Osteoarthritis is derived from the prefix osteo—(from Ancient Greek: ὀστέον, romanized: ostéon, lit. “bone”) combined with arthritis (from ἀρθρῖτῐς, arthrîtis, lit. “of or in the joint”), which is itself derived from arthr—(from ἄρθρον, árthron, lit. “joint, limb”) and -it is (from -ῖτις, -îtis, lit. “pertaining to”), the latter suffix having come to be associated with inflammation [1]. Some clinicians refer to this condition as osteoarthrosis to signify the lack of inflammatory response, the suffix -osis (from -ωσις, -ōsis, lit. “(abnormal) state, condition, or action”) simply referring to the pathosis itself [2].

Osteoarthritis is a disorder involving movable joints characterized by cell stress and extracellular matrix degradation initiated by micro- and macro-injury that activates maladaptive repair responses including pro-inflammatory pathways of innate immunity. The disease manifests as a molecular derangement (abnormal joint tissue metabolism) followed by anatomic, and/or physiologic derangement (characterized by cartilage degradation, bone remodeling, osteophyte formation, joint inflammation and loss of normal joint function), that can culminate in illness [3].

Worldwide, as of 2010, nearly 250 million people had osteoarthritis of the knee joint (3.6% of the population). Hip joint osteoarthritis affect approximately 0.85% of the population. Both, knee and hip osteoarthritis had a ranking for disability worldwide of 11th among 291 disease conditions assessed [4]. In the United States, there were just about 964,000 hospitalizations for osteoarthritis in 2011, a rate of 31 stays per 10,000 population [5]. With a summary cost of $14.8 billion ($15,400 per stay), it was the second most expensive condition seen in USA hospital stays in 2011. By payer, it was the second most costly condition billed to private insurance and Medicare program [6][7]. Aiyong Cui et al. included 88 studies in the current analysis, 18 were published between 2017 and 2020. Based on the study findings, the global prevalence of knee joint OA was 16% among individuals aged 15 years or more and 22.9% among those aged 40 years or more. Further, about 654.1 million individuals aged ≥ 40 years globally had knee joint OA in 2020. The global incidence of knee joint OA was 203 per 10,000 person-years in individuals aged 20 years or more. Appropriately, just about 86.7 million people aged 20 years or over, had an incident of knee OA worldwide in 2020. The ratios of prevalence and incidence of knee OA in female and male were 1.69 and 1.39 correspondingly [8]. OA has a multi-factorial etiology and can be considered the product of an interaction between systemic and local factors. Old age, female gender, overweight and obesity, knee injury, repetitive overuse of joints, bone density, muscle weakness, and joint laxity (unstable knee joint)—all play role in the development of joint osteoarthritis, particularly in the weight-bearing joints. Modifying these factors may reduce the risk of osteoarthritis and prevent subsequent pain and disability [9]. Females are not only more likely to have OA than males, they also have more severe condition of OA [10]. The definite increase of OA in women around the time of menopause has led investigations hypothesize that hormonal factors may impact on the development of OA. However, results on effect of estrogen, either endogenous or exogenous, on OA from observational studies have been conflicting [11][12]. In a randomized clinical trial (the Heart and Estrogen/Progestin Replacement Study) in a group of older postmenopausal women with heart disease, no significant difference was found in the prevalence of knee pain or its associated disability between those taking estrogen plus progestin therapy or those taking placebo [13]. Data from the Women’s Health Initiative showed that women on estrogen replacement therapy were 15% less likely to require total knee or hip replacement surgery than those not taking such medication, but that estrogen combined with progestin therapy was not associated with the risk of joint arthroplasty [14]. Results from several studies have shown that OA is inherited and may vary by joint location. Twin and family studies have estimated the heritable component of OA to be between 50 and 65% with larger genetic influences for hand and hip joint OA than for knee joint OA [15][16]. In a genome-wide association study, Kerkhof et al. reported that the C allele of rs3815148 on chromosome 7q22 was linked with a 1.14-fold increased prevalence of knee joint and/or hand OA and also with a 30% increased risk of knee OA progression. Several studies also found that an inverse association between general joint hypermobility, alone benign trait, with hand and knee OA and serum cartilage oligomeric matrix protein levels [17]-[19]. A few congenital or developmental abnormalities (i.e., congenital subluxation, Legg-Calvé-Perthes disease, and slipped capital femoral epiphysis) have been associated with occurrence of hip joint OA in later life [20]-[22]; however, because these developmental deformities are uncommon, they probably only account for a small proportion of the hip OA in the general population. Several studies have examined sub-clinical acetabular dysplasia, a more common, milder developmental abnormality, in relation to hip OA, with conflicting results [23]-[27]; Lane and colleagues reported that abnormal center-edge angle or acetabular dysplasia were each associated with an approximately threefold increased risk of incident hip joint OA in female patients, suggesting that subclinical acetabular dysplasia may be a significant risk factor for the development of hip OA [23]. Dietary factors are the subject of considerable interest in OA, results of studies, however, are conflicting. One of the most promising nutritional factors for OA is vitamin D. Without sufficient vitamin D, bones can become thin, brittle, or deformed. In the Framingham Study subjects in the lowest <27 ng/ml and middle 27.0 - 33.0 ng/ml tertile of serum 25-hydroxyvitamin D had a 3-fold increased risk for progressive knee OA compared with those in the highest tertile; nevertheless, no such effect was observed for risk of incident disease [28]. However, results from two cohort studies failed to confirm protective effect of vitamin D on the structural worsening of knee joint OA [29]. McAlindon et al. have made conclusion in A Randomized Controlled Trial, Vitamin D supplementation for 2 years at a dose sufficient to elevate plasma levels of 250HD to > 36 ng/ml, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee osteoarthritis [30].

