma and plasma were not superior to placebo for pain and function improvement over 24 weeks [140]. Platelet-rich plasma injections are considered appropriate in patients aged ≤80 years with knee Kellgren-Lawrence 0–III osteoarthritis grade after failed conservative non-injective or injective treatments [238]. Platelet-rich plasma injections are not considered appropriate as first treatment nor in Kellgren-Lawrence IV osteoarthritis grade [238].

Intra-articular mesenchymal stromal cells demonstrated efficacy and safety supporting their implementation as a treatment option for symptomatic knee osteoarthritis [50]. The symptomatic treatment effect of stromal vascular fraction injections was found to be dose dependent, and the efficacy, safety, and ease of use support its use as a treatment option [115]. Some degree of efficacy has been shown for cartilage regeneration with intra-articular injection of autologous adipose-derived stem cells or stromal vascular fractions, although the evidence remains limited [69]. The clinical outcomes of mesenchymal stem cell implantation are encouraging [149]. The efficacy of mesenchymal stem cell treatment regarding clinical outcomes and cartilage regeneration remains unclear due to large heterogeneity in cell sources, preparation methods, and delivery techniques [141]. Biologic therapies appear to have evidence justifying their use, though more high-level, larger human studies utilizing standardized protocols are needed [46]. Available clinical practice guidelines favor intra-articular corticosteroid and intra-articular hyaluronic acid for different needs, while platelet-rich plasma currently has insufficient evidence to make a conclusive recommendation for or against its use [151]. Authors of a systematic review and meta-analysis were not able to make recommendations for clinical practice regarding platelet-rich plasma [161]. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early knee osteoarthritis [62]. Further studies are necessary to increase the limited medical evidence on conservative treatments, optimizing results, application modalities, indications, and focusing on early knee osteoarthritis [74]. Harms-related data are poorly reported within randomized controlled trials cited as supporting evidence for the American Academy of Orthopaedic Surgeons management for hip and knee osteoarthritis Clinical Practice Guideline [37]. Unequal healthcare costs in the nonoperative treatment of late-stage knee osteoarthritis are driven by differences in prevalent management strategies [179]. The evidence base for the surgical management of knee osteoarthritis has been constructed from studies which fail to consider race and ethnicity [245].

Operative Management

Indications: The literature lacks well-designed studies to evaluate the efficacy of arthroscopic procedures for knee osteoarthritis, with most demonstrating equivalent outcomes to nonsurgical treatment at mid to long-term follow-up [5]. In the absence of mechanical symptoms, arthroscopic débridement has not been shown to be an effective treatment strategy [55]. In the absence of mechanical symptoms, knee arthroscopy with débridement is not effective in managing osteoarthritis of the knee [55]. The evidence does not support the effectiveness of arthroscopic knee surgery compared to conservative treatments [58]. Arthroscopic surgery provides no added benefit over non-surgical treatment [68]. Arthroscopic debridement for the management of mild to moderate knee osteoarthritis is effective at short-term follow-up in patients who have exhausted conservative care [166]. Arthroscopic knee débridement may provide relief from mechanical symptoms in carefully selected osteoarthritis patients, but should not be offered as a first-line treatment in lieu of nonsurgical measures [59]. Patients may continue to have pain because of underlying osteoarthritis after arthroscopic débridement, but mechanical symptoms are more reliably improved [59]. Arthroscopy can be beneficial for patients with osteoarthritis and mechanical symptoms recalcitrant to conservative care, but this should not be the first-line intervention [59]. The best indication for post-traumatic knee osteoarthritis treated by osteotomy only is moderate unicompartmental knee arthritis [71]. After failure of conservative care for knee osteoarthritis, total knee arthroplasty consistently provides substantial improvements in pain, function, and patient satisfaction with excellent survivorship [85].

Surgical Approach / Technique: Arthroscopic treatment is indicated for débridement, chondroplasty, loose body removal, microfracture, and partial meniscectomy [59]. The irrigation during arthroscopic lavage dilutes the joint fluid, which reduces the concentration of degradative enzymes [5]. The removal of loose cartilage, meniscus, and/or synovium during arthroscopy reduces mechanical symptoms and removes a source of irritation to the synovial tissue [5]. In abrasion arthroplasty, an arthroscopic shaver is used to débride cartilage defects and penetrate the subchondral bone plate to cause bleeding [5]. The goal of abrasion arthroplasty is formation of a blood clot, which undergoes metaplasia to become fibrocartilage; the process is estimated to take 8 weeks [5]. In subchondral drilling or microfracture, cartilage defects are débrided to a stable rim, and the resulting exposed subchondral bone is penetrated with a small drill or awl [5]. Some studies have demonstrated by 2 years post-operatively that the fibrocartilage cap from microfracture is significantly degraded or no longer present [5]. Treatment for focal cartilage lesions depends upon the lesion size, lesion location, and the status of the underlying subchondral bone [59]. Surgical options for treatment of focal cartilage injury include bone marrow stimulation techniques, osteochondral autograft or allograft transplantation, autologous cell-based therapy, and allograft therapies [59]. For isolated medial compartment degeneration, surgical options include medial opening wedge high tibial osteotomy, lateral closing wedge high tibial osteotomy, or unicompartmental knee arthroplasty [59]. Lateral compartment osteoarthritis can be treated with lateral closing wedge distal femoral osteotomy, medial opening wedge distal femoral osteotomy, medial closing wedge high tibial osteotomy, or unicompartmental knee arthroplasty [59]. Correction of ligamentous instability and limb malalignment is paramount to success of cartilage restoration procedures and meniscal transplantation [59]. In the case of symptomatic meniscal deficiency, allograft meniscal transplantation can provide significant symptomatic relief and improvements in quality of life, although radiographic osteoarthritis may still progress [59]. In case of failure of osteotomy for post-traumatic knee osteoarthritis, correction of the initial deformity facilitates the total knee replacement procedure [71].

Implant Selection: Total knee arthroplasty is effective at improving pain and function in patients with tricompartmental osteoarthritis using various surgical techniques leading to good outcomes [59]. Multiple total knee arthroplasty implant designs and surgical techniques have been successful in improving patient pain and function without any overwhelming evidence favoring one over the other [59]. Total knee arthroplasty is a highly cost-effective surgical treatment and is the mainstay of surgical approaches for addressing advanced arthritis [85]. Many studies have compared gap balancing versus measured resection techniques, and cruciate retaining versus posterior stabilized implants with essentially equivalent outcomes in terms of pain, function, and survivorship [85]. Cruciate retaining and posterior stabilized total knee arthroplasty techniques both provide good results with no difference in surgical complications, range of motion, patient-reported outcome

Alignment / Balancing Strategy: No studies have convincingly shown that minimally invasive techniques or newer technologies, such as patient-specific instrumentation, can lead to improved outcomes or decreased complications in total knee arthroplasty [85]. A recent randomized controlled trial showed no significant difference in functional outcomes at 2 years when comparing mechanical and kinematic alignment techniques in total knee arthroplasty [85].

Complications

Arthroscopic Management

The literature lacks well-designed studies to evaluate the efficacy of arthroscopic procedures for the arthritic knee, with most demonstrating equivalent outcomes to nonsurgical treatment at mid to long-term follow-up [5]. The potential for thermal damage when using a laser or radiofrequency probe for chondroplasty has resulted in decreased use of these techniques [5]. Some studies have demonstrated that by 2 years post-operatively, the fibrocartilage cap formed after subchondral drilling or microfracture is significantly degraded or no longer present [5].

