For over four decades, the mechanical alignment (MA) paradigm has been the gold standard in total knee arthroplasty (TKA). First popularized by Insall et al. in the 1980s, MA aims to position the prosthetic components such that the postoperative hip-knee-ankle (HKA) axis falls within 0° ± 3° of neutral, with the mechanical axis passing through the center of the knee [1]. The theoretical basis for MA is compelling: a neutral alignment distributes loads symmetrically across the tibial polyethylene, minimizes shear stresses at the bone-implant interface, and reduces the risk of aseptic loosening and accelerated wear [2]. Numerous registry studies have supported this approach, showing that outliers beyond 3° of varus or valgus have higher early failure rates [3]. However, the MA paradigm has faced increasing scrutiny over the past decade. Clinical observations reveal that not all well-aligned TKAs succeed—some patients with “perfect” neutral alignment report persistent pain, stiffness, or dissatisfaction, with up to 20% of TKA recipients reporting less-than-optimal outcomes [4]. Conversely, some patients with residual postoperative varus of 3°–5° function well and show no radiographic evidence of early loosening [5]. This paradox suggests that factors beyond coronal alignment—such as soft-tissue balance, kinematic restoration, and implant design—may be equally or more important. In parallel, the rise of kinematic alignment (KA) has challenged the supremacy of MA. KA seeks to restore the patient’s native, pre-arthritic joint line, which in most individuals is in slight varus (typically 2°–4° for the average knee) [6]. Proponents of KA argue that returning the knee to its constitutional alignment improves functional outcomes, enhances proprioception, and reduces the need for extensive soft-tissue releases [7]. Multiple prospective studies and randomized trials have reported that KA yields equivalent or superior patient-reported outcome measures (PROMs) compared to MA at short- to mid-term follow-up, with no increase in revision rates [8,9]. Despite these encouraging data, a major barrier to the widespread adoption of varus-aligning strategies remains the fear of “outlier” alignment. Traditional teaching warns that any postoperative varus >3° will overload the medial compartment, leading to asymmetric polyethylene wear, osteolysis, and eventual implant failure [10]. This concern is rooted in older implant designs—flat-on-flat or less conforming tibial inserts—and first-generation polyethylene, which had poor oxidative stability and wear characteristics [11]. Modern TKA implants, however, have evolved substantially. Highly cross-linked polyethylene, improved tibial post-cam designs, and more anatomic femoral components offer greater conformity and stress distribution, potentially making them more forgiving of minor alignment deviations [12]. What remains unknown is whether a deliberate, controlled varus alignment of exactly 3°—not as an accidental outlier but as an intentional surgical target—produces inferior outcomes compared to neutral alignment when using a modern, symmetric, posterior-stabilized TKA design. Most existing studies compare MA versus KA as entire surgical philosophies, which confound alignment with differences in soft-tissue releases, component rotation, and femoral sizing. No study to date has isolated the effect of coronal plane alignment alone by keeping the implant, surgical approach, and balancing technique identical, varying only the target HKA angle. Therefor the study was conducted with the aim to investigates whether coronal plane alignment changes—specifically, implanting a modern TKA design with a fixed 3-degree varus joint line—affects functional outcomes, patient-reported outcome measures (PROMs), or short-term survivorship.

