Evolving Strategies for Knee Osteoarthritis: A Narrative Review of Integrated Rehabilitation, Pharmacologic, and Joint-Preserving Interventions

Introduction

The knee is a complex weight-bearing joint consisting of the patella, femoral condyles, and tibial plateau, which, due to its intricate structure and mechanical demands, serves as a primary site for the development of knee osteoarthritis (KOA) [1]. As a multifaceted mechanobiological disorder, KOA is characterized by the progressive deterioration of articular cartilage, subchondral bone remodeling, and chronic inflammation, leading to a debilitating cycle of pain and functional impairment [2,3]. While its etiology is multifactorial – involving age, genetics, trauma, and metabolic inflammatio – overweight and obesity remain the most significant modifiable risk factors [4]. Ultimately, the disruption of joint structural integrity significantly restricts activities of daily living and increases the risk of systemic multimorbidity, such as cardiovascular events, making KOA a leading cause of global disability in the aging population [5].

KOA is the most significant contributor to the global musculoskeletal burden, accounting for approximately 60.8% of all osteoarthritis-related disability [4,6]. Recent epidemiological data indicate that the global prevalence of osteoarthritis doubled between 1990 and 2019, with KOA affecting an estimated 365 million adults as of 2020; furthermore, projections suggest a staggering 74.9% increase in prevalence by 2050 [1,4,6]. This escalating trend, driven primarily by an aging global population and rising obesity rates, imposes substantial socioeconomic strains, including diminished work productivity, significant loss of quality-adjusted life-years, and increasing direct healthcare costs [7,8]. Consequently, the surge in clinical research dedicated to optimizing KOA therapeutic strategies is of paramount importance, as refining management protocols is essential to mitigating the profound personal morbidity and broader societal economic impact associated with this debilitating condition.

Despite the high global incidence of KOA, current clinical practice often exhibits an over-reliance on end-stage surgical outcomes – specifically total knee arthroplasty (TKA) – frequently neglecting the systematic management of early-to-mid-stage disease [9]. While TKA volumes are projected to surge to several million procedures annually by 2030, the clinical reality remains that late-stage interventions, such as arthroscopic surgery, often yield suboptimal results once degeneration is advanced [10]. This surgical bias underscores a critical need to pivot toward a “total life-cycle management” strategy that prioritizes a continuum of care. Such a framework necessitates not only proficiency in non-pharmacological and pharmacological modalities to arrest early progression but also the strategic implementation of diverse joint-preserving surgeries, including high tibial osteotomy (HTO), proximal fibular osteotomy (PFO), and knee joint distraction (KJD). By integrating these stage-specific, personalized therapies, clinicians can optimize joint longevity and ensure that radical joint replacement remains a carefully timed final recourse rather than a premature default.

This narrative review selectively synthesizes the most recent clinical evidence (2020–2025) to advocate for a paradigm shift in KOA management, moving away from an over-reliance on TKA toward a comprehensive, joint-preserving framework. By prioritizing the synergy between multimodal rehabilitation and diverse joint-preservation strategies, we aim to establish a total life-cycle management strategy designed to arrest cartilaginous degradation, optimize functional recovery, and mitigate the escalating socioeconomic burden of the disease. Rejecting the conventional one-size-fits-all approach, we provide a systematic analysis of current therapeutic progressions – evaluating the specific indications, advantages, and limitations of emerging joint-preserving interventions – to offer clinicians a robust, stage-specific theoretical foundation for personalized KOA care. To minimize selection bias and ensure the inclusion of high-impact evidence, we used a standardized search strategy across PubMed, Embase, and Web of Science. The search utilized Boolean logic: (‘Knee Osteoarthritis’) AND (‘Joint Preservation’ OR ‘Rehabilitation’ OR ‘Pharmacotherapy’). We specifically applied a high-evidence filter, prioritizing multicenter randomized controlled trials (RCTs), meta-analyses, and international guidelines published between 2020 and 2025. By excluding low-quality or obsolete data and focusing on these high-impact findings, this review provides a refined, evidence-based synthesis of stage-specific interventions, aiming to offer clinicians a precise roadmap for halting disease progression and optimizing functional outcomes

