Introduction
The number of patients treated for knee osteoarthritis (OA) per year has increased from 2,200,331 in 2010 to 2,968,567 in 2019. Consequently, the cost of treatment for knee OA ranked 2nd in the total medical care benefit expenses for inpatients, and 5th in the total medical care benefit expenses for outpatients in 2019 [1].
The unclear etiopathogenesis of knee OA limits classification of subgroups of the disease [2]. However, there are distinct subtypes of knee OA, with clear differences in structural degradation and symptoms. Additionally, the different risk factors of the subtypes suggest that each risk factor leads to a different type of knee OA [3]. Recent studies have shown that knee OA is a secondary disease, and subsequently, studies have limited the classification of the disease to phenotype. This is still the most widely used subgrouping type [4]. A primary phenotype refers to those patients without a specific cause, and a secondary phenotype is knee OA caused by trauma and developmental, metabolic, endocrine, and other disorders including anterior cruciate ligament (ACL) tears, meniscal tears, and osteochondral lesions [5,6].
OA occurs in 3 compartments (medial, lateral, and patellofemoral) and these may arise either individually or simultaneously. Medial and lateral compartments show different characteristics [3], and differences in pain, stiffness, and physical function were observed in subgroups of patellofemoral alone and multi-compartment OA [7]. Additionally, a retrospective study assigned patients with knee OA into medial, lateral, and patellofemoral compartments and assessed whether partial knee replacement was appropriate in each compartment [8].
The coexisting disorders of knee OA include cardiovascular disease, obesity, and diabetes mellitus. In particular, musculoskeletal comorbidities affect the severity of the symptoms of knee OA [9]. For example, joint effusion is a key clinical sign associated with the development of pain and stiffness [10], and meniscal injury or meniscal ectomy is related to the development of knee OA [11]. Moreover, pain in patients with knee OA is also affected by subchondral bone lesions [12], and bone marrow lesions [13]. In addition, disease progression is also related to bone marrow lesions [13].
Knee OA is characterized by gradual degenerative changes in the joints and commonly affects weight-bearing joints [14]. Increased physical load on the joints stimulates degenerative changes in the joint; thus, a high body mass index (BMI) is a high risk factor for knee OA [15]. The correlation between knee OA and obesity suggest that obesity affects the onset, symptoms, and prognosis of knee OA. Therefore, management of obesity is important for improving symptoms [16].
Knee OA management aims to improve the quality of life (QoL) of patients by reducing pain and increasing mobility [17]. The Osteoarthritis Research Society International guidelines published in 2019 for knee OA core treatments included education about arthritis and structured physical exercise programs with or without dietary weight management [18]. Topical nonsteroidal anti-inflammatory drugs (NSAIDs), cyclo-oxygenase (COX)-2 inhibitors, intra-articular (IA) corticosteroids, and IA hyaluronic acid are also currently recommended for nonsurgical management of knee OA [18]. However, there are some limitations associated with the use of these drugs. NSAIDs may cause gastrointestinal conditions/diseases, such as intestinal bleeding, indigestion, nausea, vomiting, and hypersensitivity (rash) [19]. In comparison, COX-2 inhibitors cause fewer gastrointestinal disorders than general NSAIDs, however, they increase the risk of developing cardiovascular disease [20]. In addition, IA administration of steroids may lead to cartilage destruction, and infections due to repeated injections [21].
In Korea, traditional Korean medicine and Western medicine coexist, and patients can choose to receive either type of medicine or both simultaneously. In Korean medicine, acupuncture, herbal medicine, and pharmacopuncture are used in combination to treat knee OA and have been shown to give synergistic effects [22,23]. These Korean medicine treatments are provided as combination therapy, and a previous study of in patients with knee OA have been shown to be effective [24].
This study aimed to analyze the demographic characteristics, and symptom improvements of 122 patients admitted as inpatients in a Korean medicine hospital and treated for knee OA. To evaluate symptoms the numeric rating scale (NRS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) were used to determine the levels of pain, and quality of life was measured using the 5-level EuroQol-5 Dimension (EQ-5D-5L) scores.
Materials and Methods
Patients
Patients who were hospitalized for 4 days or more at the Hospital of Korean Medicine with knee pain between January 2015 and June 2020 were included in this retrospective review study. Magnetic resonance imaging (MRI) was used because it is a more suitable modality compared with an X-ray scan for diagnosing soft tissue damage and other comorbidities associated with OA. Of the 381 patients in the electronic medical records who were diagnosed with knee OA based on MRI findings, 91 patients’ chief complaint was not concerning the knee joint, 2 patients had an NRS score less than 4, 146 were hospitalized for less than 4 days, and 20 patients did not complete the questionnaire upon discharge, thus 259 patients were excluded. A total of 122 patients were included in this study (Fig. 1).
