Biologics or surgery for moderate knee osteoarthritis? a patient-centered framework for short-term relief and long-term outcomes

Abstract

Purpose

To provide a narrative synthesis comparing clinical outcomes, durability, and patient-specific suitability of autologous biologic therapies (platelet-rich plasma [PRP], bone marrow aspirate concentrate [BMAC]) versus non-TKA surgical strategies (high tibial osteotomy [HTO], unicompartmental knee arthroplasty [UKA]) in patients with moderate knee osteoarthritis (Kellgren-Lawrence grade 2–3).

Methods

A structured literature search was conducted in PubMed, Scopus, and Web of Science (January 2010–March 2024). Priority was given to prospective cohort studies, randomized controlled trials, and comparative studies involving KL grade 2–3 patients. Evidence was synthesized qualitatively, focusing on pain, function, durability, complications, and cost-effectiveness.

Results

Biologic therapies provide rapid pain relief within 3–6 months (mean VAS/WOMAC reduction: −2.6 to − 5.8 points) but show attenuation beyond 18–24 months, particularly in KL3 disease. BMAC demonstrates superior short-term outcomes compared to PRP (WOMAC mean difference − 5.8, p = 0.03). Surgical interventions exhibit slower initial improvement but superior durability, with 5-year survivorship of 92% for UKA and 85% for HTO. Complication rates are low for biologics (< 1% major) but higher for surgery (HTO 5.2%, UKA 3.8%). Cost-effectiveness remains favorable for all interventions (<$50,000/QALY). KL2 patients respond well to biologics, while KL3 patients with malalignment derive greater benefit from surgery.

Conclusions

Management of moderate knee OA is best guided by a severity-stratified, patient-centered framework. Biologic therapies may be suitable for earlier-stage disease or for patients seeking minimally invasive, short-term symptom relief, while surgical interventions represent more durable options for patients with advanced degeneration or biomechanical imbalance. Treatment decisions should prioritize patient characteristics, disease stage, values, and expectations rather than implying a hierarchical superiority of one modality over another.

Level of evidence

Narrative Review – Level V.

Supplementary Information

The online version contains supplementary material available at https://doi.org/10.1186/s13018-026-07062-1.

Introduction

Knee osteoarthritis is the most prevalent form of arthritis globally and a major contributor to chronic pain, functional limitation, and disability. Moderate OA (KL grade 2–3) represents a clinically pivotal phase in which biological degeneration and biomechanical stress coexist, often leading to progression despite conservative therapy [1–6]. Its incidence rises sharply after age 40 and peaks in individuals aged 50–59, disproportionately affecting women and those with obesity, prior knee injury, or mechanical malalignment [7–9]. Recognizing its profound impact on function, quality of life, and multimorbidity, the WHO has identified OA as a global health priority within the 2021–2030 Decade of Healthy Ageing [10–12]. Moderate OA, typically defined radiographically as Kellgren–Lawrence (KL) grade 2–3, represents a pivotal stage where patients often experience persistent symptoms despite conservative care but are not yet appropriate candidates for total knee arthroplasty (TKA) [13, 14]. At this stage, treatment strategies increasingly focus on non-TKA interventions, which can be broadly categorized into biologic therapies and joint-preserving surgical procedures. Autologous biologic therapies such as PRP and BMAC aim to modify the intra-articular biological milieu through delivery of growth factors and progenitor cells, offering minimally invasive options with rapid recovery. In contrast, non-TKA surgical interventions, including HTO and UKA, address structural and mechanical contributors to disease progression through realignment or compartmental resurfacing [15–17]. These dynamics highlight the need for interventions that can address both degenerative tissue changes and mechanical imbalance.

Current management strategies for moderate OA increasingly focus on two distinct pathways: biologic therapies and joint-preserving surgical procedures. Biologic interventions such as platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) aim to modulate the intra-articular environment by delivering autologous growth factors and progenitor cells [18, 19].

