Therapeutic efficacy observation on moxibustion w ith moxa of different storage years for moderate-to-severe primary knee osteoarthritis

Xue Shi-yong (薛世勇), Wang Chun-yan (王春艳),LiTao (李涛),Liu Shi-min (刘世敏),Shi Yin (施茵),3

1 Longhua Hospital,Shanghai University of TraditionalChineseMedicine,Shanghai200032,China

2ShanghaiUniversity of Traditional Chinese Medicine,Shanghai 201203,China

3ShanghaiResearch Institute of Acupunctureand Meridian,Shanghai 200030,China

Abstract

Keywords:Moxibustion Therapy;Moxa Stick Moxibustion;Artem isia Argyi;Moxa;Osteoarthritis,Knee;Pain Measurement; Visual Analog Scale; Random ized Controlled Trial

Knee osteoarthritis (KOA), clinically known as knee proliferative arthritis or knee osteoarthrosis,is a common degenerative articular cartilage disease. It is more common in m iddle-aged and elderly people, and it can affect both men and women. The incidence rate in women is higher than that in men. The pathological features are mostly degeneration and loss of articular cartilage,and hyperosteogeny of joint edges and subchondral bone.The clinical manifestations are mostly stiffness,pain,activity lim itation and bone crepitus of knee joint.Severe cases may have dysfunction or disability,which seriously affects the quality of life of patients. According to literature reports,gender,age,obesity,hum id living environment,standing work habits, heavy physical labor occupations,history of knee injury,and fam ily history of osteoarthritis are common risk factors for KOA[1]. It is pointed out in the literature that body mass index (BMI)raises by 5 points, the risk of KOA increases by 35%[2].

1 Clinical Materials

1.1 Diagnostic criteria

This study referred the clinical and imaging diagnostic criteria for KOA established by the American College of Rheumatology in 1995 and theGuidelines for the Diagnosis and Treatment of Osteoarthritis[3]. Recurrent knee pain in the past month; at least 1 of the follow ing 3 items should be met:①aged≥38 years;② morning stiffness＜30 m in;③ bone crepitus during movement;imaging exam ination showed osteophyte formation in the knee joint.

1.2 Inclusion criteria

Those who met the above diagnostic criteria; aged≥38 years, but ≤70 years; 3-day washout period after medication(nonsteroidal anti-inflammatory drug,analgesic, and any Chinese herbal medicine or Chinese patent medicine for KOA),w ith the total score of Western Ontario and McMaster Universities osteoarthritis index (WOMAC) ＞48 and ≤72 points, that was, the grade of KOA was moderate to severe; the Kellgren and Law recne osteoarthritis radiological classification was grade Ⅱ or Ⅲ; agreed to participate in this trial and signed informed consent.

1.3 Exclusion criteria

Non-primary KOA patients, such as secondary KOA,gonarthritis caused by inflammation or other rheumatic diseases;those w ith symptomatic coxitis or patellar arthritis affecting the ipsilateral side of the target knee;who had injury of the target knee in the past year (such as acute meniscus injury of knee joint, acute injury/ rupture of surrounding ligaments of knee joint); those w ith history of surgery, or severe joint deformity (varus or valgus angle ≥8°); patients with peripheral tumors of knee joint,tuberculosis,or idiopathic osteonecrosis;target knee joint injected with glucocorticoid in the joint cavity w ithin the past 3 months,or injected sodium hyaluronate in the joint cavity w ithin the past 2 weeks;those had to take paracetamol,nonsteroidal anti-inflammatory drugs or analgesics due to other diseases;who had uncontrolled hypertension or diabetes, severe diseases of cardiovascular, lung, liver,spleen,kidney or hematopoietic systems,tumors,hemorrhagic diseases;those had mental diseases;those w ith scar diathesis or a history of skin sensory disorder; women during pregnancy or lactation.

1.4 Statistical methods

All data were analyzed by the SPSS 19.0 statistical software.Measurement data meeting normal distribution were expressed as mean±standard deviation(±s).Thet-test was applied to the between-group comparison at that same time point,and repeated measures analysis of variance was used for intra-group comparison. Data meeting non-normal distribution were expressed as median (lower quartile,upper quartile) [M (QL, QU)], and non-parametric test was applied. Chi-square test was used for comparison of rates.Rank-sum test was used for comparison of ranked data.P＜0.05 indicated statistical significance.

1.5 General data

All cases were recruited from the Outpatient Department of Shanghai Research Institute of Acupuncture and Meridian,the Acupuncture Department of Shanghai TCM-Integrated Hospital, and Shanghai Liangcheng Community Health Service Center between October 2017 and March 2018. A total of 63 patients w ith primary KOA who met the inclusion criteria were random ly divided into two groups by central random ization system,w ith 32 cases in moxibustion group 1(during treatment,2 patients dropped out)and 31 cases in moxibustion group 2(during treatment, 1 patient dropped out). There were no significant differences in the general data of gender,age and duration of disease between the two groups (allP＞0.05),indicating that the two groups were comparable (Table 1).

