Cartilage regeneration and long term survival in medial OA knee patients treated with HTO and OATS

Abstract

Background

Osteoarthritis (OA) of the knee, in most instances primarily, affects medial compartment of knee. Combining Osteochondral Autologous Transfer System (OATS) with Medial Open-Wedge High Tibial Osteotomy (MOWHTO) may represent an integrated approach to sustaining long-term knee functionality in OA patients.

Materials and methods

From 2009 to 2016, combined OATS and MOWHTO was performed in 66 knees of 63 patients with medial compartment knee OA. Cartilage regeneration was assessed by 2nd look arthroscopy and Knee function was assessed by knee society scoring (KSS) pre-operatively and post-operatively. The survival rate of MOWHTO plus OATS was assessed. Failure is characterized by the need to convert into total knee replacement.

Results

The KSS knee score (from 48.3 to 90.4) and function score (from 42.6 to 88.7) showed a statistically significant improvement (p-value of <0.0001) at a mean follow-up period of 9.49 years. Second look arthroscopy done at the time of implant removal showed 100 % cartilage regeneration with even hyaline cartilage regeneration in 49 out of 57 knees assessed and partial regeneration in 8 knees. The Kaplan Meier survivorship analysis was 96.7 % at the mean 9.49 years after surgery. Only 2 patients needed TKA conversion in follow-up.

Conclusion

Combining OATs and valgus MOWHTO provides good option to successfully manage patients of OA and varus malalignment. This resulted in significant improvement in knee function, lowering pain intensity, good cartilage regeneration, and a high survivorship rate for 10 years postoperatively.

1. Introduction

Knee osteoarthritis is a progressive degenerative condition characterized by structural changes to articular cartilage and subchondral bone. The prevalence of knee OA among population of 60 years of age or older is estimated to be around 13 % in females and 10 % in males.¹ The prevalence of knee OA increases to 44 % in people of age 80 years or above.² Therefore, it is crucial to identify early stage of knee OA since it is a progressive disease and early intervention can prevent further deterioration of knee joint.

High tibial osteotomy (HTO) unloads the medial compartment in varus knees and delays the progression of the OA.^3,4 After unloading, cartilage regeneration begins theoretically. On histology, this regenerated cartilage is mainly fibrocartilage which is of lower quality biomechanically when compared to hyaline cartilage.^5,6 Earlier, lateral closing-wedge HTO (LCWHTO) was the common procedure. However, with the introduction of the Tomofix™ plate led to a shift towards medial open-wedge HTO (MOWHTO). MOWHTO gained popularity among orthopedic surgeons due to its simpler surgical techniques and lower risk of neurovascular injury.⁷

Isolated HTO yields favorable midterm outcomes but exhibits radiographic and clinical deterioration of cartilage as well as mechanical axis over the long term. Numerous studies have highlighted the superior clinical efficacy of combining knee osteotomy with cartilage regeneration procedure.^8,9

Various methods of cartilage regeneration are the Osteochondral Autograft Transfer System (OATS), Microfracture, Autologous Chondrocyte Implantation (ACI), Stem cell therapy, Platelet-rich plasma, etc.^8,9 OATS has proven to be particularly effective because it predominantly regenerates hyaline cartilage unlike fibrocartilage produced by most other methods.⁹ There are studies which use the cartilage regeneration techniques (like OATS) for early OA knee as a standalone procedure but chances of failure of OATS alone are high up to 5-times.^3,10 So, it is used as an adjunct to HTO in this study.

Therefore, the objective of this study was to assess the survival rates and long term outcomes and to assess the regeneration of the articular cartilage arthroscopically at 2 years follow-up in patients undergoing combined MOWHTO and OATS. The hypothesis is that unloading of medial compartment by HTO provides a favorable mechanical environment to promote biological repair of incorporated OATS in the damaged part of knee and improve the longevity of the joint.

2. Materials and methods

2.1. Patients

It was a retrospective case series, conducted from 2009 to 2016, on 66 knees of 63 patients at our institution. Out of these, there was follow-up loss of 5 patients. Three patients (three knees) were died, before completion of minimum follow-up, to causes unrelated to the surgery. Two patients (two knees) follow-up was lost before reaching the minimum follow-up duration of five years. The remaining population consisted of 61 knees in 58 patients, including 20 men (21 knees) and 38 women (40 knees). The mean age of the study population was 65.1 years at the time of surgery (range, 30–87 years) (Fig. 1).

Fig. 1.

Flow chart of the patient selection in the study.

