Clinical study of warm needling moxibustion plus intra-articular injection of sodium hyaluronate for hip involvement in ankylosing spondylitis

YE Lei (叶磊), ZOU Yichao (邹一超)

Shanghai East Hospital Affiliated to Tongji University, Shanghai 200120, China

Abstract

Keywords: Acupuncture-moxibustion Therapy; Warm Needling Therapy; Acupuncture Medication Combined; Spondylitis,Ankylosing; Hip Injures; Pain Measurement; Visual Analog Scale

Ankylosing spondylitis (AS), a chronic autoimmune disease that mainly involves the spine and peripheral joints, often occurs in young and middle-aged males[1].Data show that the hip joint is the most frequently involved peripheral joint in AS, and hip joint involvement occurs in 24% to 36% of AS patients[2]. The main histological changes of this condition are inflammation and pathological new bone formation,and the most common imaging manifestation is joint space narrowing. Without timely treatment, the gradual joint space fusion will contribute to bony ankylosis as well as motor dysfunctions of the hip joint,which is the main cause of disability in AS[3-4].Intra-articular injection of sodium hyaluronate is a common method for hip involvement in AS. This method, with clear short-term efficacy, can lubricate the joints directly to relieve pain and improve joint functions[5-6]. In recent years, acupuncture and moxibustion have been widely adopted for AS. This method can significantly improve objective indicators like chest expansion, fingertips to floor distance, occiput to wall distance, and erythrocyte sedimentation rate[7].As a promising approach, it shows clear efficacy with safety and reliability. In this study, we adopted warm needling moxibustion plus intra-articular injection of sodium hyaluronate to treat hip involvement in AS, and compared its efficacy with that of the intra-articular injection of sodium hyaluronate alone. The details are as follows.

1 Clinical Materials

1.1 Diagnostic criteria

The diagnostic criteria for AS referred to thePractical Orthopedics[8]. Low back pain presenting for more than three months, improved by exercise but not relieved by rest; limitation of lumbar spine motion in both the sagittal and frontal planes; limitation of chest expansion relative to normal values for age and sex; grades 2-4 sacroiliitis on both sides or grades 3-4 sacroiliitis on one side. A person with the fourth item as well as at least one of the other three items can be diagnosed with AS.

1.2 Inclusion criteria

Met the above diagnostic criteria; presented with unilateral or bilateral hip pain, and confirmed hip involvement by imaging examination; aged 20-50 years old; voluntarily participated in the study and signed informed consent.

1.3 Exclusion criteria

Those with advanced AS and presented with bony ankylosis as well as severe joint deformity; suffered from diseases that can impair the hip functions, e.g.,femoral head necrosis; suffered from severe cardiovascular, cerebrovascular, pulmonary, or renal diseases; had received relevant treatment in the past three months; females in pregnancy or lactation.

1.4 Dropout criteria

Those who failed to receive the required treatment;presented with severe adverse reactions or voluntarily withdrew during the study.

1.5 Statistical methods

The SPSS version 18.0 statistical software was adopted for data analysis. Chi-square test was used for the counting data. The measurement data conforming to normal distribution were expressed as mean ±standard deviation (±s). Pairedt-test was used for intra-group comparisons, and the independent samplet-test was used for inter-group comparisons. The nonparametric test was adopted for the measurement data not conforming to normal distribution.P＜0.05 indicated statistical significance.

1.6 General data

We recruited 60 patients with hip involvement in AS who received treatment in Shanghai East Hospital Affiliated to Tongji University between December 2018 and January 2020. They were randomly divided into a control group and an observation group, with 30 cases in each group. No patient dropped out during the study.There were no statistical differences between the two groups in gender, age, duration, or disease position(P＞0.05), indicating that the two groups were comparable (Table 1).

Group n Gender (case) Average age(Hip joint lesion (case)images/BZ_7_1311_2835_1350_2881.png±s, year)Average duration(images/BZ_7_1311_2835_1350_2881.png±s, year)Male Female Unilateral Bilateral Observation 30 25 5 33.0±7.0 6.2±2.6 18 12 Control 30 24 6 32.2±6.1 6.4±2.9 14 16

2 Methods

All the patients took sulfasalazine tablets [State Food and Drug Administration (SFDA) Approval No.H31020450, 0.25 g/tablet, Shanghai Zhongxi Sunve Pharmaceutical Co., Ltd., China) for treatment, 1.00 g per dose and two doses a day.

