Abstract
Background/Aim
Knee osteoarthritis (KOA) is the most common disease in adults. We conducted a clinical study to evaluate the efficacy and safety of Bach Nien Kien (BNK) in supportive therapy for patients with symptomatic KOA.
Patients and Methods
An open interventional study was performed on 60 patients aged 38 to 70 with the diagnosis of symptomatic KOA. The patients were assigned to a study group (SG) with 30 subjects and a control group (CG) with 30 subjects using a matching method. The patients in SG were treated with electroacupuncture, glucosamine supplement, and BNK, while the patients in CG received the same treatment without BNK.
Results
At the end of the 30-day treatment (d30), the SG had a reduction in VAS score compared to a pre-treatment level of 3.03±0.96 points, which was more than the CG of 2.5±0.90 points. The excellent result in the SG was 10%, and the CG had no excellent result. The good result in the SG was 56.7%, and the CG group was only 26.7%. The moderate and poor results in the CG were high, 63.3%, and 10%, respectively; in the SG, only 26.7% and 6.7%. The difference in overall treatment results between the SG and CG was statistically significant (p<0.05). During the 30-day treatment period in both groups, no patient reported any undesirable effects.
Conclusion
Bach Nien Kien health supplement is effective and safe for controlling KOA symptoms and improving joint motion and quality of life for patients with symptomatic KOA.
Keywords: Osteoarthritis, knee osteoarthritis, knee pain, herbal medicine, health supplement, Bach Nien Kien
Osteoarthritis (OA), the most prevalent form of arthritis, is characterized by progressive cartilage destruction, adaptive osteogenesis, and gradual loss of joint function (1,2). Knee osteoarthritis (KOA) is the most common disease in elderly people of both sexes. Approximately 13% of women and 10% of men aged over 60 years are suffering from symptomatic KOA worldwide (3). KOA is a chronic joint disease with swelling, pain, joint movement restriction, and gradual loss of joint function (4). The economic burden of KOA in the U.S. is estimated to be $34 billion annually in healthcare expenditures (5). The diagnosis of OA is primarily based on the clinical history and physical examination, radiographic characteristics, including nonuniform joint space narrowing, subchondral sclerosis and cysts, marginal osteophytes, and subluxation (6).
The current treatment strategies for KOA are conservative and surgical. Conservative treatment, including locomotor exercise, medication, and orthotics, is dedicated to reducing pain and functional disability associated with KOA (7,8). Treatment options for patients with KOA remain focused on pain control, viscosupplementation, and prosthesis, targeting the clinical symptoms of KOA rather than modifying the disease course (9,10). Two major therapies for KOA, nonsteroidal anti-inflammatory drugs and corticosteroids, have been widely prescribed. However, they are not recommended for long-term treatment because of multiple side effects (11). Long-term usage of drugs can induce numerous adverse effects, such as gastrointestinal bleeding, peptic ulcer, hypertension, congestive heart failure, renal dysfunction, as well as hepatotoxicity (12). Therefore, current therapies are not optimal for patients, and there is no effective treatment to halt the progression of OA (13). Surgical treatment, including periprosthetic osteotomy and arthroplasty, is used for patients who are refractory to conservative treatment, as severe OA causes significant impairment in daily living activities. The number of surgeries increases every year, which increases not only the medical and economic burden but also revision surgeries due to implant loosening and infection (14).
Recently, several researchers have focused on the use of herbal medicine as a therapeutic strategy for inhibiting OA progression (15). Bach Nien Kien health supplement (BNK) is comprised of natural herbal extracts with a long-standing reputation in traditional medicine in many regions of the world for pain and arthritis. We conducted a clinical study to evaluate the efficacy and safety of BNK in 60 patients with symptomatic KOA.
Patients and Methods
BNK health supplement tablets. BNK has been approved by the Ministry of Health of Vietnam as a safe health food supplement for human use. BNK has been studied on experimental animals at the Department of Pharmacology - Hanoi Medical University and has proven a safe food supplement. The composition of BNK is listed in Table I. The production batch number was 010121, and the production expiration date was 12/01/202.
Table I. Composition of Bach Nieu Kien.
The ingredients of BNK are well-characterized and highly reputed as traditional herbal medicine for pain and arthritis. There were numerous published studies documenting the clinical efficacy of these ingredients and biological activities in cellular and animal experiments (16-24).
