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研究生:任振輝
研究生(外文):Jenn-Huei, Renn
論文名稱:骨質疏鬆之流行病學研究-玉里研究
論文名稱(外文):Epidemiological Study of Osteoporosis in Yu-Li, Taiwan
指導教授:周碧瑟周碧瑟引用關係楊南平
指導教授(外文):Pesus ChouNan-Ping Yang
學位類別:博士
校院名稱:國立陽明大學
系所名稱:公共衛生研究所
學門:醫藥衛生學門
學類:公共衛生學類
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:128
中文關鍵詞:骨質疏鬆精神分裂
外文關鍵詞:OsteoporosisSchizophrenia
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骨質疏鬆是一種骨骼質量減少及骨骼強度減弱的一種疾病。骨質疏鬆會導致嚴重的骨折,這類骨折對病人會產生很嚴重的生理以及精神上的負擔,對病患的家庭以及社會也會造成很沈重的經濟負擔。Rigotti and colleagues 最早報告厭食症患者罹患骨質疏鬆的個案;隨後也有許多學者在精神分裂、情感性精神分裂、重度憂鬱、以及躁鬱症的患者有類似的報告,這些學者的報告中也論及精神病患的骨質密度不足的盛行率的較一般非精神病患為高。精神分裂症的盛行率在全世界各地大約是百分之一,因為服用藥物的副作用, 使得這些病患容易發生跌倒意外;加上病患的年紀大、生理功能減弱、肌肉力量不足、認知能力障礙、失智、以及營養不足等危險因子,使得機構內的慢性精神病患更容易經歷跌倒意外。曾經有一篇報導,在慢性精神病患中產生非明顯外傷骨折的盛行率約為百分之二十五。但是在之前有關於骨質疏鬆在精神病患內盛行率的研究所收集的個案數都不多,因此用比較多的個案數來調查精神病患發生骨質疏鬆的盛行率是必要的,如果同時能夠在非精神科病患族群中一起調查,並且比較精神病患及非精神科病患骨骼質量的分佈狀況更能顯示其間的差異。
高血清泌乳激素以及精神病抗精神病藥物被報告與骨質疏鬆有明顯相關性;高血清泌乳激素也曾經被報告是抗經神病藥物的副作用之一,而新一代的抗精神病藥物被報告比較不會產生高泌乳激素這種副作用。故而有關血清泌乳激素濃度、血鉀濃度、血鈣濃度、血清鏻酸鹽濃度、造骨標記(骨鈣素,Osteocalcin)、蝕骨標記( 膠原蛋白氮端 Cross-linked N-teleopeptide of type I collagen, NTX )、甲狀腺刺激素、副甲狀腺荷爾蒙以及使用何種類型抗精神病藥物與精神分裂患者骨質疏鬆密度相關性的研究,對於慢性精神分裂病患產生骨質疏鬆的危險因子以及病理生理過程是非常重要的。
本研究中收集了965個住在玉里榮民醫院的二十歲以上慢性精神分裂病患以及405個居住在與玉里榮民醫院相同區域二十歲以上的社區民眾,施予超音波骨密度儀(QUS)的檢測。社區病患是以挨家挨戶方式去執行骨質密度的檢測。雖然超音波骨密儀不是現今測量骨質密度的黃金標準方法,但由於它攜帶與使用方便、沒有輻射、適合用在大量篩檢骨質密度調查,對本研究是相當適合的。另外一個使用超音波骨密度儀的原因是超音波骨密度儀與雙能量X射線吸收測量骨密度儀(Dual energy X-ray absorptiometry, DXA)檢測結果具有相當好的相關。超音波骨質密度讀數在精神科病患以及在一般社區民眾分佈,將以分層分析方式相互比較;並且以讀數校正後的骨質疏鬆標準比較慢性精神分裂病患與社區一般民眾骨質疏鬆盛行率差異,並且與金門研究中的骨質疏鬆盛行率間進一步比較。
第二部份的研究將之前的調查過的慢性精神病患中篩選93個骨質嚴重不足病患,另外在骨質正常的慢性精神病患中,依照年齡及性別以1:1的方式篩選93名病患為對照對照組,這些病患接受問卷、以病歷回顧他們所使用的精神科藥物、及接受抽血檢驗。檢查的項目包括泌乳激素、雌二醇、睪固酮、鎂離子、鈣離子、磷酸鹽、osteocalcin、NTX、甲狀腺刺激素、副甲狀腺荷爾蒙等血清濃度,並且分析泌乳激素、雌二醇、睪固酮、鎂離子、鈣離子、磷酸鹽、osteocalcin、NTX、甲狀腺荷爾蒙、副甲狀腺荷爾蒙等血清濃度 以及所使用的精神科藥物種類跟骨量的相關性。
研究的結果顯示慢性精神分裂病患的骨量在他們還年輕的時候便比較差;但是在年齡老化的過程中,並不會像一般社區民眾出現骨量減少的情況。在慢性精神分裂女性病患也不會像一般社區民眾出現停經期過程骨質快速流失的變化。
嚴重的骨質不足與泌乳激素、鈣離子、osteocalcin、NTX、甲狀腺刺激素、副甲狀腺荷爾蒙的血清濃度以及現在使用的抗精神科藥物種類間沒有明顯相關。嚴重的骨質不足在今神分裂女性病患中與月經有無亦無明顯相關。高血清鎂離子濃度在男性精神分裂病患中與使用抗精神科藥物種類間有臨界的相關性,但是高血清鎂離子濃度只對女性精神分裂病患具有保護的作用。高血清泌乳激素濃度在女性精神分裂病患中與使用的抗精神科藥物種類間有明顯的相關,但是高血清泌乳激素濃度只在男性慢性精神科病患中提供保護作用。血清泌乳激素濃度和所使用的抗精神科藥物種類間沒有相關。
與一般社區民眾比較慢性精神分裂病患在年輕的時候便有骨量不足的現象 ,但慢性精神分裂病患的骨量在此之後就達到相對的穩定,而且在男性與女性中皆同;女性慢性精神分裂病患也不會出現停經期間骨量減少的變化。這個結果與之前文獻報導過的骨量與血清泌乳激素濃度以及骨量與血清鎂離子濃度的關係相異,也與文獻報導過的骨量與使用的抗精神病藥物種類的關係不盡相同。近一步探討慢性精神分裂病患骨質疏鬆的病理生理過程的研究以及骨質與血清泌乳激素、血清鎂離子、和個別抗精神病藥物的關係的研究是必要的,以達到延緩或避免慢性精神分裂病患發生骨質疏鬆的狀況。