Both therapies have demonstrated short-term improvements in pain and function, particularly in patients with early degenerative changes or focal chondral pathology [20, 21]. In contrast, joint-preserving surgical options including high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) target structural correction. HTO corrects varus alignment to unload the medial compartment, while UKA resurfaces the affected compartment while preserving much of the native joint structure [22, 23]. These procedures are particularly attractive for younger, active patients aiming to delay or avoid TKA and maintain high functional capacity [24, 25].

Despite the clinical adoption of both biologic and surgical modalities, direct comparisons of their long-term outcomes remain limited. While biologic therapies offer advantages in accessibility, minimal invasiveness, and rapid recovery [22, 26], their efficacy tends to decline beyond 12–24 months. Surgical interventions, though more invasive, have demonstrated superior durability, particularly in patients with KL3 disease or axial malalignment [27–29]. Recent systematic reviews have highlighted the potential of HTO to correct malalignment and reduce joint loading, while UKA has shown excellent survivorship and functional outcomes in properly selected patients [28, 30, 31]. Nevertheless, the literature lacks comprehensive comparisons between these fundamentally different treatment paradigms, leaving clinicians without clear guidance for therapeutic decision-making in moderate knee OA [32–34].

This narrative review is based on a structured literature search conducted in PubMed, Scopus, and Web of Science covering January 2010 to March 2024. Search terms included combinations of “knee osteoarthritis,” “moderate OA,” “platelet-rich plasma,” “bone marrow aspirate concentrate,” “high tibial osteotomy,” and “unicompartmental knee arthroplasty. Priority was given to prospective cohort studies, randomized controlled trials, and comparative studies involving KL grade 2–3 patients. Studies were selected based on relevance to clinical outcomes, durability, and patient-specific factors rather than formal meta-analytic eligibility. Data extraction focused on pain, function, survivorship, complications, and cost-effectiveness. Evidence was synthesized qualitatively to reflect methodological heterogeneity across interventions. Although UKA is not strictly joint-preserving, it is included as a non-TKA option that maintains more native anatomy than total arthroplasty and is frequently considered in moderate OA. By integrating biological and mechanical perspectives, this review proposes a stratified, stage-based treatment framework for moderate knee OA and identifies priorities for future research, including protocol standardization, long-term comparative studies, and evaluation of combined modalities.

Methods

This narrative review is based on a structured literature search conducted in PubMed, Scopus, and Web of Science covering January 2010 to March 2024. The search strategy employed MeSH terms and free-text keywords combined with Boolean operators. Primary search strings included combinations of (“knee osteoarthritis” OR “moderate OA” OR “Kellgren-Lawrence grade 2” OR “Kellgren-Lawrence grade 3”) AND (“platelet-rich plasma” OR “PRP” OR “bone marrow aspirate concentrate” OR “BMAC”) for biologic therapies, and (“knee osteoarthritis” OR “moderate OA”) AND (“high tibial osteotomy” OR “HTO” OR “unicompartmental knee arthroplasty” OR “UKA”) for surgical interventions. Secondary searches incorporated outcome-specific terms including “pain,” “function,” “survivorship,” “complications,” and “cost-effectiveness.” No language restrictions were applied.

Studies were included if they were prospective cohort studies, randomized controlled trials, or comparative studies primarily involving patients with Kellgren-Lawrence grade 2–3 knee osteoarthritis and reporting relevant clinical outcomes (pain, function, structural changes, survivorship, complications, or cost-effectiveness). Exclusion criteria included studies focused exclusively on KL grades 0–1 or 4, those primarily evaluating total knee arthroplasty, retrospective case series with fewer than 20 patients, animal or in vitro studies, and conference abstracts without full-text publication. Titles and abstracts were screened independently by two reviewers, with full-text assessment of potentially eligible articles. Discrepancies were resolved through discussion with a senior author. Due to substantial clinical and methodological heterogeneity across interventions, evidence was synthesized qualitatively.

Current evidence landscape in moderate knee osteoarthritis

The contemporary evidence informing the management of moderate knee osteoarthritis is built upon a substantial and methodologically diverse body of clinical research. Across the past decade, high-quality investigations including randomized controlled trials and prospective cohort studies have collectively reported outcomes in more than 3,000 patients with radiographically confirmed KL2–3 OA. These studies span the full spectrum of current interventions, providing a balanced representation of biologic therapies, alignment-correcting procedures, and joint-preserving arthroplasty techniques. Notably, a considerable proportion of this literature consists of direct, head-to-head comparisons, such as BMAC versus PRP or HTO versus UKA, offering valuable insight into the relative performance of these modalities. Complementing these are well-designed single-intervention cohorts that further characterize patient trajectories and treatment durability.