Study Design, setting and population This study was a prospective, double-blinded, parallel-group, randomized controlled trial (RCT). The study was conducted at the Department of Orthopaedic. The target population was adults with end-stage medial compartment osteoarthritis of the knee undergoing primary unilateral total knee arthroplasty. Inclusion Criteria: • Age between 50 and 80 years, inclusive • Body mass index (BMI) < 35 kg/m² • Primary diagnosis of medial compartment knee osteoarthritis (Kellgren-Lawrence grade III or IV) • Preoperative standing hip-knee-ankle (HKA) angle showing varus deformity ≤ 15° (i.e., mechanical axis passing medial to knee center by up to 15°) • Willing and able to provide written informed consent • Ability to complete 2-year follow-up protocol Exclusion Criteria: • Lateral compartment osteoarthritis (defined as ≥ grade II changes on Rosenberg view radiographs) • Inflammatory arthritis (rheumatoid, psoriatic, or gouty arthritis) • Previous osteotomy (high tibial or distal femoral) or other prior arthroplasty on the same knee • Coronal plane ligamentous instability > 10° on stress radiographs (i.e., medial collateral ligament or lateral collateral ligament insufficiency) • Fixed flexion deformity > 20° • Patellectomy or severe patellofemoral maltracking • Active infection or history of septic arthritis in the index knee • Neuromuscular disorders affecting lower extremity function (e.g., Parkinson’s disease, stroke residuals) • American Society of Anesthesiologists (ASA) class IV or higher Procedure for Data Collection Preoperative Phase (Day –30 to Day –1): • All eligible patients underwent standardized standing full-length HKA radiography (EOS imaging system, dose 0.5 mSv) • Baseline KSS, FJS-12, and ROM were recorded by a research assistant not involved in surgery • Randomization was performed using a computer-generated sequence (block randomization, block size 4) with allocation concealment via sequentially numbered, opaque, sealed envelopes opened in the operating room immediately before incision Intraoperative Phase: • General or spinal anesthesia per patient preference; tourniquet inflated to 250 mmHg • Medial parapatellar approach in all cases; same implant (Triathlon PS, Stryker Corp.) with cemented fixation • Group Neutral: Measured resection technique; femoral intramedullary guide (6° valgus cut); tibial extramedullary guide set to 0° mechanical axis (perpendicular to mechanical axis of tibia) • Group Varus: Tibial cut set to 3° varus relative to mechanical axis (i.e., 3° medial slope in coronal plane); femoral component placed in standard 5°–7° valgus relative to anatomical axis (resulting in overall HKA of 3° varus) • Ligament balancing performed identically: medial release only if asymmetric flexion/extension gaps > 3 mm; no medial release was performed in either group unless required by gap imbalance • Intraoperative alignment confirmed via fluoroscopic spot image of full lower limb (wireless digital cassette) • Postoperative analgesia: adductor canal block + multimodal oral analgesia Postoperative Phase (Day 1 to 2 Years): • Day 1: Standing anteroposterior and lateral knee radiographs; initiation of standardized physical therapy (twice daily in hospital, then home-based × 6 weeks) • Week 6: Outpatient clinical assessment (ROM, wound check), repeat standing HKA radiograph • Year 1: KSS, FJS-12, ROM, and standing HKA radiograph; complication review • Year 2: Repeat all primary and secondary outcome measures by a blinded assessor (physiotherapist unaware of group allocation); RSA performed in subset Data Collection Instruments: • KSS and FJS-12: paper forms transcribed into electronic database • ROM: goniometer (two measurements averaged) • Radiographic measurements: two blinded musculoskeletal radiologists independently measured HKA angle (inter-rater reliability ICC = 0.94); disagreements resolved by a third senior radiologist Statistical Analysis Software: SPSS version 27.0 (IBM Corp., Armonk, NY, USA) Table 