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Is microfracture sufficient for high-tibial osteotomy, or should intra-articular hyaluronic acid and oral glucosamine-chondroitin be used as additional treatments?

Journal of Orthopaedic Surgery and Research volume 19, Article number: 601 (2024) Cite this article

Abstract

Background

This study aimed to compare the effects of microfracture (MF) versus intra-articular hyaluronic acid (HA) + oral glucosamine and chondroitin sulfate (GC) in addition to MF in patients with osteoarthritic knees who underwent medial open wedge high tibial osteotomy (MOWHTO) after an average follow-up of five years.

Methods

The study was designed retrospectively and included patients who underwent MOWHTO due to gonarthrosis, the MF method performed on these patients, and HA + GC treatments applied in addition to MF. Three groups consisting of 79 patients were formed: only HTO (Group 1), HTO + MF (Group 2), and HTO + MF + HA + GC (Group 3). The groups were compared using knee injury and osteoarthritis outcome score (KOOS), visual analog scale (VAS) for pain, and range of motion (ROM). The associations between the degree of correction and function and pain were evaluated. Additionally, the KOOS subparameters were compared between the groups.

Results

There were significant improvements in the postoperative KOOS and VAS scores in all three groups (p < 0.05). However, the ROM did not improve in Group 1. There was no significant difference in the postoperative KOOS, VAS, or ROM values ​​between Groups 2 and 3, but these values ​​were significantly better in Groups 2 and 3 than in Group 1 (p < 0.05). When the degree of correction increased, there were no significant positive changes in the postoperative KOOS or VAS score in Group 1, unlike in the other two groups (p < 0.05). In corrections of ≥ 10°, while there was no significant difference in the postoperative KOOS or VAS score ​​between Groups 2 and 3, these parameters significantly improved in these two groups compared to Group 1 (p < 0.05). Among the KOOS subparameters, pain and activities of daily living scores ​​were greater in Groups 2 and 3 than in Group 1 (p < 0.05).

Conclusions

In MOWHTO, MF is a sufficient treatment method that improves the patient’s clinical condition without requiring additional treatments such as HA and GC.

Level of evidence

III, retrospective cohort study.

Background

Degradation of cartilage tissue results from mechanical and metabolic mechanisms contributing to knee osteoarthritis (OA) progression. One of the most essential factors in etiology is malalignment of the lower extremity, which increases the load within the impacted compartment and thus results in further deterioration of the articular cartilage [1]. This condition is exacerbated by the local biochemical response to various degradation products, such as proinflammatory cytokines, proteinases, and free radicals, which are increased in osteoarthritis. This causes an imbalance in articular cartilage homeostasis and decreased synovial fluid viscosity [2].

Medial open wedge high tibial osteotomy (MOWHTO) is a surgical procedure that balances the load distribution in the knee joint by correcting the lower extremity mechanical axis in medial compartment osteoarthritis, thus relieving pain and increasing function [3]. Damaged cartilage can be clinically healed only by relieving the affected compartment from the load via high tibial osteotomy (HTO) [4, 5]. However, the healing fibrocartilage cartilage tissue has a weaker structure than hyaline cartilage [6]. For this reason, current research has focused on how beneficial additional procedures can be for cartilage healing during HTO and how much knee joint function can be increased [7, 8]. Many additional interventions, such as microfracture (MF), autologous chondrocyte or osteochondral graft applications, and intra-articular (IA) injections, and oral supplements (glucosamine and chondroitin sulfate (GC) are currently applied in HTOs to restore cartilage regeneration [9,10,11].