Total Knee Arthroplasty (TKA)

Infection: Infection is the number one reason for revision TKA and the number one reason for revision within 2 years of index primary TKA [249]. Patients with rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis have higher revision rates compared to patients with osteoarthritis due to increased risk for infection and altered bone metabolism [249].

Aseptic loosening: Aseptic mechanical implant loosening is the second most common reason for revision TKA [249].

Patellar / Extensor-mechanism: Patellofemoral complications occurred in 4% of patients with patellar resurfacing compared with 12% of patients in whom the patella was unresurfaced [255]. Significant residual anterior knee pain was the most common complication in the unresurfaced patella group [255]. Secondary resurfacing of the patella for residual anterior knee pain after TKA has a higher rate of complications, including patellar fracture and postoperative stiffness, compared to primary resurfacing [255].

Other Considerations: Total knee replacement plus a 12-week nonsurgical treatment program was associated with more serious adverse events compared to nonsurgical treatment alone [6]. No studies have convincingly shown that minimally invasive techniques or newer technologies, such as patient-specific instrumentation (PSI), can lead to improved outcomes or decreased complications in TKA [85]. Bearing spin-out can occur in the presence of a loose flexion gap when using mobile bearing TKA implants [85]. Bicruciate retaining (BCR) knee arthroplasty has shown high early failure rates in some studies, leading to limited adoption [85]. Patients who do not have complete cartilage space loss before surgery tend to be less satisfied with their clinical result after TKA [39]. A recent review noted an increasing rise in infection and other complications as obesity classification increased from severe to super-obese [39].

Osteotomy (HTO/DFO)

Patellar / Extensor-mechanism: Patella baja (scar contracture of tendon) is the most common complication of the open-wedge high tibial osteotomy technique [227]. Patella baja is the most common complication of the closed-wedge high tibial osteotomy technique [227].

Stiffness / Arthrofibrosis: Loss of flexion and loss of posterior slope are complications of the closed-wedge high tibial osteotomy technique [227].

Nerve palsy: Peroneal nerve palsy due to aberrant retractor placement is a complication of the closed-wedge high tibial osteotomy technique [227].

Other Considerations: Collapse of the open wedge is a complication of the open-wedge high tibial osteotomy technique [227]. Nonunion is a complication of the open-wedge high tibial osteotomy technique [227]. Bone harvest site pain is a complication of the open-wedge high tibial osteotomy technique [227]. Nonunion is a complication of distal femoral osteotomy (DFO) [227]. Loss of wedge correction is a complication of distal femoral osteotomy (DFO), most common in patients with osteoporotic bone [227]. Residual patellofemoral maltracking is a complication of distal femoral osteotomy (DFO) that may require patellofemoral realignment [227]. The rate of conversion to TKA following high tibial osteotomy is 13% at 6 years [227]. Conversion to TKA following high tibial osteotomy requires longer operative time and more frequent use of revision implants [227].

Unicompartmental Knee Arthroplasty (UKA)

Other Considerations: Long-term survivorship of unicompartmental knee arthroplasty is not comparable with total knee arthroplasty when measured by revision rates [227]. In patients with BMI >40, unicompartmental knee arthroplasty has an increased clinical failure rate at 2 years (29%) compared to total knee arthroplasty (3%) [227].

Knee Dislocation Reconstruction

Infection: Infection is a common complication associated with the management of knee dislocation, with a reported rate of 12.5% [194].

Stiffness / Arthrofibrosis: A mean of 38% of patients (range, 5% to 71%) require surgical management of arthrofibrosis following knee dislocation reconstruction [194].

Instability: Recurrent instability following knee dislocation reconstruction has a mean incidence of approximately 40% [194].

Other Considerations: Heterotopic ossification is a common complication associated with the management of knee dislocation, with a reported incidence of approximately 25% [194]. PCL reconstruction is one independent risk factor for the development of heterotopic ossification following knee dislocation [194]. The incidence of posttraumatic arthritis following multiligament reconstruction is 23% [194]. The incidence of pain following knee dislocation injuries has been reported from 25% to 68% [194].

General and Diagnostic

Other Considerations: Harms-related data are poorly reported within randomized controlled trials cited as supporting evidence for the American Academy of Orthopaedic Surgeons management for hip and knee OA Clinical Practice Guideline [37].

Recovery

Natural History and Progression: The natural history of accelerated knee osteoarthritis (AKOA) is conceptualized as three phases, beginning at least 2 years in advance of radiographic onset with greater effusion-synovitis, thicker articular cartilage, diffuse meniscal pathology, and degenerative changes in the cruciate ligaments and extensor mechanism [2]. During the 12-month phase preceding radiographic onset of AKOA, there is a dramatic rate of worsening in effusion-synovitis, bone marrow lesions, and articular cartilage [2]. Within 12 months before radiographic onset, adults with AKOA report more joint symptoms, frequent use of pain medication, frequent knee swelling, and daily knee pain compared with those who develop typical knee osteoarthritis [2]. Bilateral knee osteoarthritis is very common over time, as the majority of sufferers will eventually develop radiographic disease in both knees [3]. In a community-based cohort, more than 1 in 7 women with incident knee osteoarthritis had accelerated knee osteoarthritis [72]. In a 3-year longitudinal study of elderly community residents in Korea, the yearly incidence and progression of knee OA was higher than those previously reported in Western populations [90]. Patients with hip OA progressed faster and to a greater extent to arthroplasty than patients with knee OA [274]. In 2 multicenter cohorts of patients with knee osteoarthritis, substantial numbers of patients had premature total knee replacement, while others for whom total knee replacement was potentially appropriate had not undergone the procedure more than 2 years after it became potentially appropriate [7].

Risk Factors and Predictors: Obesity, female sex, and preexisting early-stage OA are features associated with poor self-reported and radiographic outcome 15 to 22 years after meniscectomy [32]. Women who developed radiographically defined knee OA had significantly greater odds of having baseline endogenous early follicular phase estradiol concentrations in the lowest tertile (OR 1.86, 95% CI 1.01-3.44) [273]. At 10-year follow-up after ACL reconstruction, radiological signs of OA were present in 53.5% of subjects, with meniscectomy prior to or at the time of ACL reconstruction and chondral lesions at the time of ACL reconstruction identified as risk factors [272]. Clinical measures of knee function were most predictive of subsequent OA development following an extended period of rehabilitation early after ACL injury [84]. Age at surgery was a predictor of OA development in patients undergoing knee dislocation surgery [29].

Non-Operative Management: Ultrasound may be used as a conservative non-pharmaceutical and non-invasive treatment option for patients with knee osteoarthritis [23]. At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo [30]. For short-term follow-up (≤1 year), intra-articular PRP injection is more effective in terms of pain relief and function improvement in the treatment of KOA patients than HA and placebo, and there is no difference in the risk of an adverse event between PRP and HA or placebo [57]. PRP did not improve pain at 24 weeks of follow-up in patients with mild-to-moderate knee osteoarthritis compared with exercise alone [225]. The sustained efficacy of PRP, particularly when combined with HA, provides superior long-term pain relief and functional improvement in knee OA compared to other intra-articular injectables [67]. A short cycle of intra-articular treatment with polynucleotides in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone at 2-year follow-up [276]. RFA is effective in improving both knee pain and function in patients with OA, at least in the short term (6 months) [203]. Activity modification and load management interventions for adolescents with patellofemoral pain were supported by improvements in symptoms and objective measures of hip and knee torque [75].