Within this body of evidence, BMAC has been evaluated in approximately 842 patients across nine prospective studies, while PRP outcomes have been reported for more than 700 individuals in eight trials. These biologic interventions typically feature follow-up durations ranging from 12 to 24 months, reflecting their role as minimally invasive treatments with short- to mid-term therapeutic horizons. In contrast, the surgical literature on high tibial osteotomy and unicompartmental knee arthroplasty encompasses nearly 1,500 patients across eleven studies with substantially longer observation periods. HTO cohorts commonly report results up to four to five years post-procedure, and UKA studies frequently extend follow-up to 36–60 months. This discrepancy in follow-up length is crucial when interpreting treatment durability, as biologic therapies are inherently assessed over shorter timescales, whereas surgical interventions are evaluated across multiple years of functional demand and structural adaptation.

Across studies, methodological quality is generally strong, though certain heterogeneities are characteristic of this field. Biologic preparation protocols differ meaningfully between investigations especially for PRP, where leukocyte concentration, activation method, and final platelet dose vary considerably. Similarly, surgical techniques are not uniform; variations exist in HTO approach, fixation hardware, correction angle planning, and in UKA implant design and kinematic philosophy. These technical nuances are consistently documented in the literature and must be considered when comparing outcomes across modalities, as they can influence both early recovery dynamics and long-term structural results.

Included studies consisted primarily of prospective cohort studies and randomized controlled trials. The majority of biologic therapy studies (PRP and BMAC) were Level II evidence, while surgical studies (HTO and UKA) included both Level I and Level II evidence. No formal risk of bias assessment was performed, consistent with the narrative review design. However, priority was given to higher-quality prospective designs, and studies were qualitatively evaluated for methodological rigor, sample size, follow-up duration, and relevance to KL grade 2–3 patients. This approach allows for a balanced synthesis while acknowledging the inherent heterogeneity across intervention types (Fig. 1).

Fig. 1.

Visualization of the evolving evidence landscape in knee osteoarthritis research. The 2024 Dubin [35] study forms the central node linking foundational biologic therapy and surgical intervention studies from 2015–2022 to emerging publications in 2024–2025, highlighting continuity and growth in the field

Pain relief trajectories

Analysis of pain relief patterns revealed fundamentally different trajectories between biologic and surgical interventions, though both demonstrated statistically significant reductions from baseline (p < 0.001 for all comparisons) [36]. Across included prospective studies, biologic therapies (PRP and BMAC) demonstrated a rapid onset of pain relief, typically within the first 3–6 months following intervention. Mean reductions in pain scores ranged from − 2.6 to − 5.8 points on VAS or WOMAC pain subscales, with peak benefit observed between 6 and 12 months. However, symptom relief showed gradual attenuation beyond 18–24 months, particularly in KL3 disease.

BMAC tended to show greater short-term pain and functional improvement compared with PRP in several KL2–3 cohorts. For example, In the study by Beckers et al. (2019), reported larger WOMAC improvements with BMAC than PRP (mean difference − 5.8, p = 0.03) (Table 1) [37]. These findings suggest a potential short-term advantage, although heterogeneity in preparation protocols limits definitive conclusions. In contrast, surgical interventions exhibited slower initial pain reduction but greater durability. Both HTO and UKA showed progressive improvement up to 12–18 months, with sustained pain relief maintained through 36–60 months. In KL3 patients, UKA demonstrated greater functional pain-related improvement than HTO, as reported by Chen et al. (2020) (Table 1) [38]. The temporal divergence in pain relief trajectories between biologic and surgical approaches has important clinical implications for patient selection and expectation management.

Table 1.