Non-Pharmacological Rehabilitation

KOA is a prevalent, debilitating chronic joint disease characterized by pain, stiffness, and functional limitations. Multiple modifiable risk factors for KOA have been identified, including physical inactivity [11], obesity [12], abnormal limb alignment [13], gait biomechanical alterations [14], and joint injury/trauma [12]. Thus, various rehabilitation interventions targeting the modifiable risk factors of KOA aim to disrupt this self-perpetuating cycle. Non-pharmacological rehabilitation is a fundamental management strategy. Building upon the understanding of KOA pathology and its significant impact on functional disability, particularly muscle weakness and altered joint biomechanics, effective treatment strategies are crucial for pain alleviation and restoration of mobility. Patients with KOA can benefit considerably from various modern physiotherapy programs and helpful tools, such as knee braces, orthopedic insoles, and mobility aids, as well as from treatments such as shock wave therapy, manual therapy, and traditional interventions, including acupuncture and acupotomy. A comprehensive rehabilitation approach for KOA necessitates active interventions designed to mitigate these pathological consequences and improve patient outcomes. This section will explore the various evidence-based non-pharmacological interventions that make up the integrated framework for KOA rehabilitation.

Exercise Therapy

Exercise therapy serves as a cornerstone of non-pharmacological management for KOA, exerting multi-dimensional effects on joint physiology, biomechanical stability, and patient-centered outcomes. In managing KOA, it is crucial to distinguish between general physical activity and therapeutic exercise. While increasing daily physical activity is beneficial for general health, therapeutic exercise, specifically targeted at quadriceps strengthening and neuromuscular control, is required to achieve symptomatic relief and functional improvement. Fundamentally, mechanical loading during activity stimulates synovial fluid circulation, which facilitates nutrient delivery to the avascular cartilage and promotes metabolic waste removal [15]. This process is critical for preventing cartilage degradation and mitigating the loss of subchondral bone and metaphyseal trabeculae. Furthermore, exercise exerts potent anti-inflammatory effects by reducing local and systemic biomarkers, which contributes to pain reduction and may decelerate disease progression [16]. Beyond biological modulation, exercise addresses the altered muscle activation patterns and periarticular muscular deficiencies, specifically quadriceps and hamstring atrophy, which is common in patients with KOA [17]. By optimizing neuromuscular recruitment and enhancing muscle strength and endurance, structured training provides greater joint stability and improves shock absorption during weight-bearing activities [18]. This redistribution of mechanical stress reduces abnormal loading across symptomatic compartments, thereby improving walking ability, daily activities, and overall mobility [19]. Consequently, structured programs significantly enhance physical functions such as walking speed and stair-climbing ability, directly addressing the limitations imposed by the disease [20]. While exercise may not reverse established structural damage, it optimizes the joint environment and re-educates the nervous system for safer, more efficient movement patterns [21].

The clinical efficacy of exercise is highly contingent upon individualized prescriptions, with precise parameters, including mode, frequency, intensity, and duration, tailored to disease severity and functional goals [22]. Unlike general physical activity, which primarily targets metabolic health and cardiovascular fitness, therapeutic exercise in KOA aims to modify the biomechanical environment of the knee joint. Specifically, progressive resistance strength training targets the quadriceps and hip abductors to enhance joint stability and reduce the medial compartment load. Meta-analyses consistently indicate that such targeted training significantly improves quality of life and reduces pain within a few weeks of initiation [20,23,24]. Authoritative guidelines therefore strongly recommend regular aerobic, strengthening, and range-of-motion exercises as primary interventions [3]. Crucially, the success of these programs is bolstered by health education, which plays a vital role in patient decision-making and treatment adherence. By aligning patient expectations with realistic management goals and providing psychological guidance to eliminate negative emotions, health education empowers patients in disease self-management and optimizes long-term clinical outcomes [25].

Weight Intervention

Dietary intervention is a pivotal component of the multimodal management of KOA, primarily by addressing excessive body weight and systemic inflammatory states. For patients with overweight or obesity, weight reduction is considered a therapeutic cornerstone, as minimizing adiposity significantly alleviates the mechanical load exerted on the knee joint, thereby reducing pain and restoring physical function. Evidence indicates that a weight loss of 5% to 10% yields clinically meaningful improvements in symptomatic relief [26]. Consequently, international clinical practice guidelines universally recommend that patients with KOA and a high body mass index pursue weight loss through a strategic combination of caloric restriction and physical activity [27–29].

