High tibial osteotomy combined with cartilage restoration: A systematic review of clinical outcomes and prognostic factors

Abstract

Background

Focal chondral defects are often treated with cartilage restoration procedures. Malalignment often accompanies chondral defects. High tibial osteotomy (HTO), classically utilized to treat uni-compartmental knee osteoarthritis, corrects malalignment. HTO combined with cartilage restoration procedures can treat uni-compartmental osteoarthritis and focal chondral defects.

Purpose

To assess outcomes of combined HTO and cartilage restoration procedures and review prognostic factors that may assist in preoperative planning and patient counseling.

Study design

Systematic Review of published literature.

Methods

A systematic review of PubMed and Scopus was performed following PRISMA guidelines. Thirty-four papers were included in qualitative considerations.

Results

Thirty-four papers that reported the combined outcome of HTO and cartilage repair were included. Twenty of the 34 included papers reported prognostic factors that affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee osteoarthritis. Cartilage repair techniques that were combined with HTO and included in this review are bone marrow stimulation, allograft transplantation, osteochondral autograft transplantation, autologous chondrocyte implantation, and mesenchymal stem cell implantation.

Conclusions

HTO with adjunctive cartilage repair procedures improve clinical outcome scores and restore alignment in patients with medial compartment osteoarthritis and isolated focal chondral defects. HTO with adjunctive cartilage procedures produces optimal results in younger, non-obese patients with focal chondral defects and varus malalignment, without significant lateral compartment and patellofemoral involvement.

1. Introduction

Management of isolated cartilage defects in the knee is challenging. These injuries are painful and impair participation in sport and everyday activities. There are numerous treatment options for managing this type of cartilaginous lesion including microfracture (MFX), allograft transplantation, autograft transplantation, autologous chondrocyte implantation (ACI), and mesenchymal stem cell (MSC) implantation. Frequently these injuries are associated with ligamentous or meniscal damage, further complicating treatment and recovery. Malalignment is present in approximately half of cases with isolated cartilage defects and has been significantly associated with failed cartilage restoration attempts.¹ A varus knee, which overloads the articular cartilage of the medial compartment and may lead to medial compartment osteoarthritis, is the most prevalent malalignment. High tibial osteotomy (HTO), developed by Jackson et al. and later improved upon by Coventry to treat uni-compartmental osteoarthritis (OA), unloads the medial compartment thus decreasing pain associated with weight bearing.^2,3 This change of the weight-bearing axis can augment the biological effect of a chondral restoration procedure. The amount of recommended valgus correction, represented by a mechanical axis shift to a point that effectively unloads the involved compartment, varies in reported studies. In a biomechanical study, Mina et al. suggests an optimal correction angle of three to four degrees valgus.⁴ Interestingly, the incorporation of HTO with chondral restoration has been reported in patients with focal cartilage defects and those with uni-compartmental OA.5, 6, 7, 8, 9, 10, 11, 12 This article aims to assess clinical outcome scores of HTO combined with various cartilage restoration procedures and to review prognostic factors that may affect the outcome of this procedure in order to assist in preoperative planning and patient counseling.

2. Methods

In this systematic review, we searched PubMed and Scopus from their inception through December 2023 following PRISMA guidelines. Search keywords included “high tibial osteotomy”, “cartilage”, “bone marrow stimulation”, “microfracture”, “abrasion”, “osteochondral autograft transplantation”, “allograft”, “autologous chondrocyte implantation”, and “mesenchymal stem cell”. Only papers in the English language and those involving human subjects were included in the initial search. Two authors were involved in the paper selection process. Any discrepancies regarding study inclusion were decided by the senior author.

3. Results

Four-hundred sixty-seven papers from PubMed and 698 papers from Scopus fit the search criteria. There were 530 papers after removing duplicates. The abstract and title of the papers were reviewed, and papers that did not evaluate HTO combined with cartilage repair procedures were excluded. With the remaining papers, we performed a manual search of the references of the papers discussing combined HTO and cartilage restoration procedures. Ultimately, we found 34 papers that reported the outcome of combined HTO and cartilage repair (Table 1). However, some of the studies reported the radiological and histological outcome and did not mention the clinical outcome, while some of them did not consider the combined HTO and chondral repair patients as a distinct group. Among the 34 included papers, 20 papers also discussed prognostic factors which affected the success or failure of combined HTO and cartilage repair surgery for focal articular defect and uni-compartmental knee OA (Table 2). Overall, included in this review are 14 papers evaluating HTO and bone marrow stimulation (BMS) techniques, 6 papers utilizing allograft transplantation and HTO, 3 osteochondral autograft and HTO papers, 6 studies that combined ACI and HTO, and 7 MSC and HTO papers (Fig. 1).

