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研究生:呂炳榮
研究生(外文):Ping-Wing Lui
論文名稱:精神分裂症之住院病患使用抗精神藥物治療發生骨質疏鬆症的研究
論文名稱(外文):The Study of Antipsychotic-induced Osteoporosis in Inpatients with Schizophrenia
指導教授:錢慶文錢慶文引用關係
指導教授(外文):Ching-Wen Chien
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:醫務管理研究所
學門:商業及管理學門
學類:醫管學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:144
中文關鍵詞:精神分裂症骨質疏鬆症骨質流失症危險因子骨質疏鬆相關骨折超音波密度測量儀雙能量X光骨質密度掃瞄儀台灣全民健康保險研究資料庫骨質疏鬆相關骨折直接費用估算
外文關鍵詞:schizophreniaosteoporosisrisk factorsosteoporosis-related fracturedual-energy x-ray absorptiometryTaiwan National Health Insurance Databasedirect costs estimation of osteoporosis fractures
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關鍵詞:精神分裂症、骨質疏鬆症、骨質流失症、危險因子、骨質疏鬆相關骨折、超音波密度測量儀、雙能量X光骨質密度掃瞄儀、台灣全民健康保險研究資料庫、骨質疏鬆相關骨折直接費用估算。

前言: 骨質疏鬆症常導致骨折,己成為全球公衛健康的一大課題,在衆多危險因子中,精神分裂症病人服用抗精神藥物己被認為係導致骨質疏鬆症的因素之一,此現象可能是抗精神藥物使血中泌乳激素升高所致。骨質疏鬆症相關骨折帶給社區沈重的負擔。
目的: 本論文旨探討 (1)精神分裂症病人罹患骨質疏鬆或流失症的盛行率是多少? (2)有多少危險因子與骨質疏鬆有關? (3)血中相關生化指標的改變如何? (4)透過台灣全民健康保險研究資料庫分析過去三年(2003~2005)罹患精神分裂症的病人,於2006年當中服用抗精神藥物後是否有較高的骨質疏鬆症及其相關骨折的發生率? (5) 上述這些病人骨質疏鬆相關骨折的直接費用估算如何?
方法: 本論文分兩部份;第一部份選取195位因罹患精神分裂症住院病人的基本資料,包括: 年齡、性別、骨折史、停經史、抽煙史、喝酒史、體位指標及服用抗精神藥物等。利用脚跟超音波骨密度測量儀作初步篩檢,再利用腰椎雙能量X光骨質密度掃瞄儀作最後診斷。抽取靜脉血測量下列生化指標包括: 促甲狀腺激素荷爾蒙、泌乳激素、男性睪丸激素、副甲狀腺素、二氫基女性素、25-羥基維生素D等。第二部份透過台灣全民健康保險研究資料庫的分析,將2003~2005三年罹患精神分裂症的病人,曾於門住診服用抗精神藥物治療,於2006年中因骨質疏鬆發生的發生率,並估算其相關骨折的醫療直接費用。利用t檢定、變異數分析、或卡方檢定比較三組 (骨質疏鬆、骨質流失、正常骨質)的各變項差異。經過性別修正後,利用費氏精確檢定法、t檢定、羅吉斯迴歸法分析各變項與骨質疏鬆的關係。至於台灣全民健康保險研究資料庫的分析,經年齡或性別修正後,利用羅吉斯迴歸法分析各抗精神藥物與骨質疏鬆引起相關骨折的關係。最後,根據台灣對骨質疏鬆症的盛行率來推算台灣罹患精神分裂症住院的病人發生骨質疏鬆引起相關骨折的的醫療直接費用。
結果: 骨質流失症的盛行率為31.6%,骨質疏鬆症為5.2%;年齡愈大低骨質密度的發生率愈高,三組有明顯關係;女性及高齡患者較易發生低骨質密度,罹患骨質疏鬆症的男性有較低的體位;至於骨折、停經、抽煙與否,三組間沒有差異;血中生化指標除二氫基女性素外,三組間沒有差異;低骨質密度的男性病人有較低的副甲狀腺素,女性病人有較低濃度的二氫基女性素及25-羥基維生素D,但三組間沒有差異。若不考慮性別,生化指標與骨質疏鬆無關;服用升高泌乳激素的抗精神藥物有較高的骨質疏鬆發生率,骨質疏鬆病人有較高的累積劑量。無喝酒者、二氫基女性素較低者、低體位者、最後服用一種抗精神藥物若為haloperidol者較易發生骨質疏鬆;至於服用sulpiride、 trazodone或quetiapine者也有較高的骨質疏鬆發生率。
健保資料庫之各參數經控制後發現年齡對骨質疏鬆及骨質疏鬆引起相關骨折成正向相關,前者尤以女性病人明顯;服用抗精神藥物如haloperidol, fluanxol或 sulpiride者發生骨質疏鬆相關骨折的風險較高。至於累積劑量,高齡者較容易發生骨質疏鬆,尤以女性病人明顯。至於骨質疏鬆相關骨折則與年齡、服用haloperidal或sulpiride等成正向相關。健保資料庫分析發現26,511位病人罹患精神分裂症,其中有631位發生骨質疏鬆相關骨折,骨折之年醫療總費用估計為1900萬台幣。若根據員山榮民醫院所得的盛行率,骨質疏鬆相關骨折之年醫療總費用估計為348.9萬台幣。
討論: 雖然健保資料庫的分析顯示服用抗精神藥物對骨質疏鬆並沒有有影嚮,但從員山榮民醫院資料的結果顯示高齡女性病患服用升高泌乳激素的抗精神藥物有較高的骨質疏鬆發生率。因此本研究建議精神分裂症病人若服用抗精神藥物,尤以能升高泌乳激素的藥物,或具高危險因子者如女性、低體位者或高齡者應定期做骨質密度測量,並即時介入治療,除可避免因骨質疏鬆導致骨折的發生外,還可減少骨折所致的醫療費用。
Keywords: schizophrenia, osteoporosis, risk factors, osteoporosis-related fracture, ultrasound bone densimeter, dual-energy x-ray absorptiometry, Taiwan National Health Insurance Database, direct costs estimation of osteoporosis fractures.