Osteoporosis is a bone disease that can reduce both bone mass and bone strength. It can cause serious bone fractures that can have significant and even devastating physical, psychological and financial consequences for patients and their family. Rigotti and colleagues first reported decreased bone density in patients with a confirmed mental disorder (anorexia nervosa). Many researchers reported similar condition in schizophrenia, schizoaffective disorders, major depression, and bipolar disorder. Many of them reported that the prevalence of decreased bone density is higher while compared with non-psychological diseased population. The prevalence of schizophrenia is about 1% worldwide. Chronic schizophrenic patients have been reported as having higher osteoporosis prevalence. Side effects of psychotropic medications received by schizophrenic patients may predispose them to fall. Advanced age, poor physical function, low muscle strength, decreased cognition, dementia and poor nutrition also predispose institute-resident chronic schizophrenic patients further to fall. Prevalence of non-traumatic fractures in chronic schizophrenic patients has been reported to be about 25% in a cross-sectional survey. But all the reports of prevalence of osteoporosis in schizophrenia patients are of limited collected number of cases. A prevalence survey with more number of cases of schizophrenia is necessary. Meanwhile, the survey that conducted in the non-schizophrenic population simultaneously is also necessary to compare the pattern of bone mass distribution between schizophrenic patients and general population.
Hyperprolactinemia and antipsychotics are reported to be associated with osteoporosis in chronic schizophrenic patients. Hyperprolactinemia is also reported to be a side effect of antipsychotic medication. New generation medications, called atypical antipsychotics, are proposed to have less hyperprolactinemia side effect. Study about associations between serum prolactin level, magnesium level, calcium level, phosphate level, bone forming marker (osteocalcin), bone degradation marker (Cross-linked N-teleopeptide of type I collagen, NTX), thyroid stimulating hormone, parathyroid hormone and types of antipsychotics and bone mass was designed based on the previous survey result is also necessary in the characterizing risk factors and pathophysiological process of osteoporosis in schizophrenic patients.
Nine hundreds and sixty five schizophrenic patients aged 20 years and over in Yuli Veterans Hospital and 405 members aged 20 and over of the community lived in the same town as the institute received bone mass examination by a heel qualitative ultrasound (QUS) device. Community population was collected by door-to-door visits. QUS device is not the present gold standard method of detecting bone density. It was used due to its portability, no radiation and suitable for large numbers cases survey. The other reason for using QUS is that well correlation between QUS and DXA has been reported. BUA value distribution of schizophrenic patients was stratified to analyzed and compared with community population in the same town of the institute and in Kinmen, Taiwan.