The MF repairs cartilage lesions in the knee by creating fibrocartilage tissue through mesenchymal stem cells or progenitor cells [12]. Its simple and inexpensive arthroscopic application has made MF one of the world’s most commonly used cartilage repair techniques [13]. For the knee joint, while the hyaluronic acid (HA) concentration varies between 2.5 and 4.0 mg/ml in healthy adult knees, it decreases by 33–50% in OA patients [14]. In addition to its viscosupplementary effects, IA HA is a widely accepted therapeutic option for treating knee pain due to OA [15]. In terms of oral supplements, although debatable, the use of GCs in OA knees is known to decrease joint space narrowing protect joint cartilage, and decrease the progression of pathological conditions and pain [16, 17].

This study aimed to compare the effects of MF versus IA HA + oral GC with MF in patients with osteoarthritic knees who underwent MOWHTO after an average follow-up of five years. The first hypothesis was that the MF applied to cartilage in MOWHTO would positively impact clinical outcomes. The second hypothesis was that IA HA + oral GC use in addition to the MF in MOWHTO would not provide additional benefit to clinical outcomes.

Methods

Study design

The institutional ethics committee approved this retrospective cohort study. Data from 105 patients who underwent MOWHTO with a diagnosis of OA between January 2016 and November 2020 were obtained from the hospital archive. The data were collected prospectively and analyzed retrospectively.

The inclusion criteria for patients in the study were as follows: < 65 years old, OA only in the medial compartment of the knee (Kellgren Lawrence (KL) grade 3, 4) [18], unilateral MOWHTO, body mass index (BMI) < 30 kg/m2, stable joints with no knee contraction, knee flexion > 100° and varus 5–15° prior to surgery, MF to the medial condyle of the femur, only IA HA injection and oral GC use in specified postoperative (postop) periods. The medial compartment’s large-area full-thickness articular cartilage defects were verified via arthroscopy under the parameters set forth by the International Cartilage Research Society (ICRS) [19].

The exclusion criteria were as follows: additional knee surgery other than MF in the same session (e.g., meniscus or anterior cruciate ligament), the presence of a kissing lesion, the development of complications (tibia plateau fracture, compartment syndrome, infection), previous knee surgery, inflammatory disease (e.g., rheumatoid arthritis), allergy to the drugs used in the study, and the use of any painkillers (such as NSAID or paracetamol) within one month before the final follow-up. Thus, 79 patients were included in the study.

The patients were divided into three groups: those who underwent HTO only (Group 1), those who underwent HTO + MF (Group 2), and those who underwent HTO + MF + HA + GC (Group 3). An intraknee injection of HA (30 mg/2 mL, molecular weight 2900 kDa) was applied as a postop single dose at the 2nd, 4th, 6th, and 12th months and as a single dose annually until the final follow-up. The oral intake of GC (glucosamine HCL 750 mg, chondroitin sulfate 600 mg) was started during the postop suture removal period and continued twice daily for six months.

Evaluation of clinical and radiological parameters

Clinical and demographic data of the patients were obtained. The knee injury and osteoarthritis outcome score (KOOS) [20] was used for functional evaluation, and the visual analog scale (VAS) [21] was used for pain evaluation. The range of motion (ROM) values and functional and pain scores of the patients in the preoperative (preop) period and the final postop follow-up period were compared within and between groups. The degree of correction made during HTO and the KOOS and VAS scores at the final follow-up were evaluated within and between groups. Additionally, the KOOS parameters were evaluated in detail.

Correction angle measurements for osteotomy were made according to the Miniaci method on standing scanograms (Fig. 1a) [22]. During the surgical procedure, all patients were examined arthroscopically, and MOWHTO was performed as described elsewhere (Fig. 1b-c) [23]. Hernigou’s chart was used to establish a relationship between the width of the tibia and the necessary degree of correction at the osteotomy location [24, 25]. All patients received autografts from the ipsilateral iliac crest. In accordance with Steadman et al. [26], the remaining patients underwent MF. Postoperatively, a similar rehabilitation protocol (no brace use, full ROM for eight weeks, continuous passive motion (3 times a day for half an hour), and limited weight bearing to 15 kg) was applied to all patients.

