A narrative review of clinical research on knee osteoarthritis in 2025

Abstract

Background and Objective

Knee osteoarthritis (KOA) is the most common degenerative joint disease, causing significant social and economic burden globally. KOA management typically follows stepped-care approaches, including lifestyle changes, pharmacological treatments, and surgery. Driven by recent translational breakthroughs in KOA research, clinical management paradigms are increasingly characterized by high degrees of personalization and diagnostic precision. This review aimed to summarize key therapeutic research on KOA over the past year.

Methods

This narrative review was conducted using the PubMed database, focusing on English-language studies involving human participants published between January and December in 2025. Eligible studies mainly included observational longitudinal studies, systematic reviews, meta-analyses, and randomized controlled trials (RCTs) examining KOA treatment. Priority was given to studies with the potential to influence current treatment paradigms.

Key Content and Findings

The management of KOA is evolving toward a stepwise and individualized paradigm. In early disease stages, patient education, exercise, and weight control constitute the foundation of treatment. In addition to standard pharmacotherapies such as non-steroidal anti-inflammatory drugs (NSAIDs), some drugs originally used for other conditions are increasingly applied in KOA management. Metabolic agents and intra-articular injections have shown promising therapeutic potential. In terms of surgery, partial knee arthroplasty and high tibial osteotomy (HTO) techniques continue to be optimized. Total knee arthroplasty (TKA), as a definitive intervention for advanced KOA, has benefited from advances in personalized alignment, robotic assistance, novel prosthetic materials, and enhanced recovery after surgery (ERAS) protocols. These innovations collectively contribute to improved surgical precision, prosthesis durability, and perioperative safety.

Conclusions

The management of KOA is shifting toward increasingly personalized and precision-driven paradigms, grounded in conservative care, emphasizing knee preserving for early intervention, and leveraging enabling technologies in TKA to enhance long-term outcomes. Although integrated enhanced recovery pathways demonstrably optimize perioperative outcomes, the enduring clinical utility of these disruptive technologies necessitates rigorous validation through high-certainty evidence.

Introduction

Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degeneration, synovitis, subchondral bone sclerosis and osteophyte formation (1,2). Joint pain, stiffness, and functional impairment are typical clinical manifestations of OA. Currently, over 600 million people worldwide are estimated to suffer from OA. From 1990 to 2021, the age-standardized incidence and prevalence rates of OA increased by 13.86% and 14.34%, respectively, imposing a substantial social and economic burden (3,4). Currently, the treatment for OA mainly focuses on symptom relief, while early diagnosis and standardized treatment still require improvement (5).

In 2025, the Osteoarthritis Research Society International (OARSI) began developing classification criteria for early-stage symptomatic knee OA (EsSKOA), aiming to identify symptomatic individuals before radiographic changes appear (6). This initiative marks a conceptual shift from the traditional “wear-and-tear” model toward earlier structural intervention. As a first step, the EsSKOA working group identified conditions requiring differential diagnosis, including patellofemoral pain syndrome, meniscal and ligament injuries, and inflammatory arthritides (7,8). This ongoing effort to refine early diagnosis has direct implications for the treatment strategies discussed in this review.

Knee osteoarthritis (KOA) is the most common form of OA in the lower extremities (9). The management of KOA follows a stepwise paradigm. Current guidelines recommend commencing with non-pharmacological interventions, including structured exercise therapy for muscle strengthening and weight management, which offer modest yet clinically meaningful symptom relief (10,11). When non-pharmacological measures prove insufficient, pharmacological intervention typically begins with topical or oral non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. However, long-term use carries well-documented cardiovascular, gastrointestinal, and renal risks, necessitating careful patient selection (12). For more targeted local therapy, intra-articular injections serve as a key option: corticosteroid (CS) provide potent, short-term anti-inflammatory effects, while hyaluronic acid (HA) aims to improve joint lubrication and homeostasis, although its clinical benefit remains debated (13). For KOA caused by lower limb malalignment, high tibial osteotomy (HTO) may delay disease progression (14), and in cases of single-compartment involvement, unicompartmental knee arthroplasty (UKA) can achieve favorable clinical outcomes (15). For end-stage KOA, total knee arthroplasty (TKA) substantially enhances patients’ quality of life, despite inherent risks including infection and the risk of revision surgery (16).

This review synthesizes key clinical evidence on the treatment of KOA in 2025. By evaluating advances in conservative management, knee-preserving surgery, and TKA, we aim to outline the current landscape and future directions of comprehensive KOA management. We present this article in accordance with the Narrative Review reporting checklist (available at https://aoj.amegroups.com/article/view/10.21037/aoj-2026-0018/rc).

