Correlation between Osteoarthritis Knee Damage Based on Ultrasound with Kellgren-Lawrence Classification

Research Abstract: The classic standard criteria to diagnose osteoarthritis (OA) of the knee is the conventional radiological imaging. Ultrasonography could assess the osteoarthritis early and show invisible joint structures in osteoarthritis. This study aimed to compare the cartilage changes of trochlear femur and osteophytes (femur and tibia) through ultra-sound examination with the radiological imaging in stages to Kellgren-Lawrence (KL) classification. This is an observational study using cross-sectional design, involved 33 patients with knee OA who underwent conventional photo examination and ultrasonography at dr. Wahidin Sudirohusodo Makassar Hospital in the period of June August 2019. Spearman's test showed that there is a significant correlation between the stage of OA by KL and the stage of femoral trochlear cartilage damage (p 0.001) with strong correlation (r 0.828). Significant correlation is also between the stage of OA and the stage of osteophytes on the femur-lateral condyles both medial and lateral sides (p 0.001) with strong correlation (r 0.823; 0.79; 0.816, and 0.818). It concluded that the higher grade of femoral trochlear cartilage damage will result in the higher the stage of OA. The higher grade of osteophytes in knee joints will also result in the higher the stage of OA.


INTRODUCTION
Arthritis is a general term to describe a joint that experiences pain, stiffness and inflammation. Osteoarthritis (OA) is a degenerative disease of the joints, generally occurs at the age above 50 years with the characteristics of the cartilage degradation, bone hypertrophy at the edges (osteophytes), subchondral sclerosis and biochemical and morphological changes in the synovial membrane area and joint capsule. The classic standard criteria for conventional radiological imaging to establish the diagnosis and classify the stage of osteoarthritis of the knee is the Kellgren-Lawrence (KL) classification system; this system will assess the presence of osteophyte, narrowing joint gap and changes in bone morphology. While the conventional radiological examination is very limited in evaluating soft tissue changes and others changes related to inflammation, ultrasonography, on the other hand, could assess invisible joint structures on conventional photo examinations in osteoarthritis patients. 1,2,3,4 This study was conducted to examine cartilage changes of trochlear femur and osteophytes (femur and tibia) through ultrasonography examination. The purpose of this study is to assess the correlation between trochlear of femur and osteophyte condyles femur-tibia damage in stages to Kellgren-Lawrence classification of osteoarthritis. In this study, it is expected that there is a match between the stages of trochlear of femur cartilage and femoral-tibia osteophyte damage based on ultrasonography with the stages of osteoarthritis according to the Kellgren-Lawrence classification on conventional radiography. This research is expected to take part in promoting the use of ultrasound in assessing musculoskeletal diseases including in patients with osteoarthritis; Ultrasound could also assess the joint structures, in which the conventional photo examination could not. 5,6

MATERIALS AND METHOD
This is an observational study using cross-sectional method to examine the correlation between trochlear of femur and osteophyte condyles femur-tibia damage in stages to Kellgren-Lawrence classification of osteoarthritis in conventional radiological imaging. The minimal number of patients in this study were 32 samples of osteoarthritis patients using consecutive sampling method. The estimated sampling size (n) was calculated using the formula below: The study used 33 samples that were diagnosed as patient primary osteoarthritis according to the American College of Rheumatology criteria in Rheumatology Department in Wahidin Sudirohusodo Hospital. These research samples are men and women over 50 years old without any history of trauma. The osteoarthritis patient was taken as an outpatient or inpatient care at Dr. Wahidin Sudirohusodo Hospital from June to August 2019 and fulfilled the inclusion criteria. The sample that was diagnosed with primary knee osteoarthritis got their conventional knee photo taken and examined by radiology specialists according to the Kellgren-Lawrence classification. After that, the sample went through knee ultrasonography examination using a transducer linear with frequency 7-15 MHz in supine position. The results of the conventional imaging and ultrasonography was recorded and examined according to statistic method using Spearman correlation test.

a. Conventional Radiography
In osteoarthritis patients, conventional radiography of the antero-posterior position performed, where the patient holds the load with both knees in extension. This conventional knee photo was then examined by radiology specialists according to the Kellgren-Lawrence classification. In the Kellgren-Lawrence (KL) classification system, osteoarthritis is divided into 4 grading. 4 The grades 1-2 highlighted the findings of osteophytes while grades 3-4 more focused on the narrowing of the joint gap. Musculoskeletal ultrasound (USG) examination using a transducer linear with frequency 7-12 MHZ. OA knee patients were examined with ultrasound to assess cartilage trochlear of femur and femur-tibia osteophyte condyles on the medial and lateral sides. 7,8 On this research, we only use one of the patient's knees according