4. Discussion

This systematic review aims to summarize the clinical outcomes after combined HTO and different chondral repair techniques. Also, prognostic factors for combined HTO and chondral repair procedures were extracted from the studies to help the surgeon in planning and decision making. There are several papers that demonstrate good outcomes after HTO and cartilage repair for focal chondral lesions as well as medial compartment osteoarthritis with reported different correction angles. Mina et al. reported three to four degrees valgus optimal correction angle from a biomechanical standpoint.⁴

4.1. Pathophysiology

Untreated malalignment is a major reason that focal cartilage defect repair fails. In allograft transplantation, the failure rate is five times higher in patients with malalignment.⁹ In normal knee alignment, up to 60% of the compressive load is distributed across the medial compartment. With a varus knee deformity, this load increases up to 80–90%.²⁴ Normal cartilage requires some pressure and mechanical stimulus for proper function and regeneration, but additional pressure can be pathologic and thus must be mitigated for effective repair to occur. Abnormally high pressure in the rim of chondral defects, defined as rim stress concentration, may interfere with cartilage repair by chondrocytes and increase the rate of apoptotic death of viable chondrocytes around the lesion, perpetuating progression to diffuse OA over time.⁴ Mina et al. demonstrated that effective medial compartment unloading was achieved with six to ten degrees of valgus alignment. The authors proposed that correcting the alignment to six to ten degrees of valgus in patients with medial compartment OA may therefore improve functional outcomes. However, this valgus alignment can overload the lateral compartment and is not a reasonable solution for patients with a solitary focal chondral defect. For these patients, correction to neutral or slight valgus is preferred with correction of knee alignment to zero to four degrees.⁴

Lesion size is also an important component to consider in planning for HTO for the patient with a focal cartilage defect. Guettler et al. reported that stress from an osteochondral defect up to 8 mm in diameter will be carried within the meniscus and thus, there will be no stress concentration around lesions of this small a diameter. However, osteochondral lesions greater than 10 mm have been shown to contain rim stress. According to Guettler, HTO is optimally indicated for defects of 10 mm or more in patients with an intact meniscus.³¹

Lesion location in the knee can also influence outcome. Femoral lesions have better clinical outcomes than tibial lesions. This can be attributed to the alteration of the loading site with flexion and extension in the femoral condyle, as compared to the nearly constant loading over the tibial condyle throughout the range of motion. Also, meniscus function is more important in distributing the load across the tibial plateau, so meniscus degeneration may have a greater effect on outcomes of repaired tibial lesions.⁵

4.2. Indications, contraindications and planning

The general indications for combining HTO with cartilage restoration surgery include a localized medial compartment cartilage defect (Outerbridge grade three or four) and varus deformity in an active patient for whom prosthetic arthroplasty is not indicated due to age or desired activity level. The inclusion criteria regarding severity of varus deformity reported in the reviewed studies varied from one to more than five degrees.^12,23,24 Sterett et al. considered patients with varus deformity greater than five degrees, in the absence of meniscus degeneration, as candidates for HTO. In patients with diffuse meniscus degeneration, smaller varus deformity was actually considered an indication for HTO.¹² Minzlaff et al. included patients with varus deformity greater than two degrees while Bode et al. included patients with varus deformity of one to five degrees as surgical candidates.^9,24 Several studies considered HTO if a varus deformity of at least three degrees was present.^10,25,27 Schuster et al. found that more than 53% of their cases had concomitant complete or subtotal resection of the medial meniscus.¹⁵ Bauer et al. used a defect size of 2–14 cm² as inclusion criteria while Sterett et al. did combined HTO and cartilage repair for localized lesions with varus deformity including those smaller than 2 cm^12,23