Methods

This review is primarily based on a literature search of the PubMed database that published from January 1, 2025 to December 31, 2025. Keywords included “knee osteoarthritis (KOA)”, “conservative interventions”, “non-pharmacological treatment”, “pharmacological treatment”, “intra-articular injection”, “knee-preserving surgery”, “unicompartmental knee arthroplasty (UKA)”, “patellofemoral arthroplasty (PFA)”, “high tibial osteotomy (HTO)”, “cartilage repair”, “total knee arthroplasty (TKA)”. We started by screening abstracts for relevance and included the studies that were eligible. The reference lists of the papers we had chosen were also checked to find any other relevant publications. The specific search methods are reported in Table 1.

Table 1. The search strategy summary.

Items	Specification
Date of search	January 15th, 2026
Database	PubMed
Search terms used	This research was conducted using the following keywords: “knee osteoarthritis (KOA)”, “conservative interventions”, “non-pharmacological treatment”, “pharmacological treatment”, “intra-articular injection”, “knee-preserving surgery”, “unicompartmental knee arthroplasty (UKA)”, “patellofemoral arthroplasty (PFA)”, “high tibial osteotomy (HTO)”, “cartilage repair”, “total knee arthroplasty (TKA)”
Timeframe	From January 1, 2025 to December 31, 2025
Exclusion criteria	Non-English language publications
Selection process	Selection conducted by the first four authors

Several limitations of our search strategy should be noted. First, the exclusive use of PubMed may have missed studies indexed only in other databases such as Embase or the Cochrane Library. Second, restricting to English-language publications excludes evidence from regional databases, which may be relevant for integrative therapies. Third, our search terms targeted broad therapeutic categories and may not have captured all emerging preclinical or early-phase studies. These limitations should be considered when interpreting our findings; future updates could benefit from a broader multi-database approach.

Results

Conservative interventions

Conservative interventions are primary approaches for early-stage KOA, including non-pharmacological therapy, pharmacological therapy, and intra-articular injection therapy. Non-pharmacological interventions, such as patient education, dietary management, weight reduction, exercise therapy, and physical therapy, serve as the foundation of KOA management. NSAIDs remain the first-line pharmacological treatment, while medications used for other diseases are also being increasingly explored for KOA therapy. Intra-articular injection therapy targets localized joints, helps elevate local drug concentrations, and represents a commonly employed treatment modality.

Non-pharmacological treatments

First, patient self-management and education are critical determining factors for OA treatment. If patients passively believe OA is an irreversibly progressive disease, this will cause them distress during treatment and consequently reduce its effectiveness (17).

Dietary interventions have been increasingly recognized as a promising strategy (18). While traditional high-protein diets may carry greater inflammatory potential, emerging research focuses on specific metabolic pathways, such as those involving bile acid-coated chitosan complexes and arginine metabolism, that warrant further investigation (19). High-fat diets are generally discouraged; however, polyunsaturated fatty acids, in contrast to saturated fats, have demonstrated analgesic effects and improved joint function. Low-carbohydrate and fiber-rich diets may mitigate systemic inflammation, thereby reducing OA risk. Ultimately, the synergistic interplay of multiple nutrients must be considered in dietary recommendations for KOA management (20).

Exercise therapy is now mandated in all international guidelines for KOA management, with aerobic exercise recommended as a first-line intervention (21). Flexibility training and mind-body practices such as yoga have also demonstrated efficacy in KOA symptom control (22). Regarding weight loss, a systematic review supports combined interventions integrating psychological support, dietary modification and exercise for optimal outcomes (23).

The pathogenesis of KOA is closely linked to lower limb biomechanics. In order to improve the biomechanical conditions of the joints, various externally applied devices and therapies designed to instruct patients on alternative joint loading techniques have been emerged, which collectively referred to as biomechanical interventions (17). In a randomized controlled trial (RCT), personalized gait retraining has been used to improve pain and reduce knee loading for patients with medical compartment KOA (24).

Physiotherapy includes manual therapy under the guidance of therapists and adjunctive therapies. Manual therapy aims to restore joint mechanics, alleviate pain and improve range of motion, while traditional adjunctive therapies such as cryotherapy and thermotherapy remain widely used clinically (17). New technologies are currently under development. Transcutaneous electrical nerve stimulation combined with home exercise showed lower visual analogue scale (VAS) scores and increased knee extensor strength (25). Low-level laser therapy provided benefits for stiffness and function with little side effects, making it a valuable adjunct in OA pain management (26). In contrast, high-intensity laser therapy provided no additional benefits when combined with physiotherapy and daily exercises (27). Low dose radiation therapy at 3 Gy may help relieve pain and enhance joint function (28), while it is limited to patients of more advanced age and remains controversial (29).