Analysis of Pain/Function Outcomes

Study (Author, Year)	Intervention	Comparator	Outcome Measure	Mean Change / Finding	p-value	Clinical Interpretation
Beckers et al., 2019 [37]	BMAC	PRP	WOMAC	−5.8	0.03	Greater functional improvement with BMAC in KL2–3
Patel et al., [39]	PRP	Placebo	Pain/function outcomes	PRP showed greater symptomatic improvement than placebo	Reported significant	PRP superior to placebo
Filardo et al., [40]	PRP	Control treatments	Pain/function outcomes	PRP improved pain and function across RCTs	Not applicable	PRP improves short-term function
Zhang et al., [41]	UKA	HTO	WOMAC	UKA showed favorable pain/WOMAC outcomes; HTO showed advantages in ROM/revision in selected patients	Not applicable	UKA more suitable for KL3 functional outcomes
Konopka et al., [42]	HTO	Non-operative	WOMAC	−17.7	< 0.001	HTO effective for malaligned knees

Negative values indicate symptom reduction. Positive values indicate improvement relative to comparator.Clinically, BMAC/PRP provide moderate pain relief (-2 to -6 points), whereas surgical approaches (HTO/UKA)

Functional outcomes

Functional improvement patterns closely paralleled pain trajectories but highlighted more pronounced long-term differences between intervention categories. At mid- to long-term follow-up (≥ 24 months), surgical strategies maintained superior functional outcomes, particularly in patients with advanced structural degeneration. As summarized in Table 1, UKA was associated with higher KOOS functional scores than HTO in KL3 patients in one comparative study (mean difference + 5.8, p = 0.01). This observation suggests a possible advantage of UKA in this subgroup, although further comparative data are needed given methodological heterogeneity. Conversely, biologic therapies yielded moderate but clinically meaningful functional gains, particularly in KL2 disease. PRP outperformed physiotherapy and sham injections in short-term functional recovery, while BMAC consistently demonstrated greater WOMAC improvements than PRP.

These findings indicate that while biologic therapies may facilitate early functional recovery, surgical interventions provide more durable improvements in activities of daily living, especially when mechanical and structural factors dominate disease progression.

Structural and imaging outcomes

MRI-based assessments provided objective insights into treatment-related structural changes (Table 2). Among biologic therapies, BMAC demonstrated a greater reduction in bone marrow lesion (BML) size at 12 months (mean 68%) compared with PRP (42%). These findings support the biological plausibility of enhanced symptom improvement observed with BMAC. HTO produced the most pronounced structural changes, achieving an average 81% reduction in BML size by 24 months, reflecting effective unloading of the medial compartment. MRI outcomes following UKA were not directly comparable due to compartmental resurfacing and limited postoperative imaging applicability.

Table 2.

Summary of Primary Outcomes by Intervention

Intervention	Studies (n)	Mean WOMAC Improvement (12 mo)	5-Year Survivorship	MRI Structural Change
BMAC	9	−24.6 (95% CI − 27.1 to − 22.1)	73%	68% BML reduction
PRP	8	−19.8 (95% CI − 22.3 to − 17.3)	67%	42% BML reduction
HTO	7	−31.2 (95% CI − 33.7 to − 28.7)	85%	81% BML reduction
UKA	4	−34.5 (95% CI − 37.8 to − 31.2)	92%	Not applicable

Values represent descriptive synthesis across multiple prospective studies; no pooled meta-analysis was performed

Importantly, Table 2 presents a descriptive synthesis across multiple prospective studies rather than pooled meta-analytic estimates, reflecting heterogeneity in imaging protocols and follow-up duration.

Treatment survivorship and failure rates

Clear differences in treatment durability emerged when failure was defined as conversion to TKA or clinically significant deterioration (Table 2). Surgical interventions demonstrated superior long-term survivorship, with UKA achieving 92% and HTO 85% survivorship at 5 years. In contrast, biologic therapies showed declining durability, with 3–5-year survivorship rates of 73% for BMAC and 67% for PRP.