Fig. 1
figure 1

Miniaci method (a) and anteroposterior and lateral knee X-ray images of a patient who underwent MOWHTO (b, c)

Full size image

Statistical analysis

The statistical package for social sciences (SPSS) for Windows 25.0 (SPSS Inc., Chicago, IL) was used to analyze the data. The data were assessed via descriptive statistics (count, percentage, mean, standard deviation, and min–max values). The data were evaluated for a normal distribution using the Shapiro‒Wilk test. The Kruskal‒Wallis H test and the Bonferroni correction were used to compare quantitative data across more than two independent groups in the non-normal dataset and identify the groups with differences, respectively. The Wilcoxon signed-rank test was used to compare preop and postop measurements within the groups. Chi-square test was used to analyze the relationships between independent categorical variables. P < 0.05 was considered statistically significant.

Results

Seventy-nine patients (63 females, 16 males) with a mean age of 53.78 ± 4.72 years were followed for a mean of 67.4 ± 5.5 months. There was no significant difference in demographic or clinical characteristics among the three groups (p > 0.05) (Table 1).

Table 1 Distribution of the demographic and clinical characteristics of the patients
Full size table

There was no significant difference in preop KOOS, VAS for pain, or ROM between the groups (p > 0.05). The postop KOOS improved significantly compared to preop in all three groups (p < 0.05). While Group 3 had the highest postop KOOS, there was no significant difference between Group 2 and Group 3, and the postop KOOS in Group 1 remained significantly lower than the postop scores in Groups 2 and 3 (p < 0.05) (Table 2). Compared with the preop values, the postop VAS pain scores of all three groups improved significantly (p < 0.05). While Group 3 had the lowest postop VAS score, there was no significant difference between Group 2 and Group 3, and the postop VAS score in Group 1 was significantly higher than Groups 2 and 3 (p < 0.05) (Table 2). While there was no significant difference between the preop and postop ROM in Group 1, the postop ROM in Groups 2 and 3 was significantly greater than the preop values (p < 0.05). There was no significant difference in postop ROM ​​between Groups 2 and 3, and the postop ROM ​​in those two groups was significantly greater than the postop ROM ​​in Group 1 (p < 0.05) (Table 2).

Table 2 Comparison of preoperative and postoperative KOOS, VAS, and ROM within and between groups
Full size table

As the degree of correction in osteotomies increased, the KOOS in Group 1 was not affected, whereas the KOOS in Groups 2 and 3 increased significantly (p < 0.05). While the KOOS ​​at the correction level of ≥ 10° did not significantly differ between Groups 2 and 3, the scores were significantly greater in Groups 2 and 3 than in Group 1 (p < 0.05) (Table 3). There was no significant difference in the VAS score of the patients in Group 1 as the degree of correction increased. However, the VAS scores of the patients in Groups 2 and 3 decreased significantly as the degree of correction increased (p < 0.05). While VAS scores ​​at the correction level of ≥ 10° did not show a significant difference between Groups 2 and 3, these scores were significantly lower in Groups 2 and 3 than in Group 1 (p < 0.05) (Table 3).

Table 3 Comparison of the associations of the KOOS and VAS scores with the degree of correction within and between groups
Full size table

When the KOOS parameters were further evaluated in pain and ADL, the scores ​​in Group 2 and Group 3 were higher than those in Group 1, and the scores in Group 3 were higher than those in Group 2 (p < 0.05). There was no significant difference between the groups in symptoms, sport, or quality of life (QoL) parameters (p > 0.05) (Table 4).