Follow-up assessments were performed regularly, first at 6 weeks, and then at 3, 6, 9, and 12 months post-operatively, followed by evaluations every 1–2 years subsequently. Patients who missed scheduled follow-up appointments were contacted via telephone. Additionally, two nurses and one physician undertook efforts to locate and visit non-responding patients. The clinical evaluation was assessed using the Knee Society (KSS) knee score and function (F) score. The radiological assessment measured the anatomical tibio-femoral angle before surgery and two years after the operation.

Inclusion criteria: Medial compartmental OA knee, and an intact lateral compartment or lateral compartment with grade less than 1 cartilage lesion on International Cartilage Repair Society (ICRS) grading.

Exclusion criteria: active infection of the knee, >10° anatomic varus malalignment and knee flexion contracture of >15°, patients with coronal plane instability >10° on a stress view and patients of anterior cruciate ligament (ACL) insufficiency.

2.2. Pre-operative planning

The mechanical axis was employed to assess the alignment of the knee and to ascertain the required degree of correction with patient standing on afflicted limb with the knee in full extension. The points on tibial plateau was described as a percentage of the tibial condyle's width where 0 % was defined as most medial point on tibial plateau while 100 % was defined as most lateral point of the plateau. We performed HTO to align the mechanical axis so that it passed at 62 % from the medial edge. The amount of preoperative correction was assessed using the Miniaci technique on full-leg weight-bearing radiographs with the patella oriented forward.¹¹

2.3. Surgical procedure

Diagnostic arthroscopy was done to evaluate the articular cartilage and to perform OATS in every patient undergoing HTO (mini-open surgery was performed in some difficult to approach cases for OATS harvesting). To assess cartilage degeneration, the condition of the articular cartilage was classified as per the ICRS grading system. Using the cylindrical hollow chisel, osteochondral autograft were harvested, ranging from 6 mm to 8 mm, from lateral facet of trochlea above the sulcus terminalis and securely transferred in a “press-fit manner” into the prepared lesion site. The number of cylinders transplanted varied depending on the area of the defect. After arthroscopy, MOWHTO was performed using TomoFix™ plate. A porous tricalcium phosphate (β-TCP) wedge was used for insertion at the osteotomy gap which not only provides structural stability but also helps in bone union.

Complications after surgery were retrospectively analyzed using patient charts and it included issues such as infections, non-union, and correction failure (either revarization or overcorrection). The failure is defined as conversion of the above procedure into total knee arthroplasty (TKA).

2.4. Second-look arthroscopic evaluation

Before and approximately 2 years after MOWHTO, the implanted cartilage was re-examined via arthroscopy. For the assessment of cartilage regeneration, the regenerated cartilage is categorized into two distinct grades. Grade 1 indicated an absence of regenerative change, whereas Grade 2 encompassed a range from white scattering to partial or even complete coverage of articular cartilage. Furthermore, the “maturation” of cartilage regeneration is characterized by even coverage. Conversely, “immaturation” was identified either as white scattering or only partial coverage.⁶

2.5. Statistical analysis

We performed paired t-tests to compare preoperative Knee Society (KSS) knee scores and function scores with their respective scores at the latest follow-up. Kaplan-Meier survival analysis was employed to evaluate all knees with a minimum 10-year follow-up, using conversion to total knee arthroplasty as the endpoint. Statistical analyses were conducted using SPSS version 20.0 (SPSS, Chicago, IL, USA)

3. Results

A total of 66 knees were operated (27 were right and 39 were left), out of which 42 were females and 21 were males. Mean defect size after arthroscopic debridement was found to be 22.94 mm diameter (range 9 mm–54 mm). They were analyzed clinically for a mean follow-up period of 9.49 years and statistically significant improvement was seen in mean KSS knee score from 48.3 (±9.81) to 90.4 (±9.48) and KSS function score from 42.6 (±15.93) to 88.7 (±12.97) with a p-value of <0.0001. Mean correction of 7° was seen between pre-operative anatomical femoro-tibial angle (pre-op FTA) and post-op FTA. Except for 9 knees in which there was no second-look arthroscopy, we found even coverage in 49 knees out of 57 knees (86 %), partial coverage in 8 knees (14 %) and 0 knees with no coverage (Table 1).

Table 1.

Descriptive analysis of patients included in the study.

Descriptive analysis	N	Minimum	Maximum	Mean	Standard deviation
Age (in years)	61	30.00	87.00	65.1148	9.65246
Height	61	146.00	181.00	161.9672	7.46540
Weight	61	50.00	105.00	66.4426	10.29648
BMI	61	20.04	36.78	25.2744	3.10594
Follow-up (in years)	61	4.00	15.00	9.49	1.903
Pre-KSS	61	30.00	70.00	48.2787	9.81008
Pre-FTA	61	−6.00	9.00	2.6885	2.94698
Post-FTA	61	5.00	15.00	9.7705	1.82020
Pre-KSS function	61	00	70.00	42.6230	15.93232
Post-KSS	61	51.00	100.00	90.3934	9.47853
Post-KSS function	61	50.00	100.00	88.6885	12.97117

The mean chance of survival rate during 15 years was 96.7 % (95 % confidence interval, 0.956–0.979), with two patients requiring conversion to TKA (Fig. 2). The first conversion was necessitated by a chronic ACL tear and an increased posterior tibial slope post-operatively. The second was due to complications from donor site morbidity, specifically trochlear cartilage detachment and the progression of patello-femoral arthritis.

