The Study of Chinese Medicine for the Treatment of Primary Osteoporosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and possible mechanism of traditional Chinese medicine in the treatment of primary osteoporosis (Kidney Yang Deficiency Syndrome).It is a randomized, placebo-controlled trial.

Detailed Description
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The subjects are selected according to the inclusion criteria and exclusion criteria. Using the network random system, 120 subjects who meet the research criteria are randomly divided into control group and experimental group, with 60 cases in each group. Patients in treatment group take the granule of traditional Chinese medicine prescription, while the control group take simulate granule of the prescription. Both two groups are under symptomatic treatment. Twice a day, in the morning and evening, 30 minutes after meals.The experimental drugs were provided by the pharmacy department of Wangjing hospital, Chinese Academy of traditional Chinese medicine, and the course of treatment was 3 months.The observation time points were before treatment, 2 weeks after treatment, 1 month after treatment and 3 months after treatment. Visual Analogue Score (VAS), Traditional Chinese Medicine（TCM）syndrome score, SF-12 scale and bone metabolism index were used as observation indexes.At the same time, it is planned to determine EphrinB2, EphB4, Runx2 and VEGF in serum by ELISA. Tele-medicine and information management system is established to help achieve follow-up interviews.Random numbers are generated by SAS 9.4 software. The subjects, caregivers, investigators and outcomes assessors in this study are all blinded.

Official Title
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Clinical Study of Bugu Shengsui Decoction for the Treatment of Primary Osteoporosis (Kidney Yang Deficiency Syndrome)

Conditions
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Primary Osteoporosis

Intervention / Treatment
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* Drug: Caltrate D
* Drug: Chinese medicine prescription
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: It meets the diagnostic criteria of Western medicine for primary osteoporosis. the diagnostic criteria of osteoporosis based on the bone mineral density of central axis (lumbar spine 1-4, femoral neck or total hip) or 1/3 bone mineral density of distal radius measured by DXA is t-value ≤ - 2.5; It meets the syndrome differentiation standard of primary osteoporosis with Kidney Yang Deficiency Syndrome; Female menopause > 2 years and 45 years ≤ age < 80 years, or 50 years ≤ male < 80 years; Visual Analogue Score (VAS) was used to evaluate pain ≥ 4 points; Voluntarily participate in this clinical study and sign the informed consent form. Exclusion Criteria: Osteoporotic fracture has occurred, or t-value > - 2.5; Female premenopausal or menopausal years ≤ 2 years, female age < 45 years or ≥ 80 years, male age < 50 years or ≥ 80 years; VAS pain score < 4; Lumbar fusion or severe degenerative changes hinder the measurement of normal bone mineral density, and there are less than 2 consecutive intact lumbar vertebrae for DXA measurement and evaluation; Patients with malignant tumor, cardiovascular, cerebrovascular, liver disease, kidney disease, hematopoietic system and other serious primary diseases; secondary osteoporosis: diabetes, thyroid disease, Cushing syndrome and other metabolic diseases, rheumatoid arthritis, multiple myeloma, gout, absorption syndrome, systemic lupus erythematosus and other systemic diseases. Use drugs affecting bone metabolism, such as bisphosphonates, glucocorticoids, calcitonin, anticonvulsant drugs, heparin and other drugs within 3 months before signing the informed consent; History of serious mental illness or poor compliance; Allergic constitution, allergy to known components of the drug, allergy to calcium or vitamin D; Those who participated in other clinical trials within 3 months. Rejection Criteria: False diagnosis and false inclusion; Not receiving one treatment; During the study, in addition to the study medication, drugs known or likely to affect bone metabolism were used. Shedding Standard: The subjects withdrew from the test by themselves; Loss of follow-up; The subject received treatment at least once, and there were serious complications or complications and serious adverse events; Although the test was completed, the dosage of the subject was not within the range of 80%-120% of the dosage that should be taken.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Traditional Chinese medicine<br>On the basis of general symptomatic treatment of caltrate D，patients in experimental group use the traditional Chinese medicine application prescription. | Drug: Caltrate D<br>* Caltrate D is allowed for basic treatment when the patient is diagnosed with primary osteoporosis (Kidney Yang Deficiency Syndrome).Take it continuously for 3 months.<br>Drug: Chinese medicine prescription<br>* The Chinese medicine application prescription is composed of Rhizoma Drynariae 12g, psoralen 10g, dog ridge 10g, medlar 10g, raw oyster 10g, ginseng 6g, Panax notoginseng 3g, Amomum villosum 6g.Patients take 200ml each time, twice a day. Treatment duration are 3 months.<br>|