Table 4 Detailed comparison of the KOOS parameters between the groups
Full size table

Discussion

Previous studies have reported contradicting results of MF application in HTO. Studies have been conducted on the macroscopic appearance of cartilage damage resulting from MF application and the failure rate, and it has been reported that defect filling on magnetic resonance imaging (MRI) is correlated with functional scores [27, 28]. Regarding clinical outcomes, Sterett et al. [29] reported that the need for arthroplasty may be delayed in active patients with gonarthrosis, with survival rates of 97% at five years and 91% at seven years after MF with open wedge HTO. Pascale et al. [8] reported that, in patients with medial compartmental OA in the genu varum and Outerbridge grade III and IV chondropathy on the femoral and/or tibial joint surface, wedge HTO plus MF application increased patient satisfaction compared to HTO alone. They reported that the use of MF with osteotomy was more effective in the femoral condyle than in the tibial plateau based on subjective results at the 5-year follow-up. In another study, positive results were shown in patients’ subjective International Knee Documentation Committee (IKDC) scores as a result of MOWHTO and abrasion-MF application, one of the cartilage renewal procedures, in 91 knees with KL grade 3–4 OA, varus aligned, and full-thickness cartilage defects. A high survival rate of 95.2% was observed at five years [30]. When the study’s ten-year survival rate and functional results, which included 79 knees, were examined, HTO, together with the chondral resurfacing procedure, was a good to excellent treatment option. Additionally, a greater preop tibial bone varus angle (TBVA, > 6°) was linked to improved functional outcomes at the final follow-up [31]. However, the lack of a control group in these studies calls into question the results of the cartilage regeneration technique.

Akamatsu et al. [32] evaluated cartilage regeneration monitoring in patients with severe medial knee OA where they performed open and closed wedge HTO. The study found a notable improvement in clinical condition, with no difference between the two groups. In patients with an advanced preop ICRS degree and open wedge HTO, a substantially improved rate of cartilage healing was observed. In a review evaluating the mid- and long-term results of HTO with cartilage restoration procedures that included eight hundred twenty-seven patients (839 knees), MOWHTO was the most commonly used HTO, and MF was the most frequently used cartilage regeneration technique. As a result, HTO combined with cartilage regeneration techniques can potentially postpone or obviate knee arthroplasty surgery while offering a consistent improvement in functional status in the mid- and long-term following surgery [33].

Ferruzzi et al. [34] conducted a study of 56 patients who had a mean varus deformity of 8° with KL grade III/IV OA and were treated with MOWHTO, MOWHTO + ACI (autologous chondrocyte implantation), or MOWHTO + MF. All therapy groups reported clinical benefits at the 11-year follow-up. Compared to the MOWHTO-MF group, the MOWHTO and MOWHTO-ACI groups had better WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) and HSS (Hospital for Special Surgery) ratings. Arthritis has been reported to progress more often in the HTO group with MF [34]. Jung et al. [35] reported no difference in clinical or arthroscopic fibrocartilage formation between patients who underwent MOWHTO with and without subchondral drilling on knees with medial OA at the 24-month follow-up. A review assessing whether HTO with cartilage treatment achieves greater therapeutic benefits than HTO alone concluded that combined cartilage therapy is not indicated in routine clinical practice. In addition, injection therapies that target the entire joint environment demonstrated encouraging results, but surgical procedures that solely target the cartilage layer did not result in any clinical improvement [36].

IA HA injections have anti-inflammatory and antinociceptive effects, regulate HA synthesis, and restore the elastic and viscous qualities of synovial fluid [37]. Compared with the control group that received HTO alone at the end of the first year postop, Chareancholvanich et al. [38] reported that a series of HA injections in patients receiving HTO decreased the need for painkillers, created an increase in total cartilage volume on MRI, and may help prevent postop lateral tibiofemoral joint cartilage loss. In a study conducted over 24 months, Wang et al. [39] assessed the changes in structure caused by HA injections. They reported that patients with OA who had an intraknee Hylan G-F 20 lost 2.8% less tibial cartilage in the lateral compartment and 2.6% less in the medial compartment. The cartilage defect score in the medial compartment of those who did not receive HA increased. Listrat et al. [40] and Pham et al. [41] followed patients with OA for one year after they underwent a series of IA HA procedures and reported no significant differences in joint space width loss between treatment groups. They reported improvements in pain in patients but did not observe any differences between them and the control groups. Studies by Wang et al. [39] and Listrat et al. [40] were supported by pharmaceutical companies. The two most important variables influencing how resistant synovial fluid is to shear stress are the HA concentration and the molecular weight of the solution [42]. A reduced HA molecular weight and concentration in the joint cause increased mechanical damage susceptibility in OA [43]. The molecular weight of HA varies across studies, and Wang et al. [39] used a formulation with a large molecular weight (6000 kDa) and focused on the effects of HA on articular cartilage. The scientific quality of clinical trials needs to be improved. The study showed that administering high-molecular-weight formulations for one year could have structural benefits [40]. Another study did not provide evidence supporting high or low molecular weights [14].