Pharmacological treatments

Pharmacological treatments are recommended for patients with OA whose symptoms are not adequately controlled by non-pharmacological measures such as exercise and weight management. Oral and topical NSAIDs, including COX-2 inhibitors, are strongly recommended as first-line pharmacotherapy for KOA, though their well-documented adverse effect profile necessitates cautious use (12,30,31). Acetaminophen, duloxetine, tramadol, and topical capsaicin are conditionally recommended (31). In addition, several agents originally indicated for other conditions have emerged as promising candidates for KOA treatment. Metformin, which possesses anti-inflammatory and metabolic-regulating properties, was shown to reduce knee pain in overweight or obesity patients with KOA (32). Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management, significantly decreased Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain scores at week 68 in a clinical trial involving 407 patients with KOA and mean body mass index (BMI) of 40.3 kg/m² (33). Notably, emerging evidence hints at potential weight-loss-independent metabolic effects of GLP-1 receptor agonists on joint cartilage, though this mechanism remains speculative and requires dedicated investigation. Supplementation with native (undenatured) type II collagen (UC-II) and hydrolyzed collagen has been shown to mitigate inflammation and support cartilage repair, potentially via oral tolerance mechanisms (34,35). Methotrexate, widely used in rheumatoid arthritis, is under investigation for OA; however, its efficacy remains inconclusive, with one meta-analysis reporting reduced stiffness and another RCT finding no benefit (36,37).

Intra-articular injectables

HA, a non-sulfated glycosaminoglycan, in responsible for lubricating articular surfaces and absorb mechanical shock. A systematic review, involving 24,101 participants from 168 studies, proved that HA interventions were more effective than placebo, but the clinical importance was limited. Although intra-articular HA injection is widely used clinically, its efficacy remains controversial (38). It is conditionally recommended against in patients with KOA by the American College of Rheumatology (ACR) (31). What does this mean? The clinical benefit, while statistically significant, may be too small to be relevant for the average patient.

CS show anti-inflammatory and immunosuppressive effects and help to relieve inflammation and alleviate symptoms, which have been used for decades clinically (39). While their main limitation is clear: a meta-analysis found the clinical benefit is lost after 6 weeks (40). Moreover, the number of studies focusing solely on CS is now gradually decreasing, with more research using it as a control for other novel injection therapies such as platelet-rich plasma (PRP) (39,41).

PRP is a mixture of concentrated platelets and growth factors separated from autologous blood through centrifugation (42). It could promote tissue regeneration by promoting angiogenesis, modulating inflammatory cascades and stimulating cellular proliferation, thus has been applied in orthopedics (43). Multiple studies have confirmed that PRP is equivalent to or even surpasses treatment methods such as HA and CS (39,41,44,45). Indications and contraindications have been established by an international expert group (46). However, consensus remains lacking regarding optimal dosage, injection frequency, and preparation protocols. A greater dose (5,464±511 ×10⁶) showed better clinical outcomes than a lower dose (2,253±753 ×10⁶), which may help establish a standardized platelet dosage (47). Several studies have emphasized the value of combination therapy, with PRP plus HA showed better outcomes in pain relief and functional improvement (41,48). Yet, a lot of these pooled analyses have to be taken with a grain of salt, as the conclusions are limited by small sample sizes in some individual trials and high heterogeneity in how the PRP is prepared.

Stem cells, as specialized precursor cells, possess the theoretical capacity to differentiate into chondrocytes, which is the primary cell involved in the pathogenesis of OA (49). A randomized trial showed that intra-articular adipose-derived mesenchymal stem cell (MSC) injections provided superior cartilage restoration than HA injection (50). Moreover, MSCs modulate immune-inflammatory responses by contacting with immune cells and secreting cytokines, further supporting the application of stem cell injections (51). The main sources of MSCs are bone marrow and adipose tissue, with a smaller portion derived from umbilical cord and placenta (52-54). Some studies focused on MSCs-related exosome, considering the defects and paracrine mechanism of MSCs injection (55,56). A 2025 Cochrane review covering 25 randomized trials and 1,341 participants downgraded the evidence certainty for pain and function to low, largely due to substantial heterogeneity in cell source, preparation methods, and dosage (57). Another meta-analysis, including where 8 RCTs and 502 patients, evaluated intra-articular MSCs monotherapy and found significant improvements in WOMAC, VAS, and Knee Injury and Osteoarthritis Outcome Score (KOOS) scores at 6 and 12 months, supporting stem cell injection as a promising intervention. Meanwhile, a high dose (1×10⁸ cells) may yield better therapeutic outcomes (52). So, while the promise is there, the field absolutely needs more standardized protocols. The evidence for exosomes is even more preliminary, with most data coming from preclinical animal models and a few very small clinical studies.