Inclusion criteria
Patients in the electronic medical records diagnosed with knee OA based on MRI findings, whose chief complaint was knee pain, whose knee pain NRS score was ≥ 4, and were hospitalized for ≥ 4 days were included in this study.
Exclusion criteria
Patients who had knee pain following a car accident, those patients who had been diagnosed with other serious conditions/diseases around the knee (malignant tumor, fracture, and infection), those who did not complete the questionnaire upon discharge, and those unsuitable for this research, as per the investigator’s discretion, were excluded from the study.
Ethics statement
This retrospective study was approved by the institutional review board of the Jaseng Hospital and research ethics were adhered to. To protect the patients’ personal information, their medical records were accessed after approval from the Institutional Review Board of the Jaseng Hospital of Korean Medicine (no.: 2020-09-014).
Baseline characteristics
Demographic data of the participants included sex and age. The cause of knee OA was divided into 4 categories: (1) unknown; (2) overwork or over-exercise; (3) fall or trauma; and (4) surgery. Based on the Asia-Pacific BMI standards of the World Health Organization, the patients’ BMI was divided into underweight/normal/pre-obese/obese Class 1/obese Class 2 [25]. Medical history included hypertension, diabetes mellitus, depression, and cardiovascular, respiratory, gastrointestinal, and musculoskeletal diseases. The OA compartment was classified into medial, lateral, and patellofemoral. The OA phenotype was divided into primary and secondary. Comorbidities included chondral lesions, fluid, meniscus tears, cysts, bone marrow edema, and ACL tears. The distribution of hospitalization length was divided into 7 days.
Treatments
Inpatient treatment included acupuncture, cupping, pharmacopuncture, herbal medicine, chuna therapy, medicinal steaming therapy, manual therapy, and extracorporeal shock wave therapy.
Acupuncture
Stainless steel disposable sterile needles (0.25 × 40 mm) were used for acupuncture treatment (Dong-bang Medical Equipment Manufacturer, Boryung, Korea). Electroacupuncture was performed at 1.0–2.5 cm depth at ST34, SP10, SP9, ST36, ST35, and EX-LE4 acupoints and ashi-points twice a day for 15 minutes each (2–8 Hz).
Cupping
The cups used for cupping were disposable and 37 mm in diameter (Dong-bang Medical Equipment Manufacturer, Boryung, Korea). Wet and dry cupping was performed at BL40 and ashi-points twice daily for 4 minutes each.
Pharmacopuncture
Disposable, single-use, 26-gauge, 13 mm needles with a 1 cc syringe (Sungshim Medical, Bucheon, Korea), filled with 6 cc of refrigerated Shinbaro pharmacopuncture solution (Jaseng herbal medicine dispensary, an extramural facility meeting Korean Good Manufacturing Practice standards) was injected into the acupuncture point (ST35 and EX-LE4) to a needle depth of 0.5–1.0 cm.
Herbal medicine
The patients were prescribed Chungpajun-shinBang No. 2 decoctions (120 mL/package) and Chungshinbaro-Hwan (tablet) 3 times a day (Table 1).
Chuna therapy
The patient underwent chuna therapy once daily. Chuna therapy includes joint mobilization and traction techniques.
Medicinal steaming therapy
Medicinal steaming therapy was administered once daily. Geoseubhwalhyeoljitongtang, which is used to treat musculoskeletal disorders, was placed in a medicine bag, steamed, and placed on the affected knee joint for 15–20 minutes (Table 2).
Assessment methods
NRS
The extent of knee pain and discomfort was assessed using the NRS which is a subjective pain scale where the patient indicates their pain as a whole number from 0 to 10. where 0 indicates “no pain or discomfort” and 10 indicates “the most severe pain and discomfort imaginable.” NRS scores were recorded at admission and discharge from the hospital.