A wide range of patient ages have been included in reports of HTO ranging from 19 to 70 years.^9,23

Minzlaff et al. considered the young and active patient for HTO and cartilage repair.²² They included patients between the ages of 19–62. Overall, however, an average age range of 40–60 was most frequently reported in the literature.^23,26 Despite patient age, inclusion criteria consisting of only medial knee pain was considered an appropriate indication for combined HTO and cartilage repair in some papers.^6,12 Failed previous chondral surgical repair was another cited indication for inclusion of HTO.⁶

Not surprisingly, concurrent involvement of the patellofemoral or lateral compartments in the knee was one of the contraindications to HTO surgery in multiple papers.^32,33 A ‘kissing lesion’ with involvement of the corresponding tibial side of the joint across from a focal femoral osteochondral defect was also considered a contraindication to combined HTO and cartilage restoration.^9,24 That being said, Bauer et al. included 15 cases with ‘kissing lesions’ and 15 cases with patellofemoral cartilage lesions (grade two to three) in their study. These authors instead considered total loss of medial joint space and full-thickness lateral or patellofemoral chondral lesions as contraindications.²³ Schuster et al. included patients with anterior compartment pain and did not consider trochlear or patellar cartilage defects as contraindications.¹⁵

Flexion contracture exceeding ten degrees, knee range of motion less than 90°, and a history of fracture in the lower extremity of the affected knee were considered contraindications in the Bode et al. study.²⁴ These conditions individually are generally contraindications to HTO, whether or not cartilage restoration is intended.

Body mass index (BMI) greater than 35 kg/m² and extensive loss of the lateral meniscus were contraindications in the Schuster et al. study. Wong et al. excluded cases with varus deformity originating from the femoral side. Additionally, they did not consider HTO and stem cell therapy for patients with a joint line congruity angle greater than two degrees.³⁰ HTO in patients with inflammatory disease was contraindicated according to Ferruzzi et al.²⁶

4.3. Surgical planning

In planning tibial osteotomy surgery, Sterett et al. proposed beginning with arthroscopic evaluation and if the lesion was determined to be a grade three or four, smaller than 2 cm in the medial compartment, and without diffuse grade four changes, then HTO would be performed. The goal was achieving neutral alignment in their study. A combined abrasion to remove sclerotic subchondral bone and improve the cartilage repair with HTO was described.¹²

Minzlaff et al. utilized arthroscopic evaluation to determine whether to perform HTO and to aid in defining the amount of correction based on differences in chondromalacia between medial and lateral compartments. In the presence of a grade four Outerbridge cartilage degeneration in the lateral compartment, they chose to avoid HTO. In the presence of lateral femoral condyle grade three changes, they corrected the alignment to neutral, for grade two changes they corrected to two degrees valgus and for all others, corrections to four degrees valgus were performed.⁹

If a previous partial lateral meniscus resection was present, Schuster et al. performed a slight under-correction versus their standard goal of the mechanical axis intersecting the tibial plateau at 62% of the mediolateral tibia diameter, which they performed in patients with an intact lateral meniscus and intact chondral surface.^15,16

Hsu et al. considered correction to neutral for small lesions, and if medial compartment OA was present, they overcorrected the alignment to the lateral tibial eminence.⁶ The goal of correction was zero to three degrees valgus in the Bauer et al. study.²³ The median valgus angle after HTO was four degrees in Ferruzzi et al.’s study with two to eight degrees of valgus as the goal.²⁶ The mean valgus angle after HTO was eight degrees in the study reported by Bode et al.²⁴

4.4. Prognostic factors and causes of failure

An integral part of planning these complex surgeries is appropriate patient selection. Pre-operative planning should include a complete discussion of possible outcomes of surgery and a description of expectations based on patient characteristics. There are several cartilage repair procedures used in combination with HTO in the studies we reviewed. The prognostic factors that affected the results and predisposed to failures were evaluated.