| Placebo Comparator: Comparator: placebo<br>On the basis of general symptomatic treatment of caltrate D，patients in placebo group use the simulate granule of traditional Chinese medicine application prescription. | Drug: Caltrate D<br>* Caltrate D is allowed for basic treatment when the patient is diagnosed with primary osteoporosis (Kidney Yang Deficiency Syndrome).Take it continuously for 3 months.<br>Drug: Placebo<br>* The placebo is simulate granule of Chinese medicine application prescription. Patients take 200ml each time, twice a day. Treatment duration are 3 months.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of VAS pain score of low back | Draw a straight line with a length of 10 cm on the white paper and mark painless and severe pain on both ends respectively to form VAS. The patient makes a mark on the straight line according to the degree of pain he feels. The distance from the starting point to the mark is the quantified degree of pain. Painless is represented by 0; 1-3 points represent mild pain; 4-6 points represent moderate pain, which is strong but tolerable; 7-10 points represent severe pain, gradually reaching intolerable level, which is severe pain. | Change from baseline VAS score at 2 weeks. | 
| Change of VAS pain score of low back | Draw a straight line with a length of 10 cm on the white paper and mark painless and severe pain on both ends respectively to form VAS. The patient makes a mark on the straight line according to the degree of pain he feels. The distance from the starting point to the mark is the quantified degree of pain. Painless is represented by 0; 1-3 points represent mild pain; 4-6 points represent moderate pain, which is strong but tolerable; 7-10 points represent severe pain, gradually reaching intolerable level, which is severe pain. | Change from baseline VAS score at 1 month. | 
| Change of VAS pain score of low back | Draw a straight line with a length of 10 cm on the white paper and mark painless and severe pain on both ends respectively to form VAS. The patient makes a mark on the straight line according to the degree of pain he feels. The distance from the starting point to the mark is the quantified degree of pain. Painless is represented by 0; 1-3 points represent mild pain; 4-6 points represent moderate pain, which is strong but tolerable; 7-10 points represent severe pain, gradually reaching intolerable level, which is severe pain. | Change from baseline VAS score at 3 months. | 
| Change of Traditional Chinese medicine (TCM) syndrome score | According to the《expert consensus on the prevention and treatment of primary osteoporosis with reference to traditional Chinese medicine (2020)》, the quantitative evaluation table of TCM syndrome differentiation for osteoporosis with Kidney Yang Deficiency syndrome was formulated to evaluate the symptoms. Symptoms include primary and secondary symptoms, the primary symptoms were low back pain and soreness and weakness, the secondary symptoms include restricted movement of the lumbar spine，fear of cold and like to be warm，degree of frequency of urination. The primary symptom score was 0 (absent), 2 (mild), 4 (moderate), or 6 (marked)，the secondary symptom score was 0 (absent), 1 (mild), 2 (moderate), or 3 (marked).The obtained scores were summed to calculate the total score. | Change from baseline TCM syndrome score at 2 weeks. | 
| Change of Traditional Chinese medicine (TCM) syndrome score | According to the《expert consensus on the prevention and treatment of primary osteoporosis with reference to traditional Chinese medicine (2020)》, the quantitative evaluation table of TCM syndrome differentiation for osteoporosis with Kidney Yang Deficiency syndrome was formulated to evaluate the symptoms. Symptoms include primary and secondary symptoms, the primary symptoms were low back pain and soreness and weakness, the secondary symptoms include restricted movement of the lumbar spine，fear of cold and like to be warm，degree of frequency of urination. The primary symptom score was 0 (absent), 2 (mild), 4 (moderate), or 6 (marked)，the secondary symptom score was 0 (absent), 1 (mild), 2 (moderate), or 3 (marked).The obtained scores were summed to calculate the total score. | Change from baseline TCM syndrome score at 1 month. | 