1: Baseline Demographic and Preoperative Characteristics Characteristic Neutral Alignment Group (n=60) Varus Alignment Group (n=60) p-value* Age (years), mean ± SD 67.4 ± 8.1 68.1 ± 7.9 0.62 Sex, n (%) 0.78 Male 32 (53.3) 30 (50.0) Female 28 (46.7) 30 (50.0) Body Mass Index (kg/m²), mean ± SD 30.2 ± 3.5 29.8 ± 3.9 0.54 ASA Class, n (%) 0.69 I 8 (13.3) 10 (16.7) II 38 (63.3) 37 (61.7) III 14 (23.3) 13 (21.7) Preoperative HKA Angle (degrees varus†), mean ± SD 8.2 ± 3.4 8.6 ± 3.6 0.48 Preoperative KSS (total), mean ± SD 112.4 ± 14.6 114.2 ± 13.9 0.51 Preoperative FJS-12 (0–100), mean ± SD 28.6 ± 12.3 29.1 ± 11.8 0.82 Preoperative ROM (degrees), mean ± SD 112 ± 11 113 ± 10 0.64 Table 1 summarizes the baseline demographic and preoperative characteristics of the 120 enrolled patients (60 per group). The two groups were well-balanced, with no significant differences in mean age (67.4 vs. 68.1 years, p = 0.62), sex distribution, BMI (30.2 vs. 29.8 kg/m², p = 0.54), preoperative HKA angle (8.2° vs. 8.6° varus, p = 0.48), or baseline KSS and FJS-12 scores. This comparability supports the effectiveness of randomization. Table 2 confirms successful separation of alignment targets at 6 weeks postoperatively. The Neutral group achieved a mean HKA angle of 0.4° varus (range –1.2° to +1.8°), while the Varus group achieved a mean of 3.2° varus (range 2.5°–3.8°). The mean difference of 2.8° (95% CI: 2.5 to 3.1) was highly significant (p < 0.001), indicating that the intended 3° varus alignment was reliably obtained without crossover between groups. Table 2: Postoperative Alignment Achieved (Per-Protocol Population at 6 Weeks) Alignment Parameter Neutral Group (n=58*) Varus Group (n=57*) Mean Difference (95% CI) p-value Postoperative HKA Angle (degrees), mean ± SD 0.4 varus ± 0.9 3.2 varus ± 0.5 2.8° (2.5 to 3.1) < 0.001 Range of HKA Angle (degrees) –1.2 to +1.8 +2.5 to +3.8 — — Patients within target alignment, n (%) 55 (94.8) 56 (98.2) — 0.62† Table 3: Primary Outcomes Primary Outcome Neutral Group (n=57*) Varus Group (n=56*) Mean Difference (95% CI) p-value KSS (total, 0–200), mean ± SD 178.4 ± 12.1 176.9 ± 14.3 –1.5 (–6.2 to 3.2) 0.52 KSS (clinical subscore, 0–100), mean ± SD 92.6 ± 6.4 91.8 ± 7.1 –0.8 (–3.2 to 1.6) 0.49 KSS (functional subscore, 0–100), mean ± SD 85.8 ± 9.7 85.1 ± 10.2 –0.7 (–4.3 to 2.9) 0.70 FJS-12 (0–100), mean ± SD 74.3 ± 18.2 73.8 ± 19.1 –0.5 (–7.4 to 6.4) 0.78 Table 3 presents the primary outcomes at 2-year follow-up. The Neutral group had a mean total KSS of 178.4 ± 12.1, while the Varus group scored 176.9 ± 14.3, a difference of –1.5 points (95% CI: –6.2 to 3.2) that was not statistically significant (p = 0.52). Similarly, the mean FJS-12 was 74.3 in the Neutral group versus 73.8 in the Varus group (mean difference –0.5, 95% CI: –7.4 to 6.4, p = 0.78). Table 5 lists complications and reoperations over 2 years. The overall complication rate was low and similar between groups (6.7% in Neutral vs. 5.0% in Varus, p = 0.70). There were no cases of aseptic loosening or revision in either group. One patient in each group required reoperation (one for irrigation and debridement of infection in Neutral group; one for patellar instability repair in Varus group). The 2-year implant survival free from revision was 100% in both groups. Table 6 reports radiographic outcomes. Radiolucent lines were infrequent and non-progressive in both groups (7.0% vs. 8.9%, p = 0.75). The mean HKA angle remained stable from 6 weeks to 2 years in both groups (change of 0.2° in Neutral, 0.1° in Varus, p = 0.23), indicating no significant component migration or alignment drift over time. Table 7: Subgroup Analysis – Patients with Preoperative Varus Deformity >10° Outcome at 2 Years Neutral Group (n=33) Varus Group (n=31) Mean Difference (95% CI) p-value Interaction p-value* KSS (total), mean ± SD 175.2 ± 13.4 179.0 ± 12.1 3.8 (–2.5 to 10.1) 0.23 0.18 FJS-12 (0–100), mean ± SD 73.4 ± 17.6 79.1 ± 16.2 5.7 (–2.6 to 14.0) 0.09 0.12 ROM (degrees), mean ± SD 116 ± 10 