Introduction: Osteoporosis is a global public health problem that frequently results in fractures. Though various risk factors are involved, of primary concern is the impact of anti-psychiatrics on the risk in the development of osteoporosis. Hyperprolactinemia induced by antipsychotics is recognized as one of the major potential risk factors. Of late, osteoporosis-related fractures has become a heavy economic burden in the community.
Purpose: This thesis aims to answer: (i) What is the prevalence of osteoporosis and osteopenia in schizophrenic inpatients? (ii) How many risk factors would be significantly associated? (iii) Were the biochemical markers related to the risk in the development of osteoporosis? (iv) Using Taiwan’s National Health Insurance Database from 2003 through to 2006, would patients with schizophrenia who had been taken prolactin-raising antipsychotic drugs suffer from higher incidence of osteoporosis-related fractures in comparison to those who had not been taking these drugs? (v) What is the estimated total cost for osteoporosis and its related fractures?
Methods: In Part I, a total of 195 inpatients with schizophrenic disorders were recruited. The demographic data included age, gender, fracture history, menopausal activity, cigarette smoking, alcohol drinking, body mass index (BMI), and antipsychotics drugs. A calcaneous ultrasound densitometer test followed by a dual-energy x-ray absorptiometry test in the lumbar spine was used for the screening process. Venous blood was then sampled for the measurements of thyroid stimulating hormone (TSH), cortisone, prolactin, testosterone, parathyroid hormone (PTH), estradiol (E2), and 25-hydroxyvitamin D (25(OH)D). In Part II, data from the Taiwan National Health Insurance Database (TNHID), including data for patients with claims of schizophrenia between 2003 and 2006, were retrospectively reviewed. Data from 2003 through to 2005 were retrieved for schizophrenic inpatients who had been taking antipsychotics. Subsequently, patients with osteoporosis-related fractures during the year 2006 were identified. Finally, the direct costs of dealing with the osteoporotic fractures in 2006 were estimated using data from TNHID.
The Student’s t-test, analysis of variance (ANOVA), and chi-square tests were used to compare differences among three groups related to osteoporosis, osteopenia and normal patients. Variables included age (or stratified ages), gender, body mass index (BMI), biochemical data, and others. Gender-adjusted correlations between these variables and osteoporosis were assessed using Fisher’s exact tests, Breslow-Day test, independent-t test, and logistic regression where appropriate. For data retrieved from the TNHID, age and gender-adjusted logistic regressions were used to determine the relationship between types of antipsychotics and osteoporotic-related fractures. Total costs on osteoporosis-related fractures in schizophrenic patients were estimated based on the associated prevalence in Taiwan.
Results: Using dual-energy X-ray absorptiometry (DXA), the prevalence of osteopenia in schizophrenic inpatients was 31.6% while osteoporosis was 5.2%. Age differed significantly among groups with a positive correlation to osteoporosis. Female patients outnumbered male patients in terms of low bone mineral density (BMD). A higher proportion of elderly patients were found to have osteoporosis or osteopenia than that of younger patients.
Patients with osteoporosis have lower BMI, especially in males. Fracture history, menopausal activity, and cigarettes smoking did not significantly differ among groups. None of the biomarkers differed significantly except estradiol where patients with osteoporosis had a lower serum level. Male patients with low BMD had a lower level of PTH. Female patients had lower levels of E2 and 25(OH)D among three groups. With exception to gender, no correlation was noted between biomarkers and osteoporosis. Patients who had been taking prolactin-raising antipsychotics had higher incidence of osteoporosis, whereas those taking other types of antipsychotics did not carry this risk. The cumulative doses of chlorpromazine, haloperidol, and risperidone were significantly higher in patients with osteoporosis. A positive relationship was demonstrated between age and osteoporosis. However, alcohol drinking, BMI value and, E2 were negatively associated with osteoporosis. Patients taking haloperidol as the last antipsychotic carried a higher risk of developing osteoporosis compared to those not taking any antipsychotics. Patients taking sulpiride, trazodone, and quetiapine had a higher risk of osteoporosis.