WOMAC
WOMAC is an index for the assessment of pain in patients with OA and is one of the most widely used indexes to assess disorders related to OA pain and joint function. The WOMAC index consists of 3 subdomains with a total of 24 items. Among these, there are 5, 2, and 17 items on pain, stiffness, and physical function, respectively, to evaluate the overall functional capacity of the joints. Each item was evaluated on a 5-point Likert scale (0 = none, 1 = mild, 2 = moderate, 3 = severe, 4 = extreme) or using 2 types of visual analog scale (a score of 0 to 10 divided into 5 levels). The total points of items on pain, stiffness, and physical function were 0–20, 0–8, and 0–68 points, respectively, and each item was given the same weighted value. The validity of the WOMAC index was validated in 1988 by Bellamy et al [26], whereby scores were recorded at admission and discharge from hospital. In this study, the WOMAC scores were used to evaluate each category (pain, stiffness, and physical function) by comparing before and after treatment between the subgroups.
EQ-5D-5L
The EQ-5D-5L is a method of indirectly calculating the weights of certain health states for QoL after a multidimensional investigation of state of health, and is the most widely used instrument for this purpose [27]. The EQ-5D consists of 5 questions about current health state (mobility, self-care, usual activities, pain, and anxiety/depression), and each question is scored on a 5-point Likert scale (1 = no problems, 2 = slight problems, 3 = moderate problems, 4 = severe problems, 5 = extreme problems). In this study, the Korean version of EQ-5D-5L was used, which has been validated for evaluating knee OA [28]. The EQ-5D-5L scores were recorded at admission and at discharge from hospital.
Data analysis method
Statistical analysis was conducted using SPSS Version 27.0 for Windows (IBM Corporation, USA). Categorical variables, such as baseline characteristics, are presented as frequencies and percentages. Continuous variables are presented as the mean ± standard deviation (SD) of the scores for changes in the NRS, WOMAC index, and EQ-5D-5L index. Comparisons before and after treatment shown in Tables 3–5 were examined for normality before statistical analysis using a paired t test for parametric data and the Wilcoxon signed-rank test for nonparametric data. The differences between groups shown in Tables 3–9 were analyzed by the Student t test when the number of variables was 2, and by the 1-way ANOVA test when the number of variables was more than 3. Statistical significance was reached when p values were < 0.05.
Results
Baseline characteristics
The total number of inpatients was 122, with 17 males and 105 females. The mean age was 63.44 years, with 68 patients in their 60s (55.74%). There were 93 cases (76.23%) with unknown causes and 16 (13.11%) from falls or trauma. The inpatient mean value for BMI was 24.04 (pre-obese). There were 47 cases (38.52%) in the normal range, 31 cases (25.41%) were pre-obese, 37 cases (30.33%) were obese Class 1, and 5 cases (4.10%) were obese Class 2. The distribution of inpatients’ medical history consisted of 90 cases (73.77%) of musculoskeletal disease, 35 cases (28.7%) of hypertension, and 26 cases (21.31%) of cardiovascular disease. The distribution of the knee compartment affected by OA, as discovered by MRI findings, included 35 cases (28.69%) in the medial compartment, 24 cases (19.67%) in the patellofemoral compartment, and 43 cases (35.25%) in both the medial and patellofemoral compartments. In the distribution of phenotypes discovered by MRI, there were 118 cases (96.72%) classified as a primary phenotype and 4 cases (3.27%) which were classified as a secondary phenotype. Regarding the distribution of comorbidities with OA, 82 patients had meniscal tears (67.21%), 82 patients had cysts (67.21%), and 81 had a bone marrow edema (66.39%). The mean hospitalization period for all inpatients was 28.16 days (Table 10).
Treatments
The means and SDs of treatment times are shown in Table 11. Korean medicine and physiotherapy treatments are shown as the number of times an inpatient received treatment (Table 12). Spearman’s correlation coefficient analysis for the number of treatments and changes in NRS scores were as follows: acupuncture (0.319; p < 0.001), herbal medicine (0.298; p < 0.001), pharmacopuncture (0.27; p < 0.01), chuna therapy (0.275; p < 0.01), medicinal steaming therapy (0.308; p < 0.01), cupping (0.231; p < 0.05), and manual therapy (0.192; p < 0.05). The correlation coefficient of ESWT was not statistically significant (Table 13).
Assessments
In a comparison before and after treatment, the NRS score significantly decreased from 5.39 ± 0.85 to 3.60 ± 1.02 (p < 0.001), the WOMAC (pain, stiffness, physical function, total) scores significantly decreased from 10.22 ± 3.56 to 7.42 ± 3.14 (p < 0.001), 4.09 ± 1.68 to 3.02 ± 1.53 (p < 0.001), 37.02 ± 11.43 to 26.16 ± 10.83 (p < 0.001), 51.34 ± 15.66 to 36.60 ± 14.68 (p < 0.001), respectively, and the EQ-5D-5L score significantly improved from 0.57 ± 0.17 to 0.62 ± 0.02 (p < 0.05; Table 14).