Operative Management: Long-term studies show better clinical outcomes and less degenerative osteoarthritis changes following meniscal repair than following partial meniscectomy [201]. Articular cartilage debridement for large focal chondral defects in the setting of mild to moderate osteoarthritis results in significant improvements in physical function and knee-specific PROs at minimum one-year follow-up [81]. The survival rate of closed-wedge high tibial osteotomy (CWHTO) for severe medial knee OA was 90.1% at 10 years, 83.8% at 15 years, and 75.9% at 20 and 35 years [209]. Patients and clinicians can expect an average procedure survival of 12.5 years and a maximum of 21 years for medial opening wedge high tibial osteotomies, with effective pain relief influenced by cartilage treatment and preoperative pain score [275]. Long-term clinical trials are required to determine if the biological advantages of high tibial osteotomy with concurrent medial meniscus root repair translate into a delay in the progression of knee osteoarthritis [36]. MSC implantation provided encouraging outcomes with acceptable duration of symptom relief at midterm follow-up in patients with early knee OA [77]. The association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up [202]. The study of nonoperative treatment of anterior cruciate ligament injury had a favorable long-term outcome regarding incidence of radiographic knee OA, knee function and symptoms, and need for ACL reconstruction at 15 years [73]. Patients reported improved knee function and minimal-to-moderate pain at a minimum 10-year follow-up after knee dislocation surgery [29].