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to the OA grading value on the conventional photo. Trochlear femur cartilage examination is taken in the anterior compartment with the knee fully flexed with transverse transducer position. Description of cartilage damage trochlear femur on ultrasonography was divided into 4 grading. 9 Grade 0; shows the homogeneity of anechoic matrix cartilage with anterior edges and clear posterior. Grade 1; indicates the obfuscation or obliteration of cartilage edge. Grade 2; shows fatigue accompanied by obliteration of the cartilage edge as well narrowing of the cartilage band. Grade 3 if the cartilage band cannot be visualized.
An ultrasound examination to assess condyles femur and tibia were taken on the medial and lateral compartments are in the longitudinal transducer position parallel to the cortex femur bone and tibia bones tend to osteophyte findings on ultrasonography divided into 5 grading. Grade 0; no osteophytes, femoral condyles and tibia appear regular. Grade 1; osteophyte minor, only a small protrusion of the femoral condyles and tibia. Grade 2; small osteophytes are prominent on the surface of the condyles femoral and tibia, as well as large osteophytes separated from the surface of the condyles but has an inferior part in the joint space. Grade 3; large osteophytes appear with the inferior part in the joint space while the superior part slightly parallel to the femur and tibia. Grade 4; osteophytes largely parallel to the femur and tibia as well as little or no part in the inferior of joint space. 10

RESULTS
The data analysis consists of descriptive and Spearman correlation test. Descriptive analysis was conducted to see the number and percentage distribution characteristics for sex, age, body mass index (BMI), stage of OA of the knee by using a conventional photo KL classification, stage of femoral trochlear cartilage, osteophytes stage condyles medial and lateral femur, tibia condyles osteophyte stage medial and lateral knee by ultrasound. The number of patients in this study were 33 samples of osteoarthritis patients. Spearman's test was conducted to analyze the correlation between the stages of knee OA based on photographs of conventional (Classification KL) with the stages of damage to structures of the knee (cartilage and osteophytes) based on ultrasonography. Spearman correlation test results determined that there is a relationship statistically significant if p < 0.05. The distribution of OA patients by severity according to conventional radiography is shown in Table 2. It shows that the largest OA cases is in grade 2 with 10 patients (30.3%), and the smallest is at grade 3 with 6 patients (18.2%). Table 3 illustrates the distribution of the sample based on the stage of damage to the femoral trochlear cartilage by ultrasound. The table shows the patients with grade 2 femoral cartilage damage having the most samples 10 (30.3%) and we could still find a picture of normal cartilage in OA patient samples as many as 6 samples (18.2%).    Source: Primary Data Table 4 illustrates the distribution of samples by the stage of osteophyte. In medial femoral condyles, the grade 4 osteophytes were found with 16 samples (48.5%) while those with normal or without osteophytes in the medial femoral condyles were 3 samples (9.1%). Based on the stage of osteophyte at condyles medial of tibia, grade 4 osteophytes were found the highest with 15 samples (45.5%), the lowest number was in grade 2 with 3 samples (9.1%) while those who were still normal or invisible osteophytes in the medial tibia condyles were 4 samples (12.1%). Based on the stages of lateral femoral condyles osteophytes, grade 4 osteophytes were found the highest with 12 samples (36.4%) while those who were still normal or not visible osteophytes in the lateral femoral condyles were 5 samples (15.2%). Based on the stage of osteophytes lateral tibia condyles, grade 4 osteophytes were found the highest with 12 samples (36.4%) whereas the lowest is in grade 2 with 3 samples (9.1%) while those who were still normal or invisible osteophytes in lateral tibia condyles were 5 samples (15.2%). Table 5 shows that there are five samples of patients with osteoarthritis of Grade 1 who still has a normal femoral trochlear cartilage while there were 7 samples of Grade 4 OA patients who have a stage of cartilage damage Grade 3. With the results of the correlation analysis obtained by the p value of 0.001 (<0.05), it could be concluded that there is a significant correlation between the stage of OA by KL with the stage of femoral trochlear cartilage damage and has strong correlation with r value of 0.828.  Table 6 indicates a significant correlation between the stage of osteophytes on the femur-lateral condyles both medial and lateral sides with a stage of ostearthritis where a P value of 0.001 (<0.05). The correlation is strong with r values of 0.823 (medial condyles femur), 0.79 (medial tibia condyles), 0.816 (lateral condyles femur) and 0.818 (lateral tibial condyles).