A systematic review found that the use of GCs in patients with OA or who are at risk may be a nonsurgical method to protect articular cartilage and delay the progression of OA. While the study revealed improvements in joint space narrowing and pain, 800 mg chondroitin sulfate and 1500 mg glucosamine sulfate taken orally once a day may help individuals at risk of developing OA by slowing disease progression [44]. The study’s most significant limitation was that all positive results came from industry-supported studies. In most cases, studies supported by industry typically produced more favorable outcomes than unaffiliated studies [45]. The results of these studies for chondroitin and glucosamine must be interpreted in light of potential biases, even if the trials were of excellent scientific quality and without recognizable sources of bias. Additionally, the research found that variations in dosages, treatment plans, formulations, lengths of time, and outcome evaluations among studies increased the complexity of comparisons and their susceptibility to bias. According to a meta-analysis, oral chondroitin improved physical function and reduced pain more effectively than a placebo. The results indicated that glucosamine affected the hardness. Due to the limited number of studies, further evidence is needed to indicate that combination therapy is superior to placebo [46]. Another meta-analysis revealed that oral glucosamine or chondroitin sulfate supplementation reduced pain in patients with knee OA. However, combining these two therapeutic agents to treat symptomatic knee OA has no additional effect [47]. The effects of varus deformity on HA and chondroitin sulfate contents in various knee joint compartments were examined. They play essential roles in the treatment and diagnosis of OA, and HA and chondroitin sulfate contents in the medial femoral condyle are negatively correlated with the radiographic femorotibial angle [48].

In this study, the postop KOOS and VAS scores were better in all groups compared to preop, indicating that HTO is an effective surgical method. We attributed the better postop ROM in the two groups, except for Group 1, to the suppression of the OA environment, better healing of the cartilage tissue, and decreased pain. Not performing surgical intervention on other tissues outside the MF, such as the meniscus and anterior cruciate ligament, and applying the MF to the complete defect along with unloading may have improved the results. Studies have suggested that repairing a partial-thickness cartilage defect is more complicated than repairing a full-thickness cartilage defect [49,50,51]. We attributed Group 1 lags in the KOOS, VAS score, and ROM to the effect of the cartilage-supportive treatment methods. Although the best results with MF are observed in patients under the age of 40 [52], our application of additional treatment drugs at high doses and concentrations in Group 3 may have contributed to the highest KOOS and better VAS scores by suppressing the cytogenetic environment in osteoarthritis. In addition, we attribute the fact that we obtained better KOOS and VAS values in Groups 2 and 3 in corrections of ≥ 10° to the synergistic effect of the two treatment methods on unloading. This finding seems to be related to studies indicating that as the degree of correction increases, the function increases, and there is greater cartilage repair in those with advanced preop cartilage damage [31, 32].