Key Evidence

• [L5] Recognizing and addressing this broader pathophysiological landscape will enable clinicians to refine surgical indications, personalize treatments, and ultimately improve long-term outcomes in patients with knee OA. [1] (10.1002/arj.70051)
• [L5] [2] (10.1186/s12891-020-03367-2)
• [L2] Bilateral knee osteoarthritis is very common with time, as the majority of sufferers will eventually develop radiographic disease in both knees. [3] (10.1186/1471-2474-13-153)
• [L1] In patients with knee osteoarthritis, total knee replacement plus a 12-week nonsurgical treatment program was more effective than nonsurgical treatment alone but was associated with more serious adverse events. [6] (10.2106/jbjs.16.00208)
• [L3] In 2 multicenter cohorts of patients with knee osteoarthritis, we observed substantial numbers of patients who had premature total knee replacement as well as of patients for whom total knee replacement was potentially appropriate but had not been performed >2 years after it had become potentially appropriate. [7] (10.2106/jbjs.19.00432)
• [L2] Knee biomechanical markers are associated with patient-reported knee function to a greater extent than X-ray grading, but both provide complementary information in the assessment of OA patients. [8] (10.1186/s12891-022-05845-1)
• [L1] It also demonstrated a good safety profile in symptomatic knee osteoarthritis. [9] (10.1186/s12891-026-09625-z)
• [L1] Radiographic signs of osteoarthritis are significant at 8 to 16 years' follow-up after knee arthroscopic partial meniscectomy, but clinical symptoms of knee arthritis are not significant. [10] (10.1016/j.arthro.2010.08.016)
• [L3] Patients with knee osteoarthritis experienced greater progression of osteoarthritis when the contralateral knee was also affected. [11] (10.1186/s12891-024-07292-6)
• [L4] The highest early knee osteoarthritis prevalence was observed in middle-aged adult females (50–59 years old). [12] (10.1007/s00167-019-05614-z)
• [L3] More than 50% of patients referred with mild-moderate knee OA may not need surgery at 7 years. [13] (10.1016/j.arth.2020.01.086)
• [L3] Among symptomatic clinically diagnosed OA knees, cartilage lesions observed in the first MRI examinations were not found to be associated with the occurrence of joint surgery within a 5-year period. [14] (10.1186/s12891-024-07225-3)
• [L3] A lack of association between MRI and clinical definitions of early-stage knee OA suggests a possible symptom-structure discordance in the early stages of post-traumatic OA disease. [15] (10.1177/23259671261455852)
• [L2] [16] (10.1186/s12891-020-03338-7)
• [L1] Patients with knee osteoarthritis are more likely to display a number of biomechanical characteristics. [17] (10.1186/s12891-018-2202-8)
• [Paper] [18] (10.1186/1471-2474-5-4)
• [L5] This consensus presents nine recommendations that advocate an algorithmic approach in the management of patients living with knee OA. [19] (10.1186/s12891-021-04381-8)
• [L5] Experts identified a large number of characteristics for describing patients with knee osteoarthritis. [20] (10.1186/1471-2474-14-369)
• [L2] Pain remained stable across a one and a half-year period in adults with or at risk for knee osteoarthritis, based on quarterly assessments. [21] (10.1186/s12891-021-04284-8)
• [L2] The presence of mixed patellofemoral osteoarthritis might be an indicator of severe clinical knee osteoarthritis. [22] (10.1186/s12891-017-1486-4)
• [L1] The clinical findings suggest that ultrasound may be used as a conservative non-pharmaceutical and non-invasive treatment option for patients with knee osteoarthritis. [23] (10.1186/s13018-018-0965-0)
• [L4] There were clear associations between metabolic factors and radiographic knee osteoarthritis in individuals with knee pain, also in those with normal BMI. [25] (10.1186/s12891-022-05881-x)
• [L4] In the short term, running is not associated with worsening patient-reported outcomes or radiological signs of knee osteoarthritis and may be protective against generalized knee pain. [26] (10.1177/23259671231152900)
• [L1] Comparing short-term outcomes of HA injections with oral NSAIDs for treatment of knee OA, HA injections provided statistically significant but not clinically important improvements in knee pain and function, along with a lower overall risk of AEs. [28] (10.1177/2325967119897909)
• [L3] Patients reported improved knee function and minimal-to-moderate pain, with age at surgery being a predictor of OA development. [29] (10.1007/s00167-017-4443-8)
• [L1] At a minimum 6-month follow-up, PRP demonstrated significantly improved pain and function for patients with knee osteoarthritis compared with placebo. [30] (10.1016/j.arthro.2024.01.037)
• [L3] Obesity, female sex, and preexisting early-stage OA are features associated with poor self-reported and radiographic outcome. [32] (10.1002/art.20489)
• [L3] One in 3 patients considered to have mild to moderate knee OA on extension AP radiography is upgraded to severe knee OA (KL grade 4) on flexion PA radiography. [35] (10.1177/2325967117706692)
• [L2] Long-term clinical trials are required to determine if these biological advantages translate into a delay in the progression of knee osteoarthritis. [36] (10.1002/ksa.12796)
• [L4] Harms-related data are poorly reported within RCTs cited as supporting evidence for the American Academy of Orthopaedic Surgeons management for hip and knee OA Clinical Practice Guideline. [37] (10.1016/j.arth.2022.06.004)
• [L1] The 25 recommendations should standardize and facilitate the use of intra-articular PRP injections, which are considered by experts as an effective treatment especially in early or moderate knee osteoarthritis. [38] (10.1007/s00167-020-06102-5)
• [L1] Radiographic knee osteoarthritis is likewise an imprecise guide to the likelihood that knee pain or disability will be present. [43] (10.1186/1471-2474-9-116)
• [L2] [44] (10.1186/s12891-021-04690-y)
• [L3] [45] (10.1186/s12891-016-1158-9)
• [L2] Despite these limitations, there appears to be evidence justifying their use for knee osteoarthritis management, though more high-level, larger human studies utilizing standardized protocols are needed. [46] (10.1016/j.arth.2018.12.001)
• [L1] These findings suggest that MRI-detected osteoarthritis features are common in asymptomatic individuals and may not necessarily be the source of pain in symptomatic patients. [47] (10.1136/bjsports-2018-099257)
• [L1] Moderate- to low-quality evidence suggests no association with OA diagnosis, a positive association with OA diagnosis, and a negative association with knee OA surgery. [48] (10.1177/0363546516657531)
• [L2] [49] (10.1186/1471-2474-13-246)
• [L1] The efficacy and safety demonstrated in this placebo-controlled trial support its implementation as a treatment option for symptomatic knee OA. [50] (10.1177/0363546519899923)
• [L1] [51] (10.3390/cells10061365)
• [L1] Hip and knee OA are common in Europe, though prevalence varies widely across studies and diagnostic approaches. [52] (10.1186/s12891-026-09493-7)
• [L2] Knee OA risk factors and joint symptoms, along with co-existing multi-site pain are associated with the presence and development of depression. [53] (10.1186/s12891-020-03875-1)
• [L2] The symptoms of knee OA patients tend to be worse when joint space narrowing is underway. [54] (10.1186/1471-2474-11-269)
• [L3] Despite evidence against APM in patients with knee OA, more than half of the patients (55.3%) had a previous diagnosis of OA within 12 months of surgery and 27.0% received a new diagnosis of knee OA within one year of surgery. [56] (10.5435/jaaos-d-22-00804)
• [L1] For short-term follow-up (≤1 year), intra-articular PRP injection is more effective in terms of pain relief and function improvement in the treatment of KOA patients than HA and placebo, and there is no difference in the risk of an adverse event between PRP and HA or placebo. [57] (10.1186/s13018-019-1363-y)
• [L1] The evidence does not support the effectiveness of arthroscopic knee surgery compared to conservative treatments in knee OA. [58] (10.1186/s12891-024-07813-3)
• [L4] Artificial intelligence offers a promising solution to improve detection and management of knee osteoarthritis. [60] (10.1186/s42836-022-00118-7)
• [L4] These findings highlight the value of a novel clinical assessment strategy for patients with knee OA. [61] (10.2519/jospt.2016.6311)
• [L4] Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. [62] (10.1007/s00167-016-4089-y)
• [L2] The introduction of AI-based computer-aided assessment systems can increase the agreement rate and overall accuracy for knee OA diagnosis among board-certified orthopaedic surgeons. [63] (10.1007/s00167-022-07220-y)
• [L1] Patients undergoing treatment for knee OA with PRP can be expected to experience improved clinical outcomes when compared with HA. [64] (10.1177/0363546520909397)
• [L4] This study identified speciality-related variability in some aspects of the management of knee OA. [65] (10.1186/1471-2474-12-72)
• [L4] Patients with end-stage knee osteoarthritis may be classified into four different clinical phenotypes: 'isolated end-stage knee osteoarthritis', 'obesity + hypertension', 'depression + anxiety', and 'rheumatoid arthritis', which may help guide individualized patient care and treatment strategies. [66] (10.1186/s12891-024-07394-1)
• [L1] These findings emphasize the sustained efficacy of PRP, particularly when combined with HA, in providing superior long-term pain relief and functional improvement in knee OA compared to other intra-articular injectables, highlighting its potential as a preferred treatment modality. [67] (10.1186/s13018-025-05574-w)
• [L1] These findings provide strong evidence that arthroscopic surgery provides no added benefit over non-surgical treatment for knee OA. [68] (10.1016/j.arthro.2009.04.054)
• [L1] Some degree of efficacy has been shown for cartilage regeneration in knee OA, although the evidence remains limited. [69] (10.1177/03635465211053893)
• [L4] The BMAC injection is effective in improving pain and patient-reported outcomes in patients with knee OA at short-to midterm follow-up. [70] (10.1177/03635465211018837)