Other injectables are also being explored. Ozone therapy, a strong oxidant with anti-inflammatory effects, has gained some attention (58). When combined with HA, an RCT showed it resulted in a lower VAS score, a higher health-related quality of life (HRQL) score, and better sleep quality than HA alone (59). Hypertonic dextrose prolotherapy (DPT), which may work by inducing a controlled inflammatory response to promote tissue repair, has also emerged as a potential regenerative treatment (60). However, clinical data on its safety and efficacy are limited, so it’s still quite investigational (61).

Finally, to boost retention time and targeted delivery, drug carriers like nanoparticles are being explored. Liposome-based systems, in particular, are interesting because they can act as lubricants. Metamizole-based intra-articular injections and TLC599, a liposomal dexamethasone formulation, have shown some promise, but further investigation is warranted to ensure the safety and efficacy (60).

Knee-preserving surgery

When conservative treatments fail to effectively relieve pain or improve function, knee-preserving surgery emerges as an effective therapeutic option for joint degeneration. This series of surgical procedures utilize techniques such as osteotomy or partial joint replacement to correct abnormal alignment and repair localized damage. By alleviating symptoms and delaying or obviating the need for TKA, these approaches serve as a strategic intermediate intervention.

Partial knee arthroplasty

For patients with single-compartment KOA, UKA offers favorable clinical outcomes. Recent studies highlight several emerging trends in this field. An RCT by Deng et al. reported that patient-specific instrumentation (PSI)-assisted UKA did not yield superior clinical outcomes compared with conventional Oxford microplasty instrumentation (MPI)-assisted UKA. Nevertheless, with the potential to reduce the learning curve, PSI may still serve as an alternative instrumentation option (62). In parallel, Haaker et al. found no clinically significant benefit from PSI that would justify the additional cost and effort of this technique in “standard” patients with medial compartment OA (63). With respect to robot-assisted procedures, Farhan-Alanie et al. noted that robotic-assisted cruciate-retaining bilateral UKA (bi-UKA) achieved clinical outcomes at 2 years comparable to those of mechanically aligned TKA, with no significant difference in complication rates-suggesting that longer follow-up may be required to clarify the long-term value of this newer approach (64). In contrast, Blyth et al. reported that, at 10 years, robotic arm-assisted medial compartment knee arthroplasty was associated with a lower risk of reoperation and revision, and appeared to be cost-effective, with greater gains in quality-adjusted life years (QALYs) (65). Thus, novel surgical techniques still require further external validation as for broader applications.

When discussing UKA surgical techniques, Liu et al. reported that the measured resection method is a reliable approach to help surgeons select an appropriate meniscal-bearing thickness in mobile-bearing UKA, thereby achieving adequate gap balance (66). Regarding implant design, Hajiaghajani et al. reported that metal-backed tibial components in medial fixed-bearing UKA provide comparable patient-reported outcome measures and range of motion, while demonstrating significantly lower revision rates compared with all-polyethylene designs (67). Furthermore, on the topic of fixation (cemented vs. cementless), Risager et al. found that the risk of early surgery-related periprosthetic tibial fracture (PPTF) was higher after cementless medial UKA than after cemented pattern. Identified risk factors for early PPTF included cementless fixation, female sex, age ≥70 years, BMI ≥40 kg/m², and height <160 cm (68). Meanwhile, Ten Noever de Brauw et al. reported an age-dependent pattern of failure modes: revisions for tibial loosening were more frequently associated with cemented UKA in younger patients, whereas revisions for periprosthetic fractures were specifically observed among elderly patients undergoing cementless UKA (69).

When comparing UKA with patellofemoral arthroplasty (PFA) and TKA, several clinically relevant themes emerge. Kuntze et al. concluded that UKA preserved native knee kinematics better, as reflected by greater similarity in the shape of sagittal-plane gait patterns and smaller-magnitude changes in coronal-plane knee angles in an RCT (70). Focusing on PFA, Omenas et al. reported that PFA was predominantly performed in younger female patients. Among patients younger than 60 years, PFA demonstrated superior 10-year survivorship comparable to TKA, but inferior survivorship beyond 15 years. In addition, revision rates for PFA were reported to be comparable to UKA, yet higher than TKA (71). To maximize health care value, Sauder et al. further argued that patients with single-compartment disease should preferentially be treated with UKA, given comparable outcomes but lower costs relative to primary TKA (72).