Several studies reported the outcome of combined HTO and microfracture or abrasion in uni-compartmental knee OA.^5,7,8,10, 11, 12, 13, 14, 15, 16, 17^,34

Sterett and Schultz showed that cartilage repair outcomes improved by combining HTO with cartilage repair in medial uni-compartmental OA.^12,16 However, other literature suggests that clinical results in medial uni-compartmental OA may not change in this group compared to HTO alone.^5,7,35 Lee et al. concluded in a meta-analysis that combined HTO and cartilage restoration has little beneficial effect on the radiologic and clinical outcome in patients with uni-compartmental OA.³⁶ It seems that correction of the alignment with HTO is essential to achieving favorable outcomes after combined HTO and bone marrow stimulation in generalized medial uni-compartmental OA.⁵ Matsunaga et al. reported that cartilage repair was better in HTO combined with abrasion compared to HTO and microfracture.³⁵ Spahn et al. proposed a predictive scoring system for HTO in uni-compartmental knee OA. Female gender, obesity, smoking, symptoms greater than 24 months, pre-operative knee injury and osteoarthritis outcome score (KOOS) greater than 50, medial tibial exophyte, impossibility of microfracture due to severe sclerosis, medial joint space less than 5 mm, and cartilage defect international cartilage research society (ICRS) grade four on the tibial side were all correlated with poor outcomes.³⁷

Concerning focal cartilage defects, in a systematic review, Harris et al. demonstrated that the survival of combined HTO with articular cartilage restoration surgery is better than HTO alone, suggesting that combined HTO and cartilage restoration in focal cartilage defects might be a preferred solution for preserving long-term knee function.³⁸ In general, clinical outcome scores improved over time for combined HTO and cartilage restoration procedures. Laprade et al. reported gradual clinical outcome improvements in the first few years post-HTO procedures.³⁹ Bode et al. reported an increasing IKDC score in the first three years after surgery and concluded that the removal of the HTO implant in 40% of the cases alleviated the discomfort and positively affected clinical outcomes.³² Meanwhile, Schuster et al. demonstrated a slight deterioration of the clinical score occurring after the peak value one year after surgery. These authors proposed that this deterioration was the result of the limited fibrocartilage durability.¹⁵

The impact of age on clinical improvement is controversial. Akizuki reported that age is the only factor that affected outcomes.⁵ Meanwhile, Miller reported that age does not correlate with success in combined HTO and microfracture surgery.⁸

Pascale et al. performed microfracture and HTO in their study. The mean femorotibial angle before surgery was 178 + 1.5 varus and changed to 184.5 + 0.9 valgus alignment after surgery. The authors concluded that the primary reason for failures was under-correction of the varus deformity.¹⁴

As previously discussed, the location of the lesion also affects the outcome of microfracture combined with HTO. Localized articular defects are more common on the femoral condyle.²³ These lesions can progress to OA. Schuster reported that the result of combined surgery is better for femoral condyle lesions. In addition, outcomes for patients with full coverage of the cartilage defect were better than partial coverage.¹⁵ Yamada et al. evaluated femoral trochlear articular cartilage after combined HTO with abrasion arthroplasty, and found improvements of degenerated femoral trochlear cartilage after the combined procedure. In the study, 18 patients with varus OA and femoral trochlear chondral lesions underwent abrasion arthroplasty of the chonral lesion in addition to open wedge HTO, followed by second look arthroscopy. 61% of patients demonstrated improved International Cartilage Repair Society graded cartilage lesions at the time of second look arthroscopy. These findings indicate that HTO can be performed without negatively impacting regeneration of trochlear lesions.⁵³

Minzlaff showed that the most significant risk factors for failure in autograft transplantation combined with HTO were high degrees of correction and advanced age. All failure cases that required conversion to total knee arthroplasty were older patients. A history of previous knee surgery was also more frequently noted in failed cases. Femoral chondral lesions had less favorable outcomes in their study. They concluded that combined autograft transplantation and HTO is a better option for younger patients.⁹ Andres et al. similarly reported poor outcomes in their study in which they performed osteochondral autograft transplantation combined with closing wedge osteotomy for four cases. They reported three failures, one due to collapse of the osteotomy site and two due to persistent pain in the knee after surgery. They postulated that the reasons for poor outcomes were prolonged non-weight bearing rehabilitation program for the healing osteotomy site and large size of cartilage defects in failed cases.²¹