Table 1.Com parison of general data between the two groups

2 Treatment Methods

The two groups received same treatments except that the moxa was of different storage years.

2.1 Moxibustion group 1

The moxa from Qichun,Huanggang City,Hubei Province, China, and stored for 3 years was used.

2.2 Moxibustion group 2

The moxa from Qichun,Huanggang City,Hubei Province, China, and stored for 1 year was used.

2.3 Moxibustion methods

2.3.1 Moxibustion material

The moxa stick (1.75 cm in diameter and 20 cm in length) wasmade ofAi Ye(Folium Artem isiae Argyi)w ith a leaf/floss ratio of 10:1. A self-made four-head floor-standing moxibustion instrument was applied.It consisted of a base, an adjustable bracket, an arbitrary bending shaped tube, and clips.

2.3.2 Acupoints

Neixiyan (EX-LE 4), Dubi (ST 35) and Heding (EX-LE 2)on the affected side.

2.3.3 Methods

The patient took a sitting position, and had the skin around acupoints of the affected knee disinfected routinely. The bracket of the moxibustion instrument was adjusted to a suitable height.Each moxibustion instrument was equipped w ith 3 clips for holding moxa sticks.Moxa sticks were fixed in the clips of the moxibustion instrument, and placed 2 cm away from the selected acupoints for m ild moxibustion.After reaching the highest temperature that the patient could tolerate, the distance between the moxa stick and skin was adjusted. It was better for the patient to feel warm and com fortable or slight prickling pain.The moxibustion was performed 20 m in per time.

2.3.4 Treatment course

The treatment was performed 3 times a week, and the efficacy was observed after a total of 6 times of treatment.

3 Observation of Curative Efficacy

3.1 Observation items

3.1.1 WOMAC score

WOMAC assessed the structure and function of the hip and knee joints from three aspects (pain, stiffness and joint function), w ith a total of 24 items (pain: 5 items; stiffness: 2 items; joint function: 17 items). Each item was scored according to Lister's 5-grade scoring method:none (0 point),m ild(1 point),moderate(2 points),severe (3 points),and extremely severe(4 points). The sum of the scores of 24 items was the total WOMAC score(0-96 points).KOA was graded according to the total WOMAC score as follows.

None to m ild:WOMAC total score＞0 point,but≤24 points.

3.1.2 Pain degree

The visual analog scale (VAS) was scored (0-10 points)and used to evaluate the severity of knee joint pain in the past 24 h. The higher the score, the more serious the pain.

3.2 Criteria for curative efficacy

According to the criteria of curative efficacy in the

Guidelines for the Diagnosis and Treatment of Osteoarthritis[3], and the reduction rate of WOMAC[4],the efficacy criteria of this study were established.If both knee joints of the same patient were diagnosed KOA, only the knee joint w ith more serious condition at baseline was evaluated.The curative efficacy was evaluated at the end of the treatment, and followed up at 4 weeks after the end of the treatment.

WOMAC reduction rate = (WOMAC total score before treatment - WOMAC total score after treatment)÷ WOMAC total score before treatment × 100%.

Under control:Knee joint pain and swelling disappeared; no difficulty or discom fort when going up and down stairs;the WOMAC reduction rate after treatment was ≥80%.

Markedly effective: There was no pain or swelling in the knee joint at rest,only occasional pain during activities, while walking didn't cause pain, daily life and work were unaffected; the WOMAC reduction rate after treatment was ≥50%, but ＜80%.

Effective: Knee joint pain occurred from time to time,w ith m ild pain during walking, and difficulty in going up and down stairs, and the joint movement was slightly lim ited; WOMAC reduction rate was ≥25%, but ＜50%.

Invalid: There were no significant improvements in knee joint pain,swelling and dysfunction;WOMAC reduction rate was ＜25%.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The total WOMAC scores in the two groups at each time point were counted, and the clinical efficacy was calculated according to the efficacy evaluation criteria.

After treatment,the total effective rate in moxibustion group 1 and moxibustion group 2 was 83.3% and 60.0%, respectively. Fisher exact probability test, theP-value was 0.162, indicating that there was no significant difference between the two groups (P＞0.05),(Table 2).

At the 4-week follow-up, the total effective rate in moxibustion group 1 and moxibustion group 2 was 80.0% and 66.7%, respectively. Fisher exact probability test, theP-value was 0.413, indicating that there was no significant difference between the two groups (P＞0.05),(Table 3).