With respect to revision and survivorship after UKA, evidence suggests that the 2-year survivorship free from any re-revision after conversion to TKA was 96%, compared with 75% after UKA-to-UKA revision (73). Beyond implant survival, recent work has emphasized recovery pathways and expanding surgical indications. One study reported that integrating a mobilization-with-movement protocol could synergistically promote early functional recovery outcomes after UKA (74). Another meta-analysis, synthesizing evidence from four RCTs and ten cohort studies including 671 patients, concluded that bicompartmental knee arthroplasty may serve as an alternative surgical option for patients with medial-patellofemoral OA compared with TKA (75). Finally, Steffensmeier et al. reported that outpatient simultaneous bilateral UKA can be performed safely in carefully selected patients, with no significant difference in functional outcomes between outpatient and inpatient enrollment pathways (76).

HTO

For patients with lower limb malalignment, HTO can correct the mechanical axis and delay the progression of KOA (77). In a single-center, assessor-blinded trial involving patients (n=145) with varus medial-compartment OA, adding medial opening-wedge (MOW) HTO to nonsurgical care reduced 2-year medial cartilage loss on magnetic resonance imaging (MRI) and improved KOOS more than nonsurgical care alone, though generalizability is limited by the single-center design (78). In a 9-center RCT, HTO also demonstrated superior 12-month pain relief than a valgus unloader brace (79). With the overall benefit of HTO reasonably well established, the focus has increasingly shifted toward surgical technique selection and the balance between efficacy and complications. Both MOW and lateral closed-wedge (LCW) HTO improved alignment and patient-reported outcomes with broadly similar 10-year survivorship, though some comparative studies suggested higher TKA conversion after LCW. MOW tends to increase tibial slope and decrease patellar height with more tibial fractures, whereas LCW decreases slope, preserves patellar height, but carries a higher risk of peroneal nerve injury (80). In a retrospective cohort, adding lateral hinge-crossing K-wires in MOW HTO reduced hinge fracture rates and facilitate earlier return to work, without significant differences in KOOS-12 scores, medial proximal tibial angle (MPTA) correction, or operative time. Beyond technique refinements, combined surgical strategies have been proposed to further enhance structural and biological outcomes (81).

Based on a cohort study, adding gracilis graft reconstruction to HTO for medial meniscus posterior root tear resulted in superior MRI healing rates (85.7% vs. 45.4%), improved functional recovery, reduced meniscal extrusion, and more frequent improvement in Kellgren-Lawrence grade compared with HTO alone, indicating a meaningful added benefit of the combined approach (82).

Cartilage repair

Beyond alignment correction, the surgical management of established cartilage defects represents a key frontier in joint preservation. A phase II multicenter RCT demonstrated that implantation of tissue-engineered grafts using in vitro-matured nasal chondrocytes achieved superior clinical outcomes compared with cell-activated matrices for full-thickness knee cartilage defects, with higher 24-month KOOS scores and improved MRI-based cartilage composition, particularly in larger defects or revision cases (83). In a separate RCT evaluating isolated femoral cartilage lesions smaller than 2 cm², microfracture was not superior to arthroscopic debridement at two-year follow-up, with no meaningful differences in KOOS Quality of Life or other secondary outcomes (84). Similarly, in patients with International Cartilage Repair Society (ICRS) grade 3–4 knee cartilage defects, both collagen-augmented chondrogenesis and microfracture led to comparable improvements in pain and function at 2 years. However, the collagen-augmented technique resulted in superior repair tissue quality on follow-up imaging, an effect which was not modulated by patient age (85).

In a retrospective cohort (n=95; mean follow-up approximately 5 years) for patellofemoral cartilage defects, osteochondral allograft (OCA) transplantation and autologous chondrocyte implantation, including matrix-induced autologous chondrocyte implantation (ACI/MACI), demonstrated similar overall functional outcomes and rates of return to sport (52% vs. 58%; overall 54%). Reoperation occurred in 27% of cases, while graft failure was reported in 5%. Although KOOS pain score was lower after OCA (74.7 vs. 83.6), other KOOS subscales were comparable between groups. Increasing age and larger defect size were identified as predictors of poorer outcomes (86).