Several studies showed positive results with allograft transplantation.^6,19,20 Mechanical malalignment was seen more commonly in failed allograft transplantations.⁴⁰ Hsu et al. showed a decreased failure rate of 12% and emphasized the importance of precise realignment to a neutral position for small lesions and to the lateral tibial spine for large lesions in order to maximize results.⁶ Gross et al. recommended simultaneous HTO and fresh osteochondral allograft instead of staged procedures.¹⁸ Willey et al. reported that the complication rate after combined surgery (HTO with chondral repair, meniscal transplant or ligament reconstruction) is the same as a staged operation.⁴¹ Shon et al. reported that combining particulated costal hyaline cartilage allograft with subchondral drilling in patients undergoing medial open wedge HTO improves cartilage regeneration compared to HTO with subchondral drilling alone. However, despite superior cartilage regeneration, there was no difference in clinical outcomes between the group receiving particulated costal hyaline cartilage allograft in addition to subchondral drilling, and the group receiving subchondral drilling alone.⁵⁴

Combined HTO and autologous chondrocyte implantation was explored by Bode et al. and the authors found higher survivorship and lower failure rates in the group that underwent ACI with HTO as compared to the group with ACI alone.²⁴ Reasons for revision in the HTO combined with ACI group were overcorrection (exceeding the mechanical axis on 70% of the lateral plateau), nonunion of the osteotomy site and ACI failure on magnetic resonance imaging (MRI). Bode et al. conducted a study on the result of ACI and HTO in 40 patients with mean age 36.8 SD ± 8.1 years. They performed osteotomy for cases with over two degrees of varus deformity and 10% of patients in their study needed re-operation. Overcorrection of alignment, failure of ACI on MRI and nonunion of the osteotomy site were reasons for failure.²⁵ Franceschi et al. reported one case with an abnormal IKDC outcome score among eight cases after combined ACI and HTO. The minimum varus deformity in their study was four degrees (4°–14°) and they achieved 2.8° (range 1°–4°) of valgus alignment after surgery.²⁷ Ackerman et al. performed a study comparing graft survivorship, depending on lower extremity alignment, in patients receiving HTO combined with either ACI or osteochondral allograft transplantation. Interestingly, the findings suggest that regardless if physiologic or due to HTO, neutral mechanical alignment improves graft survivorship in patients undergoing medial compartment ACI.⁵⁵

Some studies focusing on combined MSC and HTO found improvement in cartilage repair.28, 29, 30 Koh et al. compared combined MSC, platelet-rich plasma (PRP) and HTO with HTO and PRP. These authors found that cartilage repair and clinical outcomes improved in the MSC inclusive group. Curiously, they reported no correlation between patient demographics and outcome of surgery. Age did not affect outcome and they proposed that use of MSC's improves filling of the cartilage defect with fibrocartilage regardless of age and BMI or radiologic parameters.²⁸

4.5. Chondral lesions and meniscal injury in the varus knee

Treatment of a chondral lesion with concomitant meniscal injury of the knee in young patients with varus deformity is a challenging proposition. In young and high activity patients, arthroplasty is not an advisable treatment option for chondral lesions with concomitant meniscal injury due to anticipated wear, potential loosening, and ultimate need for revision. Malalignment is usually considered a contraindication for meniscal allograft transplantation (MAT). The combination of HTO with chondral restoration surgery and MAT was evaluated in some studies, and the outcome of this combined procedure was found to be comparable to isolated MAT.^42,43 Malalignment, however, is considered an important predictor of MAT failure.⁴⁴ Weber et al. proposed contraindications for this combination including coronal deformity greater than 15°, medial or lateral tibial subluxation greater than 1 cm, tricompartmental OA, limited range of motion, inflammatory arthritis, BMI greater than 35 kg/m², and smoking history. They recommended that combination surgery be reserved for patients less than 60 years old. An intact ligamentous status was also deemed necessary for this operation.⁴⁵

The amount of varus deformity correction and specifically, the goal of surgery was defined in several studies. Weber et al. demonstrated that HTO should be considered in candidates in which the mechanical axis (MA) crosses the knee in the affected compartment with varus deformity. The goal for surgery was to correct to neutral or three degrees valgus alignment. Transferring the MA to the lateral compartment unloads the meniscal allograft so it was recommended to consider HTO with MAT only in patients with neutral alignment or where neutral knee alignment could be achieved.^43,45