2.1 Control group

The patients in the control group were given intraarticular injection of sodium hyaluronate (SFDA Approval No. H20051837, 2 mL/syringe, Shanghai Haohai Biological Technology Co., Ltd., China).Specifically, the patient took a supine position, with the affected limb straightening and extending. The entry point was 2 cm below the intersection of the inguinal ligament and femoral artery. After routine disinfection,the operator perpendicularly inserted the needle till touching the surface of the femoral head and then slightly withdrew the needle. At this time, the needle tip was in the articular cavity. The operator injected 2 mL sodium hyaluronate when there was no backflow of blood. The injection was given once a week for 5 weeks.

2.2 Observation group

The patients in the observation group were given additional warm needling moxibustion.

Points: Bilateral Shenshu (BL23), Guanyuanshu (BL26),and Pangguangshu (BL28), as well as the Ashi points(one or two), Juliao (GB29), and Huantiao (GB30) on the affected hip.

Methods:The patient lay on the healthy side. After routine disinfection, the operator adopted the needles of 0.30 mm in diameter and 40 mm in length to puncture the bilateral Shenshu (BL23), Guanyuanshu(BL26), and Pangguangshu (BL28) perpendicularly with nail-pressing insertion method. The insertion depth was 20-25 mm. The operator inserted the needles of 0.30 mm in diameter and 50 mm in length into the selected Ashi points perpendicularly. Juliao (GB29) was needled with the same insertion method, and the insertion depth was 30-40 mm. The operator inserted the needle of 0.30 mm in diameter and 75 mm in length into Huantiao (GB30) perpendicularly, and the insertion depth was 60-70 mm. Then, the needles were lifted,thrust, and twirled. After the arrival of Qi (Deqi), the operator placed a moxa stick of about 15 mm in length on the handle of each inserted needle. The needles were retained for 30 min. The patients with bilateral hip involvement were given the warm needling moxibustion on the right side first and then on the left side. The treatment was given once a day, consecutive 5-day treatments in one week, with a 2-day interval between two sets of 5-day treatments. The clinical efficacy was evaluated 5 weeks later.

3 Observation of Clinical Efficacy

3.1 Observed items

3.1.1 Hip pain and functions

Before and after treatment, the intensity of hip pain was evaluated by visual analog scale (VAS), and the functions of the affected hip joint were evaluated by the Harris scoring system[9].

3.1.2 Bath ankylosing spondylitis radiology index-hip(BASRI-hip)

Before and 6 months after treatment, the affected hip joint was examined by X-ray. The BASRI-hip was adopted to evaluate its status with a score between 0 and 4 points.

Zero point: normal, no change; 1 point: suspicious focal joint space narrowing; 2 points: mild circumferential joint space narrowing, ＞2 mm; 3 points:moderate circumferential joint space narrowing,≤2 mm, or bone-on-bone apposition, ＜1 cm; 4 points:severe bone deformity, or bone-on-bone apposition,≥1 cm[10].

3.1.3 Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI)

Before and after treatment, the disease activity and physical functions of the patients were evaluated by BASDAI and BASFI. The scores of BASDAI and BASFI are between 0 and 10 points. The higher the score, the more severe the condition[11].

3.1.4 Serum cartilage oligomeric matrix protein(COMP) and interleukin (IL)-17

Before and after treatment, 3-5 mL venous blood was taken from each patient, and the enzyme-linked immunosorbent assay was adopted to measure the levels of serum COMP and IL-17.

3.2 Efficacy evaluation criteria[12]

Markedly effective: The hip joint pain was significantly relieved or even disappeared, the joint motion function was significantly improved, and the Harris score increased by ≥30%.

Effective: The hip joint pain was relieved, the joint motion function was improved, and the Harris score increased by ≥10% but ＜30%.

Invalid: The hip joint pain was not relieved, the joint motion function was not improved, and the Harris score increased by ＜10%.

3.3 Results

3.3.1 Comparison of the clinical efficacy

The total effective rate in the control group was 66.7%, and that in the observation group was 93.3%.The total effective rate in the observation group was higher than that in the control group (P＜0.05), (Table 2).of the control group (P＜0.05). Check Table 4 for details.