After controlling all variables in the data collected from TNHID, a positive relationship was noted between age and osteoporosis, especially in female patients. Exposure to antipsychotics was not related to osteoporosis. After controlling all variables, a positive relationship was found between age and osteoporosis-related fractures. Patients taking haloperidol, fluanxol, or sulpiride had higher risk of developing these factures. Regarding cumulative dose, the older the patients, the higher the risk of osteoporosis, especially in female patients. The cumulative dose of risperidal was negatively associated with the risk of osteoporosis. Regarding the risk of osteoporosis-related fractures, similar results were seen in age, haloperidol, and sulpiride. Based on data from TNHID, there were 26,511 schizophrenic patients, of whom 631 were found to have osteoporosis-related fractures. The annual total cost for these fractures were estimated to be 19,007,695 NT. According to the prevalence of osteoporosis in Yuanshan Veterans Hospital, the estimated total cost would amount to 3,489,503 NT.
Discussion: Although results from TNHID demonstrated that the exposure to antipsychotics was not related to the risk of developing osteoporosis, data from Yuanshan Veterans Hospital did, however, display a higher incidence of osteoporosis in patients taking prolactin-raising antipsychotics. We recommended that cautious intervention should be taken against the risk of osteoporosis in schizophrenic patients who had been given antipsychotics, especially the prolactin-raising types, as well as those who carry other potential risk factors including gender, BMI, and age. Early intervention on osteoporosis can attenuate its related fractures, which is cost-saving in health care utilization.
THESIS APPROVAL FORM………………………………………………………..i~ii
ACKNOWLEDGMENTS .………………………………………………………….…1
ENGLISH ABSTRACT …………………………………………………………….2~6
CHINESE ABSTRACT .……………………………………………………..……..7~9
TABLE OF CONTENTS .…………………………..……………………….……10~11
LIST OF FIGURES & TABLES …………………………..……….....................12~14
CHPATER 1. INTRODUCTION AND LITERATURES REVIEW
Section 1.1. Global Healthcare Problem and Osteoporosis ………………………15~18
Section 1.2. The Economic Impacts of Osteoporotic Fractures …………….........19~22
Section 1.3. Definition of Osteoporosis and Osteopenia …………………..……..23~24
Section 1.4. Measurements of Osteoporosis …. …………………………….........25~27
Section 1.5. Risk Factors in Osteoporosis ……….…..…………………….……..27~30
Section 1.6. Schizophrenia and Osteoporosis …….……………………......……..31~35
Section 1.7. Purpose of Study………………..……………………….……….......35~36
CHPATER 2. METHODOLOGY
Section 2.1. Osteoporosis in Schizophrenic Patients……..…………………….....37~41
2.1.1. Screening by Calcaneous Ultrasound Densitometer
2.1.2. Dual-energy X-ray Absorptiometry Biochemical Markers
Section 2.2. Fracture and Prolactin-raising Antipsychotics in Schizophrenic Patients in Taiwan National Health Insurance Database……………………….42~44
Section 2.3. Total Costs Estimation on Osteoporosis-related Fractures………......45~45
Section 2.4. Statistical Analysis…………………………………………………...45~47
CHPATER 3. RESULTS
Section 3.1. The Prevalance Of Osteoporosis And Osteopenia ..…………………48~49
Section 3.2. Associated Risk Factors ……………………………………………..50~54
Section 3.3. Related Biochemical Markers ………………………………………55~67
Section 3.4. Antipsychotics and The Risk of Osteoporosis ………………............68~72
Section 3.5. Prolactin-Raising Antipsychotic and Osteoporosis-related Fractures in Schizophrenic Patients From Taiwan National Health Insurance Database 2004~2006 ........................................................................................73~80
Section 3.6. The Estimated Total Costs on Osteoporosis-related Fractures in Schizophrenic Patients in Taiwan.....................................................81~84
CHPATER 4. DISCUSSION
Section 4.1. Osteoporosis and Schizophrenia…………………………………85~94
Section 4.2. Antipsychotics and Other Risk Factors on Osteoporosis…………94~99
Section 4.3. Aging and Body Mass Index on Osteoporosis…………………..99~103
Section 4.4. Prolactin-raising Antipsychotics And Osteoporotic Fracture From Taiwan National Health Insurance Database …………………103~106
Section 4.5. Total Costs on Osteoporosis and its related Fractures …………107~109
Section 4.6. Limitations of Study …………………………………………...109~112
Section 4.7. Suggestions ……………………………………….……………113~113
REFERENCES ………………………………………………………………...114~144
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