Highlight
– Medial opening-wedge high tibial osteotomy (HTO) reduced 2-year medial tibiofemoral cartilage loss (2% vs 9%) compared with nonsurgical care, exceeding the pre-specified minimal clinically important difference (MCID).
– HTO produced a large, clinically meaningful improvement in patient-reported outcomes (mean KOOS change 24.95 vs 9.06; between-group difference 15.9 points [95% CI, 8.94–22.84]), exceeding the KOOS MCID of 10 points.
– Results were consistent in both randomized and parallel preference arms, supporting HTO as an effective structure-preserving option for selected patients with medial-compartment knee osteoarthritis and varus alignment.
Background and Unmet Need
Knee osteoarthritis (OA) is a leading cause of pain, disability, and reduced quality of life worldwide. A common mechanical phenotype is varus malalignment producing medial-compartment overload, accelerated cartilage degeneration, and symptomatic disease localized to the medial tibiofemoral compartment. For younger or active patients with unicompartmental disease, joint-preserving alignment surgery—most commonly high tibial osteotomy (HTO)—has long been proposed to offload the medial compartment, redistribute load to the healthier lateral compartment, relieve pain, and delay or avoid total knee arthroplasty (TKA).
Despite decades of surgical experience and observational data suggesting benefit, high-quality randomized evidence with structural endpoints (e.g., quantitative cartilage change on MRI) has been limited. The randomized trial by Birmingham and colleagues (Ann Intern Med. 2025) addresses this gap by assessing the effect of medial opening-wedge HTO on cartilage thickness and clinical outcomes in adults with symptomatic medial-compartment OA and varus alignment.
Study Design
This was a single-center, open-label, assessor-blinded randomized trial with a parallel preference arm (ClinicalTrials.gov NCT02003976) enrolling 145 adults with varus alignment and symptomatic, predominantly medial compartment knee OA. Participants either underwent medial opening-wedge HTO plus a standardized nonsurgical program or received the standardized nonsurgical program alone (control). The nonsurgical program included supervised therapeutic exercise for 3 months, nutrition counseling, and as-needed acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs).
The trial specified a primary structural endpoint of 2-year change in medial tibiofemoral articular cartilage thickness measured on masked 3-Tesla MRI. A 6.3% cartilage loss was defined a priori as the minimal clinically important difference (MCID) for the structural endpoint. A key secondary (patient-centered) outcome was change in the total Knee Injury and Osteoarthritis Outcome Score (KOOS; range 0–100), with an MCID of 10 points.
Key Results
Follow-up at 2 years was robust: 83% of randomized participants and 88% in the preference arm were assessed at baseline and 2 years. Analyses were reported separately for the randomized and preference arms and were also directionally consistent.
Primary structural outcome
In the randomized arm, mean 2-year change in medial tibiofemoral cartilage thickness was −0.07 mm in the HTO group (representing a 2% loss) versus −0.25 mm in controls (a 9% loss). The mean between-group difference in absolute thickness was 0.18 mm (95% CI, 0.18 to 0.19 mm). Interpreting these numbers relative to the predefined MCID (6.3% loss), the control group exceeded the MCID for cartilage loss (9% loss), whereas the HTO group did not (2% loss). In other words, HTO limited cartilage loss to below a prespecified clinically important threshold while controls experienced clinically meaningful progression of cartilage thinning.
Patient-reported outcomes
Change in the total KOOS at 2 years strongly favored HTO. Mean KOOS change was 24.95 points in the HTO group versus 9.06 points in controls, yielding a between-group difference of 15.89 points (95% CI, 8.94 to 22.84). This exceeds the established KOOS MCID of approximately 10 points and indicates a clinically meaningful symptomatic benefit associated with HTO, encompassing pain, function, and quality-of-life domains captured by KOOS.
Consistency and preference arm
Results in the parallel preference arm—where patients chose their treatment—were directionally consistent and supported benefit from HTO in both structural and clinical outcomes. Consistency across randomized and preference cohorts strengthens the plausibility of an HTO effect while acknowledging potential selection biases inherent to the preference design.
Safety and adverse events
The trial report as summarized here emphasizes efficacy outcomes; detailed adverse event rates were not provided in the supplied summary. In general, HTO is associated with surgical risks including wound complications, infection, delayed union or nonunion, neurovascular injury, symptomatic hardware, and the potential need for subsequent surgeries including conversion to TKA. The balance of symptom and structure benefit against these surgical risks is central to individual decision-making.