Research has established a clear dose-response relationship between the magnitude of weight loss and the degree of symptomatic benefit [26]. RCTs, such as the Intensive Diet and Exercise for Arthritis (IDEA) trial, have demonstrated that while diet-only and exercise-only approaches are beneficial, the most robust outcomes are achieved through their integration [30]. Specifically, the IDEA trial revealed that participants in the combined diet and exercise group achieved superior weight loss (11.4%) compared with those in diet-only (9.5%) or exercise-only (2.0%) groups over an 18-month period [31]. Most importantly, this synergistic approach resulted in significantly lower pain scores and enhanced functional capacity compared with either intervention alone, highlighting the necessity of a comprehensive lifestyle strategy in KOA rehabilitation [28,31]. In addition, Bliddal [32] et al found that the STEP 9 trial, in which weekly semaglutide treatment led to substantial weight loss and functional gains, provided robust clinical evidence for the necessity of weight reduction in the structural and symptomatic protection of the knee joint.

Biomechanical Therapy

Biomechanical factors, including obesity, muscular weakness, altered activation patterns, and limb malalignment, contribute significantly to abnormal joint loading and KOA progression. To address these stressors, biomechanical therapies and externally applied assistive devices are often integrated into comprehensive treatment plans, particularly for patients with identifiable risk factors, thereby augmenting the efficacy of primary interventions such as exercise therapy [33]. Three-dimensional gait analyses indicate that reducing the external knee adduction moment (KAM) during ambulation correlates strongly with improved pain relief and functional outcomes [34].

Specific innovations, such as orthotic insoles, knee braces, and walkers, serve as essential supplementary management tools. Lateral wedge insoles, for instance, are designed to correct knee varus malalignment, a hallmark of medial compartment KOA, by shifting the ground reaction force vector laterally and reducing the medial joint load [35]. Similarly, knee braces provide significant symptomatic relief (SMD=0.63) and functional enhancement (SMD=0.71) through targeted biomechanical modifications [36]. Furthermore, walkers have been shown to drastically improve mobility, as evidenced by increased distances in the 6-minute walk test, while simultaneously mitigating discomfort (SMD=1.72) and enhancing physical function (SMD=1.03) [37].

Despite these benefits, clinical recommendations remain nuanced. While some meta-analyses report short-term advantages, the 2019 Osteoarthritis Research Society International (OARSI) guidelines advise against the routine use of certain orthotics due to low certainty of evidence, suggesting instead that their efficacy may be contingent upon individual biomechanical profiles, such as significant varus alignment or foot abnormalities [38]. Conversely, the use of gait assistive equipment, including braces and walkers, is strongly recommended for patients whose ambulatory stability is substantially compromised or who experience significant pain, highlighting the importance of a personalized approach to biomechanical intervention [39].

Physical Therapy

Physical therapy for KOA utilizes diverse modalities, ranging from extracorporeal shock wave therapy and manual therapy to traditional interventions such as acupuncture and acupotomy, to modulate the joint environment. These therapies collectively enhance local microcirculation, suppress inflammatory cascades, and accelerate metabolic waste clearance. Biologically, they serve to arrest chondrocyte apoptosis and inhibit cartilaginous degeneration while facilitating connective tissue regeneration and alleviating muscular hypertonicity [40]. Specifically, a systematic review of 32 RCTs highlighted extracorporeal shock wave therapy as a premier intervention for pain attenuation and functional restoration [41]. Similarly, manual therapy aims to restore joint biomechanics and expand the joint space, thereby reducing intra-articular pressure. Clinically, manual therapy encompasses a range of techniques, such as joint mobilization at various directions and speeds, stretching, passive range of motion, mobilization with active patient participation, resisted techniques involving patient force against clinician resistance, and soft tissue interventions, which are all intended to improve mobility and function [42]. Although evidence indicates that manual therapy offers superior short-term analgesic effects compared with strengthening exercises, its long-term efficacy remains debated. As such, manual therapy is currently recommended primarily as an adjunct to exercise programs rather than a standalone intervention [40,43,44].

However, traditional Chinese medicine approaches remain highly effective. Network meta-analyses involving nearly 10 000 participants confirm that acupuncture significantly improves physical function and reduces pain [45,46]. Furthermore, recent 2025 evidence indicates that combining acupuncture with moxibustion offers a safer and more potent long-term therapeutic profile than standard care [47]. Acupotomy has also emerged as a superior alternative to conventional acupuncture [48]. When integrated with biological agents such as mesenchymal stem cells, acupotomy synergistically promotes chondrocyte proliferation via the GSK3β/cyclin D1 pathway [49]. Similarly, acupotomy bone decompression combined with sodium hyaluronate significantly lowers systemic inflammatory markers, such as interleukin (IL) 6, tumor necrosis factor (TNF) α, and matrix metalloproteinase 3 and 9, and reduces bone marrow edema, offering a robust biomechanical and biochemical integrative strategy for joint preservation [50].

