2.9. Intervention

The study schedule is presented in Table ​Table1.1. At the screening visit, participants will sign the informed consent form. In a baseline questionnaire, the following information will be obtained: age, occupation (physical/nonphysical), education level, last menstrual period, previous use of acupuncture, and expectation to acupoint thread embedding treatment. Moreover, Short-Form of McGill Pain Questionnaire (SF-MPQ), Osteoporosis Symptom Score, Osteoporosis Quality of Life Scale (OQOLS), 16-item Assessment of Health-Related Quality of Life in Osteoporosis (ECOS-16) must be completed at the baseline (week 0). Thereafter, study subjects will be randomized. There is a 3-month study period and a 1-month follow-up period for each group. In the study period, SF-MPQ, OQOLS, ECOS-16, and Osteoporosis Symptom Score will be evaluated every 4 weeks. fMRI and bone density test will be tested 2 times: in week 0 and week 12.

Trial flow and time schedule: enrollment, interventions and assessments.

Acupoint thread embedding treatment will be applied to patients in the treatment group fortnightly, a total of 6 times during 3 months. Main acupoints are BL23, SP6, and RN4. If it is a liver-kidney deficiency case, BL18, GB39, BL11 will be added. If it is a kidney yang deficiency case, BL20, ST36 will be added. In each treatment, RN4 is a required acupoint. The rest acupoints can be used in the alternation of the left/right side. The location method is according to Location of Acupoints the National Standards of P.R promulgated by the State Bureau of Technology Supervision. The operating method follows the National Standards of P.R (GB/T 21709.10-2008) manipulations of acupuncture and moxibustion—Part 10 Acupoint catgut embedding. Details about the intervention group interventions and the acupoints location are described in the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTE) checklist in Tables ​Tables22 and ​and33.^[12]

Acupoints selects.

Acupoints location.

Medical material information includes that the needles will be sterile disposable No.8 injection needles, size 0.8 × 38TW LB (Zhejiang Kangkang Medical Devices Co., Ltd., Chumen Town, Yuhuan County). The core needles will be sterile disposable No.28 acupuncture needles, size 0.35 × 50 mm (Rui Qier), used after their pinpoints rubdown. The thread will be absorbable surgical suture (medical thread), size3/0 (Shanghai Pudong Jinhuan Medical Products Co., Ltd., Shanghai, China).

Operating method (implantation with needles): According to National Standards of P.R (GB/T 21709.10-2008) manipulations of acupuncture and moxibustion—Part 10.

Cut the 3/0 thread into 1.5 cm segments and soak them in disinfectant.

During the treatment, patients take prone position to get back-shu point implantation and supine position to get RN4, SP6, GB39, and ST36 implantation. On the basis of location method above, disinfect routinely at acupoint and its skin around with Anerdian, take one self-made embedding needle, stick the core into needle tubing, and then pull out the core about 2 cm, implant one 1.5 cm sterile thread into the front of the tubing, and tighten or pinch the local skin around the acupoint with left thumb and forefinger, stick the needle into the acupoint rapidly with the right hand, and the lift and down the needle until receiving qi. Push the core and withdraw the tubing slowly, and finish implanting the thread deep down the acupoint. Hold pressure for a moment after withdraw the needle, check for exposure of thread out of the skin and bleeding, cover the wound with a piece of gauze or band-aid for 1-2 days.

Direction, angle, and depth of implantation: BL23, SP6, RN4, GB39 are required vertical puncture into the acupoint for about 0.8 to 1.0 cun (approximately 20--25 mm); ST36 is required to vertical puncture into the acupoint for about 1.0 to 1.5 cun (approximately 25–40 mm); BL20 is required vertical puncture into the acupoint for about 0.5 to 0.8 cun (approximately 13–20 mm); BL18, BL11, DU4 is required oblique puncture toward the spine into the acupoint for about 0.5 to 0.8 cun (approximately 13–20 mm).

