內(nèi)分泌性骨病2

內(nèi)分泌代謝性疾病與骨質(zhì)疏松癥,江蘇省人民醫(yī)院 內(nèi)分泌科 何畏,骨質(zhì)疏松癥的定義,骨質(zhì)疏松癥是一種因骨量低下、骨微結(jié)構(gòu)破壞，導(dǎo)致骨脆性增加、易發(fā)生骨折為特征的全身性骨病 世界衛(wèi)生組織(WHO)骨質(zhì)疏松癥是以骨強(qiáng)度下降、骨折風(fēng)險(xiǎn)增加為特征的骨骼系統(tǒng)疾病，骨強(qiáng)度反映骨骼的兩個(gè)主要方面，即骨礦密度和骨質(zhì)量 美國(guó)國(guó)立衛(wèi)生研究院(NIH),電鏡下正常骨微結(jié)構(gòu),電鏡下骨量減少和骨質(zhì)疏松微結(jié)構(gòu),中華醫(yī)學(xué)會(huì) 骨質(zhì)疏松診治指南,骨質(zhì)疏松性骨折治療的現(xiàn)狀,調(diào)研： 來自于6國(guó)的3422骨科醫(yī)師首次骨折后，90%醫(yī)師沒有常規(guī)地測(cè)量骨密度75%的醫(yī)師缺乏適當(dāng)?shù)墓琴|(zhì)疏松癥知識(shí),Dreinhfer et al. Osteoporos Int 2005; 16:S44-S54,對(duì)于385位脆性骨折患者的調(diào)研“您是否曾聽說骨質(zhì)疏松癥?”沒有: 20 % 有: 80 %“您是否認(rèn)為：您所遭遇的骨折可能由于骨頭的脆性所引起?“否: 73 % 是: 27 %,An Osteoporosis Clinical Pathway for the Medical Management of Patients with Low Trauma Fracture,Chevalley et al. Osteoporos Int. 2002; 13:450-455,骨折患者對(duì)于骨質(zhì)疏松癥的認(rèn)識(shí)和知識(shí)非常少,Purpose: China has the largest osteoporosis-affected population in the world. However, population-based survey for osteoporosis awareness has not been reported. This study was to determine the basic awareness status of osteoporosis in a large community in China. The relationship between awareness and calcaneus quantitative ultrasound (QUS) was also assessed.,定量骨超聲測(cè)定結(jié)果包括寬頻超聲衰減(BUA)和超聲傳導(dǎo)速度(VOS)，前者反映骨量的高低，骨量高者BUA值較高；后者反映骨骼的連續(xù)性，連續(xù)性越好，VOS值越高。QUI/sti是將寬帶超聲衰減組合成的一個(gè)單一的臨床量度,對(duì)骨強(qiáng)度的反映更具有代表性,-Awareness of osteoporosis and its relationship with calcaneus quantitative ultrasound in a large Chinese community population, Clinical Interventions in Aging 2013:8 789796,Results: The proportion of people who have osteoporosis awareness was very low. Only 30.7% of the subjects had heard of osteoporosis, and the rate of having heard of osteoporotic fracture was 18.5%. Subjects drinking milk occupy 52.9%, taking calcium 16.0%, taking vitamin D 7.1%, and taking physical activity 47.2%. In logistic regression analysis, high educated elder women showed better awareness (P 0.05). Similar to previous studies, female, old