TKA

TKA is a treatment method for end-stage KOA, and it is very commonly used in clinical practice. TKA can effectively improve the pain and movement disorders caused by KOA, result in improved quality of life. Because the global demand for TKA is increasing, its future development pressure lies not only in the supply of quantity but also in technological innovation. Innovations in surgical techniques, individualized prosthesis design for different populations, further research and development of prosthetic materials, and individualized postoperative enhanced recovery strategies are the important parts. As these issues continue to deepen, more clinical challenges will still exist in the future.

Alignment theory in TKA

Mechanical alignment (MA) is the important standard in TKA. It aims to optimize soft tissue balance, load distribution, and implant longevity. Now its limitations are increasingly recognized. It fails to account for individual anatomical and kinematic variations. At the same time, it may not be suitable for all KOA patients. In multiple previous studies, the MA method has been compared with other alignment strategies featuring personalized characteristics. Ettinger et al. found that kinematically-aligned TKA with a medial pivot prosthesis achieved higher patient satisfaction than MA. They also underscore the latter’s limitation in addressing individual biomechanical needs (87). A recent RCT found that MA leads to greater soft tissue imbalance than kinematic alignment (KA). This result led to aberrant movement patterns and reduced ability to restore native knee function (88). Based on plantar pressure and gait analysis, Wang et al. found that mechanically aligned TKA resulted in load distribution during walking that deviated from natural patterns. Modified KA did not occur this situation. This highlighted a gap between static implant alignment and dynamic function. It suggested MA may not adequately restore physiologic motion (89). Aside from biomechanical studies, imaging findings also showed that postoperative standing X-rays of KOA patients were closer to the natural state (with the tibial joint line more parallel to the ground). But MA patients performed relatively worse and showed differences from physiological conditions (90).

However, a two-year study indicated that while functional alignment (FA) achieves superior soft tissue balance compared to traditional MA, its long-term patient satisfaction and recovery are similar. Therefore, they hypothesized that FA might confer greater benefit in a specific subtype of patients rather than in the general population (91). The clinical outcomes of the joint movement pattern with a lateral pivot are worse compared to the movement pattern with a medial pivot. Among them, MA often exhibits a kinematic pattern of lateral pivoting. In TKA, FA can achieve a medial pivot kinematic pattern through soft tissue balancing (92).

Robotics and intelligent navigation

In recent years, surgical robots have been increasingly promoted, but there are still many controversies regarding robotic technology. Zak et al. reported that early postoperative pain was not clearly related to the surgical method. Navigation-assisted and robot-assisted TKA did not show significant improvement in postoperative pain. Although they achieved higher intraoperative component positioning accuracy and bone-cutting precision than traditional TKA (93).

Early postoperative recovery, in addition to pain, also includes postoperative functional scores and postoperative imaging assessments. Jhurani et al carry out a prospective study about this part. It reported that robot-assisted TKA showed better postoperative alignment accuracy and prosthesis positioning compared with traditional TKA. And it required less soft tissue release. At the same time, its postoperative short-term functional scores are relatively better than those of traditional TKA (94).

Although short-term postoperative outcomes may not differ significantly, Mostafa et al. suggested that robotic TKA may confer long-term survival advantages. Their analysis showed that robotic TKA achieved superior accuracy in multi-planes (sagittal and coronal) and better prosthesis positioning compared with traditional TKA (95). These findings are corroborated by a study of 139 TKA patients. The study used standing full-length lower limb X-rays at 12 weeks postoperatively to assess the proportion of patients with postoperative deviations of less than 3°, and to evaluate their functional scores. The results showed that the new robot-assisted TAK leads to better bone resection and prosthesis placement, but there was no significant difference in functional scores (96). To be fair, the evidence here primarily relies on cohort studies and RCTs that were not designed with enough statistical power to detect small but clinically meaningful functional differences. So while the radiological precision is nice, we still don’t have definitive proof of a long-term functional or cost benefit.

Advances in prosthesis materials

Patients undergoing TKA highly concern about the lifespan of the prosthesis. At present, polyethylene antioxidant stabilization technology and three-dimensional (3D)-printed highly porous titanium for biological fixation are research hotspots. Their clinical effects have been supported by long-term follow-up data (97,98). Hamada et al. conducted a large retrospective study. They compared non-crosslinked vitamin-E-enhanced polyethylene (VEPE) to conventional polyethylene in fixedbearing TKA. Results showed that VEPE demonstrated lower wear and loosening rates. The improved antioxidant stability of VEPE reduces oxidative degradation, making it particularly suitable for higher-weight patients (97).