In the second study, 93 schizophrenic patients with severely poor bone mass and 93 age and sex matched patients with normal bone mass from a previous survey study were selected. Data were collected via questionnaires and reviews of antipsychotic medication. Blood samples were drawn and serum levels of prolactin, estradiol, testosterone, magnesium, calcium, phosphate, osteocalcin, Cross-linked N-teleopeptide of type I collagen (NTX), thyroid hormone, and parathyroid hormone were checked. Association between bone mass condition and serum level of the above items and type of received antipsychotics was evaluated.
The result shows schizophrenic patients have lower bone mass while they are young. There is no bone mass decrease during aging process in chronic patients as in general population. Accelerated bone mass loss during menopausal transition was not observed in the female schizophrenic patients as in the subjects of the community female population. There is no significant association between severely poor bone mass and serum prolactin, calcium, phosphate, osteocalcin, NTX, thyroid stimulating hormone, and parathyroid hormone level. There is also no association between bone mass and types of currently received antipsychotics. There is no association between bone mass and menstruation condition in female patients. Hypermagnesemia has borderline association with classical and combined (classical and atypical) antipsychotic medications in male patients. Nevertheless, hypermagnesemia is a significant protective factor of severely poor bone mass in female patients. Hyperprolactinemia is significantly associated with classical and combined antipsychotic medications in female patients. Hyperprolactinemia, however, provides protective effect on severely poor bone mass in male patients. There is no significant association between serum prolactin level and the type of antipsychotic received.
Chronic schizophrenic patients have lower bone mass than community population since they are young. But bone mass condition achieves stable status during aging process in chronic schizophrenic patients of both genders. Bone mass does not decreased in the menopausal transition period in female chronic schizophrenic patients. The results of the second study are in contrast with the literatures that have been reported in the association between bone mass and serum prolactin level, serum magnesium level and types of received antipsychotics. Further study to investigate the pathophysiological process and the association between bone mass and serum prolactin level, serum magnesium level, and specific antipsychotics is necessary.
摘 要 i
ABSTRACT v
Acknowledgements x
TABLE OF CONTENTS xi
LIST OF TABLES xiv
LIST OF FIGURES xvi
CHAPTER ONE: INTRODUCTION 1
1.1 Bone, Bone Quality and Osteoporosis 1
1.2 Schizophrenia 4
1.3 Schizophrenia and osteoporosis 6
CHAPTER 2. LITERATURE REVIEW 8
2.1 Prevalence of osteoporosis in Schizophrenia 8
2.2 Pathophysiological process of osteoporosis
in schizophrenia patients 10
2.2.1 Common risk factors 10
2.2.2 Hyperprolactinemia 11
2.2.3 Hypogonadism 13
2.2.4 Other Hormones, Electrolytes 14
2.3 Quantitative Ultrasound 17
CHAPTER THREE: METHOD 21
3.1 Cross-Sectional Survey of BUA in Schizophrenic
Patients And Community Population 21
3.1.1 Study Population 22
3.1.2 Bone Mass and Quantitative Ultrasound 23
3.1.3 Statistical Analysis 24
3.2 Case-Control Study of Poor Bone Mass and
Normal Bone mass Schizophrenic Patients 25
3.2.1 Study Population 25
3.2.2 Laboratory Tests, Questionnaire and
History Review 26
3.2.3 Statistical Analysis 28
CHAPTER FOUR: RESULT 30
4.1 Bone Mass Distribution In Schizophrenic
Patients and Community Population 30
4.1.1 Demographic Data 30
4.1.2 Descriptive Statistical Result 32
4.1.3 Inference Statistical Result 34
4.1.4 Prevalence of Osteopenia and Osteoporosis 36
4.2 Case Control Study in Schizophrenia Patients 39
4.2.1 Demographic Data 39
4.2.2 Descriptive Statistical Result 41
4.2.3 Inference Statistical Result 42
CHAPTER FIVE: DISCUSSION 52
5.1 Cross Sectional Study of Bone Survey 52
5.2 Case Control Study for Risk Factors and
Pathophysiological Process 56
5.2.1 Hypermagnesemia 56
5.2.2 Hyperprolactinemia 57
CHAPTER 6: STUDY LIMITATION 61
REFERENCES 62
APPENDIX A: PUBLISHED 69
APPENDIX B: SUBMITTED AND THIRD REVISE 76
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