Pharmacological Management

The management of KOA follows a hierarchical and individualized approach, prioritizing non-pharmacological interventions such as weight loss, exercise, and physical therapy as the foundation of primary care. Pharmacological options are typically reserved for cases in which conservative measures fail to adequately restore function or alleviate symptoms. Given the complex etiology of KOA and the current lack of curative medications, therapeutic strategies focus on a multidimensional set of goals: mitigating pain, improving joint mobility, enhancing quality of life, and delaying structural progression to prevent deformity [51]. Since pain relief is the primary clinical objective, management strategies transition toward various pharmacological modalities, ranging from oral and topical agents to intra-articular injections of corticosteroids, hyaluronic acid, and regenerative therapies such as platelet-rich plasma (PRP), along with other adjuvant interventions.

Oral and Topical Pharmacological Interventions

The pharmacological landscape for KOA is primarily dominated by non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics, categorized by their systemic or localized delivery [52]. Oral NSAIDs, including diclofenac, celecoxib, and etoricoxib, remain a cornerstone of treatment due to their ability to inhibit prostaglandin synthesis, thereby suppressing inflammation and pain. Clinical data indicates that while etoricoxib may offer the highest efficacy rate, diclofenac often demonstrates a superior safety profile regarding adverse reactions [53]. Despite the potent analgesic effects of NSAIDs, the 2019 OARSI guidelines prioritize topical NSAIDs over oral formulations due to their localized delivery, which minimizes systemic gastrointestinal toxicity while maintaining comparable efficacy, particularly in the early stages of treatment [54,55]. While topical agents can cause minor local irritation, such as rashes or itching, they are generally well tolerated and recommended as a first-line non-core intervention [55].

Other pharmacological options, such as acetaminophen, capsaicin, and duloxetine, show more varied clinical consensus. Acetaminophen is frequently used for mild-to-moderate pain due to its gastrointestinal safety; however, its therapeutic benefits are modest, and concerns regarding hepatotoxicity have led to conflicting recommendations between the American College of Rheumatology/Arthritis Foundation (ACR/AF) and OARSI guidelines [55–57]. Similarly, topical capsaicin is conditionally suggested by some frameworks but discouraged by OARSI due to low-quality evidence and risk of ocular irritation [55,57]. For chronic pain management, duloxetine is conditionally recommended as an adjunct. Conversely, opioids are largely excluded from modern evidence-based endorsements for KOA management due to their limited applicability and potential for dependency, with major bodies like the American Academy of Orthopaedic Surgeons (AAOS) and OARSI emphasizing oral and topical NSAIDs as the more robust alternatives [55,57].

Symptomatic slow-acting drugs for osteoarthritis (SYSADOAs), such as crystalline glucosamine sulfate, chondroitin sulfate, and diacerein, are integral to long-term KOA management [58]. Unlike NSAIDs, SYSADOAs provide delayed but sustained symptomatic relief with a superior safety profile, often persisting after treatment cessation, and the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis guidelines advocate for high-quality SYSADOAs as first-line background therapy to reduce reliance on rescue analgesics [59]. Recent multicenter trials demonstrate that combined chondroitin and glucosamine are non-inferior to celecoxib in alleviating pain and stiffness over 6 months [60]. Furthermore, evidence suggests that SYSADOAs, including SKCPT, can effectively supplement or even replace long-term NSAIDs, mitigating their associated systemic risks [61]. The synergistic use of chondroitin sulfate with low-dose NSAIDs, such as diclofenac, represents a promising, proactive strategy to enhance functional outcomes while ensuring patient safety [62].

Intra-Articular Injection Therapy

Intra-articular injections should be viewed not merely as a secondary alternative to oral or topical pharmacotherapy but as a complementary intervention with distinct physiological targets. While oral and topical NSAIDs primarily address systemic inflammation and acute pain flares, intra-articular treatments aim to restore the joint’s local homeostasis and rheological properties [57,63]. Consequently, they are recommended by ACR/AF and conditionally by OARSI for acute symptom management. However, their long-term or frequent use is discouraged and specifically limited to no more than once every 4 months, due to risks of accelerated joint damage and poor systemic absorption profiles [63]. Furthermore, the evidence for steroid efficacy beyond 6 weeks remains low-quality and inconclusive [63].