Failure rates were strongly influenced by disease severity. In KL3 patients, biologic therapies exhibited approximately 2.5-fold higher failure rates compared with surgical interventions, underscoring their limited durability in advanced degeneration. The study by Hinarejos et al. (2019) [43] provided particularly robust long-term data on UKA survivorship, reporting 94% survivorship at 5 years in their prospective cohort. Similarly, the HTO survivorship data from Konopka et al. [42] showed excellent durability in properly selected patients. UKA’s effects on BMLs are not directly comparable to non-replacement therapies, as it involves resurfacing. These descriptive trends suggest that while biologics may provide satisfactory short-term outcomes, surgical interventions demonstrate greater durability in the available studies, particularly for patients with more advanced disease. However, direct head-to-head comparisons remain limited. The declining success rates of biologics over time highlight the importance of considering long-term outcomes when making treatment decisions, rather than focusing solely on short-term gains.

Complication profiles

Complication patterns differed substantially between biologic and surgical interventions and are summarized in Table 3. Biologic therapies demonstrated excellent safety profiles, with major complications remaining rare (< 1%). Minor adverse events, such as transient effusion or post-injection flare, were relatively common but self-limiting. Surgical interventions were associated with higher complication and reoperation rates. HTO demonstrated the highest major complication rate (5.2%), primarily related to non-union or infection, whereas UKA showed lower but clinically relevant risks of aseptic loosening and postoperative stiffness. These findings emphasize the importance of risk stratification and patient counseling when selecting surgical options. Minor complications were more common with both surgical approaches, including hardware irritation (22.4%) with HTO and postoperative stiffness (18.6%) with UKA.

Table 3.

Safety and Complications Across Interventions

Intervention	Total Patients	Major Complications	Minor Complications	Reoperation Rate
BMAC	842	0.7% (osteomyelitis)	12.3% (effusion/pain)	4.1%
PRP	776	0.3% (septic arthritis)	15.8% (flare reaction)	6.9%
HTO	932	5.2% (non-union, infection)	22.4% (hardware irritation)	11.3%
UKA	592	3.8% (aseptic loosening)	18.6% (stiffness)	8.2%

Major complications were rare with biologic therapies (BMAC 0.7%, PRP 0.3%) but higher for surgical procedures (HTO 5.2%, UKA 3.8%). Minor complications occurred most frequently after HTO (22.4%) and UKA (18.6%), with reoperation rates ranging from 4.1% (BMAC) to 11.3% (HTO)

Biologic therapies demonstrated an excellent safety profile overall, with major complications being rare (0.7% osteomyelitis for BMAC, 0.3% septic arthritis for PRP). Minor complications were more frequent, including transient effusion (12.3%) with BMAC and post-injection flare reactions (15.8%) with PRP. Reoperation rates were predictably higher for surgical interventions (HTO: 11.3%; UKA: 8.2%) compared to biologics (BMAC: 4.1%; PRP: 6.9%). The study by Hampp et al. (2022) [44] provided interesting insights into complication reduction with patient-specific HTO guides, showing lower complication rates compared to conventional techniques. These safety data are crucial for informed consent processes and shared decision-making, particularly when weighing the risks and benefits of more invasive but potentially more durable surgical options against less invasive but potentially less definitive biologic therapies.

Disease severity and treatment response

Stratification by radiographic severity revealed distinct response patterns (Table 4). KL2 patients achieved favorable outcomes with biologic therapies, demonstrating meaningful symptom relief and functional improvement. In contrast, KL3 patients benefited more consistently from surgical interventions, particularly when mechanical malalignment was present. Age and alignment further modified outcomes. Younger, active patients with varus malalignment derived greater benefit from HTO, while UKA was more suitable for older or lower-demand patients with isolated compartmental disease. These relationships are synthesized into a patient-specific treatment suitability framework, emphasizing individualized rather than hierarchical treatment selection. The integrated findings from pain, functional, structural, and survivorship outcomes informed a patient-specific decision framework to guide individualized treatment selection (Table 6).

Table 4.

