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系統識別號 U0026-2701201921485200
論文名稱(中文) 以高濃度自體血小板、玻尿酸、及生理食鹽水注射治療退化性膝關節病變: 前瞻性、三盲、隨機分配、分組對照性臨床研究並以廣義估計方程式行統計分析
論文名稱(英文) Comparing Intra-articular Injections of PRP, HA, and NS in Treatment of Knee Osteoarthritis: A Randomized, Double-blind, Triple-paralleled, Placebo-Controlled Clinical Trial
校院名稱 成功大學
系所名稱(中) 生物醫學工程學系
系所名稱(英) Department of BioMedical Engineering
學年度 107
學期 1
出版年 108
研究生(中文) 林冠宇
研究生(英文) Kuan-Yu Lin
學號 P88031070
學位類別 博士
語文別 英文
論文頁數 54頁
口試委員 口試委員-林睿哲
口試委員-洪飛義
口試委員-陳嘉炘
口試委員-許弘昌
指導教授-葉明龍
中文關鍵字 自體高濃度血小板  玻尿酸  安慰劑  廣義估計方程式  退化性關節炎  膝關節 
英文關鍵字 platelet-rich plasma  hyaluronic acid  placebo  GEE  osteoarthritis  knee 
學科別分類
中文摘要 膝蓋關節炎(OA)是造成骨骼肌肉失能的主要原因之一。其臨床症狀非常廣泛,而造成的主要原因,直到今日仍不清楚。由於目前治療成效有限,因此生物醫學和再生醫學技術逐漸受到重視,期待能得到更好的療效。目前研究欲評估刺激修復或更換受損的軟骨治療方法,而最主要的研究目標鎖定在生長因子(GFs)的再生能力,預期運用生長因子來修復已退化的組織。目前,全球骨科界正在熱門以體內和體外的試驗方式,來評估此生長因子是否可被用來修復已退化的關節軟骨。自體血小板生長因子療法 (PRP)是一個簡單,低成本,且微創方法,讓受試者從自體血液中獲得生長因子。透過關節動態平衡和軟骨代謝間交互作用,刺激成長因子來改善退化性關節炎。本研究乃是前瞻性、臨床研究,用來評估PRP對此病變的治療成效。針對退化性關節炎患者電腦隨機分別注射PRP、關節內玻尿酸HA (實驗組),以及生理食鹽水NS (控制組),進行分析與比較。本篇研究假設為,透過釋放生長因子和生物活性分子,PRP會改善退化性關節炎患者的膝蓋功能。研究期間共完成53位受試者,共91隻退化性關節炎之個案收集,並分別接受自體血小板生長因子療法(n=31)、關節內玻尿酸療法(n=29)及關節內生理食鹽水注射(n=27),期間並無任何受試者出現不良反應。目前業已完成所有參與本試驗之受試者分別接受上述治療方式後1、2、6及12個月的臨床症狀追蹤。經追蹤6個月後的初步研究結果顯示於日常生活功能評估(WOMAC, IKDC)分數改善率比較中, 接受自體血小板生長因子療法的關節試驗組表現最好,且改善的情況至6個月時仍持續著,反觀其他2組對照組別的生活功能分數改善皆維持不到2個月。
英文摘要 Osteoarthritis (OA) of the knee is one of the main causes of musculoskeletal disability. It is clinically heterogenous, and the processes that cause deterioration are still poorly understood. Current research efforts are focused on the identification of key biochemical pathways that can be targeted therapeutically through biological intervention and the testing of protein biotherapeutics for restoring the metabolic balance within the joint. Autologous platelet-rich plasma (PRP) is a simple, low cost, and minimally invasive method that allows one to obtain from his/her own blood a natural pool of growth factors. The aim of this prospective study was to evaluate the role of PRP in treating degenerative lesions of articular cartilage of the knee, analyzing and comparing them with the results obtained with another common injectable treatment, hyaluronic acid viscosupplementation, and with normal saline being the placebo control. This study was designed to be a prospective, randomized and placebo-controlled clinical trial. The hypothesis was that PRP would improve symptoms and function both statistically and clinically, possibly through the release of growth factors and bioactive molecules, in patients affected by knee OA.
From April to August 2014, a total of 87 osteoarthritic knees (53 patients) who met our inclusion criteria were randomly assigned into 3 groups of 3 weekly injections with either leukocyte-poor PRP (31 knees), HA (29 knees), or normal saline (NS) (27 knees). Functional outcomes evaluated by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the International Knee Documentation Committee (IKDC) subjective score were to be collected at baseline and at 1, 2, 6, and 12 months after treatments. Data were analyzed using generalized estimating equations (GEE).
All three groups had statistically significant improvement in both outcome measures at 1 month; however, only the PRP group sustained such significant improvement in both scores at 12 months (WOMAC 63.71±20.67, 21% increased; IKDC 49.93±17.74, 40% increased). For the inter-group comparison, except for the first month, there is a statistically significant difference between the PRP and NS groups in both scores throughout the study duration (WOMAC, regression coefficient / P value: 8.72 / 0.0015, 7.94 / 0.0155, and 11.92 / 0.0014, at 2-, 6-, and 12 months, respectively; IKDC, 9.1 / 0.0001, 10.28 / 0.0002, and 13.97 / <0.0001); there was no significant difference in both functional outcomes between the HA and NS groups at any time point. Younger and male patients had statistically significant improvement in outcomes; OA stage and BMI were not influential factors statistically. Only the PRP group reached the minimal clinically important differences of WOMAC at every evaluation (15%, 21%, 18%, and 21% at 1-, 2-, 6, and 12 months, respectively), and that of IKDC at 6 months (improvement of 11.6).
In conclusion, intra-articular injections of leukocyte-poor PRP can provide both statistically and clinically significant functional improvement for patients with mild to moderate osteoarthritis of knee for at least one year.
論文目次 中文摘要………………………………I
Abstract………………………………II
TABLE OF CONTENTS………………………………VI
CHAPTER 1: INTRODUCTION………………………………1
Background………………………………1
Objective of Study………………………………7
Hypothesis………………………………10
CHAPTER 2: MATERIALS AND METHODS………………………………11
Study Design………………………………11
Participants………………………………11
Sample Size………………………………12
Outcome Measures………………………………13
Randomization………………………………14
Blinding and Intervention Protocol………………………………14
Preparation of PRP………………………………15
Statistical methods………………………………16
Source of Funding………………………………17
CHAPTER 3: RESULTS………………………………18
CHAPTER 4: DISCUSSION………………………………23
REFERENCES………………………………32
FIGURES………………………………44
Figure 1………………………………44
Figure 2………………………………45
Figure 3………………………………46
Figure 4………………………………47
TABLES………………………………49
Table 1………………………………49
Table 2………………………………50
Table 3………………………………51
Table 4………………………………53
Table 5………………………………54
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