In contrast, intra-articular hyaluronic acid (also known as sodium hyaluronate) aims to restore the viscoelastic properties of the synovial fluid, which is often degraded in KOA. Hyaluronic acid functions by lubricating the articular surfaces, reducing friction, and providing shock absorption, while simultaneously penetrating the cartilage to inhibit degeneration and stimulate chondrocyte metabolism [64]. Meta-analyses suggest that hyaluronic acid can provide moderate pain relief and functional gains for up to 6 months, particularly in patients with mild-to-moderate KOA who fail to respond to conservative treatments [65]. OARSI conditionally recommends hyaluronic acid for long-term management due to its superior safety profile, compared with that of repeated steroids, and its ability to improve symptoms beyond 12 weeks [55]. When used as an adjunct to NSAIDs, hyaluronic acid may even reduce the required dosage of systemic drugs, thereby lowering the risk of adverse effects. Despite these benefits, clinical consensus is divided: while ACR/AF views it as a secondary option for refractory pain, the AAOS recommends against its routine use due to inconsistent results in large-scale trials and questions regarding its cost-effectiveness compared with placebos [29,64].

Platelet-Rich Plasma Biotherapy

PRP is an autologous concentrate derived from centrifuged blood, characterized by a supraphysiological concentration of platelets that release a complex milieu of growth factors and cytokines [66]. These bioactive mediators interact with endogenous cells within the joint to modulate the microenvironment and facilitate tissue repair [67]. Recent evidence from 2025 highlights both the potential of PRP and the current controversies regarding its efficacy. A meta-analysis of 12 RCTs found that leukocyte-poor PRP provides significantly superior pain relief and functional restoration compared with hyaluronic acid at 3, 6, and 12 months, with a comparable safety profile [68]. Furthermore, evidence from 28 RCTs suggests that while PRP and hyaluronic acid may offer similar analgesic effects, PRP yields superior functional gains, particularly when administered as a combined therapy. Optimal outcomes are associated with early-stage intervention (Kellgren-Lawrence grades I–II), a concentration of 600–900×109/L, and a regimen of 3 to 5 injections [25].

Despite these positive findings, the clinical consensus remains tempered by significant heterogeneity in study outcomes. Some 2025 systematic reviews comparing PRP to saline placebos observed only weak, short-term efficacy up to 6 months, with benefits disappearing by the 12-month mark, leading researchers to question its overall clinical relevance and call for standardized preparation protocols [69,70]. To address the limitations of monotherapy, emerging integrative approaches have shown promise. For instance, combining ultrasound-guided PRP injections with stromal vascular fraction has been shown to significantly alleviate pain and enhance mobility even in patients with severe KOA, with therapeutic benefits sustained for up to 1 year [71]. This move toward personalized therapy, potentially guided by machine learning models, represents the next frontier in optimizing regenerative treatments for KOA [25].

Adjuvant Therapy

Beyond conventional pharmacological treatments, modern research into KOA is increasingly focused on targeted molecular inhibitors and regenerative orthobiologics [72]. Pro-inflammatory cytokines, specifically IL-1 and TNF, are recognized as primary mediators of cartilage degradation and catabolic processes [73–76]. Clinical studies have demonstrated that IL-1 inhibitors can effectively alleviate pain and enhance joint function [72,75]. Similarly, TNF inhibitors, such as etanercept, have shown superior efficacy in early-stage pain management, compared with traditional sodium hyaluronate, highlighting the potential of cytokine-targeted therapies to arrest cartilaginous loss [76,77].

Innovative pharmacological interventions, particularly the use of carboxymethyl-chitosan (CM-C), are redefining the treatment landscape for recalcitrant KOA. As a specialized therapeutic agent, CM-C provides significant immediate pain relief and functional restoration, particularly in difficult-to-treat subgroups, such as patients who have demonstrated inadequate responses to conventional hyaluronic acid therapy [78]. Beyond its acute efficacy, clinical evidence indicates that CM-C offers sustained symptomatic improvement for up to 1 year, even in challenging cohorts characterized by obesity or advanced radiographic stages [79]. By bridging the gap between conventional supplement and more invasive procedures, CM-C emerges as a robust option for individualized, stage-specific management in high-burden patient populations.