In planning for surgery, Harris et al. reported on chondral repair and MAT and corrected malalignment in patients with 7.5 ± 2 degrees of varus deformity to 1.2 ± 1.5 degrees of valgus. Although outcomes and survival were generally good, the reoperation rate was 56% in their case series. Among 13 reoperations, there was one total knee arthroplasty revision and one MAT and cartilage repair revision. The most common complication was arthrofibrosis.⁴⁶ However, the risk of reoperation in isolated MAT has been shown to be high, and thus it has been proposed to perform the combination in different stages to reduce the risk of reoperation.⁴⁷

Verdonk reported greater improvements in clinical outcomes in patients with combined HTO and MAT versus isolated MAT. They concluded that unloading the degenerative articular cartilage in the involved compartment not only improves graft survival but also improves the clinical outcome.⁴³

4.6. Limitations

This systematic review was subject to several limitations. The reported outcomes differed among the papers and some summary measures (standard deviations or pre- or post-means) were missing, so no single analysis was able to capture information from the same outcome for all manuscripts. We were also unable to adjust for differences in cohorts in potentially confounding variables due to a lack of consistent reporting of this data.

5. Conclusions

Patients with either focal chondral defects or medial uni-compartmental OA can be good candidates for HTO combined with cartilage restoration procedures. HTO should be considered in patients with varus malalignment greater than three to five degrees, especially in the presence of meniscal deficiency. In addition to the aforementioned chondral defect and varus deformity, the best candidates for combined HTO and cartilage restoration surgery are the following: non-obese (BMI less than 35), younger than 60 years old, localized medial knee pain, no significant degeneration of the lateral or patellofemoral compartment, knee range of motion greater than 90°, and no flexion contracture. The optimal correction angle for varus knees varies between neutral to four degrees of valgus and is dependent on the condition of the lateral compartment, the lateral meniscus, and the defect size.

Furthermore, the prognosis of the procedure is better in patients with an intact medial meniscus, a femoral condyle lesion, full coverage of the articular defect, and a precise alignment correction. A worse prognosis is associated with alignment over- or under-correction, older age, large and grade four chondral defects, nonunion of the osteotomy site, and extensive loss of the medial meniscus.

CRediT authorship contribution statement

S. Ali Ghasemi: Conceptualization, Methodology, Investigation, Writing. Evan Kolesnick: Methodology, Validation, Investigation, Data curation. Benjamin C. Murray: Conceptualization, Methodology, Writing, Visualization, Formal analysis, Resources, Data curation. Benjamin E Leiby: Data curation, Formal analysis. Arthur R. Bartolozzi: Conceptualization, Methodology, Supervision. Kenneth R. Zaslav: Conceptualization, Methodology, Supervision.

Appendix

Search Strategy: (High tibial osteotomy) AND ((cartilage) OR (bone marrow stimulation) OR (microfracture) OR (abrasion) OR (osteochondral autograft transplantation) OR (allograft) OR (autologous chondrocyte implantation) OR (mesenchymal stem cell))

Fig. 1.

Flowchart depicting search strategy. Two of the 34 included studies (Ackerman et al. Shon et al.) evaluated two different cartilage repair techniques, and thus were included in the two respective cartilage repair sub-groups.

Table 1.

