Knee osteoarthritis (OA) is a common articular disease, affecting not only the joints but also the surrounding muscles and causing falls, disabilities, and dependency in older people [
There is no gold standard treatment for knee OA. Pharmacological approaches include analgesics, anti-inflammatory agents, intra-articular corticosteroids or hyaluronic acid, glucosamine sulphate, chondroitin sulphate, and some experimental treatments already widely used. However, these drugs have some adverse effects such as constipation, nausea, and excessive sedation in older people, and their effect on cartilage with OA symptoms remains controversial [
The herbal drug Guilu Erxian Jiao (GEJ) is a multicomponent Chinese herbal supplement that has been used for treatment of degenerative joint diseases without adverse effects for two thousand years [
The primary purpose of the present study was to investigate the therapeutic effects of 12 weeks of GEJ treatment on muscle strength in elderly male patients with knee OA. The secondary purpose was to investigate the effects of the same regimen on articular pain, the Lequesne disability index, and blood markers (liver and renal function).
A total of forty-two elderly men with knee OA who were regularly followed up at outpatient clinics of the departments of rheumatology and traditional Chinese medicine (TCM) were enrolled. Patients were included if they met the following criteria: males aged 65 years or older who could walk independently, fulfilled the 1986 American College of Rheumatology (ACR) classification of knee OA [
We enrolled 42 elderly men with knee OA, including 21 patients who received the herbal drug GEJ as the case group and 21 patients who did not receive GEJ and received the same Western medication as the control group. This study evaluated the effects of 12 weeks of GEJ treatment on muscle strength of lower limbs, physical function, and articular pain. The dominant side of the OA knee was defined as the joint with articular pain (VAS) > 5.
Twenty-one patients received four capsules three times a day of Guilu Erxian Jiao extract, 6 g/daily for 12 weeks. The GEJ capsules (batch number: CB118-091610) were prepared according to the well-documented TCM formula described in a TCM book known as “The Golden Mirror of Medicine,” and provided by the Sun Ten Pharmaceutical Company, Ltd., Taiwan (drug permit license number-042004, Department of Health, Taiwan). The Sun Ten Pharmaceutical Company, Ltd. has received the herbal Good Manufacturing Practice (GMP) certification in Taiwan. The components of the GEJ capsules are Carapax and Plastrum Chrysemys (species:
Muscle strength of the knee extensors and flexors was assessed by an isokinetic dynamometer (Biodex Medical Systems, Inc., Shirley, NY, USA) according to the peak torque/body mass variable (Nm/kg) at a velocity of 60°/s. Maximum strength tests (one repetition maximum or 1RM) were performed fortnightly. Then, a new 80% load was prescribed during the interval between the strength tests. Participants were given 3% increments in load per session as tolerated [
The pain severity of knee OA was evaluated by the visual analogue scale (VAS) at baseline and after 12 weeks in the two groups on a weight-bearing posture (walking) for 5 minutes. The instrument consists of horizontal lines 10 cm long, with anchor points of 0 (indicates no pain) and 10 (indicates maximum degree of pain.). The average of three measurements was recorded, and a 10-minute interval was set between tests to allow for more consistent measurement conditions [
Disability of patients with knee OA was evaluated using the Lequesne index (LI) [
Descriptive statistics were run on all variables. Associations among variables, including baseline characteristics, muscle strength, the Lequesne index, and pain outcomes, were evaluated with the Mann-Whitney
We used logistic regression to estimate the ORs and 95% CIs for the association between the GEJ-treated group and the non-GEJ-treated group. Effects of herbal drug treatment were also assessed and the results were analyzed to identify any trends. The level of significance was established at
Table
Baseline clinical characteristics of the non-GEJ-treated group and the GEJ-treated group.