Concurrently, stem cell therapy represents a paradigm shift from symptomatic relief to structural repair [80]. Given that articular cartilage has a limited intrinsic capacity for self-repair – often resulting in suboptimal fibrous scarring – cell-based interventions utilizing mature chondrocytes or mesenchymal stem cells are being explored to facilitate hyaline-like cartilage regeneration [81,82]. Meta-analyses from 2025 involving RCTs confirm that intra-articular injection of mesenchymal stem cells significantly improves pain and physical function at 6 and 12 months with a safety profile comparable to traditional controls [83].

Arthroscopic Debridement

Since its inception in the 1960s, arthroscopic debridement has evolved into a surgical intervention for KOA. The procedure typically encompasses joint lavage and the mechanical removal of inflammatory debris, loose bodies, and osteophytes, while also addressing meniscal tears and synovial hyperplasia. By clearing inflammatory mediators, such as giant cells, neutrophils, and cytokines, and smoothing irregular articular surfaces, the surgery aims to reduce mechanical irritation, restore joint stability, and alleviate functional disturbances. Arthroscopic intervention directly mitigates these issues by excising damaged menisci and removing free fragments, thereby providing immediate symptomatic relief for many patients.

However, the clinical consensus regarding the long-term efficacy of arthroscopic surgery is highly debated. Major clinical guidelines, including those from the AAOS, generally do not recommend joint lavage or debridement for routine KOA management, citing large-scale, sham-controlled trials that found no significant therapeutic advantage at 6 months, 1 year, or 2 years postoperatively compared with nonoperative care [84,85]. Long-term longitudinal data further indicates that adding arthroscopy to conservative management does not significantly delay or prevent the eventual necessity for TKA [86,87].

Despite these broad conclusions, arthroscopic debridement may still hold value as a selective short-term adjunct. Recent meta-analyses suggest it is effective for patients with mild-to-moderate KOA who have exhausted conservative options, providing relief for up to 2 years, although durability beyond this period is limited [88]. The procedure is most successful in patients with mechanical symptoms (such as locking caused by loose bodies), low levels of degenerative change, and sudden-onset symptoms [89,90]. Conversely, it offers poor outcomes for patients with severe malalignment, significant joint space narrowing, or advanced bony hyperplasia. Ultimately, while arthroscopy excels at short-term symptom management and addressing specific mechanical obstructions, it does not alter the long-term radiographic or clinical progression of the disease [89].

High Tibial Osteotomy

HTO is a well-established surgical strategy for managing unicompartmental KOA, specifically targeting medial compartment degeneration associated with varus malalignment. Popularized in the 1960s by Coventry, the initial lateral-closing wedge technique aimed to shift mechanical loads from the diseased medial compartment to the healthier lateral side, achieving a 75% survival rate at 10 years [91,92]. Although the rapid success of TKA led to a temporary decline in the popularity of HTO, the procedure has seen a modern resurgence [93]. The contemporary gold standard, medial opening wedge HTO, utilizes low-profile, high-tensile strength plates to achieve precise alignment correction with reliable union rates, transforming it from a niche intervention into a reproducible treatment option [94].

Mechanistically, HTO functions by correcting the lower limb’s mechanical axis, which not only redistributes mechanical pressure but also improves the biological environment of the joint. Clinical data from 10-year follow-ups demonstrate that HTO effectively preserves physical activity levels and work capacity, particularly in younger patients, thereby serving as a valuable alternative to TKA that reduces economic burdens and optimizes medical resource allocation [95–97]. While unicompartmental knee arthroplasty (UKA) may offer slightly higher patient-reported satisfaction, the clinical difference is often marginal, suggesting that HTO is not inferior to UKA, especially for active patients aged 50 to 60 years [98].

Current clinical consensus identifies the ideal HTO candidate as a relatively young patient (typically <65 years) with a BMI under 30 kg/m2, stable knee ligaments, near-normal range of motion, and disease confined strictly to the medial compartment (Kellgren-Lawrence grade <IV) after failed conservative management [99,100]. However, the age criterion remains a subject of debate; recent studies suggest that medial opening wedge HTO can yield comparable clinical outcomes in patients over 65, provided they meet strict physiological indications [101]. Despite its high survival rates, the risk of failure increases significantly with advanced age, severe pre-existing cartilage damage, or postoperative under-correction of the hip-knee-ankle angle [102].