Highly porous titanium implants are gaining use in TKA due to quickly developed 3D printing. A recent review by Tigani et al. summarizes their early clinical applications. These implants exhibit an elastic modulus similar to cancellous bone. They can promote osseointegration for biological fixation. And they also offer high surface friction to enhance initial stability and reduce loosening risk. This material also shows broad applicability without requiring custom design, offering a convenient surgical option (98).

The use of bone cement is also essential in total knee replacement surgery. Recently, a type of minocycline-poly methyl methacrylate (MC-PMMA) has been found to have safety comparable to traditional PMMA, but follow-up results show that patients regain functional levels earlier (99).

Prosthesis longevity in TKA

Currently, the lifespan of prostheses generally exceeds 10 years (95%), a result reported in a study. Research by Chen et al. indicates that different surgical methods, including traditional knee replacement and robotic total knee replacement, do not affect the mid-term survival rate of the prosthesis. The different approaches mainly aim to improve surgical accuracy, thereby indirectly affecting the usage time, rather than directly impacting the lifespan of the prosthesis (100).

However, in a prospective study, different choices of tibial shaft fixation and non-fixation affected changes in bone density. This affects the effective usage time of the prosthesis. In this study, the bone density of the cemented tibial stem remained at a higher level, which in turn helps maintain the mechanical stress environment (101).

Although the survival rate over ten years is over 95%, the reasons for the termination of prosthesis lifespan still need to be analyzed. In a study, Lakpriya et al. investigated the reasons for revision TKA. The main causes included infection, aseptic loosening, and instability. Based on the chronological classification, it can be observed that early-stage issues are primarily associated with infection and surgical technique, while late-stage problems are typically related to wear, osteolysis, and loosening (102).

Enhanced recovery after TKA

Recent years, the enhanced recovery after surgery (ERAS) pathway has been increasingly adopted in TKA. By coordinating perioperative components—from preoperative preparation to postoperative care-ERAS aims to facilitate earlier mobilization, reduce pain and complications, and shorten hospital stays. This integrated approach has proven particularly valuable in managing special populations, such as patients with diabetes or obesity, who face higher perioperative risks.

Currently, multimodal analgesia is widely used following TKA. In a randomized controlled study, Chan et al. found that the rational use of glucocorticoids reduced patients’ pain scores and decreased their dependence on opioid medications. The combined use of intravenous and local administration reduces patients’ perception of pain (103).

Especially when performed with intramedullary alignment, TKA requires careful management of postoperative bleeding. The use of tranexamic acid is a common method for managing bleeding and can help reduce related complications. In a 2025 study, the combination of tranexamic acid with hemostatic materials was found to achieve better hemostatic effects. It can reduce postoperative hidden blood loss, thereby lowering perioperative risks (104).

Infection is the most critical complication following TKA. A multicenter RCT conducted by Saba et al. confirmed that diluted povidone-iodine irrigation combined with vancomycin powder can reduce early wound complications and infections (105). Additionally, for patients assessed preoperatively as having a high risk of infection, as demonstrated in the study by Wininger et al. intraosseous antibiotic injection can be utilized to reduce the infection risk (106).

Thrombosis is common after TKA, and postoperative oral aspirin can significantly reduce its incidence. This reduction was comparable to that seen in the enoxaparin treatment group, with no significant difference. Currently, aspirin is the preferred medication for preventing thrombosis (107). In our center’s clinical practice, we have observed that early postoperative ultrasound screening can proactively identify high-risk patients, promote targeted anticoagulation, and shift management from empirical to personalized strategies.

The structured ERAS pathway is especially beneficial for high-risk groups. Diabetic patients, for example, face significantly elevated risks of periprosthetic joint infection (43% higher), deep vein thrombosis (45% higher), and readmission (~28% higher), with risks further increased in those on long-term insulin therapy (108). Similarly, obese patients exhibit poorer early functional recovery and higher complication rates, though long-term outcomes may align with normal-BMI groups if comprehensive perioperative support is provided (109). For elderly, high-BMI patients, prolonged hospitalization is linked to poorer recovery, highlighting the need for integrated rehabilitation and nutritional strategies within an accelerated discharge framework (110).