Comparative effect sizes and heterogeneity of key interventions for moderate knee osteoarthritis

Study	Intervention	Comparator	Direction of Evidence	Interpretation
Zhang et al., [41]	UKA	HTO	Mixed	UKA favored for pain/WOMAC; HTO favored for ROM/revision in selected patients
Patel et al., [39]	PRP	Sham	Favours PRP	PRP showed greater symptomatic improvement than placebo
Filardo et al., [40]	HTO	Non-op	Generally favours PRP	PRP improved pain/function, with heterogeneity across studies

Negative values favor the intervention, positive values favor the comparator. Heterogeneity is classified as low (I² <25%), moderate (25–50%), or high (> 50%)

Table 6.

Patient-factor–based suitability of biologic and surgical interventions for moderate knee osteoarthritis

Patient Factor	Biologics (PRP/BMAC)	HTO	UKA
KL Grade 2	Highly suitable	Selective	Rare
KL Grade 3	Limited durability	Suitable if malaligned	Highly suitableHighly suitable
Varus malalignment	Limited benefit	Optimal	Selective
Age < 55 years	Suitable	Preferred	Selective
Desire for minimal invasiveness	Preferred	Less suitable	Less suitable

This table outlines the relative appropriateness of biologic therapies (PRP/BMAC), high tibial osteotomy (HTO), and unicompartmental knee arthroplasty (UKA) according to key patient factors, including Kellgren–Lawrence (KL) grade, limb alignment, age, and preference for minimally invasive treatment. The framework supports individualized clinical decision-making by matching intervention type to patient characteristics rather than implying treatment superiority

Cost-effectiveness

Cost-effectiveness analyses (Table 5) demonstrated that all interventions fell well below commonly accepted willingness-to-pay thresholds. While biologic therapies incurred lower initial costs, repeated treatments reduced long-term cost-effectiveness in KL3 disease. In contrast, UKA demonstrated the most favorable cost-utility profile ($5,781 per QALY), followed closely by HTO.

Table 5.

Cost-effectiveness of selected interventions for moderate knee osteoarthritis

Study	Intervention	Cost per QALY (USD)	Cost Savings vs. TKA	Interpretation
Hinarejos 2019 [43]	UKA	$5,781	$12,300	Most cost-effective for KL3
Samuelson and Brown, [45]	PRP vs HA	$3,444	$8,200	PRP may be economically reasonable depending on durability and treatment frequency
Konopka et al., [42]	HTO	$5,448	$10,700	Surgical options may be economically reasonable in appropriate patients

This table presents cost-utility outcomes expressed as cost per quality-adjusted life year (QALY) and estimated cost savings relative to total knee arthroplasty (TKA). Findings are stratified by intervention type and interpreted in relation to disease stage and mechanical factors, highlighting the differential economic value of unicompartmental knee arthroplasty (UKA), biologic therapies (BMAC), and high tibial osteotomy (HTO) in specific patient subgroups

These observations are based on a limited number of economic evaluations identified in the narrative review and should be regarded as illustrative rather than conclusive.

These findings suggest that integrating disease stage and mechanical factors into reimbursement and resource-allocation models may optimize value-based care and avoid under- or over-treatment [46].

All interventions remained well below the WHO cost-effectiveness threshold of $50,000/QALY, suggesting good value across approaches. The study by Hinarejos et al. (2019) [43] provided particularly robust economic data on UKA, demonstrating $12,300 in long-term savings compared to TKA. Similarly, Konopka et al. [42] showed that HTO could generate $10,700 in savings versus non-operative management when considering delayed TKA. These economic considerations are increasingly important in value-based healthcare systems and should be factored into treatment algorithms alongside clinical outcomes. The superior cost-effectiveness of surgical interventions, despite higher upfront costs, reflects their greater durability and lower need for revision procedures in appropriately selected patients. These findings have important implications for healthcare policy and reimbursement decisions, particularly in resource-constrained environments. However, given the non-systematic nature of the economic literature search and the relatively small number of studies providing cost data, these findings must be interpreted with caution. Dedicated health economic analyses are needed to provide more robust evidence.

Importantly, considerable variability exists in biologic preparation protocols (particularly PRP leukocyte content, activation methods, and platelet concentration) and surgical techniques (including HTO correction angles, fixation methods, and UKA implant designs and alignment philosophies). These differences should be considered when interpreting comparative outcomes across studies.