• [L4] The best indication is moderate unicompartmental knee arthritis, and in case of failure, correction of the initial deformity facilitates the total knee replacement procedure. [71] (10.1016/j.otsr.2010.06.012)
• [L2] In a community-based cohort, more than 1 in 7 women with incident knee osteoarthritis had accelerated knee osteoarthritis. [72] (10.1186/s12891-020-3073-3)
• [L2] The study had a favorable long-term outcome regarding incidence of radiographic knee OA, knee function and symptoms, and need for ACL reconstruction. [73] (10.1177/0363546508316770)
• [L4] Further studies are necessary to increase the limited medical evidence on conservative treatments, optimizing results, application modalities, indications, and focusing on early OA. [74] (10.1007/s00167-011-1713-8)
• [L2] These short- and longer-term outcomes were supported by improvements in symptoms and objective measures of hip and knee torque. [75] (10.1177/0363546519843915)
• [L5] CRFA is not likely to replace the current treatments for OA, but it may have a role in delaying the need for knee replacement in some patients or may benefit patients who are not candidates for knee replacement. [76] (10.2106/jbjs.20.01209)
• [L4] MSC implantation provided encouraging outcomes with acceptable duration of symptom relief at midterm follow-up in patients with early knee OA. [77] (10.1177/2325967120969189)
• [L3] Articular cartilage debridement for large focal chondral defects in the setting of mild to moderate osteoarthritis results in significant improvements in physical function and knee-specific PROs at minimum one-year follow-up. [81] (10.1177/2325967125s00234)
• [L3] ChatGPT-4o has the potential to rapidly identify and binary classify knee OA on radiographs. [82] (10.1002/ksa.12639)
• [L2] Clinical measures of knee function were most predictive of subsequent OA development following an extended period of rehabilitation early after ACL injury. [84] (10.1177/2325967118810775)
• [L4] [88] (10.1186/s12891-026-09747-4)
• [L2] [89] (10.1186/s12891-019-2685-y)
• [L2] In this 3-year longitudinal study, the yearly incidence and progression of knee OA was higher than those previously reported in Western populations. [90] (10.1186/s12891-018-1999-5)
• [L2] The incidence of knee radiographic osteoarthritis in a Chinese suburban area was high. [91] (10.1186/s13018-021-02577-1)
• [L5] Knee OA management and prevention necessitate a paradigm shift from viewing it as a localized knee disease to recognizing related mechanical overloads of the human complex motion system, emphasizing the importance of understanding biomechanical risk factors and individualized interventions based on biokinetic profile analysis. [96] (10.1016/j.jisako.2024.100381)
• [L2] [97] (10.1186/s12891-015-0725-9)
• [L2] [101] (10.1186/1471-2474-9-108)
• [L2] Specific knee OA-related manifestations predict depression and anxiety cross-sectionally, 3 years in the future, and for depression, 7 years in the future. [105] (10.1186/s12891-020-03496-8)
• [L1] The symptomatic treatment effect was found to be dose dependent, and the efficacy of SVF injections, in combination with its safety and ease of use, supports its use as a treatment option for symptomatic knee osteoarthritis. [115] (10.1177/2325967120s00127)
• [L3] These findings support the utility of pain localization as a prognostic tool for patient selection in advanced knee OA. [116] (10.1186/s12891-026-09506-5)
• [L4] Intra-articular knee injection of SVF is safe and effective to ameliorate the clinical and functional scores in patients with early knee osteoarthritis for 6 months. [120] (10.1186/s13018-022-03196-0)
• [L4] Walking in minimalistic footwear without sufficient accommodation affected kinetic and kinematic parameters and could increase the risk of early development of knee osteoarthritis. [131] (10.1177/23259671231183416)
• [L1] This meta-analysis showed that RF is an efficacious and safe treatment for relieving knee pain and improving knee function in patients with knee OA. [132] (10.1186/s13018-021-02906-4)
• [L4] These findings emphasize the importance of weight examination and management in outpatients with knee osteoarthritis for healthcare providers. [133] (10.1186/s12891-025-08432-2)
• [L4] The static alignment of the knee as assessed by the mechanical axis was the best single predictor of the peak external knee adduction moment in subjects with milder symptomatic knee osteoarthritis. [134] (10.1016/s0736-0266(01)00081-x)
• [L5] Symptoms and difficulties experienced by patients with knee OA should be managed by evidence-based information integrating their perceptions and beliefs toward knee OA. [135] (10.1186/s12891-021-04641-7)
• [L4] The results support the use of IA HA as an effective and safe treatment for advanced knee OA, providing significant improvements in pain, stiffness, and function over six months. [136] (10.1186/s12891-025-08875-7)
• [L3] This finding suggests that oral NSAID therapy early after the initial diagnosis is associated with a reduced risk of knee replacement in patients with symptomatic knee osteoarthritis. [137] (10.1186/s12891-023-06415-9)
• [L1] Both treatments are effective and well tolerated for knee osteoarthritis. [138] (10.1186/s12891-025-08580-5)
• [L2] Both PRP and BMC were effective in improving patient-reported outcomes in patients with mild to moderate knee OA for at least 12 months; neither treatment provided a superior clinical benefit. [139] (10.1177/2325967119900958)
• [L1] PRP and plasma were not superior to placebo for pain and function improvement in knee osteoarthritis over 24 weeks. [140] (10.1186/s12891-021-04706-7)
• [L5] The efficacy of mesenchymal stem cell treatment regarding clinical outcomes and cartilage regeneration in knee osteoarthritis remains unclear due to large heterogeneity in cell sources, preparation methods, and delivery techniques; future studies with consistent protocols are required to validate the theoretical potential of stem cell treatments. [141] (10.1016/j.arthro.2020.11.017)
• [L3] These results suggest that care should be taken to account for gender when investigating the biomechanical aetiology of knee OA and that gender-specific analysis and rehabilitation protocols should be developed. [142] (10.1186/s12891-016-1013-z)
• [L3] These results suggest that clinical symptoms in patients with osteoarthritis of the knee may be caused by meniscal tears. [143] (10.1007/s00167-014-2939-z)
• [L4] This highlights a potential role of gait biomechanics in short-term osteoarthritis pain fluctuations. [145] (10.1186/s12891-019-2493-4)
• [L4] Nearly one-third of patients with symptomatic knee osteoarthritis had clinically significant depressive symptoms, with a higher proportion among women. [146] (10.1186/s12891-025-09453-7)
• [L4] The clinical outcomes of MSC implantation for knee OA are encouraging. [149] (10.1177/0363546515588317)
• [L3] This study provides further evidence that proper alignment and morphology of the patella might be associated with maintaining normal biomechanical function. [150] (10.1186/s13018-024-05001-6)
• [L1] Available clinical practice guidelines provide recommendations on injectables for knee OA treatment, favoring IA-CS and IA-HA for different needs, while PRP currently has insufficient evidence to make a conclusive recommendation for or against its use. [151] (10.1177/23259671211030272)
• [L1] BMAC injections demonstrated effectiveness in providing pain relief and functional improvement for patients with knee OA. [152] (10.1177/23259671241296555)
• [L2] The administration of three or five injections of platelet-rich plasma is safe, substantially more effective than single injections, and leads to remarkable clinical improvement by significantly reducing knee pain, improving joint stiffness, and enhancing physical function in patients with grade I-III knee osteoarthritis. [153] (10.1186/s13018-024-04736-6)
• [L4] Micro-fragmented aspirated tissue injection therapy for the treatment of symptomatic knee osteoarthritis is effective and improves pain and functional outcomes. [154] (10.1016/j.arthro.2024.03.002)
• [L3] Early-stage knee OA directly influences specific temporal and spatial gait characteristics during stair climbing. [155] (10.1016/j.arth.2012.01.018)
• [L3] Although a high proportion of patients with knee OA have avoided surgery at 5 years, their outcomes show no improvement from baseline and are poorer than those who have undergone TKA. [156] (10.1016/j.arth.2020.04.087)
• [L2] Therefore, the authors are not able to make recommendations for clinical practice regarding PRP for knee osteoarthritis. [161] (10.1177/03635465211062243)
• [L4] No significant associations were observed between pain catastrophizing and objective knee function (range of motion and muscle strength) or knee biomechanics during gait in patients with severe knee OA. [163] (10.1186/s12891-025-08993-2)
• [L3] Crespine Gel Plus may be considered a non-surgical option providing year-long symptomatic relief for patients with knee OA. [164] (10.1186/s12891-026-09588-1)
• [L2] The KOGS classification provides a reliable and accurate tool to assess suitability of an individual patient for undergoing PKA or TKA. [165] (10.1016/j.arth.2018.11.011)
• [L4] Arthroscopic debridement for the management of mild to moderate knee OA is effective at short-term follow-up in patients who have exhausted conservative care. [166] (10.1016/j.arthro.2024.03.016)
• [L4] Patient preferences for various treatment attributes varied among patients in a knee osteoarthritis population. [171] (10.2106/jbjs.20.00132)
• [L4] Adding an objective functional spatiotemporal gait test may assist in the diagnostic process of knee pathologies by detecting differences between knee osteoarthritis, degenerative meniscal lesion, and spontaneous osteonecrosis of the knee. [177] (10.1016/j.otsr.2017.02.006)
• [L3] The spatio-temporal differences between genders may suggest underlying differences in the gait strategies adopted by males and females in order to reduce pain and cope with the loads acting on their affected joints, two key aspects of knee OA. [178] (10.1186/1471-2474-10-127)