Papers Discussing Patient Outcomes of HTO with Adjunctive Cartilage Techniques

Author	HTO with Bone Marrow Stimulation Techniques Paper
Akizuki5	Does arthroscopic abrasion arthroplasty promote cartilage regeneration in osteoarthritic knees with eburnation? A prospective study of high tibial osteotomy with abrasion arthroplasty versus high tibial osteotomy alone.
Jung7	Comparison of results of medial opening-wedge high tibial osteotomy with and without subchondral drilling.
Lee48	Comparison of the regeneration of cartilage and the clinical outcomes after the open wedge high tibial osteotomy with or without microfracture: a retrospective case control study
Miller8	Patient satisfaction after medial opening high tibial osteotomy and microfracture.
Niemeyer13	Open-wedge osteotomy using an internal plate fixator in patients with medial compartment gonarthritis and varus malalignment: 3- year results with regard to preoperative arthroscopic and radiographic findings
Pascale14	Do microfractures improve high tibial osteotomy outcome?
Schultz10	Articular cartilage regeneration of the knee joint after proximal tibial valgus osteotomy: a prospective study of different intra- and extra-articular operative techniques.
Schuster15	Open-Wedge High Tibial Osteotomy and Combined Abrasion/Microfracture in Severe Medial Osteoarthritis and Varus Malalignment: 5-Year Results and Arthroscopic Findings After 2 Years.
Schuster16	Ten-Year Results of Medial Open-Wedge High Tibial Osteotomy and Chondral Resurfacing in Severe Medial Osteoarthritis and Varus Malalignment.
Shon54	Particulated Costal Hyaline Cartilage Allograft With Subchondral Drilling Improves Joint Space Width and Second-Look Macroscopic Articular Cartilage Scores Compared with Subchondral Drilling Alone in Medial Open-Wedge High Tibial Osteotomy
Sterett11	Chondral resurfacing and high tibial osteotomy in the varus knee.
Sterett12	Chondral resurfacing and high tibial osteotomy in the varus knee: survivorship analysis.
Takeuchi17	Clinical results and radiographical evaluation of opening wedge high tibial osteotomy for spontaneous osteonecrosis of the knee.
Yamada53	Abrasion arthroplasty promotes improvement of degenerated femoral trochlear cartilage after medial open wedge high tibial osteotomy
Author	Allograft Transplantation and HTO Papers
Ackerman55	The Effect of Mechanical Leg Alignment on Cartilage Restoration With and Without Concomitant High Tibial Osteotomy
Gross18	Long-term follow-up of the use of fresh osteochondral allografts for posttraumatic knee defects.
Hsu6	Osteochondral Allograft Transplantation and Opening Wedge Tibial Osteotomy: Clinical Results of a Combined Single Procedure.
McCullough19	Prospective evaluation of prolonged fresh osteochondral allograft transplantation of the femoral condyle: minimum 2-year follow-up.
McDermott20	Fresh small-fragment osteochondral allografts. Long-term follow-up study on first 100 cases.
Shon54	Particulated Costal Hyaline Cartilage Allograft With Subchondral Drilling Improves Joint Space Width and Second-Look Macroscopic Articular Cartilage Scores Compared with Subchondral Drilling Alone in Medial Open-Wedge High Tibial Osteotomy
Author	HTO with Osteochondral Autograft Papers
Andres21	Treatment of osteoarthritic cartilage lesions with osteochondral autograft transplantation.
Minzlaff9	Osteochondral autologous transfer combined with valgus high tibial osteotomy: long-term results and survivorship analysis.
Minzlaff22	Can young and active patients participate in sports after osteochondral autologous transfer combined with valgus high tibial osteotomy?
Author	ACI and HTO Papers
Ackerman55	The Effect of Mechanical Leg Alignment on Cartilage Restoration With and Without Concomitant High Tibial Osteotomy
Bauer23	Knee joint preservation with combined neutralizing high tibial osteotomy (HTO) and Matrix-induced Autologous Chondrocyte Implantation (MACI) in younger patients with medial knee osteoarthritis: a case series with prospective clinical and MRI follow-up over 5 years.
Bode24	A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5°.
Bode25	Clinical outcome and return to work following single-stage combined autologous chondrocyte implantation and high tibial osteotomy.
Ferruzzi26	Cartilage repair procedures associated with high tibial osteotomy in varus knees: clinical results at 11 years' follow-up.
Franceschi27	Simultaneous arthroscopic implantation of autologous chondrocytes and high tibial osteotomy for tibial chondral defects in the varus knee.
Author	MSC and HTO Papers
Kim49	Implantation of mesenchymal stem cells in combination with allogenic cartilage improves cartilage regeneration and clinical outcomes in patients with concomitant high tibial osteotomy
Koh28	Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: A prospective study.
Lee52	Allogenic Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells Are More Effective Than Bone Marrow Aspiration Concentrate for Cartilage Regeneration After High Tibial Osteotomy in Medial Unicompartmental Osteoarthritis of Knee
Park51	Allogenic Umbilical Cord-Blood-Derived Mesenchymal Stem Cells and Hyaluronate Composite Combined with High Tibial Osteotomy for Medial Knee Osteoarthritis with Full-Thickness Cartilage Defects
Saw29	High tibial osteotomy in combination with chondrogenesis after stem cell therapy: a histologic report of 8 cases.
Song50	High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration
Wong30	Injectable cultured bone marrow-derived mesenchymal stem cells in varus knees with cartilage defects undergoing high tibial osteotomy: a prospective, randomized controlled clinical trial with 2 years' follow-up.