BNK dosage. During the first 14 days, the patients were administered three tablets twice a day. From the 15th to the 30th day, they were administered a maintenance dose of two tablets twice a day. BNK was recommended to be taken with warm water 1 h after meals.
Glucosamine sulfate tablets. The patients in the CG were administered two tablets of 500 mg glucosamine (vorifend forte, stada; Production lot: 350718; Expiration date: 14/05/2023), one in the morning and one in the afternoon on an empty stomach.
The formula for electroacupuncture. Acupuncture points were selected according to the regimen of the electroacupuncture technique for KOA treatment accepted by the Hanoi Hospital of Traditional Medicine.
Patient inclusion criteria. A total of 60 patients aged 38 to 70 years, regardless of sex, occupation, and disease duration, were recruited. The diagnosis of KOA was made according to the American Society of Rheumatology 1991 diagnostic criteria (25). The following were symptoms of KOA in the patients for the study: knee pain, osteophytes at the joint margins on radiographs, joint fluid (clear synovial fluid, reduced viscosity or synovial leukocytes less than 2,000 cells/mm³), and morning stiffness for less than 30 minutes. The selected patients with moderate pain had 3 ≤VAS scores ≤7. Patients voluntarily participated and followed the study protocol.
Patient exclusion criteria. Patients who received a nonsteroidal anti-inflammatory drug within 10 days or had received a topical corticosteroid injection within the last three months; patients with gastritis or stomach ulcer; patients who had a history of allergies, experience undesirable effects with aspirin, and people with digestive disorders, and digestive sensitivities; patients sensitive to the ingredients of BNK; patients with secondary knee arthritis; patients with acute comorbidities requiring special medical intervention; pregnant and lactating women.
Research method. The study was conducted according to the principles of an open intervention study, comparing different parameters before and after treatment in each group and comparing the SG with the CG.
Data processing. The data were processed using SPSS 20.0 software (IBM, Armonk, NY, USA) and expressed as percentages, means, and standard deviation. The mean values were compared using the student’s t-test and ratios using the c2 test. The results were considered statistically significant when p<0.05.
Location and time of study. The study was performed at the Department of Geriatrics, Hanoi Hospital of Traditional Medicine, between June 2021 and October 2022.
Research ethics. The study was approved by the Scientific Council of Hanoi Hospital of Traditional Medicine and the Biomedical Ethics Council of the Vietnamese Institute of Functional Foods. Before the study, patients were asked to agree to participate in the study, clearly explained the process and research purpose, and signed a commitment to participate in the study. The patients were given the opportunity to withdraw from the study for any reason.
Research protocol. Patients were comprehensively examined and selected in accordance with the study’s criteria, divided into study group (SG) and control group (CG) according to the matching method, ensuring the similarity between the two groups in terms of age, sex, severity, and duration of disease.
The treatment of the SG included electroacupuncture [30 min/time/day×10 consecutive days×2 times (between each 2-day break)], oral glucosamine sulfate 500 mg tablets (one tablet twice a day×30 days), and BNK for 30 days (the first 14 days three tablets twice a day and from the 15th day two tablets twice a day.
The treatment of the CG included electroacupuncture according to the regimen of the Ministry of Health [30 min/time/day×10 consecutive days×2 times (between each 2-day break)], oral glucosamine sulfate 500 mg (one tablet twice a day×30 days).
Clinical evaluation follow-up interval. The timeline of monitoring, evaluation, and comparison before and after treatment included: d0: the day before the treatment; d5: after 5 days of treatment; d10: after 10 days of treatment; d15: after 15 days of treatment; d20: after 20 days of treatment; d30: after 30 days of treatment.
Evaluation of clinical progress. Evaluation of pain level using visual analogue scales (VAS). The patient’s pain level was assessed on a VAS scale from 1 to 10 using the Astra-Zeneca scale (26). The ruler has two sides, one side divided into 11 equal lines from 0 to 10 points. On the one side, there are 5 images that can be conventionalized and describe the pain levels: no pain, little pain, moderate pain, much pain, and great pain. Pain scores are specifically assessed according to the score levels and were translated into a scoring system demonstrated in Table II.
Table II. Pain assessment according to Visual Analogue Scale (VAS).
Evaluation of knee function according to the Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Patients’ function was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score in Table III (27,28).
Table III. Evaluation of motor function according to the WOMAC index.