Nowadays, a widely used knee joint replacement with artificial endoprothesis in the age of 60 or over. Expected revision rate after knee joint replacement surgery is about 6% after five years and 12% after ten years. Revision rate is one of the most important outcome measures of joint replacement surgery. The lifetime risk of requiring revision is 22.4% in those aged between 46 and 50 years at the time of the initial surgery. The three commonest indications for revision are aseptic loosening, infection, and unexplained pain. Young males, aged between 46 and 50 years, have the highest lifetime risk of revision (25.2%). Therefore, in young population there is a big challenge to treat knee joint osteoarthritis.

Figure 1. The Schematic photo of knee joint osteoarthritis (OA) development, mechanical etiological and biological multiple factors and vicious cycle of OA. HTO as a possible mechanical solution to break through vicious cycle which is mainly based on the redistribution or shifting of the deforming axial mechanical forces on the two condyles of the knee joint.

The aim of our work is to prove the effectiveness of the simultaneously performed HTO and arthroscopic chondroplasty in patients with medial compartment osteoarthritis (osteoarthritis) of the knee joint. Correction of varus deformity in knee joint OA is based on: patient’s knee joint morphology, ROM (range of motion), X-ray and MRI results. It depends on patient’s complaints and duration, patient’s expectations and rehabilitation time, on general factors such as cigarette smoking, presence of concomitant diseases, status of peripheral blood vessels, nutritional status, presence of diabetes, sports activity or less active lifestyle. The primary indication for HTO is an active patient between the ages of 40 and 60, with varus deformity of the knee joint, as well as a patient whose tibia has been radiographically confirmed to be free of lateral subluxation. Patient should not have symptoms of OA of the patellofemoral compartment. Also, the patient should have knee joint pain only in the projection of medial compartment, during physical activity. Patient must have possibility to make full extension in knee joint and the ROM should be equal or more than 100˚. However, in reality, there is a certain contingent of patients who do not fit into these idealized criteria, but who receive the desired results if osteotomy is performed (Hanssen & Chao) (Table 1). The following table lists patients for whom osteotomy is absolutely indicated, relatively indicated, or contraindicated. The table has been modified by the International Society of Arthroscopy, Knee Surgery and Orthopedic Sports Medicine.

Table 1. *Ahlbäck grading system for degenerative arthritis (Brinkman et al., 2008; Frey et al., 2008; Hofmann et al., 2009; Kolb et al., 2009; Rand & Neyret, 2005; Song et al., 2010). (Hanssen & Chao) HTO absolute indication, relative indication and contraindication.

Table 2. According to Ahlback grading, knee OA classified as grade 1 joint space narrowing (less than 3 mm), grade 2 joint space obliteration, grade 3 bone defects/loss (0 - 5 mm), grade 4 moderate bone defects/loss (5 - 10 mm), grade 5 severe bone defects/loss (more than 10 mm).

We have been revealing patients with knee joint osteoarthritis by collecting anamnesis and clinical assessment of the knee and hip joint. The assessment of the range of motion in the hip joint, and especially assessment of hip rotation. Preoperative instrumental investigation includes X-ray of the knee joint AP view (standing position) and LM view, topogram of whole lower extremities and MRI scan of knee joint. To evaluate the clinical condition of the patient’s knee joint, the following is used: The Western Ontario and McMaster Universities Osteoarthritis Index/Knee-WOMAC and KOOS knee survey—Knee injury and Osteoarthritis Outcome Score. This allows us to evaluate the condition subjectively perceived by the patient with points, which in turn simplifies the comparison of pre- and post-operative results. It is also noted that the following conditions are bad prognostic factors: According to “Ahlback” classification (Table 2, Figure 2(b)) III - IV or higher grade osteoarthritis of the knee joint, patient more than 65 years old, severe osteoarthritis of the hip joint, knee range of motion less than 90˚, flexion contracture equal to or greater than 15˚, joint instability, lateral subluxation of the tibia, 20˚ or more correction angle and rheumatoid arthritis. The majority of authors are coming in agreement that in overweight patients, the procedure of tibial osteotomy is a more valid intervention than single-compartment endoprosthesis. However, the influence of a large body mass index on the outcome of the HTO procedure remains controversial [9] (Table 2).