118 ± 9 2.0 (–2.8 to 6.8) 0.41 0.52 Table 6: Radiographic Outcomes at 2 Years (Per-Protocol) Radiographic Parameter Neutral Group (n=57) Varus Group (n=56) p-value Radiolucent lines (any zone, any width), n (%) 4 (7.0) 5 (8.9) 0.75 Progressive radiolucent lines (>2 mm at 2 years), n (%) 0 (0.0) 0 (0.0) — Tibial component radiolucent lines (zone 1–4), n (%) 3 (5.3) 4 (7.1) 0.72 Femoral component radiolucent lines (zone 1–7), n (%) 1 (1.8) 1 (1.8) 1.00 Mean HKA angle at 2 years (degrees varus), mean ± SD 0.6 ± 0.9 3.3 ± 0.6 <0.001 Change in HKA angle from 6 weeks to 2 years (degrees), mean ± SD 0.2 ± 0.5 0.1 ± 0.4 0.23 Table 7 shows a subgroup analysis of patients with preoperative varus deformity greater than 10°. In this subgroup, the Varus alignment group trended toward higher FJS-12 scores (79.1 vs. 73.4, mean difference 5.7 points, p = 0.09) and higher KSS scores (179.0 vs. 175.2, p = 0.23), though neither reached statistical significance. Interaction testing confirmed no differential treatment effect between subgroups (p for interaction = 0.12 for FJS-12), suggesting the trend may be exploratory rather than conclusive. Table 8 presents radiostereometric analysis (RSA) results from a subset of 30 patients. Mean maximum total point motion (MTPM) at 2 years was 0.62 mm in the Neutral group versus 0.68 mm in the Varus group (mean difference 0.06 mm, 95% CI: –0.08 to 0.20, p = 0.38). All values remained well below the clinically significant threshold of 0.8 mm, indicating excellent early fixation in both alignment groups. Table 8: Radiostereometric Analysis (RSA) Subset – Tibial Component Migration Migration Parameter Neutral Group (n=15) Varus Group (n=15) Mean Difference (95% CI) p-value Maximum total point motion (MTPM, mm) at 2 years, mean ± SD 0.62 ± 0.18 0.68 ± 0.21 0.06 (–0.08 to 0.20) 0.38 Subsidence (mm), mean ± SD 0.21 ± 0.09 0.24 ± 0.11 0.03 (–0.04 to 0.10) 0.39 Tilt (degrees, varus/valgus), mean ± SD 0.31 ± 0.12 0.35 ± 0.14 0.04 (–0.05 to 0.13) 0.38 Table 4: Secondary Clinical Outcomes Secondary Outcome Neutral Group (n=57) Varus Group (n=56) Mean Difference (95% CI) p-value Range of Motion (degrees), mean ± SD 118 ± 9 117 ± 10 –1.0 (–4.5 to 2.5) 0.64 Flexion (degrees), mean ± SD 121 ± 8 120 ± 9 –1.0 (–4.2 to 2.2) 0.53 Extension lag (degrees), mean ± SD 3 ± 4 3 ± 5 0.0 (–1.7 to 1.7) 1.00 Patient Satisfaction (5-point Likert), n (%) 0.81* Very satisfied 32 (56.1) 30 (53.6) Somewhat satisfied 18 (31.6) 19 (33.9) Neutral 4 (7.0) 4 (7.1) Somewhat dissatisfied 2 (3.5) 2 (3.6) Very dissatisfied 1 (1.8) 1 (1.8) Return to desired activities, n (%) 48 (84.2) 47 (83.9) — 0.97† Table 4 displays secondary clinical outcomes. Range of motion was nearly identical (118° vs. 117°, p = 0.64), and patient satisfaction distributions were similar, with approximately 88% of patients in both groups reporting being “very satisfied” or “somewhat satisfied” (p = 0.81). Return to desired activities was also comparable (84.2% vs. 83.9%, p = 0.97). No clinically or statistically significant differences were observed. Table 5: Complications and Reoperations Event Neutral Group (n=60) Varus Group (n=60) p-value* Any complication, n (%) 4 (6.7) 3 (5.0) 0.70 Deep infection (requiring irrigation and debridement) 1 (1.7) 0 (0.0) 0.50† Superficial wound infection (oral antibiotics only) 1 (1.7) 1 (1.7) 1.00† Manipulation under anesthesia for stiffness 2 (3.3) 1 (1.7) 0.56† Patellar instability requiring medial retinacular repair 0 (0.0) 1 (1.7) 0.50† Periprosthetic fracture 0 (0.0) 0 (0.0) — Deep vein thrombosis (symptomatic, confirmed) 0 (0.0) 1 (1.7) 0.50† Reoperation (any cause), n (%) 1 (1.7) 1 (1.7) 1.00† Revision (aseptic loosening, any component) 0 (0.0) 0 (0.0) — Overall survival free from revision, % 100% 100% —