Assess the degree of joint mobility limitation by measuring the knee range of motion. The measuring tool is a specialized ruler with an angle scale graduated from (0-180 degrees) (29,30). The normal flexion amplitude of the knee joint is 135-140, and the maximum flexion is 150 degrees. The normal range of extension of the knee joint is 0 degrees (Table IV). The range of motion limitation was also estimated according to the heel-buttock distance (31) (Table V).
Table IV. Evaluation of knee range of motion.
Table V. Estimation of range of motion limitation according to the heelbuttock index.
Evaluation of paraclinical data. The paraclinical analyses included complete blood count (d0, d30) and blood biochemistry (d0, d30); X-ray of the knee joint in two upright positions before treatment; Ultrasound of knee joints in cases of suspicion of knee joint fluid (d0, d30).
Evaluation of the overall effectiveness of treatment. The overall results of the treatment were calculated by summarizing the points converted according to the VAS score, WOMAC index, knee range of motion measurement, and heel-buttock distance before and after treatment using the following formula:
Treatment effectiveness=
Excellent: treatment effect≥75%
Good: 50%≤treatment effect<75%
Moderate: 25%≤treatment effect<50%
Poor: treatment effectiveness<25%
Monitor for undesirable effects. The following clinical symptoms were monitored: pain, bleeding, and stinging at the place of electroacupuncture; nausea, vomiting, abdominal pain, gastrointestinal disturbances, diarrhea/constipation, allergies, and itchiness; pulse, blood pressure, and breathing rate as vital indicators; headache, dizziness, vertigo, and fatigue as central nervous system adverse effects; hematological and biochemical parameters at d0 and d30.
Results
General characteristics of the study patients. The average age of patients in the SG and CG was 60.03±7.80 years, ranging from 39 to 70 years. Patients aged 60 to 69 in both groups accounted for the highest percentage. The female population in both groups accounted for 83.3%. There was a similarity between the two groups of patients in terms of age, sex, and occupation (p>0.05). In both groups, manual labor accounted for a higher percentage than intellectual workers; the SG was 66.7%, and the CG group was 80% (p>0.05).
The disease duration was mainly over 3 years, with 56.7% in the SG and 63.3% in the CG. The mean disease duration of the 60 patients in the study was 5.33±4.06 years, 5.00±4.04 years for the study group, and 5.67±4.11 years for the control group. There was no difference between the two groups (p>0.05).
The percentage of patients with damage to both knee joints accounted for 56.7%, of which 50% were in the SG and 53.3% were in the CG. There was no statistically significant difference between the two groups (p>0.05).
All patients in the two groups had signs of joint pain. The sign of humping at the joints in the SG (66.7%) was lower than in the CG (76.7%). The limitations on knee flexion and extension in the SG (86.7%) were higher than those in the CG (83.3%). The difference in clinical symptoms between the two groups was not statistically significant (p>0.05).
Before treatment, the pain was mainly moderate to severe in both groups. Moderate pain was 60% in the SG and 66.7% in the CG. The severe level of pain in both groups was the same, accounting for 6.7%. At the time before treatment, 78.3% of patients in both groups had a very severe heel-buttock index, which was 70% in the SG and 86.7% in the CG. The severe limitation was 30% in the SG and 13.3% in the CG. The extent of knee injury on radiographs, mainly at grade II (according to the Kellgren and Lawrence classifications), accounted for 73.3% (32). Grade III was 13.3% in the SG and 10% in the CG. The differences between the two groups were not statistically significant (Table VI).
Table VI. Pain level, heel-buttock distance and extent of knee injury on x-ray before treatment.
Evaluation of treatment results. The pain reduction, according to the VAS scale, at all time points was better in the SG than in the CG. The difference in pain levels between the two groups after treatment was statistically significant (p<0.05) (Figure 1).
Figure 1. Comparison of pain levels according to the VAS scale of the two groups before and after treatment.
At all times, the performance in the SG decreased more than that in the CG. After 15 days of treatment, the WOMAC index was 12.07±5.59 (27.2% reduction) in the SG and 7.83±4.04 in the CG (17.5% reduction). After 30 days, the WOMAC index performance was 20.30±7.02 in the SG (45.8% reduction) and 13.00±6.18 in the CG (29.0% reduction) (p<0.01) (Table VII).
Table VII. Performance of WOMAC index over time of two groups.