Although the unloading effect of HTO causes injured cartilage in the affected area to regenerate [53], OA involves a complex array of cytokines. As it affects the knee joint as a whole, this may influence the regenerative potential of the applied cartilage techniques [54]. There is an increased likelihood of clinical improvement if the overall environment of the OA joint is addressed. One of the limitations of this study was that we could not evaluate the results of additional treatment methods for cartilage with interventions such as postop MRI or arthroscopic second look. Considering the legal aspects of this process, the effects of treatment methods on patient function parameters cannot be ignored. The difference in sex distribution and limited sample size, although the study power is sufficient, can be considered among the other limitations. Nonetheless, this study compared different additional cartilage interventions with the control group. In addition, this study may guide research from a different perspective, as it shows that mesenchymal stem cells or progenitor cells obtained via MF in HTO are areas that should be focused on in cartilage healing.

Conclusion

MOWHTO is an effective surgical method for eligible patients with medial knee OA. However, in MOWHTO, MF application and IA HA + oral GC in addition to MF resulted in better outcomes measured by KOOS, VAS and ROM than osteotomy alone. IA HA + oral GC in addition to MF did not significantly differ from MF in those measures. In advanced varus deformities, MF and IA HA + oral GC in addition to MF yielded better results than osteotomy alone in terms of the KOOS and VAS scores, but there were no differences between the two groups. As a result, in MOWHTO, MF application is a sufficient treatment that further improves the patient’s clinical condition on its own without requiring additional treatments such as HA or GC.

Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request Sincerely.

Abbreviations

OA:

Osteoarthritis

MOWHTO:

Medial open wedge high tibial osteotomy

HTO:

High tibial osteotomy

MF:

Microfracture

IA:

Intra-articular

GC:

Glucosamine and Chondroitin sulfate

HA:

Hyaluronic Acid

KL:

Kellgren Lawrence

BMI:

Body mass index

Preop/postop:

Preoperative/Postoperative

ICRS:

International Cartilage Research Society

KOOS:

Knee injury and osteoarthritis outcome score

VAS:

Visual Analogue Scale

ROM:

Range of Motion

ADL:

Activities of daily living

QoL:

Quality of life

MRI:

Magnetic resonance imaging

IKDC:

International Knee Documentation Committee

TBVA:

Tibial bone varus angle

WOMAC:

Western Ontario and McMaster Universities Osteoarthritis Index

HSS:

Hospital for Special Surgery

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Acknowledgements

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Funding

The study did not receive any funding.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Orthopaedics and Traumatology, Ağrı İbrahim Çeçen University, Ağrı, Türkiye

    Ümit Aygün, Mehmet Fatih Aksay & Ali Can Çiçek

  2. Faculty of Medicine, Department of Orthopaedics and Traumatology, Atatürk University, Erzurum, Türkiye

    Eyüp Şenocak

  3. Orthopedics and Traumatology Clinic, Ağrı Training and Research Hospital, Ağrı, Türkiye

    Orkun Halaç

  4. Department of Orthopaedics and Traumatology Clinic, Başakşehir Çam ve Sakura City Hospital, İstanbul, Türkiye

    Serdar Toy

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  1. Ümit Aygün
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Contributions

U.A., E.S. and M.F.A. contributed to the study’s conception and design. A.C.C. O.H., and U.A. contributed to material preparation and data collection. Statistical analysis was performed by U.A., E.S., and S.T. The first draft of the manuscript was written by U.A. A.C.C. O.H. and S.T. reviewed the manuscript. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Ümit Aygün.

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Ethics approval and consent to participate

The research follows the basic principles of the Declaration of Helsinki, the study protocol was approved by the Ethics committee of Istinye University (Date: 17.03.2022- No; 3/2022.K-24), and all individuals signed informed consent when participating in this study.

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The authors declare no competing interests.

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Aygün, Ü., Şenocak, E., Aksay, M.F. et al. Is microfracture sufficient for high-tibial osteotomy, or should intra-articular hyaluronic acid and oral glucosamine-chondroitin be used as additional treatments?. J Orthop Surg Res 19, 601 (2024). https://doi.org/10.1186/s13018-024-05095-y

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Keywords

Journal of Orthopaedic Surgery and Research

ISSN: 1749-799X