The participants in the control group will be prescribed oral administration of Climen (2 mg Estradiol 17β-valerate and 1 mg Cyproterone 17α-acetate) tablets (1 tablet 30 minutes before sleep once per day for 21days and then stop medicine for a week; lasting for 12 weeks). The Climen tablets are produced by Schering GmbH Und Co. ProduktinosKG (Guangzhou, China) (Approval No. J20130006).

During the research, some adverse reactions may occur. Researchers will monitor every patient with adverse reaction.

The following adverse reactions may happen after the acupoint thread embedding:

Local reaction: mostly some sterile inflammation with inflamed hot pain within 5 days. Some cases may be more severe, like a small amount of milky-white exudation at the embedding spot caused by fat liquefaction because of thread stimulation. Circumstances above should not require any special treatment.

General reaction: some patients may experience temperature rising after the treatment 4 to 24 hours, which mostly around 38°C. It will fade away in 2 to 4 days by itself. Usually, hemogram of each patient may rise in different levels, and it will return to normal in 3 to 5 days.

If adverse reactions occur, the following treatment will be used.

Pain at implantation acupoint: Apply hot compress.

Local swelling, progressive pain, and fever 3 to 4 days after the implantation: Lack of strict asepsis and inappropriate protection of the wound could cause secondary infection, which mostly occurs some inflammatory symptoms. Apply hot compress and anti-infective treatment would help.

Nerve injury: It is usually caused by incorrect operation or excessive stimulation or carelessness, and can be avoided with the careful operation.

Hemorrhage: It is usually caused by the puncture on the vessels or excessive stimulation, in which case pressure dressing on the puncture point would stop the bleeding.

Thread allergy: local itching or swelling or fever can be remitted by antianaphylaxis treatment.

Climen, which includes estradiol and cyproterone acetate, is one of the estrogen and progestogen/anti-androgen (HRT). It is used in HRT for women with an intact uterus, used to substitute for a lack of estrogen production by the ovaries during menopause. It helps prevent postmenopausal bone loss (osteoporosis) and reduce risk of fracture. The most commonly reported side effects when taking Climen include breast tenderness, breast pain, abdominal pain, nausea, edema, headache, depression, changes in body weight, and changes in libido.

Other interventions such as medications, injections, physical therapy, surgical procedures, acupuncture, cupping, and moxibustion will not be permitted during the 12-week treatment period (not applicable to the follow-up phase). However, any concomitant medications are taken by the subject within 4 weeks before trial participation, which will not affect the interpretation of the trial outcomes, will be allowed at the discretion of the investigator.

The fMRI examination (PRISMA 3.0T Magnetic Resonance Imaging Scan; Siemens Shanghai Medical Equipment Ltd.) will be performed to collect brain images offering more visualized proof. During the scanning procedure, subjects will be asked to keep quiet and their eyes closed. In the meantime, they need to keep their mind empty but avoid sleeping. The researcher will check whether the participants are awake during the process. The MRI protocol for this study consists of the following parameters: T1 scanning: repetition time (TR) = 2300 ms, echo time (TE) = 2.32 ms, flip angle = 8°, the field of view (FOV) = 240 × 240 mm², matrix size = 256 × 256 mm², voxel size = 0.9 × 0.9 × 0.9 mm³, 192 sections, 0.9 mm thickness, 0.45 mm slice gap, 200 Hz/pixel bandwidth. MRS scanning: TR = 1700 ms, TE = 135 ms, 1 mm thickness, no slice gap. DTI scanning: matrix size = 128 mm × 128 mm, FOV = 220 mm × 220 mm, 3.8 mm slice thickness, 33 slices centered on the corpus callosum, b-value = 1000 s/mm². Blood oxygen level dependent scanning: TR = 3000 ms, TE = 30.0 ms, flip angle = 90°, the FOV = 192 × 192 mm², voxel size = 3 × 3 × 3 mm³, 36 sections, 3.0 mm thickness.

The bone density test (DPX Bravo Dual-energy X-rays Absorptiometry; General Electric Co., Ltd.) will be performed to collect bone mineral density (BMD) data.