Table 2.

Papers Discussing Prognostic Factors of HTO with Adjunctive Cartilage Techniques

Author	Prognostic Factors for Combined HTO and Bone Marrow Stimulation Techniques for Unicompartmental Knee OA Papers
Akizuki5	Does arthroscopic abrasion arthroplasty promote cartilage regeneration in osteoarthritic knees with eburnation? A prospective study of high tibial osteotomy with abrasion arthroplasty versus high tibial osteotomy alone.
Jung7	Comparison of results of medial opening-wedge high tibial osteotomy with and without subchondral drilling.
Miller8	Patient satisfaction after medial opening high tibial osteotomy and microfracture.
Schuster15	Open-Wedge High Tibial Osteotomy and Combined Abrasion/Microfracture in Severe Medial Osteoarthritis and Varus Malalignment: 5-Year Results and Arthroscopic Findings After 2 Years.
Sterett11	Chondral resurfacing and high tibial osteotomy in the varus knee.
Sterett12	Chondral resurfacing and high tibial osteotomy in the varus knee: survivorship analysis.
Yamada53	Abrasion arthroplasty promotes improvement of degenerated femoral trochlear cartilage after medial open wedge high tibial osteotomy
Author	Prognostic Factors for Combined Procedures for Focal Lesions with Allograft Transplantation and HTO Papers
Ackerman55	The Effect of Mechanical Leg Alignment on Cartilage Restoration With and Without Concomitant High Tibial Osteotomy
Gross18	Long-term follow-up of the use of fresh osteochondral allografts for posttraumatic knee defects.
Hsu6	Osteochondral Allograft Transplantation and Opening Wedge Tibial Osteotomy: Clinical Results of a Combined Single Procedure.
Author	Prognostic Factors for Combined Procedures for Focal Lesions with HTO and Osteochondral Autograft
Andres21	Treatment of osteoarthritic cartilage lesions with osteochondral autograft transplantation.
Minzlaff9	Osteochondral autologous transfer combined with valgus high tibial osteotomy: long-term results and survivorship analysis.
Minzlaff22	Can young and active patients participate in sports after osteochondral autologous transfer combined with valgus high tibial osteotomy?
Author	Prognostic Factors for Combined Procedures for Focal Lesions with ACI and HTO Papers
Ackerman55	The Effect of Mechanical Leg Alignment on Cartilage Restoration With and Without Concomitant High Tibial Osteotomy
Bauer23	Knee joint preservation with combined neutralizing high tibial osteotomy (HTO) and Matrix-induced Autologous Chondrocyte Implantation (MACI) in younger patients with medial knee osteoarthritis: a case series with prospective clinical and MRI follow-up over 5 years.
Bode24	A non-randomized controlled clinical trial on autologous chondrocyte implantation (ACI) in cartilage defects of the medial femoral condyle with or without high tibial osteotomy in patients with varus deformity of less than 5°.
Bode25	Clinical outcome and return to work following single-stage combined autologous chondrocyte implantation and high tibial osteotomy.
Ferruzzi26	Cartilage repair procedures associated with high tibial osteotomy in varus knees: clinical results at 11 years' follow-up.
Franceschi27	Simultaneous arthroscopic implantation of autologous chondrocytes and high tibial osteotomy for tibial chondral defects in the varus knee.
Author	Prognostic Factors for Combined Procedures for Focal Lesions with MSC and HTO Papers
Koh28	Comparative outcomes of open-wedge high tibial osteotomy with platelet-rich plasma alone or in combination with mesenchymal stem cell treatment: A prospective study.
Song50	High tibial osteotomy with human umbilical cord blood-derived mesenchymal stem cells implantation for knee cartilage regeneration