The NRS scores before and after treatment were grouped by hospitalization period, sex, age, BMI, history, and comorbidities (Table 3). All NRS scores decreased significantly in each group (p < 0.001). When NRS scores were grouped by knee compartment, the medial, the patellofemoral, the medial + patellofemoral, and the medial + lateral + patellofemoral compartment NRS scores decreased significantly. A comparison of the scores from patients with differing hospitalization periods indicated that the decrease in NRS scores was significant in at least 1 group (p < 0.01). A comparison of NRS scores between the groups with or without musculoskeletal disease showed a significant difference (p < 0.01).
Analyses of the WOMAC scores before and after treatment were grouped by hospitalization period, sex, age, BMI, history, and comorbidities; the scores decreased significantly in each group after treatment (p < 0.05). When the WOMAC scores were grouped by knee compartment, the medial, the patellofemoral, the medial + patellofemoral, and the medial + lateral + patellofemoral compartment WOMAC scores decreased significantly (p < 0.001) (Table 4).
Analysis of EQ-5D-5L scores before and after treatment is shown in Table 5 were grouped by hospitalization period with only 1 hospitalization period (29–42 days) which improved significantly (p < 0.05). When grouped by BMI score, only the obese Class 1 and 2 showed significant improvement (p < 0.05). When grouped by knee compartment, only the medial group improved significantly (p < 0.05). When comparing groups of patients according to hypertension, cardiovascular disease, and musculoskeletal disease, the group without each condition/disease showed significant improvement (p < 0.05). When grouped by comorbidities, the group of patients with joint effusion, without a cyst, or without ACL tears showed significant improvement (p < 0.05).
When comparing the improvement of indicators between patients with OA in the medial compartments and those with OA in the patellofemoral compartments, there were significant differences in the WOMAC (pain, stiffness) scores (p < 0.05) (Table 6). When comparing improvement of indicators of the 122 inpatients both with and without OA in the medial compartment, there were significant differences in WOMAC (pain, stiffness, total) scores (p < 0.05) (Table 7). A comparison of the improvement of indicators between those patients with and without OA in the lateral compartment, showed no significant differences (Table 8). Similarly, when comparing the improvement of indicators in patients with and without OA in the patellofemoral compartment, there were no significant differences in the indicators (Table 9).
Discussion
In this study, a total of 122 inpatients who were admitted to the Hospital of Korean Medicine for knee pain, and were diagnosed with knee OA based on MRI findings, underwent Korean medicine treatment. Seventeen males and 105 females were included in this study (ratio of 1:6.17). Having more females with knee OA was consistent with another study of knee OA [29]. The age distribution of the patients included in this study, all of whom underwent Korean medicine treatment, were mostly in their 60s. A cause of knee OA included trauma, however, the cause was unknown in most cases. This is consistent with the finding that knee OA is caused by degeneration [29]. Only one of the 122 patients were within the underweight BMI category. Approximately 38.52% patients had a BMI in the normal range, whereas most had a BMI in the pre-obese category or higher (59.84%). This finding supports the results of a previous study on the correlation between obesity and OA [15]. The high rate of hypertension and cardiovascular disease may be due to the increased frequency of these 2 conditions/diseases in those patients with a high BMI.
In this study, the MRI findings suggested that knee OA mostly manifests in the medial and patellofemoral compartments, and there were many cases of coexistence in both compartments. Furthermore, 118 (96.72%) patients had primary knee OA based on MRI findings. Since the phenotype was determined based only on MRI findings, there was a limitation in assessing whether the disease developed secondary to another disease. In the current study, the distribution of comorbidities on MRI findings was assessed. Meniscus tears, cysts, and bone marrow edema were frequently observed. This finding is consistent with the results of previous studies on common complications of knee OA [12,13,15].