• [L3] Unequal healthcare costs in the nonoperative treatment of late-stage knee OA are driven by differences in prevalent management strategies. [179] (10.1016/j.arth.2022.04.040)
• [L5] The incidence of knee osteoarthritis is significantly different with regions, age and sex. [181] (10.1186/s12891-024-07191-w)
• [L1] The evidence presented in this Level I Randomized Controlled Trial suggests that ASA injection is an effective treatment for the nonoperative management of symptomatic knee OA. [184] (10.1055/s-0039-1696672)
• [L3] In addition, alignment and tibial structural factors at baseline are useful in predicting the incidence of knee OA in daily practice. [186] (10.1007/s00167-023-07554-1)
• [L4] A CNN can identify and classify knee OA as accurately as a fellowship-trained arthroplasty surgeon. [188] (10.1016/j.arth.2020.04.059)
• [L3] The association among the coronal inclination of the medial proximal tibia, lower extremity alignment, and external knee adduction moment is one of the key factors to help better understand the etiology of knee osteoarthritis. [189] (10.1007/s00167-020-06323-8)
• [L4] The most relevant relation between the progression of the knee OA and the deformation of the meniscus was in the longitudinal direction. [190] (10.1186/s13018-017-0595-y)
• [L4] MRI contributes less than expected to the understanding of pain and function in knee OA and possibly offers little opportunity to develop structure-modifying treatments in knee OA that could influence the patient's pain and function. [191] (10.1007/s00167-013-2434-y)
• [L1] [192] (10.1186/s12891-016-1088-6)
• [L5] This review provides robust biomechanical evidence supporting the prevalence of inter-limb asymmetries in knee OA patients, underscoring the potential critical role of restoring symmetry in mitigating contralateral OA progression and improving gait rehabilitation outcomes. [193] (10.1530/eor-2025-0173)
• [L1] [195] (10.1016/j.joca.2017.12.008)
• [L5] The DMS model presents a significant advancement in predicting and grading knee OA, holding substantial clinical importance. [196] (10.1186/s13018-024-05352-0)
• [L3] Radiographic tibiofemoral OA was almost twice as common using OARSI atlas criteria compared with the K/L system. [197] (10.1007/s00167-014-3205-0)
• [L3] A low radiological severity of osteoarthritis was not associated with pain 12 months postoperatively. [198] (10.1302/0301-620x.96b11.33726)
• [L1] The 10 mg of TA is non-inferior to 40 mg TA in improving pain in patients with symptomatic knee OA. [199] (10.1186/s12891-023-06191-6)
• [L5] [200] (10.1016/j.csm.2012.08.017)
• [L5] Long-term studies show better clinical outcomes and less degenerative osteoarthritis changes following meniscal repair than following partial meniscectomy. [201] (10.3390/life12040603)
• [L4] The association of definite knee osteoarthritis in medial patellofemoral ligament reconstruction with or without lateral release was small in the long-term follow-up. [202] (10.1177/0363546507306161)
• [L1] RFA is effective in improving both knee pain and function in patients with OA, at least in the short term (6 months). [203] (10.1016/j.arthro.2022.01.048)
• [L4] Therefore, based on the data from this study, orthopaedic surgeons may consider recommending MAT as a salvage procedure even in knees affected by early to moderate OA, while advising patients that the need for combined interventions could potentially reduce graft survival. [204] (10.1177/03635465241253849)
• [L1] There is evidence in some MRI protocols that MRI is a relatively valid, sensitive, specific, accurate, and reliable clinical tool for identifying articular cartilage degeneration. [207] (10.1177/0363546511407612)
• [L2] Stage of joint destruction, assessed on either radiographs or low-field MRI (0.2T), does not preclude a symptoms relief following a clinically relevant weight loss in elderly obese female patients with knee osteoarthritis. [208] (10.1186/1471-2474-12-56)
• [L4] The survival rate of CWHTO for severe medial knee OA was 90.1% at 10 years, 83.8% at 15 years, and 75.9% at 20 and 35 years. [209] (10.1177/23259671211046964)
• [L2] Findings from this trial will contribute to evidence-based personalized treatment recommendations for a large proportion of OA patients who currently lack an effective treatment option. [210] (10.1186/s12891-021-04924-z)
• [L2] Gait analysis provides the critical information needed to understand the role of ambulatory biomechanics in OA development, and to design therapeutic interventions. [211] (10.1302/2058-5241.1.000051)
• [L4] The dynamic evaluation is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee OA. [212] (10.1186/s12891-023-06361-6)
• [L3] As the knee mechanical axis became more varus, the distal tibia plafond became more valgus, particularly in women. [213] (10.1186/s13018-019-1191-0)
• [L3] Patients who had radiographic knee OA 5 years after ACL reconstruction walked with lower knee adduction moments and medial compartment joint contact forces than did those patients without OA early after injury and reconstruction. [219] (10.1177/0363546515608475)
• [L3] Regular morphological changes take place in the lateral knee with varus OA, including lateral dislocation of the tibial plateau, proximal fibula bending, and upward movement of the fibular head. [222] (10.1186/s13018-023-03684-x)
• [L1] PRP did not improve pain at 24 weeks of follow-up in patients with mild-to-moderate knee osteoarthritis compared with exercise alone. [225] (10.1097/corr.0000000000002993)
• [L3] The MRI radiomics analysis represented promising performance in noninvasive and preoperative KOA diagnosis, especially when considering all available planes of all three compartments of knee joints. [232] (10.1186/s13018-023-03837-y)
• [L4] OA may include different inflammatory subtypes according to affected joints and distinct inflammatory processes may drive OA in these joints. [235] (10.1186/s12891-018-1955-4)
• [L4] Osteoarthritis is more prevalent among females. [236] (10.1186/s13018-025-05805-0)
• [L1] PRP injections are considered appropriate in patients aged ≤80 years with knee KL 0–III OA grade after failed conservative non-injective or injective treatments, while they are not considered appropriate as first treatment nor in KL IV OA grade. [238] (10.1002/ksa.12320)
• [L1] [241] (10.1177/0363546509338827)
• [L1] In patients with moderate knee osteoarthritis treated within a standardized SVF‐based arthroscopic pathway, adding microfracture was associated with superior 24‐month pain and WOMAC improvement and more favourable MRI‐based cartilage morphology compared with SVF without microfracture. [244] (10.1002/ksa.70377)
• [L4] This study illustrated that the evidence base for the surgical management of knee osteoarthritis has been constructed from studies which fail to consider race and ethnicity. [245] (10.1016/j.arth.2023.08.023)
• [Paper] [247] (10.1055/s-0037-1608844)
• [L4] [251] (10.3390/ijms24076405)
• [L2] Meniscal extrusion is the strongest predictor of OA progression, highlighting the importance of MRI in identifying early changes and guiding personalised management. [252] (10.1002/ksa.70016)
• [L2] Radiographic findings including joint space narrowing and MRI detected bone marrow lesions, synovitis and effusion were all significantly associated with the long term risk of TKA in persons with knee osteoarthritis. [253] (10.1186/s12891-017-1871-z)
• [L3] Higher echo intensity is a feature of early cartilage degeneration in mild knee OA. [256] (10.1007/s00167-023-07440-w)
• [L1] mFAT improves functional outcome and MRI appearance when used in association with AD, therefore supporting its use in the treatment of knee OA in an arthroscopic setting. [259] (10.1007/s00167-022-07101-4)
• [L4] The study demonstrates previously undescribed subchondral vascular marks on axial MRI scans of the tibia and their inverse correlation with the presence and severity of early knee osteoarthritis, offering new insight into the possible vascular aetiology of osteoarthritis. [262] (10.1186/s13018-018-0991-y)
• [L2] These alterations are associated with perturbations of metabolic and inflammatory pathways, imaging findings, OA-related pain, and patient-reported outcome measure performance. [263] (10.1016/j.arthro.2024.05.010)
• [L2] The MRI radiomics framework integrating cartilage and subchondral bone features effectively predicts KOA incidence and progression, enhances individualized risk stratification, and facilitates timely clinical decisions. [264] (10.1186/s12891-025-09234-2)
• [L5] [265] (10.1002/arj.70355)
• [L3] In this population-based cohort of predominantly pre-radiographic knee OA, statins did not affect MRI incidence/progression of cartilage damage, BML, osteophytes or effusion. [266] (10.1186/s12891-022-05900-x)
• [L3] In patients with KOA, the diagnostic value of single radiographic or MRI parameter in assessing the functional integrity of the ACL are equivalent. [268] (10.1186/s42836-024-00262-2)
• [L3] Moderate osteoarthritis with a joint space of at least 2 mm on AP radiographs was not a predictor for poor outcome. [269] (10.1007/s00402-021-03785-4)
• [L2] At 10-year follow-up, radiological signs of OA were present in 53.5% of subjects, with meniscectomy prior to or at the time of ACL reconstruction and chondral lesions at the time of ACL reconstruction identified as risk factors. [272] (10.1007/s00167-012-2234-9)
• [L2] Women who developed radiographically defined knee OA had significantly greater odds of having baseline endogenous early follicular phase estradiol concentrations in the lowest tertile (OR 1.86, 95% CI 1.01-3.44). [273] (10.1002/art.22005)
• [L3] Patients with hip OA progressed faster and to a greater extent to arthroplasty than patients with knee OA. [274] (10.1302/0301-620x.104b7.bjj-2021-1766.r1)
• [L4] Patients and clinicians can expect an average procedure survival of 12.5 years and a maximum of 21 years, with effective pain relief influenced by cartilage treatment and preoperative pain score. [275] (10.1136/jisakos-2017-000169)
• [L2] The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment with polynucleotides in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. [276] (10.1186/s12891-021-04648-0)