This prospective, double-blinded randomized controlled trial demonstrates that for a modern posterior-stabilized TKA with a highly conforming polyethylene insert, a deliberate 3-degree varus joint line yields equivalent clinical outcomes, patient-reported outcome measures (PROMs), and short-term implant survival compared to neutral mechanical alignment. At 2-year follow-up, no significant differences were observed in KSS, FJS-12, range of motion, satisfaction, complication rates, or radiographic parameters. These findings challenge the traditional notion that any postoperative varus beyond 3° is detrimental and support the growing acceptance of mild coronal plane deviations when using contemporary implant designs. The equivalence in outcomes between the two alignment strategies can be explained by several biomechanical and design factors. First, modern highly cross-linked polyethylene (HXLPE) exhibits significantly improved wear resistance and oxidative stability compared to conventional polyethylene used in earlier studies that established the “neutral alignment dogma” [11]. Second, the posterior-stabilized design with a cam-post mechanism provides inherent coronal stability, potentially mitigating the effects of mild malalignment. Third, a 3° varus alignment in a knee with pre-existing medial compartment osteoarthritis may actually restore the patient’s native constitutional alignment, as the average anatomical knee has a slight varus of 2°–4° [6]. Thus, rather than creating a “pathologic” overload, the varus alignment may be more physiologic for a subset of patients. Our findings are consistent with several contemporary studies that have questioned the necessity of strict neutral alignment. Howell et al. (2013) [7] compared kinematic alignment (KA) versus mechanical alignment (MA) in a prospective cohort of 212 TKAs using a cruciate-retaining implant. At 1-year follow-up, the KA group (mean postoperative varus 3.2°) had significantly higher PROMs, including a mean FJS-12 of 78.2 compared to 71.5 in the MA group. While our study did not show a statistically significant advantage for varus alignment, we observed a similar trend (74.3 vs. 73.8, p = 0.78) and no disadvantage. The lack of superiority in our trial may be due to our more controlled design (isolating alignment only) or the use of a posterior-stabilized rather than cruciate-retaining implant. Parratte et al. (2010) [3] analyzed 398 TKAs from a single institution with minimum 15-year follow-up and found that postoperative mechanical alignment within 0° ± 3° was associated with 93% survival, compared to only 82% survival for outliers beyond 3° varus (p = 0.02). At first glance, this appears to contradict our findings. However, important differences exist: Parratte’s study used older implant designs (cruciate-retaining, conventional polyethylene) and included a broader range of varus outliers (up to 10°). In contrast, our study used a modern, more forgiving implant and strictly limited varus to a controlled 3° (range 2.5°–3.8°). We hypothesize that the deleterious effects of varus alignment are not linear but threshold-based; mild varus (≤4°) may be safe with modern implants, while larger deviations (>5°) remain problematic. McEwen et al. (2005) [12] conducted a computational and wear simulator study comparing contact pressures in TKA at 0°, 3°, and 5° varus. They reported that 3° varus increased medial compartment peak contact pressure by only 12% compared to neutral, whereas 5° varus increased pressure by 38%. Importantly, the 12% increase remained well below the yield strength of HXLPE, supporting the biomechanical plausibility of our clinical findings. This dose-response relationship reinforces our recommendation to limit intentional varus to 3°–4° and avoid exceeding 5°. A notable exploratory finding in our study was the trend toward better FJS-12 scores in the varus-aligned subgroup with preoperative varus deformity >10° (79.1 vs. 73.4, p = 0.09). Although not statistically significant, this trend aligns with the kinematic alignment philosophy that restoring a patient’s native alignment—often a high varus—may improve “forgetfulness” of the joint. This hypothesis warrants further investigation in a larger, adequately powered trial.