Discussion

This review highlights that biologic and surgical interventions play complementary rather than competitive roles in the management of moderate knee OA. Biologic therapies provide short-term symptom relief and may delay surgery in early disease, while surgical strategies address mechanical drivers of progression and offer more durable outcomes in advanced degeneration. Heterogeneity in biologic preparation protocols and surgical techniques limits definitive comparative conclusions and underscores the need for cautious interpretation.

The durability of joint-preserving surgeries may be explained by their ability to correct malalignment and redistribute load [47–50]. Particularly platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC) - offer effective short-term symptom relief for moderate knee osteoarthritis (KL2-3), especially in patients with KL grade 2 disease. PRP demonstrates superior efficacy to conventional treatments like hyaluronic acid and corticosteroids, as shown by Clement et al. (2020 #44) who reported significantly greater pain reduction compared to sham injections (VAS: -3.8 vs. -1.2, p < 0.001). BMAC, with its rich content of progenitor cells, shows even greater improvements in patient-reported outcomes (WOMAC: -28.1 vs. PRP − 22.3, p = 0.03; Beckers et al., 2019 #1), likely due to enhanced regenerative potential [7]. However, the long-term durability of these biologic therapies remains limited, with success rates declining to 76.4% for BMAC and 68.9% for PRP at 3 years (Table 2), reflecting the inherent biological constraints of cartilage repair in an avascular, low-cellularity environment [7, 16, 51–53].

Interpretation of the observed trends must account for substantial heterogeneity in intervention protocols. Biologic preparations varied significantly with respect to leukocyte concentration, platelet dosing, and activation status, while surgical approaches differed in correction magnitude, hardware selection, and kinematic principles. Such variability likely contributes to differences in reported outcomes and limits the strength of direct comparisons between modalities.

In contrast, joint-preserving surgical interventions - high tibial osteotomy (HTO) and unicompartmental knee arthroplasty (UKA) - provide more sustained outcomes, particularly for KL grade 3 disease [54, 55]. HTO achieves mechanical correction of varus deformity through extra-articular realignment, redistributing load away from the medial compartment while preserving native knee kinematics [11, 13]. UKA offers compartmental resurfacing with excellent functional outcomes (KOOS: +5.8 points vs. HTO, p = 0.01; Chen et al., 2020 #43), though requires careful patient selection to avoid kinematic alterations from overcorrection [13]. Both procedures demonstrate impressive durability, with 5-year survivorship rates of 92.3% for UKA and 85.1% for HTO (Table 2), effectively delaying or preventing progression to total knee arthroplasty [9, 10, 56].

Stratified analysis reveals critical differences in treatment response based on disease severity. KL2 patients, typically younger and more active with better biomechanical alignment, achieve 73.5% success with biologic therapies (mean WOMAC improvement: -19.1 points). In contrast, KL3 patients with advanced cartilage degeneration and frequent varus malalignment derive greater benefit from surgical correction (89.1% success rate, -31.6 WOMAC points), as biologic efficacy declines when structural joint deterioration exceeds reparative thresholds (Table 5) [4–6]. These findings strongly support phenotype-based treatment selection incorporating radiographic grade, alignment, age, activity level, and patient goals [12, 17].

From a health economics perspective, our analysis demonstrates important cost-effectiveness distinctions [57, 58]. While biologics present lower initial costs and faster recovery, their frequent need for repeat administration diminishes long-term value, particularly in KL3 disease [29, 59]. Surgical interventions, despite higher upfront costs, offer superior durability and cost-effectiveness, Economic evaluations have highlighted the favorable cost-effectiveness profile of UKA compared to TKA with UKA demonstrating the most favorable profile at $5,781/QALY (Table 6) [14, 17, 58, 60, 61]. Similarly, recent meta-analyses have confirmed the short-term benefits of PRP injections [40, 62–67]. These findings have important implications for healthcare policy, suggesting that reimbursement models should integrate disease stage and mechanical factors to optimize resource allocation [17].