See Also

• High tibial osteotomy
• Distal femoral osteotomy
• Meniscal tear
• ACL reconstruction
• Partial meniscectomy
• Total Knee Replacement
• Knee arthroscopy
• Meniscal repair
• Anterior cruciate ligament injury

References

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[2] Risk factors and the natural history of accelerated knee osteoarthritis: a narrative review. BMC Musculoskeletal Disorders. 2020. DOI: 10.1186/s12891-020-03367-2

[3] Is knee osteoarthritis a symmetrical disease? Analysis of a 12 year prospective cohort study. BMC Musculoskeletal Disorders. 2012. DOI: 10.1186/1471-2474-13-153

[4] Orthopaedic Knowledge Update 13 Ebook Without Multimedia. Knee Arthroscopy and Preservation, Knee Reconstruction > Introduction.

[5] Aaos Comprehensive Orthopaedic Review 3. Nonarthroplasty Surgical Treatment of the Knee > I. Arthroscopic Management of the Arthritic Knee.

[6] Total Knee Replacement Plus Nonsurgical Treatment Was Better Than Nonsurgical Treatment Alone for Knee Osteoarthritis. Journal of Bone and Joint Surgery. 2016. DOI: 10.2106/jbjs.16.00208

[7] Examining Timeliness of Total Knee Replacement Among Patients with Knee Osteoarthritis in the U.S.. Journal of Bone and Joint Surgery. 2020. DOI: 10.2106/jbjs.19.00432

[8] Biomechanical markers associations with pain, symptoms, and disability compared to radiographic severity in knee osteoarthritis patients: a secondary analysis from a cluster randomized controlled trial. BMC Musculoskeletal Disorders. 2022. DOI: 10.1186/s12891-022-05845-1

[9] Efficacy and safety of a combination of platelet-rich plasma with non-crosslinked hyaluronic acid versus a crosslinked hyaluronic acid, in single-injection for knee osteoarthritis. Randomized, controlled, multicenter, non-inferiority trial. BMC Musculoskeletal Disorders. 2026. DOI: 10.1186/s12891-026-09625-z

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[66] Clinical phenotypes of comorbidities in end-stage knee osteoarthritis: a cluster analysis. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07394-1

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[76] Is Cooled Radiofrequency Ablation the Hot New Treatment for Knee Osteoarthritis?. Journal of Bone and Joint Surgery. 2020. DOI: 10.2106/jbjs.20.01209

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[84] Poor Performance on Single-Legged Hop Tests Associated With Development of Posttraumatic Knee Osteoarthritis After Anterior Cruciate Ligament Injury. Orthopaedic Journal of Sports Medicine. 2018. DOI: 10.1177/2325967118810775

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[90] Risk factors for progression of radiographic knee osteoarthritis in elderly community residents in Korea. BMC Musculoskeletal Disorders. 2018. DOI: 10.1186/s12891-018-1999-5

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[105] Specific manifestations of knee osteoarthritis predict depression and anxiety years in the future: Vancouver Longitudinal Study of Early Knee Osteoarthritis. BMC Musculoskeletal Disorders. 2020. DOI: 10.1186/s12891-020-03496-8

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[132] Efficacy and safety of radiofrequency treatment for improving knee pain and function in knee osteoarthritis: a meta-analysis of randomized controlled trials. Journal of Orthopaedic Surgery and Research. 2022. DOI: 10.1186/s13018-021-02906-4

[133] Body mass index and health-related quality of life of outpatients with knee osteoarthritis: evidence from a cross-sectional study. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08432-2

[134] The knee adduction moment during gait in subjects with knee osteoarthritis is more closely correlated with static alignment than radiographic disease severity, toe out angle and pain. Journal of Orthopaedic Research. 2002. DOI: 10.1016/s0736-0266(01)00081-x

[135] Perceptions, beliefs, and needs of Japanese people with knee osteoarthritis during conservative care: a qualitative study. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04641-7

[136] One shot of hyaluronic acid in advanced knee osteoarthritis: postmarketing clinical follow-up for real-world evidence in a pain unit. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08875-7

[137] Comparative effectiveness of early initiation of oral nonsteroidal anti-inflammatory drug and oral acetaminophen therapies on the time to knee replacement in patients with knee osteoarthritis in Japan. BMC Musculoskeletal Disorders. 2023. DOI: 10.1186/s12891-023-06415-9

[138] Comparison of the efficacy of ultrasound-guided dextrose 25% hypertonic prolotherapy and intra-articular normal saline injection on pain, functional limitation, and range of motion in patients with knee osteoarthritis; a randomized controlled trial. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08580-5

[139] Bone Marrow Aspirate Concentrate Is Equivalent to Platelet-Rich Plasma for the Treatment of Knee Osteoarthritis at 1 Year: A Prospective, Randomized Trial. Orthopaedic Journal of Sports Medicine. 2020. DOI: 10.1177/2325967119900958

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[141] Editorial Commentary: Stem Cell Treatment in Knee Osteoarthritis: What for? Pain Management or Cartilage Regeneration?. Arthroscopy. 2021. DOI: 10.1016/j.arthro.2020.11.017

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[143] Medial meniscus tear morphology and related clinical symptoms in patients with medial knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2014. DOI: 10.1007/s00167-014-2939-z

[145] Gait mechanics contribute to exercise induced pain flares in knee osteoarthritis. BMC Musculoskeletal Disorders. 2019. DOI: 10.1186/s12891-019-2493-4

[146] High prevalence of depression in symptomatic knee osteoarthritis: a cross-sectional study on risk factors and therapeutic implications. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-09453-7

[149] Mesenchymal Stem Cell Implantation in Knee Osteoarthritis. The American Journal of Sports Medicine. 2015. DOI: 10.1177/0363546515588317

[150] The association between patella alignment and morphology and knee osteoarthritis. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-05001-6

[151] A Systematic Review of Current Clinical Practice Guidelines on Intra-articular Hyaluronic Acid, Corticosteroid, and Platelet-Rich Plasma Injection for Knee Osteoarthritis: An International Perspective. Orthopaedic Journal of Sports Medicine. 2021. DOI: 10.1177/23259671211030272

[152] Bone Marrow Aspirate Concentrate Injections for the Treatment of Knee Osteoarthritis: A Systematic Review of Randomized Controlled Trials. Orthopaedic Journal of Sports Medicine. 2024. DOI: 10.1177/23259671241296555

[153] The varying clinical effectiveness of single, three and five intraarticular injections of platelet-rich plasma in knee osteoarthritis. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-04736-6

[154] Micro‐Fragmented Adipose Tissue Demonstrates Comparable Clinical Efficacy to Other Orthobiologic Injections in Treating Symptomatic Knee Osteoarthritis: A Systematic Review of Level I to IV Clinical Studies. Arthroscopy. 2024. DOI: 10.1016/j.arthro.2024.03.002

[155] Temporal-Spatial Gait Adaptations During Stair Ascent and Descent in Patients With Knee Osteoarthritis. The Journal of Arthroplasty. 2012. DOI: 10.1016/j.arth.2012.01.018

[156] The Functional Outcomes of Patients With Knee Osteoarthritis Managed Nonoperatively at the Joint Clinic at 5-Year Follow-Up: Does Surgical Avoidance Mean Success?. The Journal of Arthroplasty. 2020. DOI: 10.1016/j.arth.2020.04.087