Evaluation of the degree of improvement in knee range of motion. The performance improvement of the knee range of motion in the SG over time was higher than that of the CG. After 30 days, the improvement in knee mobility in the SG was 22.37±8.64 cm (19.6%) and that in the CG 17.30±6.02 cm (15.4%) (p<0.05).
After 30 days of treatment (d30), the mean buttock heel index of the two groups improved statistically significantly compared to the baseline (p<0.05). The buttock heel index was reduced from 19.07±5.61 to 9.07±2.74 in the SG and from 20.00±4.08 to 12.83±2.51 in the CG (p<0.05). After 30 days, the improvement of the heel-buttock index in the SG was 10.00±5.18 (52.4%), and that in the CG was 7.17±3.08 (35.9%) (p<0.05).
Evaluation of the overall treatment results. The overall treatment results in the SG were better than those in the CG: the level of excellent results in the SG was 10%, while the CG had no patients with excellent results. The level of good results in the SG was 56.7%, and in the CG was only 26.7%. The moderate and poor results in the CG were high, 63.3%, and 10%, respectively, and in the study group, only 26.7% and 6.7%. The difference between the two groups was statistically significant, with p<0.05 (Figure 2).
Figure 2. Comparison of the overall treatment outcomes of the study ad control groups.
Evaluation of side effects. During the 30-day treatment period, no patient had any undesirable effects, such as dizziness, headache, abdominal pain, loose stools, allergies, rash, or nausea in both groups. The index of pulse, temperature, and blood pressure before and after treatment in the two groups did not change statistically significantly (p>0.05) (Table VIII). The hematological and biochemistry profiles before and after treatment in both groups did not change statistically significantly (p>0.05) (Table IX).
Table VIII. Change in vital parameters before and after treatment in two groups.
Table IX. Changes in hematological and biochemical indicators of blood.
Discussion
KOA is a very common medical problem worldwide, and there is great concern that the number of patients will continue to increase (33,34). It is important to establish new treatments for inhibiting the progression of KOA in order to improve people’s quality of life, extend their healthy life expectancy, and reduce the burden of medical costs (5). KOA is a chronic disease that causes pain and deformity in joints, often without signs of inflammation. Pain, dysfunction, and joint deformity are common symptoms for which individuals with KOA seek medical care (35,36). The results of our study strongly suggest that electroacupuncture and glucosamine, in combination with BNK, is an effective therapeutic approach that can control the symptoms and improve knee functional limitation. The data of the study also showed that the patients in the SG, after 15 days of treatment, showed a statistically significant better analgesic effect when taking BNK at a therapeutic dose of 6 tablets per day compared to the CG. At the end of the treatment, the SG had achieved a pain control effect compared to CG, and the difference between the two groups was statistically significant (p<0.05). The overall treatment outcomes of the SG were better than that of the CG; the difference between the two groups after 15 days of therapy was statistically significant (p<0.05).
Overall, the results of the study showed that the SG showed improvement compared to CG regarding analgesic, inflammation, knee joint functional capability, and quality of life, which can be explained by the potentiating therapeutic effect of BNK.
In the present clinical study, all patients in the two groups were monitored for vital signs and unwanted effects. During 30 days of treatment, none of the patients in either group experienced any side effects, such as allergic rash, dizziness, headache, abdominal pain, nausea, or stomach and digestive disturbances. Furthermore, vital indicators in both groups were stable during treatment. There were also no significant changes in hematological and biochemical parameters in any of the groups. Taken together, these results showed that BNK is a safe and well-tolerated health supplement.
Conclusion
Bach Nien Kien health supplement is effective and safe for controlling KOA symptoms and improving joint motion and quality of life for patients with symptomatic KOA. The results of our study strongly suggest that electroacupuncture and glucosamine, in combination with BNK, may be an effective therapeutic approach that can inhibit the progression of KOA.
Conflicts of Interest
All Authors declare no conflicts of interest regarding this study.
Authors’ Contributions
HMV: Investigation, data curation, writing – original draft; HDT: Investigation, data curation, writing – review & editing; AKN: data curation, conceptualization, writing – review & editing; BH: conceptualization, writing – review & editing; BXH: Methodology, conceptualization, writing-original draft-reviewing & editing. All Authors read and approved the manuscript prior to submission.
Acknowledgements
The study was Author-initiated. Fobic Pharma LLC donated Bach Nien Kien health supplement for the study.
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