Proximal Fibular Osteotomy

Proximal fibular osteotomy (PFO) has emerged as a minimally invasive surgical alternative for medial compartment KOA, primarily based on the “non-uniform settlement” theory proposed by Yang et al [103]. This theory suggests that osteoporosis-induced weakening of the subchondral bone leads to uneven sinking of the tibial plateau; while the medial side collapses under load, the lateral side remains supported by the fibula and the structural “arch beam” formed with the posterolateral tibial cortex [104]. By resecting a small segment of the proximal fibula, surgeons can weaken this lateral support, thereby decompressing the medial compartment and redistributing mechanical stress [105,106]. Biomechanical and finite element analyses confirm that PFO effectively reduces maximal von Mises stress in the medial compartment and shifts load pathways toward the posterior plateau, providing a structural basis for rapid pain relief [106].

Clinical and radiographic evidence indicates that PFO significantly alleviates knee pain and improves joint function by correcting varus deformities and reducing the femorotibial angle [103,107]. Animal models further suggest that the procedure may delay disease progression by inhibiting subchondral osteosclerosis and preventing further articular cartilage destruction [107]. When compared with the more invasive opening-wedge HTO, PFO offers comparable short-term clinical efficacy in pain reduction and functional recovery, while significantly decreasing operative time, blood loss, and hospital stay [108–110].

Despite its simplicity and safety, the long-term validity of PFO remains a subject of ongoing investigation. While it may delay or even negate the need for TKA in select patients, its mechanical axis correction is generally inferior to that of HTO [103,109]. Furthermore, the procedure carries specific risks, such as potential injury to the common peroneal nerve or superficial peroneal nerve, and possible impacts on long-term ankle stability [103]. As current clinical experience regarding precise osteotomy length, optimal location, and specific indications remains limited, large-scale multicentric prospective studies with extended follow-up are necessary to confirm its role in routine KOA management [111].

Knee Joint Distraction

KJD is an innovative, joint-preserving surgical technique designed for patients with end-stage KOA, particularly those under the age of 65 years who wish to postpone or avoid TKA. The procedure involves the use of an external fixator to separate the joint surfaces for approximately 6 weeks, creating a unique biomechanical environment that facilitates intrinsic tissue repair [112,113]. Unlike traditional treatments that focus solely on symptom management, KJD has demonstrated the rare ability to induce structural modifications, including significant increases in joint space width and cartilage thickness, alongside a reduction in denuded bone areas [112]. Long-term follow-up data suggests a 9-year survival rate of approximately 48%, with significantly higher success rates observed in male patients (72%) and patients who exhibit an initial joint space width increase of more than 0.5 mm in the first year [114].

The therapeutic efficacy of KJD is attributed to a complex interplay of mechanical and biological mechanisms. Mechanically, the fixator provides partial unloading of the joint while allowing for synovial fluid pressure oscillations during movement, which stimulates chondrocyte activity and extracellular matrix production [115,116]. Biologically, KJD promotes a normalization of the subchondral bone by thinning the hypertrophic subchondral cortical plate and decreasing trabecular bone density, reversing the characteristic osteosclerosis of OA [114].

Despite the promising clinical and structural outcomes, several factors warrant a cautious approach to the widespread adoption of KJD. While meta-analyses confirm substantial improvements in Western Ontario and McMaster University Arthritis Index and visual analog scale scores, the evidence base is currently limited by small sample sizes and relatively short follow-up periods in many cohorts [116,117]. Additionally, the high incidence of pin-tract infections associated with external fixation remains a significant clinical concern, especially for patients who may eventually require TKA, as these infections can complicate future arthroplasty [113]. Current research is focused on defining specific regenerative biomarkers to identify ideal candidates and refining distraction protocols to ensure that the observed cartilage repair translates into a permanent cure rather than temporary symptomatic relief [117].

Unicompartmental Knee Arthroplasty

UKA has emerged as a cornerstone of the stepwise treatment philosophy for KOA, offering a high-precision surgical solution for patients whose degeneration is confined to a single compartment. Unlike total joint replacement, UKA preserves the cruciate ligaments and the healthy compartments of the knee, providing a more natural joint feel and superior functional outcomes, compared with HTO, in older populations [118]. Large-scale meta-analyses involving over 56 000 cases indicate that UKA provides significant advantages in terms of reduced postoperative pain, lower complication rates, and fewer revisions [118,119]. While HTO remains a cost-effective choice for younger, high-activity patients (<55 years) requiring mechanical axis correction, UKA is increasingly favored for older patients (>55 years) who prioritize immediate pain relief and rapid recovery [120–122].