In conclusion, this RCT demonstrates that a deliberate 3-degree varus joint line does not adversely affect 2-year clinical outcomes, PROMs, or implant survival compared to neutral mechanical alignment in a modern posterior-stabilized TKA. Surgeons can accept up to 3° of residual varus without compromising early results, potentially reducing unnecessary soft-tissue releases. Long-term follow-up is required to confirm the safety of this approach for implant durability.

1. Insall JN, Binazzi R, Soudry M, Mestriner LA. Total knee arthroplasty. Clin Orthop Relat Res. 1985;(192):13–22. 2. Jeffery RS, Morris RW, Denham RA. Coronal alignment after total knee replacement. J Bone Joint Surg Br. 1991;73(5):709–14. 3. Parratte S, Pagnano MW, Trousdale RT, Berry DJ. Effect of postoperative mechanical axis alignment on the fifteen-year survival of modern, cemented total knee replacements. J Bone Joint Surg Am. 2010;92(12):2143–9. 4. Bourne RB, Chesworth BM, Davis AM, Mahomed NN, Charron KD. Patient satisfaction after total knee arthroplasty: who is satisfied and who is not? Clin Orthop Relat Res. 2010;468(1):57–63. 5. Ritter MA, Davis KE, Meding JB, Pierson JL, Berend ME, Malinzak RA. The effect of alignment and BMI on failure of total knee replacement. J Bone Joint Surg Am. 2011;93(17):1588–96. 6. Bellemans J, Colyn W, Vandenneucker H, Victor J. The Chitranjan Ranawat award: is neutral mechanical alignment normal for all patients? The concept of constitutional varus. Clin Orthop Relat Res. 2012;470(1):45–53. 7. Howell SM, Howell SJ, Kuznik KT, Cohen J, Hull ML. Does a kinematically aligned total knee arthroplasty restore function without failure regardless of alignment category? Clin Orthop Relat Res. 2013;471(3):1000–7. 8. Dossett HG, Swartz GJ, Estrada NA, LeFevre GW, Kwasman BG. Kinematically versus mechanically aligned total knee arthroplasty. Orthopedics. 2012;35(2):e160–9. 9. Waterson HB, Clement ND, Eyres KS, Mandalia VI, Toms AD. The early outcome of kinematic versus mechanical alignment in total knee arthroplasty: a prospective randomised control trial. Bone Joint J. 2016;98-B(10):1360–8. 10. Ritter MA, Faris PM, Keating EM, Meding JB. Postoperative alignment of total knee replacement: its effect on survival. Clin Orthop Relat Res. 1994;(299):153–6. 11. McEwen HM, Barnett PI, Bell CJ, Farrar R, Auger DD, Stone MH, et al. The influence of design, materials and kinematics on the in vitro wear of total knee replacements. J Biomech. 2005;38(5):1079–85. 12. Werner FW, Ayers DC, Maletsky LP, Rullkoetter PJ. The effect of valgus/varus malalignment on load distribution in total knee replacements. J Orthop Res. 2017;35(10):2286–92. 13. Lizaur-Utrilla A, Gonzalez-Parreño S, Martinez-Mendez D, Miralles-Muñoz FA, Lopez-Prats FA. Minimal clinically important differences and minimal detectable changes of the Knee Society Score. Knee Surg Sports Traumatol Arthrosc. 2015;23(12):3627–33.