Variables | Non-GEJ-treated group ( |
GEJ-treated group ( |
|
||||
---|---|---|---|---|---|---|---|
Median |
|
|
Median |
|
| ||
Age, years | 83.00 | 81.00 | 87.00 | 82.00 | 80.00 | 86.00 | 0.528 |
BMI, kg/m2 | 24.39 | 23.11 | 25.16 | 23.44 | 21.23 | 25.79 | 0.462 |
ADL | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 100.00 | 0.075 |
Lequesne index | 4.00 | 0.00 | 6.00 | 6.00 | 3.00 | 9.00 | 0.108 |
Test for balance | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.317 |
PeakTQ-ext-nondominant (Nm) | 31.60 | 21.50 | 52.90 | 38.80 | 18.20 | 45.90 | 0.725 |
PeakTQ-ext-dominant (Nm) | 25.70 | 12.00 | 52.50 | 29.10 | 19.50 | 49.60 | 0.624 |
PeakTQ-flex-nondominant (Nm) | 17.40 | 11.60 | 26.70 | 19.50 | 14.40 | 32.60 | 0.801 |
PeakTQ-flex-dominant (Nm) | 17.30 | 10.80 | 28.90 | 18.80 | 15.70 | 33.20 | 0.345 |
TQ/BW-ext-nondominant (ft·lb/lb) | 43.10 | 29.60 | 93.10 | 66.60 | 35.30 | 83.10 | 0.538 |
TQ/BW-ext-dominant (ft·lb/lb) | 34.80 | 18.20 | 77.10 | 57.80 | 27.40 | 82.40 | 0.365 |
TQ/BW-flex-nondominant (ft·lb/lb) | 26.30 | 16.40 | 40.20 | 33.00 | 24.40 | 51.20 | 0.473 |
TQ/BW-flex-dominant (ft·lb/lb) | 25.50 | 17.90 | 46.10 | 37.30 | 24.20 | 53.80 | 0.204 |
Mann-Whitney
Table
Changes in muscle strength, VAS, and Lequesne index scores from baseline to 12 weeks in the non-GEJ-treated group and the GEJ-treated group.
Variables | Non-GEJ-treated group ( |
GEJ-treated group ( |
|
||||
---|---|---|---|---|---|---|---|
Median |
|
|
Median |
|
| ||
Incremental changes in muscle strength | |||||||
PeakTQ-ext-nondominant (Nm) | 2.10 | −4.80 | 14.30 | 17.70 | 3.90 | 28.20 | 0.090 |
PeakTQ-ext-dominant (Nm) | 4.60 | −1.60 | 11.70 | 14.80 | 3.30 | 23.20 | 0.105 |
PeakTQ-flex-nondominant (Nm) | 3.30 | −3.40 | 8.20 | 2.90 | −1.20 | 10.20 | 0.308 |
PeakTQ-flex-dominant (Nm) | 3.70 | −1.40 | 8.80 | 2.80 | −2.40 | 10.60 | 0.870 |
TQ/BW-ext-nondominant (ft·lb/lb) | 4.70 | −2.60 | 26.60 | 29.70 | 6.90 | 51.30 | 0.080 |
TQ/BW-ext-dominant (ft·lb/lb) | 6.10 | −2.90 | 20.40 | 29.30 | 6.00 | 37.30 | 0.063 |
TQ/BW-flex-nondominant (ft·lb/lb) | 5.20 | −6.00 | 11.60 | 4.90 | −1.80 | 17.90 | 0.308 |
TQ/BW-flex-dominant (ft·lb/lb) | 6.20 | −2.50 | 12.70 | 4.80 | −3.70 | 16.40 | 0.811 |
Levels of muscle strength of the two groups pre- and posttreatment | |||||||
TQ/BW-ext-dominant-pretreatment (ft·lb/lb) | 34.80 | 18.20 | 77.10 | 57.80 | 27.40 | 82.40 | 0.365 |
TQ/BW-ext-dominant-posttreatment (ft·lb/lb) | 50.20 | 26.50 | 70.00 | 87.10 | 58.90 | 99.40 | 0.012* |
TQ/BW-flex-dominant-pretreatment (ft·lb/lb) | 25.50 | 17.90 | 46.10 | 37.30 | 24.20 | 53.80 | 0.204 |
TQ/BW-flex-dominant-posttreatment (ft·lb/lb) | 27.50 | 18.30 | 52.30 | 47.50 | 38.20 | 58.60 | 0.045* |
Decremental change of visual analog pain scale score | 0.00 | −1.00 | 0.00 | 0.00 | 0.00 | 2.00 | 0.001** |
Decremental change of Lequesne index score | −1.00 | −3.00 | 0.00 | 2.00 | 1.00 | 4.00 | 0.0003** |
(I) change of pain or discomfort | 0.00 | −1.00 | 0.00 | 1.00 | 0.00 | 2.00 | 0.002** |
(II) change of maximum distance walked | 0.00 | −1.00 | 0.00 | 0.00 | 0.00 | 1.00 | 0.003** |
(III) change of activities of daily living | 0.00 | −1.00 | 0.00 | 1.00 | 0.00 | 2.00 | 0.025* |
Mann-Whitney
Measurements of muscle strength, VAS, and Lequesne index scores in the GEJ-treated group (