Table 2. Com parison of the clinical efficacy after treatment between the two groups (case)

Table 3.Comparison of clinical efficacy 4 weeks after the end of treatment between the twogroups (case)

3.3.2WOMAC score

Before treatment, after treatment, and at the 4-week follow-up, the pain, stiffness and dysfunction items of WOMAC in both groups were scored.

After treatment and at the 4-week follow-up, the scores of WOMAC pain item in both groups were significantly lower than those before treatment (allP＜0.01),while there were no statistical differences between the two groups (allP＞0.05), (Table 4).

After treatment and at the 4-week follow-up, the scores of WOMAC stiffness item in both groups were significantly lower than those before treatment (allP＜0.01). The scores in moxibustion group 1 were lower than those in moxibustion group 2 at the same time points, and the differences between the two groups were statistically significant(bothP＜0.05),indicating that the improvement of joint stiffness in moxibustion group 1 was more significant than that in moxibustion group 2 (Table 5).

After treatment and at the 4-week follow-up, the scores of WOMAC dysfunction item in the two groups were significantly lower than those before treatment (allP＜0.01), while there were no statistical differences between the two groups (bothP＞0.05), (Table 6).

Table 4. Com parison of the score of pain item in WOMAC between the two groups ( ±s, point)

Table 4. Com parison of the score of pain item in WOMAC between the two groups ( ±s, point)

Note:Compared with the same group before treatment,1) P＜0.01

Group n Before treatment After treatment Follow-up Moxibustion group 1 30 10.23±2.51 5.90±3.231) 5.80±3.221) Moxibustion group 2 30 10.40±2.31 6.20±3.101) 5.56±3.251)

Table 5. Com parison of the score of stiffness item in WOMAC between the two groups ( ±s, point)

Table 5. Com parison of the score of stiffness item in WOMAC between the two groups ( ±s, point)

Note:Compared w ith the same group before treatment,1) P＜0.01;compared w ith moxibustion group 2 at the same time point,2) P＜0.05

Group n Before treatment After treatment Follow-up Moxibustion group 1 30 4.23±1.10 1.93±1.631)2)2.23±1.471)2)Moxibustion group 2 30 4.36±1.32 2.83±1.661) 3.10±1.471)

Table 6. Comparison of the score of dysfunction item in WOMAC between the two groups ( ±s, point)

Table 6. Comparison of the score of dysfunction item in WOMAC between the two groups ( ±s, point)

Note:Compared w ith the same group before treatment,1) P＜0.01

Group n Before treatment After treatment Follow-up Moxibustion group 1 30 39.70±4.34 27.10±8.821) 25.56±8.251)Moxibustion group 2 30 40.70±4.19 27.60±8.561) 32.53±6.781)

3.3.3 Comparison of the VAS score

Before treatment, after treatment, and at the 4-week follow-up, the scores of VAS in the two groups were evaluated.

After treatment and at the 4-week follow-up, the VAS scores in the two groups were significantly lower than those before treatment (allP＜0.01), while there were no statistical differences between the two groups (bothP＞0.05), (Table 7).

Table 7.Com parison of the VAS score between the two groups ( ±s, point)

Table 7.Com parison of the VAS score between the two groups ( ±s, point)

Note:Compared with the same group before treatment,1) P＜0.01

Group n Before treatment After treatment F ollow-up Moxibustion group 1 30 6.23±1.35 4.63±1.441) 4.56±1.301)Moxibustion group 2 30 6.30±1.36 5.30±1.361) 4.76±1.471)

4 Discussion

KOA is a common global disease.According to statistics,approximately 200 m illion people worldw ide suffer from KOA,w ithmorewomen thanmen.KOA isa chronic senile disease,closely related to degenerative factors such as the loss of calcium in the bones in the elderly and the decrease in the content of chondroitin sulfate in the joints.It can cause patients pain and dysfunction, thereby affecting the quality of life[5].

KOA belongs to Bi-impediment syndrome in traditional Chinese medicine.The therapeutic effect of moxibustion for KOA is affirmative.In this study, Dubi(ST 35),Neixiyan(EX-LE 4)and Heding (EX-LE 2)were selected for moxibustion.These three acupoints are close to each other, so the heat radiation of them can basically cover the whole knee joint during moxibustion.In this study,m ild moxibustion was applied.The temperature of moxibustion rose slow ly,and the temperature that penetrated into the skin was higher,which had a better stimulating effect on the knee joint[6].The peak of the radiation spectrum of burning moxa is near 1.5µm,which belongs to the near-infrared light[7].Near-infrared radiation has a short wavelength,strong energy,and strong penetrating power. It can penetrate into the epiderm is,connective tissue,blood vessels,and nervoussystem to play a therapeutic role.TheAi Ye(Folium Artem isiae Argyi) from Qichun can release the largest heat and the strongest penetrating power when burning[8]. Among the common four kinds of moxaw ith 10:1,20:1,30:1,and 40:1 purity,the 10:1 moxa is suitable for making moxa sticks for m ild moxibustion[9].The volatile oil extraction rate ofAi Ye(Folium Artem isiae Argyi)from Qichun is high[10].A fingerprint study ofAi Ye(Folium Artem isiae Argyi) from Qichun found that naringin and kaempferol were the representative flavonoids components inAi Ye(Folium Artem isiae Argyi)from Qichun[11].It can be proved thatAi Ye(Folium Artemisiae Argyi)from Qichun is the experimental basis of genuine medicine.Therefore,Ai Ye(Folium Artem isiae Argyi)from Qichun was selected in thisstudy for moxibustion.