age, low education and osteoporotic fracture history were significantly associated with low QUS (P 0.001).,分類,原發(fā)性骨質(zhì)疏松癥繼發(fā)性骨質(zhì)疏松癥,骨丟失或骨量峰值下降,年齡 (歲),相對(duì)骨量(% 理想骨量峰值),80,60,40,20,20,30,40,50,60,70,80,100,峰值下降,快速丟失,正常,繼發(fā)性骨質(zhì)疏松癥的病因分類,內(nèi)分泌異常 甲狀腺功能亢進(jìn) 甲狀腺功能減退 垂體泌乳素瘤 甲狀旁腺功能亢進(jìn) 性腺功能減退 庫欣綜合征 風(fēng)濕疾病 藥物 糖皮質(zhì)激素 抗癲癇藥 甲狀腺素 肝素，酒精,先天性遺傳疾病骨形成不全高胱氨酸尿Marfan癥后群營(yíng)養(yǎng)不良維生素C 缺乏維生素D缺乏蛋白質(zhì)其他制動(dòng)、廢用和失重等,惡性腫瘤 多發(fā)性骨髓瘤 白血病 淋巴瘤 淋巴細(xì)胞增多癥 慢性疾病 胃腸吸收障礙 肝功能損害 慢性腎病 類風(fēng)濕關(guān)節(jié)炎 氟骨病,中華醫(yī)學(xué)會(huì) 骨質(zhì)疏松診治指南,內(nèi)分泌代謝性疾病與骨質(zhì)疏松癥,糖尿病與骨質(zhì)疏松癥,Association between bone mineral density and type 1 diabetes mellitus: a meta-analysis of cross-sectional studiesT1DM and bone mineral density,Purpose: Type 1 diabetes mellitus (T1DM) is global problem. A few studies have investigated the relationship between T1DM and bone mineral density (BMD) values. This meta-analysis was performed to explore differences between T1DM and healthy individuals in BMD values measured at five bone sites.,Association between bone mineral density and type 1 diabetes mellitus: a meta-analysis of cross-sectional studies.Pan HongWu NapingYang TaoHe WeiDiabetes Metab Res Rev2013年暫未分卷,T1DM and BMD of total body,All people,T1DM and BMD of total body,Females,T1DM and BMD of total body,Males,Conclusion: The results of this meta-analysis suggest the overall association between T1DM and reduced BMD values. Notably, the influence of T1DM on BMD seems to depend on gender or patients age. Reduced BMD values may occur early after T1DM diagnosis. Future clinical and basic research studies are needed to further understand the mechanisms of decreased BMD values in T1DM patients.,糖尿病與骨質(zhì)疏松癥,免疫因素的影響維生素D（ vitamin D，VitD）的影響骨鈣蛋白（steocalcin，OC） 腸促胰素的影響高血糖的影響胰島素的影響,免疫因素與骨質(zhì)疏松,CD4+T淋巴細(xì)胞主要參與細(xì)胞免疫應(yīng)答，并對(duì)CD8+T淋巴細(xì)胞和B細(xì)胞的活化、增殖具有重要輔助作用。