48-year-old lady. A 15 mm titanium block was used for the varus deformity correction. The open wedge was filled with beta tricalcium phosphate granules. An arthroscopic microfracture procedure was performed on the medial condyle of the femur and tibia.

(a)

(b)

(c)

Figure 2. (a) Clinical Case/LJ Clinic. (b) The Ahlback classification. LJ Clinic Cases According Table 2 with different degrees of joint space narrowing and varus deformation. (c) Lower Extremities’ Topogram of 60 years old lady; A-B line is Normal Axis of lower limb; C-D line is Mechanical Axis of left lower limb. It’s shifted on the medial edge of the tibia and femur medial condyles. α angle is aMPTA, anatomic medial proximal tibial angle. β angle is aLDFA, anatomic lateral distal femoral angle. γ angle is the femoral shaft-tibial shaft angle (anatomic angle). δ angle is the hip-knee-ankle angle (mechanical angle).

Knee joint should be evaluated with the X-ray in Anterior-posterior and Lateral view to assess osteoarthritis grading, as well as bone loss on the tibial plateau and patella position with Insall-Salvati ratio. In case of “patella alta or Baja” osteotomy of the tibial tuberosity may be necessary in combination with HTO to optimize extension apparat of knee joint and prevent contracture. The axis of the lower limb should also be evaluated (Figure 2(c)).

Magnetic resonance imaging of the knee joint can also be used to reveal osteochondral injuries of articular surfaces, meniscal injuries, ligament injuries, cartilage injuries, condyle osteonecrosis, subchondral injuries and loose bodies.

Preoperative planning has great importance to achieve a successful outcome of the operative intervention. The outcome of the operation strongly depends on the calculation of the correction angle and the precisely performed valgisation, therefore have been developed various methods to calculate angle of correction. Normally, the center point of the femoral head, the center of the knee joint plateau and the center of the ankle joint are located on the same line of the mechanical axis of the lower limb (Figure 2(c)). 3˚ - 5˚ valgus deviation from the mechanical axis or 8˚ - 10˚ anatomical valgus is considered the ideal axis of the lower extremity after surgery. Fujisawa et al. published in his publication that the postoperative mechanical axis should pass through the border of the lateral third and middle third of the tibial plateau.

Figure 3. (A), (B) Calculating new loading axis of the lower limb according to dugdale.

Figure 4. Calculating new loading axis of the lower limb according to Miniaci.

Jakob and Jacobi proposed that the mechanical axis correction depends on the thickness of the cartilage in the medial compartment of the joint. E.g.: If 1/3 of the medial compartment’s cartilage is worn away, then the mechanical axis should be shifted 10% - 15% laterally from the center of the tibial plateau. If the 2/3 of articular cartilage is worn away, then the mechanical axis should be shifted 20% - 25% laterally from the center of the tibial plateau. And if the cartilage is completely worn away, then the mechanical axis should be shifted 30% - 35% laterally from the center of the tibial plateau. The Dugdale method is also used for pre-operative planning, which is calculated by the lines drawn from the center of the femoral head and the center of the ankle joint, which intersects lateral tibial condyle, namely at the point of 60% - 62.5% of the total transverse diameter of the tibial plateau, which is anatomically located slightly lateral to the lateral eminence and corresponds to 3˚ - 5˚ valgus deviation from the mechanical axis. The α angle obtained by crossing these two lines represents the size of the correction angle. [Figure 3(A)-(B) (shows the Dugdale method of calculating the correction angle for HTO with open wedge surgical technique].

One of the ways to calculate the angle of the bone section is called Miniaci method. According to Miniaci, as with other methods, first of all, the mechanical axis of the lower limb is determined. Line has drawn vertically distally from the center of the femoral head, which crosses the knee joint and connects to the center of the ankle joint (a). The second line (b) is placed again from the center of the head of the femur, which crosses the knee joint in the area of the lateral condyle of the tibia, namely at the point of 60% - 62.5% of the total transverse diameter of the tibia, which represents new loading axis of the lower limb; Figure 3,Figure 4 descends to the level of the articular surface of the ankle joint.