The participants underwent Korean medicine treatment including acupuncture, cupping, pharmacopuncture, herbal medicine, chuna therapy, and medicinal steaming therapy, as well as Western treatments such as manual therapy, and ESWT. Acupuncture is included in the OA treatment guidelines using Korean medicine owing to its beneficial effects and low risk [30]. Various clinical trials and meta-analyses have demonstrated that acupuncture [31–36], and electroacupuncture (where an electric current is passed through a needle, has been shown to be effective for knee OA [37]. Additionally, a systematic review and meta-analysis study has shown that combination therapy of Western medicine and cupping therapy leads to greater treatment efficacy and physical function in patients with knee OA compared with Western medicine alone [38]. Pharmacopuncture is a treatment in Korean medicine where herbal medicine extracts are injected at acupuncture points related to conditions/diseases, tender points, or positive reaction points based on meridian theory [39]. Studies have shown that various types of pharmacopuncture are effective for knee OA [40–42], and both acupuncture and pharmacopuncture do not cause serious side effects in musculoskeletal diseases [43]. In this study, Shinbaro pharmacopuncture was performed, which has been reported to have a similar efficacy and safety profile to celecoxib, a COX-2 inhibitor [44]. Clinical studies have also demonstrated that herbal medicine is effective in the treatment of knee OA [45–47]. Chuna therapy is a representative Korean medicine treatment that treats an unbalanced body and a blocked meridian system using direct manual treatment. It is often used to treat spinal, joint, muscle-related, and viscerogenic conditions/diseases. Chuna therapy has been reported to improve flexor and extensor muscular tension in patients with OA [48].
Analysis of the correlation between treatment and indicator of pain improvement showed that the NRS score significantly correlated with all treatments except for ESWT. In particular, compared with the other treatments in this study, acupuncture, herbal medicine, and medicinal steaming therapy had a relatively higher correlation with NRS scores. Although the scores in this study were not high, these findings suggest that these 3 treatments played a major role in the Korean medicine treatment of knee OA when compared with the other treatments.
By comparing the NRS and WOMAC scores before and after treatment, Korean medicine treatment effectively controlled pain, stiffness, and physical function of the knee, regardless of sex, age, BMI, presence or absence of medical history, and presence or absence of comorbidities. Patients with a history of musculoskeletal disease showed less improvement in the NRS score compared with those patients without musculoskeletal disease. This indicated that patients with OA and musculoskeletal disease showed less improvement in pain after Korean medicine treatment than patients without a musculoskeletal disease. When grouped by compartment, the mean scores of all groups improved. In the group where analysis was possible, patients with medial and patellofemoral alone, patients with medial and lateral at the same time, and patients with OA in all 3 compartments showed significant improvement in NRS and WOMAC scores. It appears that Korean medicine treatment was effective in controlling knee pain, stiffness, and physical function in patients with OA in the aforementioned compartment.
When comparing EQ-5D-5L before and after treatment, the mean score showed significant improvement. This indicated that Korean medicine treatment was effective at improving the QoL of patients with OA. However, in subgroup analysis, not all groups were statistically significant. From the perspective of improving the QoL, when looking at subgroups of patients in terms of the hospitalization period, 4–6 weeks of Korean medicine treatment was the most suitable time period for improving QoL. By comparing the BMI groups, the higher the obesity index, the greater the likelihood that Korean medicine treatment could improve QoL. When looking at the subgroups in terms of the OA compartment, Korean medicine treatment was more effective in the medial compartment OA compared with other compartments in terms of improving QoL.
Korean medicine treatment was more effective in the patellofemoral compartment compared with the medial compartment in terms of pain and stiffness. Accordingly, Korean medicine treatment was more effective in patients without OA in the medial compartment compared with patients with OA in the medial compartment in terms of pain and stiffness.
This was a retrospective study where a control group for comparison with the treatment group was not included. The lack of long-term follow-up also limited the assessment of the long-term effects of Korean medicine treatment. The participants in this study could have had diseases other than OA in their knee, therefore pain experienced in these patients may have been attributable to other conditions/diseases. Additionally, the MRI findings alone where not sufficient to provide the grade of OA, and consequently the number and type of Korean medicine treatment differed for each patient. Thus, the detailed effects of each treatment could not be evaluated. In the compartment group, since the number of patients in the lateral, medial + lateral, lateral + patellofemoral compartment was too small, statistical analysis could not be performed.
The current study was a relatively large-scale analysis study compared with previous studies which have analyzed the effects of Korean medicine treatment in inpatients. This study included a larger sample size for the analysis, which supports the results of previous studies. Quantitative indicators such as the NRS, WOMAC, and EQ-5D-5L scores were analyzed to objectively assess the effects of treatment. In particular, the detailed indicators of the WOMAC index were analyzed to evaluate improvements in the levels of pain, stiffness, and physical function. The patients included in this study had been diagnosed with OA based on the MRI findings. Thus, the comorbidities of soft tissues could be analyzed which allowed evaluation of the effects of Korean medicine treatment according to the OA compartment and comorbidities based on MRI findings.
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