Interpretation and Clinical Implications
This trial provides higher-level evidence that medial opening-wedge HTO in appropriately selected patients with varus-aligned, predominantly medial compartment knee OA can both slow structural progression (as measured by MRI cartilage thickness) and produce substantial symptomatic improvement at 2 years when compared with optimized nonsurgical management.
Key clinical takeaways include:
- HTO produced a between-group cartilage preservation effect that translated into a clinically meaningful difference relative to a prespecified MCID: control knees experienced cartilage loss exceeding the MCID while HTO-treated knees did not.
- The symptomatic benefit measured by KOOS was large and clinically important (≈16-point advantage), suggesting that structural preservation translated into meaningful patient benefit over 2 years.
- Consistency across randomized and preference arms strengthens external validity, although the nonrandomized arm cannot substitute for randomization.
Who might benefit most?
The ideal HTO candidate typically is younger or middle-aged (often <65 years), relatively active, has isolated or predominant medial-compartment OA with varus alignment, reasonable range of motion, and sufficient quality of the remaining cartilage and ligaments. Patient expectations, functional goals, and willingness to undergo rehabilitation after osteotomy are also important. For patients with diffuse tricompartmental disease or severe lateral compartment involvement, HTO is unlikely to be beneficial.
Strengths
- Randomized, assessor-blinded design with a prespecified structural primary endpoint assessed on high-field (3-T) MRI.
- Parallel preference arm adds pragmatic context and supports external validity.
- Use of both structural and patient-reported outcomes with pre-specified MCIDs facilitates interpretation of clinical relevance.
Limitations and uncertainties
- Single-center study — operative technique, patient selection, and rehabilitation protocols may not be generalizable to all centers and surgeons.
- Open-label intervention — while MRI assessors were blinded, participants and treating clinicians were not, introducing possible performance or expectation effects for patient-reported outcomes.
- Two-year follow-up — important longer-term outcomes (durability of cartilage preservation, survivorship free of conversion to TKA, and late complications) remain unknown.
- Detailed safety and complication data were not summarized here; full appraisal requires trial safety tables and longer safety follow-up.
- Absolute MRI cartilage-thickness differences, while statistically significant and clinically interpreted via MCID, require cautious translation into long-term joint survival predictions.
Expert commentary and guideline context
This trial fills a key evidence gap by linking HTO to objective structural preservation and large symptomatic gains in a randomized setting. Current osteoarthritis guidelines (e.g., OARSI) emphasize nonpharmacologic care—weight management, exercise, and education—as foundational, with procedural interventions considered after optimizing conservative care. For selected patients who fail to achieve durable benefit from conservative measures and who have a mechanical varus phenotype, HTO emerges from this study as a credible joint-preserving option that can be discussed alongside alternatives such as unicompartmental or total knee arthroplasty depending on age, activity, and disease extent.
Research and practice gaps
Future work should address longer-term outcomes including conversion rates to arthroplasty, implant-related complications, cost-effectiveness, optimal osteotomy magnitude and fixation strategies, and comparative effectiveness versus unicompartmental arthroplasty in head-to-head trials for appropriately matched patients. Multi-center trials would strengthen generalizability across different surgical volumes and techniques.
Conclusion
In adults with varus alignment and symptomatic medial-compartment knee OA, medial opening-wedge HTO plus optimized nonsurgical care reduced 2-year medial cartilage loss to below a prespecified clinically meaningful threshold and produced large, clinically meaningful improvements in patient-reported outcomes versus optimized nonsurgical care alone. These findings support HTO as an effective joint-preserving option for carefully selected patients, while emphasizing the need for individualized risk–benefit discussions and longer-term data.
Funding and trial registration
Primary funding: Canadian Institutes of Health Research, Arthritis Society Canada, and Bernard and Norton Wolf Family Foundation. ClinicalTrials.gov: NCT02003976.
References
1. Birmingham TB, Primeau CA, Moyer RF, Bryant DM, Ma J, Leitch KM, Wirth W, Degen R, Getgood AM, Litchfield RB, Willits KR, Eckstein F, Giffin JR. High Tibial Osteotomy for Medial Compartment Knee Osteoarthritis: A Randomized Trial With Parallel Preference Arm. Ann Intern Med. 2025 Sep;178(9):1238-1248. doi: 10.7326/ANNALS-25-00920. PMID: 40720836.
2. Bannuru RR, Osani MC, Vaysbrot EE, Arden NK, Bennell K, Bierma-Zeinstra S, et al. OARSI guidelines for the non-surgical management of knee osteoarthritis. Osteoarthritis Cartilage. 2019 Nov;27(11):1578-1589. doi: 10.1016/j.joca.2019.06.011.