3.3.4 Comparison of the BASDAI and BASFI scores

Before treatment, there were no statistical differences in the scores of BASDAI or BASFI between the two groups (P＞0.05). After treatment, the scores of BASDAI and BASFI in both groups were lower than those before treatment (P＜0.05), and were lower in the observation group than in the control group (P＜0.05).Check Table 5 for details.

3.3.5 Comparison of the levels of serum COMP and IL-17

Before treatment, there were no statistical differences in the levels of serum COMP or IL-17 between the two groups (P＞0.05). After treatment, the levels of COMP and IL-17 in both groups were lower than those before treatment (P＜0.05), and were lower in the observation group than in the control group(P＜0.05). Check Table 6 for details.

Group n Markedly effective Effective Invalid Total effective rate (%)Observation 30 12 16 2 93.31)Control 30 3 17 10 66.7

3.3.2 Comparison of the VAS and Harris scores

Before treatment, there were no statistical differences in the scores of VAS or Harris between the two groups (P＞0.05). After treatment, the VAS scores of both groups were lower than those before treatment(P＜0.05), and the VAS score of the observation group was lower than that of the control group (P＜0.05). After treatment, the Harris scores of both groups were higher than those before treatment (P＜0.05), and the Harris score of the observation group was higher than that of the control group (P＜0.05). Check Table 3 for details.

3.3.3 Comparison of the BASRI-hip score

Before treatment, there was no statistical difference in the score of BASRI-hip between the two groups(P＞0.05). Six months after treatment, the BASRI-hip score of the control group was higher than that before treatment (P＜0.05); in the observation group, there was an insignificant intra-group difference in the score of BASRI-hip (P＞0.05), and the score was lower than that

Group n Number of affected hip Time VAS Harris Observation 30 42 Before treatment 5.61±2.29 63.95±8.15 After treatment 1.56±0.831)2) 84.36±7.531)2)Control 30 46 Before treatment 5.78±1.97 64.11±7.94 After treatment 3.47±1.531) 74.28±11.381)

Group n Number of affected hip Before treatment Six months after treatment?Observation 30 42 2.43±0.50 2.41±0.592)Control 30 46 2.45±0.50 2.82±0.531)

Group n Number of affected hip Time BASDAI BASFI Observation 30 42 Before treatment 6.13±1.04 4.58±0.90 After treatment 2.83±0.711)2) 1.89±0.471)2)Control 30 46 Before treatment 6.02±0.94 4.82±0.83 After treatment 3.34±0.721) 3.03±0.641)

Group n Number of affected hip Time COMP (ng/mL) IL-17 (pg/mL)Observation 30 42 Before treatment 73.75±15.61 26.54±5.16 After treatment 60.53±10.761)2) 16.35±3.231)2)Control 30 46 Before treatment 77.26±13.65 27.88±5.27 After treatment 67.96±12.511) 20.52±3.831)

4 Discussion

Hip involvement usually occurs in the early stages of AS. Unilateral involvement may present at the beginning, and about 70% of patients will present with bilateral involvement[13]. Hip involvement, with both high incidence and disability rates, may cause serious spinal involvement and a bleak prognosis[14]. The medications for AS mainly include non-steroidal antiinflammatory drugs (NSAIDs), slow-acting antirheumatic drugs (SAARDs), and biological agents.NSAIDs can swiftly relieve swelling and pain and increase the range of motion of the affected joint.However, the symptoms may relapse after drug withdrawal, and long-term use may cause severe gastrointestinal reactions[15]. As the most widely used SAARD, sulfasalazine can relieve joint pain, swelling, and morning stiffness caused by AS, and can also reduce disease activity indicators. It is especially suitable for peripheral arthritis caused by AS, but the effect of the drug is slow[16]. Tumor necrosis factor-α antagonists are widely used abroad and may play a positive role in delaying the progression of hip involvement, but due to the high price and the necessity of long-term adoption,they are less used in China[17]. Intra-articular injection of sodium hyaluronate is a direct method mainly adopted in China to intervene in hip involvement in AS. Sodium hyaluronate is directly injected into the affected joint to lubricate the joint and thus eliminate the pain caused by joint motion. This approach can reduce joint surface friction, protect articular cartilage, prolong the life of the joint surface, and inhibit inflammatory factors and pain-producing substances[18].