Conclusions

In conclusion, KOA treatment should follow a stepwise, individualized approach that covers both conservative and surgical strategies. Non-pharmacological interventions are the foundation, while pharmacological and injectable therapies need a careful look at their benefits and risks. PRP and stem-cell therapies have a lot of promise, but the big gap right now is the lack of standardized preparation and injection protocols, which makes it hard to compare studies and define their true role. Priority areas for future research include standardization of biologic injectables, and understanding how metabolic agents like GLP-1 agonists affect perioperative risk profiles. For knee-preserving surgeries like UKA, HTO, and cartilage repair, the evidence supports their use for localized disease, but we need longer-term data on newer variations, like robotic-assisted procedures and combined ligament reconstruction techniques. In TKA, advances in personalized alignment, robotic assistance, and novel implant materials are exciting. But let’s be clear: for many of these, the supporting clinical evidence comes from cohort studies or RCTs that aren’t powerful enough. The road ahead needs high-quality, multicenter RCTs with long-term follow-up to prove these technologies truly lead to better functional recovery and implant survival, not just better X-rays. The integration of ERAS protocols is definitely optimizing perioperative management, particularly for high-risk patients, and continues to be refined. As our understanding of KOA deepens and technology evolves, the future of treatment is poised to become more precise, personalized, and, ideally, more evidence-based. Summary of key evidence from 2025 for KOA interventions is reported in Table 2.

Table 2. Summary of key evidence from 2025 for KOA interventions.

Intervention	Key findings in 2025	Strength of evidence & critical appraisal
Conservative interventions
Non-pharmacological	Personalized gait retraining reduces knee loading. Mind-body practices and aerobic exercise show efficacy. Combined weight loss (psychology, diet, exercise) offers optimal results	Generally strong, guideline-supported evidence. Many new RCTs focus on personalization
Pharmacological	Metformin and semaglutide showed promise for pain/weight loss in specific subgroups. Methotrexate efficacy remains inconclusive	Variable. Large RCTs for repurposed drugs (metformin, semaglutide), but contradictory meta-analyses/RCTs for others (methotrexate)
Intra-articular injection	PRP + HA combination may offer superior pain relief. High-dose PRP and MSCs appear more effective. Exosomes, ozone therapy, and nano-carrier systems are still largely preclinical or based on small trials	Low certainty for MSCs due to heterogeneity. PRP evidence limited by lack of protocol standardization. Exosome evidence mostly preclinical
Knee-preserving surgery
UKA & PFA	No short-term benefit for PSI. 10-year data supports cost-effectiveness of robotic UKA. Cementless fixation has higher early fracture risk in elderly females	Moderate to strong. New evidence on technique optimization and long-term follow-up of novel technologies are emerging from registry data and RCTs
HTO & cartilage repair	HTO superior to bracing. Combined HTO + meniscus repair improves healing. Tissue-engineered grafts better for large cartilage defects	Strong for HTO. Cartilage repair evidence is evolving; a trend toward defect-specific, personalized treatment strategies
Total knee arthroplasty
Alignment	KA/FA may improve satisfaction and restore a more natural kinematic pattern compared to MA	Moderate. Short-term RCTs show functional/kinematic benefits, but long-term superiority in patient-reported outcomes is not yet fully established
Robotics	Robotic TKA yields more accurate implant positioning, but clear improvement in early pain or long-term function is not proven	Moderate. High evidence for radiological accuracy, but low evidence for corresponding functional superiority. Large, long-term RCTs are lacking
Prosthesis	VEPE shows reduced wear. 3D-printed porous titanium enhances osseointegration	Strong for VEPE (from large cohort studies). Evolving for new biomaterials. Focus is on long-term durability and biological fixation
Enhanced recovery	Multimodal analgesia with glucocorticoids reduces opioid use. Combined tranexamic acid with hemostatic agents better controls hidden blood loss. Diluted povidone-iodine lavage plus vancomycin powder lowers early wound complications. Aspirin is non-inferior to enoxaparin for thromboprophylaxis. ERAS is especially valuable in high-risk groups (diabetes, obesity)	Moderate to strong. Individual components are supported by multicenter RCTs. The ERAS bundle itself is harder to study in isolation, and the optimal combination for specific high-risk subgroups still needs refinement

3D, three-dimensional; ERAS, enhanced recovery after surgery; FA, functional alignment; HA, hyaluronic acid; HTO, high tibial osteotomy; KA, kinematic alignment; KOA, knee osteoarthritis; MA, mechanical alignment; MSC, mesenchymal stem cell; PFA, patellofemoral arthroplasty; PRP, platelet-rich plasma; PSI, patient-specific instrumentation; RCT, randomized controlled trial; TKA, total knee arthroplasty; UKA, unicompartmental knee arthroplasty; VEPE, vitamin-E-enhanced polyethylene.

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