Variables | Pretreatment | Posttreatment | |||||
---|---|---|---|---|---|---|---|
Median |
|
|
Median |
|
|
|
|
Measurements of muscle strength | |||||||
PeakTQ-ext-nondominant (Nm) | 38.80 | 18.20 | 45.90 | 52.10 | 37.90 | 65.30 | 0.007** |
PeakTQ-ext-dominant (Nm) | 29.10 | 19.50 | 49.60 | 51.60 | 40.10 | 62.60 | 0.001** |
PeakTQ-flex-nondominant(Nm) | 19.50 | 14.40 | 32.60 | 20.70 | 19.10 | 36.20 | 0.085 |
PeakTQ-flex-dominant (Nm) | 18.80 | 15.70 | 33.20 | 30.80 | 21.70 | 36.70 | 0.092 |
TQ/BW-ext-nondominant (ft·lb/lb) | 66.60 | 35.30 | 83.10 | 76.50 | 71.70 | 103.90 | 0.006** |
TQ/BW-ext-dominant (ft·lb/lb) | 57.80 | 27.40 | 82.40 | 87.10 | 58.90 | 99.40 | 0.001** |
TQ/BW-flex-nondominant (ft·lb/lb) | 33.00 | 24.40 | 51.20 | 39.70 | 31.40 | 55.80 | 0.092 |
TQ/BW-flex-dominant (ft·lb/lb) | 37.30 | 24.20 | 53.80 | 47.50 | 38.20 | 58.60 | 0.076 |
Measurements of visual analog pain scale score (VAS) | |||||||
visual analog pain scale score | 2.00 | 0.00 | 3.00 | 0.00 | 0.00 | 2.00 | 0.005** |
Measurements of Lequesne index score | |||||||
Lequesne index score | 6.00 | 3.00 | 9.00 | 3.00 | 0.00 | 6.00 | 0.001** |
(I) Pain or discomfort | 2.00 | 1.00 | 3.00 | 0.00 | 0.00 | 1.00 | 0.003** |
(II) Maximum distance walked | 1.00 | 1.00 | 3.00 | 1.00 | 0.00 | 2.00 | 0.150 |
(III) Activities of daily living | 2.00 | 1.00 | 5.00 | 1.00 | 0.00 | 3.00 | 0.032* |
Wilcoxon signed-rank test; *
Logistic regression analysis of the changes in the non-GEJ-treated group (
Variable | Regression coefficient | S.E. | Odds ratio | 95% CI of odds ratio |
|
---|---|---|---|---|---|
Incremental change of TQ/BW-ext-dominant | 0.041 | 0.022 | 1.04 | 1.00–1.09 | 0.062 |
Decremental change of visual analog pain scale score | 0.846 | 0.388 | 2.33 | 1.09–4.98 | 0.029* |
Change of (III) activities of daily living score | 0.824 | 0.364 | 2.28 | 1.12–4.65 | 0.023* |
Constant | −1.262 | 0.616 | 0.28 | 0.040 |
Accuracy of model = 78.6%.
Model III: backward regression.
Box plots showing Torque/body weight of extension and flexion-dominant side for each subgroup. A (
Table
Box plots showing decremental change of VA or LI score for each subgroup. A (
Box plots showing Torque/body weight of extension or flexion for each subgroup. A (pre) group, TQ/BW-ext-nondominant at pretreatment; B (post) group, TQ/BW-ext-nondominant at posttreatment; C (pre) group, TQ/BW-ext-dominant at pretreatment; D (post) group, TQ/BW-ext-dominant at posttreatment; E (pre) group, TQ/BW-flex-nondominant at pretreatment; F (post) group, TQ/BW-flex-nondominant at posttreatment; G (pre) group, TQ/BW-flex-dominant at pretreatment; H (post) group, TQ/BW-flex-dominant at posttreatment.
Box plots showing VAS and Lequesne index score for each subgroup. A (pre) group, VAS at pretreatment; B (post) group, VAS at posttreatment; C (pre) group, Lequesne index score at pretreatment; D (post) group, Lequesne index score at posttreatment; E (pre) group, (I) pain or discomfort at pretreatment; F (post) group, (I) pain or discomfort at posttreatment; G (pre) group, (II) maximum distance walked at pretreatment; H (post) group, (II) maximum distance walked at posttreatment; I (pre) group, (III) activities of daily living at pretreatment; J (post) group, (III) activities of daily living at posttreatment.