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[161] How Does Platelet-Rich Plasma Compare Clinically to Other Therapies in the Treatment of Knee Osteoarthritis? A Systematic Review and Meta-analysis. The American Journal of Sports Medicine. 2022. DOI: 10.1177/03635465211062243

[163] Association of knee joint performance and gait patterns with pain catastrophizing in patients with severe knee osteoarthritis: a cross-sectional study. BMC Musculoskeletal Disorders. 2025. DOI: 10.1186/s12891-025-08993-2

[164] Long-term functional and clinical outcomes of intraarticular double-cross-linked high molecular weight hyaluronic acid (Crespine Gel Plus) injection in knee osteoarthritis: a one year prospective study. BMC Musculoskeletal Disorders. 2026. DOI: 10.1186/s12891-026-09588-1

[165] The Knee Osteoarthritis Grading System for Arthroplasty. The Journal of Arthroplasty. 2019. DOI: 10.1016/j.arth.2018.11.011

[166] Arthroscopic Debridement of Mild and Moderate Knee Osteoarthritis Results in Clinical Improvement at Short‐Term Follow‐Up: A Systematic Review. Arthroscopy. 2024. DOI: 10.1016/j.arthro.2024.03.016

[171] Patient Preferences for Surgical Treatment of Knee Osteoarthritis. Journal of Bone and Joint Surgery. 2020. DOI: 10.2106/jbjs.20.00132

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[177] Knee osteoarthritis, degenerative meniscal lesion and osteonecrosis of the knee: Can a simple gait test direct us to a better clinical diagnosis. Orthopaedics & Traumatology: Surgery & Research. 2017. DOI: 10.1016/j.otsr.2017.02.006

[178] Differences in gait patterns, pain, function and quality of life between males and females with knee osteoarthritis: a clinical trial. BMC Musculoskeletal Disorders. 2009. DOI: 10.1186/1471-2474-10-127

[179] Drivers of Unequal Healthcare Costs in the Nonoperative Treatment of Late-Stage Knee Osteoarthritis Prior to Primary Total Knee Arthroplasty. The Journal of Arthroplasty. 2022. DOI: 10.1016/j.arth.2022.04.040

[181] Regional disparities, age-related changes and sex-related differences in knee osteoarthritis. BMC Musculoskeletal Disorders. 2024. DOI: 10.1186/s12891-024-07191-w

[184] A Randomized Controlled Single-Blind Study Demonstrating Superiority of Amniotic Suspension Allograft Injection Over Hyaluronic Acid and Saline Control for Modification of Knee Osteoarthritis Symptoms. The Journal of Knee Surgery. 2019. DOI: 10.1055/s-0039-1696672

[186] The Matsudai Knee Osteoarthritis Survey showed the longitudinal changes of knee phenotypes in alignment and structure during 23–28 years. Knee Surgery, Sports Traumatology, Arthroscopy. 2023. DOI: 10.1007/s00167-023-07554-1

[188] Can a Convolutional Neural Network Classify Knee Osteoarthritis on Plain Radiographs as Accurately as Fellowship-Trained Knee Arthroplasty Surgeons?. The Journal of Arthroplasty. 2020. DOI: 10.1016/j.arth.2020.04.059

[189] The medial inclination of the proximal tibia is associated with the external knee adduction moment in advanced varus knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2020. DOI: 10.1007/s00167-020-06323-8

[190] Relationship between knee osteoarthritis and meniscal shape in observation of Japanese patients by using magnetic resonance imaging. Journal of Orthopaedic Surgery and Research. 2017. DOI: 10.1186/s13018-017-0595-y

[191] Weak associations between structural changes on MRI and symptoms, function and muscle strength in relation to knee osteoarthritis. Knee Surgery, Sports Traumatology, Arthroscopy. 2013. DOI: 10.1007/s00167-013-2434-y

[192] Significant improvements in pain after a six-week physiotherapist-led exercise and education intervention, in patients with osteoarthritis awaiting arthroplasty, in South Africa: a randomised controlled trial. BMC Musculoskeletal Disorders. 2016. DOI: 10.1186/s12891-016-1088-6

[193] Asymmetrical biomechanics in knee osteoarthritis: a review of contralateral risk from primary disease to post-arthroplasty progression. EFORT Open Reviews. 2026. DOI: 10.1530/eor-2025-0173

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[195] Physical therapy vs internet-based exercise training for patients with knee osteoarthritis: results of a randomized controlled trial. Osteoarthritis and Cartilage. 2018. DOI: 10.1016/j.joca.2017.12.008

[196] Enhancing knee osteoarthritis diagnosis with DMS: a novel dense multi-scale convolutional neural network approach. Journal of Orthopaedic Surgery and Research. 2024. DOI: 10.1186/s13018-024-05352-0

[197] Defining the presence of radiographic knee osteoarthritis: a comparison between the Kellgren and Lawrence system and OARSI atlas criteria. Knee Surgery, Sports Traumatology, Arthroscopy. 2014. DOI: 10.1007/s00167-014-3205-0

[198] Low grading of the severity of knee osteoarthritis pre-operatively is associated with a lower functional level after total knee replacement. The Bone & Joint Journal. 2014. DOI: 10.1302/0301-620x.96b11.33726

[199] The efficacy of intra-articular triamcinolone acetonide 10 mg vs. 40 mg in patients with knee osteoarthritis: a non-inferiority, randomized, controlled, double-blind, multicenter study. BMC Musculoskeletal Disorders. 2023. DOI: 10.1186/s12891-023-06191-6

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[201] Degenerative Meniscus in Knee Osteoarthritis: From Pathology to Treatment. Life. 2022. DOI: 10.3390/life12040603

[202] Long-term Follow-up and Knee Osteoarthritis Change after Medial Patellofemoral Ligament Reconstruction for Recurrent Patellar Dislocation. The American Journal of Sports Medicine. 2007. DOI: 10.1177/0363546507306161

[203] Radiofrequency Ablation in Cooled Monopolar or Conventional Bipolar Modality Yields More Beneficial Short‐Term Clinical Outcomes Versus Other Treatments for Knee Osteoarthritis: A Systematic Review and Network Meta‐Analysis of Randomized Controlled Trials. Arthroscopy. 2022. DOI: 10.1016/j.arthro.2022.01.048

[204] 10-Year Survival and Clinical Improvement of Meniscal Allograft Transplantation in Early to Moderate Knee Osteoarthritis. The American Journal of Sports Medicine. 2024. DOI: 10.1177/03635465241253849

[207] The Clinical Utility and Diagnostic Performance of Magnetic Resonance Imaging for Identification of Early and Advanced Knee Osteoarthritis. The American Journal of Sports Medicine. 2011. DOI: 10.1177/0363546511407612

[208] Radiographs and low field MRI (0.2T) as predictors of efficacy in a weight loss trial in obese women with knee osteoarthritis. BMC Musculoskeletal Disorders. 2011. DOI: 10.1186/1471-2474-12-56

[209] Long-Term Survivorship of Closed-Wedge High Tibial Osteotomy for Severe Knee Osteoarthritis: Outcomes After 10 to 37 Years. Orthopaedic Journal of Sports Medicine. 2021. DOI: 10.1177/23259671211046964

[210] The effectiveness of exercise therapy and education plus cognitive behavioral therapy, alone or in combination with total knee arthroplasty in patients with knee osteoarthritis – study protocol for the MultiKnee trial. BMC Musculoskeletal Disorders. 2021. DOI: 10.1186/s12891-021-04924-z

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