| Change of Traditional Chinese medicine (TCM) syndrome score | According to the《expert consensus on the prevention and treatment of primary osteoporosis with reference to traditional Chinese medicine (2020)》, the quantitative evaluation table of TCM syndrome differentiation for osteoporosis with Kidney Yang Deficiency syndrome was formulated to evaluate the symptoms. Symptoms include primary and secondary symptoms, the primary symptoms were low back pain and soreness and weakness, the secondary symptoms include restricted movement of the lumbar spine，fear of cold and like to be warm，degree of frequency of urination. The primary symptom score was 0 (absent), 2 (mild), 4 (moderate), or 6 (marked)，the secondary symptom score was 0 (absent), 1 (mild), 2 (moderate), or 3 (marked).The obtained scores were summed to calculate the total score. | Change from baseline TCM syndrome score at 3 months. | 
| Change of 12-Item Short Form Survey (SF-12) score | The 12-Item Short Form Survey have 12 items and 8 dimensions, which are overall health, Physical Functioning, Role-Physical, Bodily Pain, Vitality, Social Functioning, Role-Emotional and Mental Health. The first four dimensions belong to the level of Physical Component Summary, and the last four dimensions belong to the level of Mental Component Summary. Each item was scored according to the corresponding options to evaluate the impact of health on an individual's everyday life. The highest score of item 2 and 3 is 3, and the lowest score is 1. The highest score of the other ten items is 5, and the lowest score is 1. The obtained scores were summed to calculate the total score to evaluate the changes of patients' quality of life.The higher the score, the better the quality of life. | Change from baseline SF-12 score at 1 month. | 
| Change of 12-Item Short Form Survey (SF-12) score | The 12-Item Short Form Survey have 12 items and 8 dimensions, which are overall health, Physical Functioning, Role-Physical, Bodily Pain, Vitality, Social Functioning, Role-Emotional and Mental Health. The first four dimensions belong to the level of Physical Component Summary, and the last four dimensions belong to the level of Mental Component Summary. Each item was scored according to the corresponding options to evaluate the impact of health on an individual's everyday life. The highest score of item 2 and 3 is 3, and the lowest score is 1. The highest score of the other ten items is 5, and the lowest score is 1. The obtained scores were summed to calculate the total score to evaluate the changes of patients' quality of life.The higher the score, the better the quality of life. | Change from baseline SF-12 score at 3 months. | 
| Changes of serum bone metabolic indexes | Serum level of Beta-CrossLaps (β-CTX) in ng/mL, N-terminal propeptide of type I procollagen (P1NP) in ng/mL，which are determined by Electrochemiluminescence Method.The normal reference ranges of serum P1NP and β-CTX are 16.3 78.2 ng/mL and 0.114 0.628ng/mL, respectively.In case of abnormal conditions,the higher the β-CTX, the more serious the bone resorption.The lower the P1NP, the less bone formation and the worse the bone condition. | Change from baseline bone metabolism index at 3 months. | 
| Changes of serum ALP | Serum level of Alkaline phosphatase (ALP) in U/L, which is determined by automatic biochemical analysis.The normal value is 40-150 U/L.When it is lower than the normal value, it indicates that bone formation is reduced. | Change from baseline ALP at 3 months. | 
| Changes of serum BGP | Serum level of bone glaprotein (BGP) in μg/L, which is determined by automatic biochemical analysis.The normal value is 4.8 10.2 μg/L.When it is lower than the normal value, it indicates that bone formation is reduced. | Change from baseline BGP at 3 months. | 
| Changes of serum 25OHD | Serum level of 25-hydroxy vitamin D (25OHD) in nmol/ml，which is determined by Electrochemiluminescence Method. Its value ≥ 30 nmol/L is normal，it may appear osteoporosis if below this value. | Change from baseline 25OHD at 3 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Therapeutic mechanism | Serum level of EphrinB2, EphB4, Runx2 and VEGF in μg/mL，which is determined by enzyme linked immunosorbent assay（ELISA）.The higher the value, the better the bone condition. So as to verify the mechanism of Bugu Shengsui decoction. | Change from baseline at 3 months. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Double blind method clinical trial, Traditional Chinese medicine intervention, Completely randomized controlled trial, Efficacy evaluation, Mechanism research