Several limitations warrant consideration. Inter-study variability exists in both biologic preparation protocols (e.g., PRP leukocyte content, centrifugation techniques) and surgical execution (e.g., implant types, correction angles). Limited economic data from 6 studies suggest UKA is cost-effective ($5,781/QALY), but our search was not optimized for health economics (e.g., missed EconLit database). Few included studies provided direct head-to-head comparisons between treatment modalities, limiting definitive conclusions about relative efficacy. Additionally, outcome reporting metrics varied across studies, complicating pooled analyses.

Despite these limitations, the evidence supports a structured treatment framework. Biologics, particularly BMAC, represent an appropriate first-line option for KL2 patients without significant malalignment [68–70]. For KL3 disease or mechanical axis deviation, HTO and UKA offer more durable solutions, with UKA showing advantages in older or less active patients [11–13, 71]. Future research should prioritize randomized controlled trials directly comparing these modalities, standardization of preparation and surgical protocols, and investigation of potential synergistic approaches combining biologic and surgical strategies [72–75]. A stage-specific, patient-centered treatment algorithm remains essential for optimizing outcomes in moderate knee osteoarthritis [76, 77].

Limitations

The evidence base comprises heterogeneous prospective studies with substantial variability in biologic preparation protocols, surgical techniques, and follow-up duration. These differences, particularly in PRP formulation and HTO/UKA technical execution, complicate direct comparisons and must be carefully considered when interpreting the reported trends. Biologic studies frequently differ in PRP leukocyte content, centrifugation techniques, platelet concentration, and activation methods, while BMAC protocols vary in harvest site and processing. Surgical studies similarly demonstrate variability in HTO correction angles, fixation methods, and UKA implant design. These methodological differences limit direct cross-intervention comparisons and require cautious interpretation of relative effectiveness.

Conclusion

Autologous biologic therapies and non-TKA surgical interventions serve distinct roles in the management of moderate knee osteoarthritis. Biologics may be more suitable for KL2 disease or patients seeking minimally invasive, short-term relief, whereas HTO and UKA offer more durable options for KL3 disease or mechanical malalignment. Clinical decision-making should be individualized, integrating disease severity, biomechanical factors, patient preferences, and health-economic considerations rather than relying on hierarchical treatment comparisons.

Practical implications

BMAC and PRP offer relatively low-cost, short-term relief but often require repeat treatments, whereas surgical interventions involve higher upfront costs but can delay or prevent the need for total knee arthroplasty, potentially saving $10,000–$12,000 over the long term. Despite these differences, the cost-effectiveness of all interventions remains favorable, with incremental cost-effectiveness ratios below the $50,000 per QALY threshold recommended by the WHO.

Abbreviations

OA

Osteoarthritis

KL

Kellgren–Lawrence

BMAC

Bone Marrow Aspirate Concentrate

PRP

Platelet–Rich Plasma

HTO

High Tibial Osteotomy

UKA

Unicompartmental Knee Arthroplasty

TKA

Total Knee Arthroplasty

KOOS

Knee Injury and Osteoarthritis Outcome Score

WOMAC

Western Ontario and McMaster Universities Arthritis Index

VAS

Visual Analog Scale

RCT

Randomized Controlled Trial

QALY

Quality–Adjusted Life Year

MRI

Magnetic Resonance Imaging

BML

Bone Marrow Lesion

AE

Adverse Event

PT

Physiotherapy

NSAID

Non–Steroidal Anti–Inflammatory Drug

Authors’ contributions

- Muhammad Adil Malik: Conceptualization, literature review, drafting of the manuscript, and figure design.- Song Wu: Supervision, methodological input, manuscript review.- Wenxiu Zhang: critical revision.- Junjie Huang: Senior oversight, manuscript editing, and funding coordination.- Xu Cao: Corresponding author responsibilities, review, and approval of final draft. All authors read and approved the final manuscript.

Funding

This work was supported by: - Youth Fund Project of Natural Science Foundation of Hunan Province (2022JJ40742). - National Natural Science Foundation of China (82302761). - These funding bodies had no role in the design, analysis, interpretation, or writing of the manuscript.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

This study is a narrative literature review that did not involve any human participants, animal subjects, primary data collection, or tissue samples. As such, it relied exclusively on publicly available, previously published data. No ethical approval was required.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.