DISCUSSION
In the results of the study shown in Table 1, it was found that more women suffer from OA compared to men. Although women have a smaller prevalence of OA than men when they are under 50 years of age, after the age of 50 years the prevalence increases in women, especially in the knee. This may be caused by the presence of postmenopausal estrogen deficiency after the age of 50 years. This sentence is in line with Price and Wilson's study which found the herbendens node was 10 times more common in women compared to men. 11, 12 At the final stage of OA, the symptoms usually receded, in addition to the patient's old age, many patients with the age above 71 no longer go to health facilities. In the Framingham OA study, 13 the prevalence of knee OA were found 1420 subjects with aged 60 years and higher. The prevalence of radiographic OA is increased with each decade of life from 33% among those aged 60-70 to 43.7% among those over 80 years of age. Whereas in Indonesia the prevalence of OA is quite high at 5% at the age of > 40 years, 30% at age 40-60 years and 65% at age of above 61.
Obesity is a risk factor and can make OA worsen. In addition to the effects of excess weight which must be tolerated by the knee in the weight bearing line, active adipose tissue is recognized in active metabolism that contributes to inflammation of the knee. Active adipose tissue increases the synthesis of proinflammatory cytokine such as leptin, adiponectin, resistin, interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF). In this study only 3 samples of obese OA patients were obtained 11,14 .
Kellgren-Lawrence classification grade ≥ 2 is indicated by the presence of osteophytes and grade ≥ 3 are indicated by narrowing of the joint gap. In several epidemiology studies, there are several different opinions regarding the prevalence of OA grading according to Kellgren-Lawrence. Preliminary studies on Caucasian ethnicities in the United States and Europe show that the prevalence of OA with KL grade ≥ 2 there are 30-40% whereas in Asia a higher prevalence is obtained, which is 60%. Then in the Johnston study and the National Health and Nutrition Examination Survey (NHANES) study reported in Africa-America has a radiological prevalence of knee OA that is higher than Caucasian. This shows the difference in prevalence is found according to KL grading which prioritizes osteophytes and narrowing of joint gaps. This is influenced by several factors involved in the formation of osteophytes and joint gaps in addition to the differences in subjectivity in assessing osteophytes in conventional radiography. 15 The loss of the classic composition of the cartilage is observed in patients with OA may be preceded by a focal process that manifests early on the surface area of the cartilage. The next step will be superficial cartilage fibrillation followed by a change in the composition of the cartilage which will give an idea of the loss of cartilage edge sharpness and reduced cartilage homogeneity on ultrasonographic examination (Grade 1). Focal lesions on these cartilages will then result in reduced cartilage volume that appears on ultrasonography as a narrowing of the cartilage band (Grade 2). The final stage can come to a state where there are no more cartilages, which in ultrasound examination found cartilage bands that can no longer be visualized (grade 3). 16,17,18 The severity of the trochlear cartilage damage is in line with the stages of OA, this has been supported by many past researchers. Okano's research also showed a strong correlation between narrowing of the tibio femoral joint in OA patients by grading cartilage damage using ultrasonography. 9 In this study, the stage of damage to Grade 2 cartilage on ultrasonography revealed as 5 cartilage thinning was found in 5 samples in Grade 2 OA patients (KL classification). Whereas in Grade 2 OA according to KL classification, no narrowing of the joints has been found. This can show that cartilage depletion does not absolutely reflects the narrowing of the joint gap. The study of Malas et al (2014) cit. Okano et al (2016), compared US meniscal bulging measurements and radiological KL grade and found a positive correlation. These results suggest that join space narrowing on radiograph may be affected by meniscal involvement and is not equal to cartilage loss 9,16 In this study out of 33 OA patients there were several patients that did not have osteophytes on either side of the condyles femur or the tibia condyles. The formation of osteophytes begins to grow on the medial side of the femur. Besides, the medial compartment is a weight bearing point. 19,20 The correlation between the stage of OA based on KL classification with the stage of osteophytes, showed that found a significant correlation (p < 0.001) and the strength of the strong correlation with the value (r) were all > 0.7. Where the heavier the stage of OA the heavier the stage of osteophytes. Some studies also suggest the same thing. Serban and Okano's research also showed a strong correlation between the stage of OA (KL) and the stage of osteophytes on ultrasonographic examination. 9,16

CONCLUSION
There is a significant positive correlation between trochlear femur cartilage damage and the stage of osteophytes on ultrasonographic examination with the stage of OA according to the KL classification on conventional radiography. The higher grade of femoral trochlear cartilage damage will result in the higher the stage of OA. The higher grade of osteophytes in knee joints will also result in the higher the stage of OA.