The third line starts from the point of the medial condyle of the tibia bone where it is planned to carry out the bone osteotomy and joins the hinge point of rotation, which is located on level of fibular head, 1cm medially from lateral cortex of tibia and at least 1.5 cm away from the articular surface (c). Subsequently, the point of rotation of the bone is connected with the old and new centers of the ankle joint. The angle created by the abovementioned action represents the amount of correction angle (Δ delta) for the valgisation. Thus, the correction angle must be calculated and performed precisely, because an inappropriate correction angle can lead to the recurrent varus deformity, whereas hypercorrection can lead to poor cosmetic and functional results. Achieving the pre-operatively calculated correction angle during valgisation is a great challenge, as it requires: sophisticated mastery of the surgical technique, handling of locking plate system and instrument set, and control of the procedure steps with the C-arm (Figure 5).

We have performed most of operations under the spinal anesthesia, which reduces the risk of post-operative complications and length of hospital stay for patients. C-arm is used intraoperatively to assess the corrected limb axis in AP and lateral projection. The operation is performed with the support of an electric pneumatic tourniquet. At the first stage, arthroscopy of the knee joint is performed. Removal of free osteochondral bodies, joint debridement, resection of degeneratively damaged medial meniscus, resection of osteophytes with electric burr head and shaver. After debridement we do articular surface chondroplasty procedure: microfracture, mosaicplasty with osteochondral autograft or minced cartilage is been harvested from healthy layer of articular surface of lateral femoral condyle and pasted it in the chondral defects of medial compartment. After completing the arthroscopy, a longitudinal medial descending incision from joint level with size of ≈ 8 - 10 cm is made in the pes anserine region of the proximal tibia. Subsequent deep dissection includes longitudinal incision of the sartorial fascia, elevation of the tendons of the semitendinosus and gracilis muscles and anterior fibers of the medial collateral ligament are released. An osteotomy of the tibia is made by an oscillating saw under the fluoroscopy control (Figure 5).

The osteotomy is followed by applying valgus stress with special in situ distractor to create open medial wedge until a pre-calculated correction angle is achieved. After the limb axis is corrected, bone fragments are fixed by puddu type or T shaped locking titanium plate and screws (Figure 6). If there is a diastasis of 10 - 12 mm between bone fragments after osteotomy, open wedge gap is filled with synthetic bone building material, which reduces the time of bone tissue consolidation. The wound is closed, 1 active vacuum drain is placed in it and definitive fluoroscopy is performed. The patient is admitted to the intensive care unit for the next 24 hours, following antibiotic and thromboprophylaxis is administered. The average length of stay of the patient in the hospital is 4 - 5 days.

Figure 5. Sequential schematic image of the surgical technique.

Figure 6. Schematic and radiographic image of Paddu type locking LCP plate (OWO plate—tst medical company) with osteoconductive material of Beta tricalcium phosphate granules.

Taking into account the bone density of the patient and the strength of the achieved fixation, the movement of the knee joint with the CPM (continuous passive motion machine Figure 7) machine starts from the second day. This measurement reduces the risks of postoperative contracture and thromboembolic complications.

Figure 7. CPM machine -Improving Knee joint ROM with CPM Machine first days after the surgery.

Figure 8. Arthroscopic Chondroplasty with minced cartilage technique with Arthrex graft net tissue collection device.

Randomized studies described in various medical literature show that the functional status of patients improves even only after HTO procedure, even in studies lasting 10 - 15 years the results are positive. However, the results worsen over time. We have performed 50 surgical procedures of HTO with Chondroplasty in our institution. The work that we have provided there was presented not only the osteotomy procedure, but also the chondroplasty procedure in combination with HTO. Therefore, we believe it improves the functional result after the combined surgery. If we compare the results of the abovementioned procedure with the results of conservative treatment, the functional result of the HTO with chondroplasty (Figure 8) combined procedure according to the scoring system of WOMAC and KOOS prevails over the functional result of conservative treatment (Figure 9).

The primary goal of ongoing researches and newly published studies is to improve the methodology of chondroplasty procedure. In our work, the single staged chondroplasty method was used, however, long-term observation is required to say final positive conclusion. The microfracture procedure is gradually being replaced by two-stage and single stage chondroplasty methods. HTO implants are modified every year allowing to correct and fix cases causing deformations of tibia. On this experience we have developed concept plate (Figure 10 and Figure 11) which has corrected puddu type and T shaped plate’s drawbacks (Increased tibial slope, limited ROM, recurrence of varus deformity, Polyaxial locking possibility).

Figure 9. Serial radiographs of 65 year old woman. Serial X-ray films in the dynamics show 5 years postoperatively the preservation and slight increase of the medial compartment joint space compared to preop X-ray image.

Figure 10. Concept HTO plate Limazuka. First modification.

Figure 11. First modification of Limazuka concept plate.

I am grateful to all with whom I have had the pleasure to work during this research. Each member of my Dissertation Committee has provided me extensive personal and professional guidance. TSMU Trauma and Orthopedy department and LJ Clinic gave me possibility to make this research, therefore thanks all of them who even made one step forward and supported our team. This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. The authors have no conflicts of interest to declare. All co-authors have seen and agree with the contents of the manuscript.