Fig. 2.

Kaplan-Meier survival curve with conversion of total knee arthroplasty as the end point shows the 96.7 % chance of survival rate during 15 years (95 % confidence interval, 0.956–0.979).

4. Discussion

Adjusted to follow-up period, the KSS knee score showed an improvement of 42 points and KSS function score showed an increase in 46 points. Donor site morbidity was present in 6 cases which was seen when more than 3 OATS were harvested from the donor site and the size of a single graft was more than 8 mm in diameter and 2 cases required conversion to TKA. TKA conversion was done in 1st case due to increased posterior tibial slope and history of chronic ACL tear while in 2nd case it was due to donor site morbidity with trochlear cartilage detachment and patella-femoral arthritis progression (Fig. 3, Fig. 4a, Fig. 5).

Fig. 3.

Donor site morbidity in a patient with number of OATS graft more than 3.

Fig. 4a.

b, 4c and 4d: Arthroscopic and post-op MRI findings of a patient with donor site morbidity resulted in TKA conversion after progression of patella-femoral osteoarthritis.

Fig. 5.

Post-operative X-ray of a patient with Patella-femoral osteoarthritis.

The literature presents a variety of techniques for cartilage regeneration, including autologous chondrocyte implantation (ACI), microfracture, subchondral bone drilling, stem cell therapy, bone marrow concentrate, and abrasion chondroplasty.^8,9 However, above methods predominantly facilitate the regeneration of fibrocartilage (except ACI), which is of a lower biomechanical quality as it does not exhibit the requisite load-bearing, also, the durability of fibrocartilage hardly spans 1–2 years; beyond this, it becomes susceptible to damage.^9,12 Furthermore, techniques such as ACI necessitate a two-stage procedure that is both complex and costly. Therefore, in summary, combining OATS with MOWHTO not only improves the joint's longevity and biology but also proves to be economical for patients.

In terms of cartilage regeneration, our study demonstrated superior outcomes with the OATS and MOWHTO combination, showcasing 100 % cartilage regeneration upon second-look arthroscopy. Specifically, we achieved complete hyaline cartilage coverage in 86 % of cases and partial coverage in 14 % cases (Fig. 6). These results significantly surpass those reported in other studies focusing on HTO alone or combined with different cartilage regeneration techniques.

Fig. 6a.

and b: Arthroscopic findings before OATS and after 2 years during second look arthroscopy resulted in even coverage articular cartilage.

Mukai et al. compared combined OATS and HTO with OATS alone and found that for a mean defect area of 4.45 cm² in OATS plus HTO cases, the mean regeneration was 44.9 %, whereas for an average defect of 3.54 cm² in OATS alone cases, the regeneration was 48.3 %. These results, while promising, do not match the complete regeneration rates observed in our study.¹³

Kim et al. also assessed the outcomes of OWHTO with 2nd look arthroscopy conducted after 2 years. Among the total of 104 knees, 52 % exhibited improved cartilage on the medial femoral condyle (MFC), while 35 % showed cartilage improvement on the medial tibial plateau (MTP). Some studies with LCWHTO showed less than 50 % even cartilage regeneration.¹⁴

Jung et al. reported that combining subchondral drilling with MOWHTO achieved complete fibrocartilage regeneration in 10 % of patients, partial regeneration in 57 % cases, while white scattering in 33 % instances. In comparison, the HTO-only group showed complete coverage in 3 % cases, partial coverage in 55 % cases, white scattering cartilage in 35 % cases, and no regeneration in 7 % cases. Additionally, cartilage maturation was observed in only 4 % of femur condyle cases and 1 % of tibial condyle cases.⁶ Schuster et al. also performed MOWHTO, subchondral arthroplasty, and microfracture in patients of medial knee OA. On second-look arthroscopy, good cartilage regeneration was seen in 50 % while excellent regeneration was seen in 25.8 % case on the tibial surface, and on the femoral surface it was 48.1 % and 39 %, respectively.¹⁵