The success of UKA is heavily dependent on stringent patient selection and precise surgical technique. Ideal candidates are typically older patients with a BMI less than 40 kg/m2 and symptomatic unicompartment osteoarthritis that has failed conservative management [122,123]. Key clinical indications include a minimum range of motion of 90°, intact anterior and posterior cruciate ligaments, a correctable varus deformity of 15° or less, and a fixed flexion contracture of 15° or less [124]. While traditional contraindications once included patellofemoral degeneration and advanced age, modern evidence suggests that these issues can be successfully managed through meticulous patient screening and improved prosthetic design [123].

Current literature highlights a distinct trade-off between UKA and other realignment surgeries: while UKA offers faster rehabilitation and better short-to-medium term satisfaction, HTO provides superior postoperative range of motion and is better suited for multiplanar corrections in active individuals [119,122]. Compared with TKA, UKA is less invasive, has a lower incidence of postoperative complications, faster recovery, better functional recovery, and is closer to the original kinematics of the knee joint [125]. Meanwhile, emerging techniques such as PFO offer lower-burden alternatives but currently lack the robust, long-term survival data associated with UKA [126]. As prosthetic materials and perioperative management continue to evolve, UKA is positioned to play an increasingly vital role in optimizing the overall treatment strategy for the aging KOA population, ensuring high levels of prosthesis survival and patient satisfaction [122,124].

Limitations and Future Perspectives

Despite its comprehensive scope, several limitations of this review warrant acknowledgment. As a narrative review authored by frontline clinicians, this study prioritizes the synthesis of a pragmatic, stage-specific strategic roadmap to counter the prevalent one-size-fits-all treatment deadlock, which inherently introduces a degree of expert-led selection bias, compared with systematic reviews. Although we employed a rigorous search strategy across major databases (PubMed, Embase, and Web of Science) using Boolean operators and a high-evidence filter (focusing on RCTs and guidelines from 2020 to 2025), the absence of a quantitative meta-analysis or formal heterogeneity assessment means that the relative effect magnitudes of the interventions should be interpreted with clinical caution. These constraints underscore the necessity for future large-scale, multicenter prospective trials to quantitatively validate these integrated pathways and develop standardized, unbiased decision-making algorithms for personalized knee joint preservation.

Future directions in KOA management are shifting from reactive palliation toward a proactive, technologically-driven paradigm centered on the integration of biotechnology and digital health. A primary frontier lies in regenerative medicine in which innovative biomaterials, such as bioactive scaffolds, hydrogels, and nanofibers, are being engineered to facilitate true hyaline cartilage restoration, offering the potential to finally halt or reverse joint degradation [127,128]. Parallel to these biological advancements, the rise of artificial intelligence and machine learning offers transformative potential for personalized medicine. By synthesizing multi-dimensional datasets, including biomechanical gait analysis, advanced imaging, and emerging omics data, machine learning models can predict disease progression trajectories and treatment response rates with unprecedented accuracy [129–131]. Furthermore, the utilization of sensor-derived real-time monitoring will empower clinicians to implement the total life-cycle management strategy, facilitating early intervention and precision-targeted care that optimizes joint longevity and significantly enhances the long-term quality of life for the aging population.

Conclusions

The comprehensive management of KOA remains a significant clinical challenge, as conventional therapeutic modalities primarily prioritize symptomatic alleviation and end-stage surgery rather than reversing the underlying degenerative process. To address this, current clinical practice should strictly adhere to a proactive, stepwise individualized framework, establishing non-pharmacological interventions – specifically exercise, weight reduction, and biomechanical aids – as the fundamental tier of care [21,26,34]. While pharmacological agents and intra-articular injections are essential for acute symptom control, they remain essentially palliative and fail to arrest structural degradation [52,55,63,64]. Consequently, joint-preserving surgical strategies are gaining widespread recognition as critical intermediaries; these include arthroscopic debridement, HTO, PFO, KJD, and UKA, each offering unique advantages tailored to specific clinical indications (Table 1) [84,85,94,103,114,118].

In conclusion, this review underscores the necessity of transitioning from reactive, surgery-centric interventions to a proactive, total life-cycle management framework for KOA. We advocate for a paradigm shift that replaces the restrictive one-size-fits-all approach with highly individualized, stage-specific strategies that integrate rehabilitation, pharmacotherapy, and joint-preserving surgeries (Figure 1). By emphasizing the early identification of KOA and providing stage-specific interventions – ranging from biological modulation to the correction of lower limb alignment – clinicians can optimize joint longevity and significantly reduce the societal economic burden. Ultimately, this individualized care plan aims to delay or even negate the long-term requirement for total knee replacement, ensuring superior functional recovery and enhanced quality of life for patients.