Table
The levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) were within normal limits after 12 weeks of GEJ treatment. There were no significant changes in renal function and urinalysis or urinary albumin-to-creatinine ratio (ACR = urine microalbumin/urine creatinine) after 12 weeks of GEJ treatment (
To the best of our knowledge, the present study is the first attempt to investigate the therapeutic effects of the herbal drug GEJ on muscle strength, articular pain, and disability (Lequesne index) in elderly men with knee OA. Our results showed that elderly men displayed significant improvements in the muscle strength of the knee and a decrease of articular pain and Lequesne index scores after 12 weeks of GEJ treatment. All patients tolerated the therapy well and reported no adverse effects or changes in liver or renal function.
Scientific data regarding the improvement of muscle strength after GEJ treatment in elderly men with knee OA are scant. In traditional Chinese medicine, GEJ has been used to treat kidney deficiency (qi, ying, and yang) and nourish blood, which plays an important role in treating joint disease at the cellular level [
Our results also showed a significant decrease in articular pain scores in GEJ-treated patients compared to non-GEJ-treated patients. An in vitro study revealed that GEJ could inhibit the apoptosis of chondrocyte-like phenotype bone mesenchymal stem cells (BMSCs), which reduced synovitis and blocked cartilage destruction [
Moreover, there were decremental changes in all components of the Lequesne index in the GEJ-treated group compared to the non-GEJ-treated group after 12 weeks of treatment. In the GEJ-treated group, there was a significant reduction in two parts of the Lequesne index: (I) pain or discomfort and (III) activities of daily living. Our results were similar to the findings of some studies showing the efficacy of individualized Chinese herbal medication, which according to TCM diagnosis can reduce symptoms of OA. The results demonstrated statistically significant improvement in global WOMAC scores and WOMAC subscale scores (for pain, stiffness, and functional impairment) for knee OA [
Our results showed no significant influence of GEJ on liver or renal function, suggesting that it had no harmful impact on the biochemical profiles of patients. In a previous study, no adverse gastrointestinal effects, such as abdominal fullness, constipation, diarrhea, or nausea, were observed during 8 weeks of GEJ therapy [
The limitations of our study included the small sample size, the enrollment of men only, the short follow-up period, the advanced stage of knee OA, and the failure to measure life quality. It is possible that the statistical power of our study may not have been sufficient to detect potential differences between the two groups. Some patients might not have taken GEJ regularly during the study period. Some important confounding variables were also not fully addressed, such as diet or dietary supplements, which are known to affect articular pain. This may explain why there were only a few differences in muscle strength between the GEJ-treated group and the non-GEJ-treated group. It is possible that our selection criteria were too stringent. Patients who had a history of coronary artery disease, previous knee surgery, severe visual impairment, stroke, severe pulmonary disease requiring the use of oxygen, hip fracture or lower extremity joint replacement in the past 6 months, and other inflammatory and/or infectious diseases, or who used other Chinese medicine or health products as indicated in their medical records, were excluded. This makes it difficult to transfer the results to the general population with knee OA. However, the stringent selection criteria were necessary to ensure the homogeneity of the groups and, furthermore, to exclude people who were at high risk of having side effects. Furthermore, the elderly people with OA knee treated by GEJ are likely to be taking other drugs, such as analgesics or anti-inflammatory agents, so caution had to be exercised to avoid drug interactions that might lead to other medical problems.
Our results showed a significant improvement of the muscle strength of the lower limbs, above all the extensor muscle on the dominant side, in elderly men with OA knee who received 12 weeks of GEJ treatment. There were also significant decreases of articular pain scores and Lequesne index scores in these patients. GEJ treatment was well tolerated and caused no significant changes in liver or renal function. An improvement in physical function is clinically important in OA patients because it is a crucial predictor of the ability to perform daily activities and avoid falls. Future clinical trials will be required to extend and confirm these findings and a long-term follow-up is necessary to verify whether the benefits can be maintained.
Body mass index
Activities of daily living
Peak torque extension of nondominant side
Peak torque extension of dominant side
Peak torque flexion of nondominant side
Peak torque flexion of dominant side
Torque/body weight extension of nondominant side
Torque/body weight extension of dominant side
Torque/body weight flexion of nondominant side
Torque/body weight flexion of dominant side
Visual analogue scale.
The authors declare that there is no conflict of interests regarding the publication of this paper.
Chen-Chen Tsai, Yin-Yi Chou, Yi-Ming Chen, Yih-Jing Tang, and Hui-Ching Ho contributed equally to this work.
The authors thank the Biostatistics Task Force of Taichung Veterans General Hospital, Taichung, Taiwan, ROC, for assistance with statistical analysis.