Stem cell therapies have also shown potential. For instance, Koh et al. compared MOWHTO combined with PRP and stem cell therapy to MOWHTO with PRP alone. At a follow-up of 19.8 months, grade 2 regeneration was seen in 50 % of the combined therapy group, compared to 10 % in the PRP-alone group.¹⁶ Lastly, Onoi et al. investigated second-look findings after the injection of adipose-derived regenerative cells in OA knee patients. They found that up to 62 % of healed cartilage was abnormal, with only 9 % showing normal healing. These results highlight the challenges faced with some regenerative techniques, emphasizing the superior outcomes achieved with our OATS and MOWHTO combination.¹⁷

Comparative studies on HTO alone have shown varied survival rates over time. Panell et al. found survival rate 56 % at 10 years among 1576 patients of MOWHTO alone.¹⁸ Lau et al. reported an 87.1 % chance of survival over a follow-up of 13.4 years for MOWHTO, with TKA conversion needed in 4 out of 31 patients.¹⁹ Hui et al. observed 79 % survival rates at 10 years.²⁰ Similarly, Miettinen et al. noted survival rates of 78 %, and 61 % at 10, and 14.5 years for MOWHTO.²¹

When comparing HTO combined with cartilage regeneration methods, Schuster et al. found an 81.7 % survival rate after a mean of 12 years follow-up for patients treated with arthroscopic abrasion and HTO.¹⁵ Sterett et al. also reported survival rate of around 90 % at 7 years for patients undergoing HTO and microfracture.²² Bode et al. reported an overall survival rate of 87.2 % for HTO alone in patients with medial OA, 89.5 % in ACI plus HTO group compared to 58.3 % in ACI only group.²³ Minzlaff et al. performed OATS plus HTO in 74 knees (mean age 38 years) for focal chondral defects, they found survival rate of 90 % at mean of 8.5 years follow-up.²⁴ Aubin et al. took fresh femoral osteochondral allograft (OCA) in 72 patients (OCA plus osteotomy in 41 patients) for osteochondral knee lesion and found 85 % survival rate of graft at 10 years and 74 % graft survival rate at 15 years follow-up.²⁵ León et al. (OCA plus osteotomy) reported 43.3 % reoperation rate after a mean 11.4 years follow-up with TKA conversion in 23.3 % cases.²⁶

Ferruzzi et al. in their study on 56 patients found significant improvement in patients with HTO alone, and HTO plus ACI group when compared with HTO plus Microfracture group. However, overall survival rate was 89.2 % with a follow-up of 11 years but among all the groups, Microfracture group has 16.7 % failure rate compared to 11.1 % failure rate in ACI group and 5 % failure rate in HTO alone group.²⁷ It could be due to already damaged subchondral bone unable to induce sufficient bone marrow stimulation required for cartilage regeneration. Therefore, the authors suggest that advanced age, extensive degenerative joint lesions, and significant involvement of subchondral bone and synovial tissue serve as contraindications for cartilage regenerative procedure.

The majority of research in the literature focuses on techniques of cartilage regeneration in younger individuals with osteochondral lesions unlike our study on older cohorts with OA knee. Still, our study surpasses previous research in terms of both cartilage regeneration and long-term survival rates.

Author's valuable insight: Our positive outcomes can be attributed to the regeneration of hyaline cartilage and the appropriate restoration of the axis. This single-step procedure involves the transplantation of native hyaline cartilage and cancellous bone, yielding favorable long-term clinical outcome which makes it more economical than other sophisticated procedures.

Donor site morbidity can be reduced by ensuring the size of OATS harvest does not exceed 8 mm in diameter and the quantity of grafts procured does not surpass three.

4.1. Limitation

The limitation of our study is that it was a retrospective study, lack of a control group and the number of participant in the study is less. A comparative study evaluating the percentage of cartilage regeneration, by incorporation of OATS, between LCWHTO and MOWHTO holds promise as a valuable field for future research.

5. Conclusion

In conclusion, our study indicates that the combination of OATS and MOWHTO not only enhances joint longevity and biological function but also proves to be more effective and economical compared to other cartilage regeneration techniques combined with HTO. This approach shows significant advantages in both survival rates and cartilage regeneration, positioning it as a superior treatment option for patients with symptomatic medial compartmental knee OA.

Funding/sponsorship

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

Institutional ethical committee

Institutional Ethical Committee Approval was taken for this study.

Patients’ consent

Written consent was taken from every patients for inclusion in the study.

CRediT authorship contribution statement

Woon-Hwa Jung: Conceptualization, Methodology, Validation, Formal analysis, Investigation, Writing – review & editing, Supervision. Vaibhav Sahu: Conceptualization, Writing – original draft, Writing – review & editing, Investigation. Minseok Seo: Conceptualization, Investigation. Ryohei Takeuchi: Writing – review & editing, Supervision.