The results of this trial suggested that moxibustion could effectively improve pain,stiffness and motor in patients w ith moderate-to-severe KOA,and could improve the quality of life,w ith significant short-term effect.4 weeks after the end of treatment,the total effective rate inmoxibustion group 2 increased by 6.7%,which m ight be that the stimulation of moxibustion activated a certainmechanism in the body to help the body to continue to recover,show ing that there was a sustained effect after moxibustion. Studies have shown that the warm ing effect of moxibustion could activate temperature receptors:the transient receptor potential(TRP) V subfam ily (TRPV).When the temperature rose from 22℃to 40℃,TRPV3 could be activated,and when the temperature was ≥43℃,TRPV1 would be activated by thermal stimulation to activate nociceptors[12].

Study showed that the effects of moxa of different storage years on skin temperature were different[13].One-year stored moxa had the fastest increase of temperature at localacupoints skin,followed by 3-year stored,and the slowest was the 5-year stored.Slow ly heating can bring com fort to patients in practical use.Between the com fortable temperature and the tolerable temperature of the human body,there is an optimal temperature zone for moxibustion that is slightly higher than the normal temperature,can achieve curative effects and avoid pain and burns.In this study, we had themoxibustion temperature reach the level that can cause thermal pain as soon as possible after the treatment began, that was to sw itch from a stimulation to temperature receptor to a stimulation to nociceptor in the early stage of treatment,for maintaining patients'feel of optimal temperature during the 20 m in period of treatment,thereby to maintain the stability of the curative effect.The analgesic effects in the two groupswere significant,and the stiffness and motor function were significantly improved.The mechanism may be that the near-infrared rays radiating from the burning moxa can provoke the hydrogen bonds of biological macromolecules in human acupoints[14],produce the stimulated coherent resonance absorption effect,and then transfer the energy required by human cells through the neurohumoral system.Experiment had shown that moxibustion could significantly increase the level of β-endorphin in the brain of rats, and played a central analgesic effect on rats[15].

In this study, we observed that moxa floss stored for 3 years had a better therapeutic effect on knee stiffness than that stored for 1 year, which m ight be related to the transdermal absorption of active ingredients during moxibustion.Study had shown that the chem ical compositions ofAi Ye(Folium Artem isiae Argyi) from Qichun of different years and moxa wool refined in different proportions were almost the same, but their floss content rates were w ith obvious difference. The relative content of volatile substances decreased w ith the storage time,and the proportion of the refined moxa wool rose,while the involatile substances increased.Involatile substances such as juniper camphor,caryophyllene oxide,caryophyllin are the main contents of high proportional aged moxa wool.And these substances may be the effective components in moxibustion treatment[16]. The flavonoids inAi Ye(Folium Artem isiae Argyi)have rich biological activities[17].The combustion products of Artem isia argyi can scavenge free radicals.It was found that 5-tert-butyl pyrogallol had stronger free radical scavenging ability than natural antioxidant vitam in C and synthetic antioxidant BHT,and it m ight be the important active factor in moxibustion[18].The combustion products of moxa can be attached to the skin, and penetrate into the skin through moxibustion heat,playing a certain therapeutic effect[19],such as improving the inflammatory response of synovial membrane, promoting the absorption of effusion in the joint cavity[20], and inhibiting synovial angiogenesis[21].

Moxibustion at Dubi (ST 35), Neixiyan (EX-LE 4) and Heding (EX-LE 2)had satisfactory clinical efficacy in treating moderate-to-severe KOA[22-24]. Moxa stored for 3 years was better than moxa stored for 1 year in relieving joint stiffness, while the mechanism needs to be explored by in-depth research. During the trial, we observed that the rise of burning temperature of moxa stored for longer time was slow and m ild,w ithout obvious sparking or bursting, so that it can bring the patients a better experience and is safer to use.

Conflict of Interest There isno potential conflict of interest in this article.Acknow ledgments This work was supported by National Basic Research Program of China (973 Program,国家重点基础研究发展计划, No.2015CB554506).Statement of Informed Consent Informed consent was obtained from all individual participants.

Received:27December 2019/Accepted:27 February