AS falls under the category of Bi-Impediment syndrome in traditional Chinese medicine. The nature of this condition is the deficient root cause and excessive manifestations. Deficiency of kidney Qi coupled with pathogenic wind, cold, and dampness may obstruct the meridians as well as the circulation of Qi and blood, and thus cause spinal stiffness, pain, and impaired movements. Treatment principles for AS are to tonify the kidney, promote blood circulation and unblock the meridians[19-20].

Warm needling moxibustion integrates the strengths of acupuncture and moxibustion to warm, unblock and tonify. In this study, we selected such points as bilateral Shenshu (BL23), Guanyuanshu (BL26), and Pangguangshu (BL28), as well as the Ashi points, Juliao(GB29), and Huantiao (GB30) on the affected hip to treat the hip involvement in AS. Shenshu (BL23) and Guanyuanshu (BL26) can tonify the kidney, warm Yang,and tonify Qi. Pangguangshu (BL28) can remove dampness and unblock the meridians. Since the three points are located in the lumbosacral region, they can directly relieve the symptoms of this disorder. The selected Ashi points, Juliao (GB29), and Huantiao (GB30)are close to the affected hip joint. In addition to significantly relieving pain, they can promote the local circulation of Qi and blood. Therefore, the combination of all the selected points can tonify the kidney, benefit Qi, unblock the meridians, promote blood circulation,and relieve pain.

In this study, we compared the hip pain intensity and joint functions between the two groups before and after treatment. The results suggest that warm needling moxibustion plus intra-articular injection of sodium hyaluronate can alleviate the pain of the affected hip and improve hip functions. The efficacy of this combined approach is clearer than that of intra-articular injection of sodium hyaluronate alone. BASRI-hip, with reliability and sensitivity, is a widely recognized and used imaging evaluation method for hip involvement in AS[21]. The results of this study indicate that warm needling moxibustion plus intra-articular injection of sodium hyaluronate can delay the destruction process of the hip structure. BASDAI and BASFI were adopted to evaluate the overall condition of AS. The results indicate that this combined therapy can improve physical functions and prevent the development of AS.

In this study, we also compared the levels of serum COMP and IL-17 between the two groups before and after treatment. COMP is an important component of the extracellular matrix. It interacts with other proteins to maintain cartilage integrity and regulate chondrocyte functions[22]. After articular cartilage injury, it will enter synovial fluids and then blood. COMP is a sensitive marker of cartilage metabolism, and its serum level can reflect the degradation and destruction intensity of articular cartilage as well as the inflammation degree of synovitis[23]. CHEN J L,et al[24]found that the serum COMP level of the active group was higher than that of the inactive and the healthy control groups, and the serum COMP level of the inactive group was higher than that of the healthy control group; after treatment,the serum COMP level of the active group decreased significantly and the serum COMP level was positively correlated with the BASDAI score and the VAS score of spinal pain. This suggests that the serum COMP can manifest the peripheral joint inflammation and the disease activity in patients with AS. IL-17 can induce T-cell activation, stimulate the production of cytokines such as IL-6 and IL-8, activate B-lymphocytes, and aggravate humoral immunity[25]. Besides, IL-17 can inhibit matrix formation in osteoblasts and chondrocytes, inhibit proteoglycan synthesis in articular cartilage, promote proteoglycan decomposition, and induce chondrocyte apoptosis. In addition, it can also induce the high expression of osteoclast differentiation factor and participate in extracellular matrix degradation and bone destruction[26]. It is involved in the inflammation and bone destruction caused by AS.This study shows that warm needling moxibustion plus intra-articular injection of sodium hyaluronate can reduce the levels of serum COMP and IL-17 in AS patients with hip involvement.

In conclusion, this combined approach shows clear efficacy for hip involvement in AS. It is worthy of clinical promotion.

Conflict of Interest

The authors declare that there is no potential conflict of interest in this article.

Acknowledgments

There was no project fund support for this study.

Statement of Informed Consent

Informed consent was obtained from all individual participants.

Received: 5 March 2021/Accepted: 28 July 2021