| 摘要: | 研究背景：
骨質疏鬆症是一種無聲但若隱若現的疾病，沒有明顯的臨床表現，特點是骨量少，微結構破壞和骨骼脆性，通常導致骨質疏鬆性骨折，並給健康和經濟造成沉重負擔，是影響老年人的重大公共衛生問題。由於隨著年齡的增長，骨密度降低和強度肌肉的喪失造成腰椎骨關節炎，並經常導致慢性疼痛，因此，疼痛的緩解與預防進一步的骨質流失同樣重要。但是由於當前西藥治療的副作用，中藥的使用經常成為另一個選擇。
研究目的：
本實驗分為兩個部分，第一部分為文獻的搜尋及實證薈萃分析的探討。搜尋在台灣以健保資料庫分析所得的臨床最常用處方獨活寄生湯的臨床研究模式，來做實證臨床試驗薈萃研究的探討。希望藉此設計出一個具備低異質性、高證據品質的中藥臨床藥效、用藥安全性評估的臨床研究來探討臨床自擬處方modified Zhi-Bo-Di-Huang Wan prescription (ZBP) 的藥效及機轉。
第二部分為臨床試驗與基因藥理學研究的結合。設計一個隨機臨床試驗（randomized controlled trial，RCT），用來探討臨床自擬處方ZBP在緩解骨質疏鬆症的腰痛患者在疼痛緩解的效果；並同時利用基因實驗室的組學研究方法，，探討複方中藥處方ZBP中的多種分子成分在人體中可能的作用機轉及多靶點治療的可能協同療效。
研究方法：
第一部分：在獨活寄生湯系統薈萃分析中，我們檢索了五個電子數據庫（Cochrane CENTRAL, 中國知網, CEPS, PubMed 和 EMBASE）中使用獨活寄生湯的隨機對照試驗，評估有效率、骨質密度 (BMD)、疼痛改善和不良事件作為研究結果。
第二部分：在臨床收案及基因組學研究上，我們收受骨密度為-2.5而近兩週內具有腰背疼痛VAS?4分的骨質疏鬆症患者，進行一個12週的隨機、單盲的臨床研究，利用VAS疼痛量表、僵直性脊椎炎整體評估量表、台灣簡明版生活品質問卷(WHOQOL-BREF Taiwan)及Oswestry Disability Index。來評估複方科學中藥處方ZBP對骨質疏鬆症患者療效。並抽取患者末端靜脈血，來推測療效之生物標記及基因相關檢測，用來探討臨床使用的複方中藥ZBP可能的療效機轉。
研究結果：
第一部分：在獨活寄生湯系統薈萃分析中，我們發現到中西藥的併用可以降低單用西藥的副作用，在疼痛緩解、骨密度改善上比西藥單用更具效果。
第二部分：在臨床及基因學研究上，我們發現在小於65歲的受試者中，在服用複方ZBP後，在與環境生活、飲食交通上有明顯的改善；在低BMI的族群中，服用ZBP的受試者在膝痛的緩解有明顯的效果。而在機轉的探討上，我們發現四種標的基因（ADRA2B、IL-1β、RMRP 和 TNF）在實驗組及安慰劑組中分別有相反的表現，認為mRNA分析方法有助於了解中藥方劑的潛在作用機制，並證明中藥複方具有多個治療靶點和協同作用。
Background:
Low back pain is prevalent among patients with osteoporosis, especially among older adults. Approaches for preventing or treating osteoporosis remain stalled owing to the side effects of current treatments.
Aim of the study:
1. We used the methodology of Evidence-Based Medicine systematic review with meta-analysis of randomized controlled trials (RCTs) to establish a clinical evidence TCM randomized controlled trial.
2. We conducted a randomized clinical study which was based on the findings of Evidence-Based Medicine systematic review with meta-analysis of randomized controlled trials. And we combined gene pharmacology research to explore the action mechanism and curative effect of the novel TCM formula, modified Zhi-Bo-Di-Huang Wan prescription (ZBP).
Methods:
1. Five important databases were searched for RCTs on this systematic review with meta-analysis, and two authors individually extracted information and data concerning study design, baseline characteristics, efficacy rate, bone mineral density (BMD), pain score, and adverse event. Meta-analysis was done mainly with risk ratio (RR) and standardized mean difference (SMD) for BMD and pain, using random-effects model; while Peto odds ratios (PORs) were used for pooling adverse event rates due to sparse data. Point estimate was reported with 95% confidence intervals (CIs).
2. We conducted a 12-week randomized clinical study. Patients were selected and categorized into two groups. We used Bath Ankylosing Spondylitis indices, WHOQOL-BREF Taiwan and Oswestry Disability Index to evaluate the curative effect of TCM prescription, ZBP, on osteoporosis patients, while we used mRNA profiling methods to investigate the potential mechanisms of action of TCM formula.
Results:
1. On the systematic review with meta-analysis, seventeen RCTs (n=1526) met eligibility criteria, and were included in this synthesis. Pooled estimates demonstrated that as compared with no TCM, TCM led to significantly higher efficacy rates (RR=1.25, 95%CI: 1.19–1.31; I2=0%), more lumbar BMD (SMD=0.61, 95%CI: 0.25-0.96; I2=20%), lower pain score (SMD=-1.10, 95%CI: -1.40–0.79; I2=33%), and lower overall adverse event rates (POR=0.40; 95%CI: 0.20–0.97; I2=27%).
2. On the RCT and gene pharmacology research, we revealed that TCM prescription ZBP was beneficial on younger than 65 years patients (WHOQOL- BREF Taiwan QoLSocialL: Difference = 1.222; p-value: < 0.001) and BMI<25 patients (VASKnee: Difference = -0.681; P value: < 0.001). We demonstrate potential for pain management in patients with osteoporosis, suggesting that the formula has multiple therapeutic targets and synergistic effects. Additionally, we determined that mRNA profiling enabled a clearer understanding of the therapeutic effects of ZBP. |