而在骨質(zhì)疏松中，CD3+T淋巴細(xì)胞、CD8+CD56+淋巴細(xì)胞、CD4+CD8+淋巴細(xì)胞比率以及CD45RO+記憶性淋巴細(xì)胞明顯增高，這些殺傷功能性淋巴細(xì)胞可以產(chǎn)生大量的炎性因子，如腫瘤壞死因子-等，這些炎性因子可以促進(jìn)骨吸收，引起骨質(zhì)和骨量的變化，參與骨質(zhì)疏松的發(fā)生發(fā)展,VD與兒童I型糖尿病,四項(xiàng)病例對(duì)照研究薈萃分析 嬰兒期補(bǔ)充VD， 型糖尿病風(fēng)險(xiǎn)降低29%一項(xiàng)出生隊(duì)列研究證實(shí) 嬰兒期補(bǔ)充VD 2000IU/d， 型糖尿病風(fēng)險(xiǎn)降低近80%C S Zipitis. Arch Dis Child 2008; 93: 512-517,腸促胰素的影響,胃腸外營(yíng)養(yǎng)與骨量減少相關(guān)，說明腸道和骨代謝之間的功能是由于吸收營(yíng)養(yǎng)物質(zhì)產(chǎn)生的激素,如腸促胰素聯(lián)系起來的。被認(rèn)為最重要的是腸道分泌的GLP-1,GLP-2,GIP,YY肽和胰腺細(xì)胞分泌的胰島素，糊精，preptin及胰多肽有實(shí)驗(yàn)表明：在鏈霉素導(dǎo)致的糖尿病小鼠及由糖激發(fā)的胰島素依賴型糖尿病小鼠的實(shí)驗(yàn)中，GLP-1及艾塞納肽都可增加骨保護(hù)素/NF-K配體受體類成骨細(xì)胞上可檢測(cè)到功能性GIP受體，GIP與受體結(jié)合后可調(diào)節(jié)類成骨細(xì)胞的增殖及活性,2型糖尿病,2型糖尿病患者的骨密度測(cè)量結(jié)果不一致2型糖尿病患者骨量減少：胰島素分泌不足、高血糖、高尿糖、滲透性利尿、腎1a-羥化酶活性減弱肥胖和高胰島素血癥對(duì)骨有保護(hù)作用糖尿病患者的骨折危險(xiǎn)性增加：骨流失、低血糖、神經(jīng)病變、視力障礙,Is obesity protective against osteoporosis?,方法,江蘇南京市鼓樓區(qū)40歲以上社區(qū)居民7489人(男2814人，女4675人)測(cè)量跟骨骨超聲密度值(QUS)問卷調(diào)查檢測(cè)血管脈搏波速率(PWV),QUS,MS組分?jǐn)?shù)目,結(jié)果3,絕經(jīng)后女性BMI正常組（18.5BMI100ng/dl (12.00-22.00) TSH 0.01mIU/ml (0.270-4.200),44,2012年開始出現(xiàn)腰疼，一直未予重視，近20天明顯加重，無法下蹲，活動(dòng)困難，患者無外傷跌倒史，在無錫第四人民醫(yī)院行DXA骨密度檢查T值為-3.55入院查: OC 26.5ng/ml (11.0-43.0) PTH 64pg/ml (12.0-88.0) 25(OH)D 39.0nmol/L 42歲絕經(jīng),45,L1L5壓縮性骨折,46,治療,小劑量強(qiáng)的松、西地蘭、心得安、碳酸鋰治療甲亢同位素治療 骨質(zhì)疏松癥治療：鈣劑、羅鈣全口服，密蓋息注射治療2周，改用密固達(dá)（唑來膦酸）5mg靜滴患者3月后復(fù)診，甲狀腺功能好轉(zhuǎn)，腰背疼痛明顯減輕，活動(dòng)自如,病例,李某，女，78歲，28年前行甲狀腺乳頭狀癌手術(shù)，術(shù)后甲狀腺素治療12年前開始無明顯誘因經(jīng)常性發(fā)生多處骨折，肱骨外髁關(guān)節(jié)、膝關(guān)節(jié)、胸腰椎的骨折，曾接受康復(fù)治療，癥狀改善不明顯，逐漸出現(xiàn)脊柱彎曲，持續(xù)性腰背疼痛，不能忍受，活動(dòng)困難，平臥好轉(zhuǎn)8年前住入我院內(nèi)分泌科，發(fā)現(xiàn)甲狀旁腺機(jī)能減退,25（OH)維生素D 64.78nmol/L（52.5-117.5)甲狀旁腺激素 1.40pg/mL (12.0-88.0)鈣 2.38mmol/L(2.20-2.65) 磷 1.20mmol/L(0.81-1.45)DXA骨密度：T值 -3.2,治療：1.羅蓋全0.25ug bid，鈣爾奇D 1# bid，優(yōu)甲樂50ug qd，甲狀腺素40mg qd2.密固達(dá)5mg靜滴患者3-4個(gè)月后腰疼明顯好轉(zhuǎn)，生活能夠自理,甲狀腺激素對(duì)骨有雙重作用，生理劑量的甲狀腺激素可促進(jìn)骨成熟，一旦過量就會(huì)加快骨轉(zhuǎn)換，減少骨礦鹽含量甲亢患者的骨密度一般會(huì)下降12% 20%，髖骨骨折率升高，特別是TSH小于0.1mIU/L時(shí)，髖骨和椎骨骨折風(fēng)險(xiǎn)分別增加3.6倍和4.6倍T4的治療，特別是大量T4的治療可以造成大量的骨丟失,甲狀旁腺疾病與骨質(zhì)疏松癥,患者姚某，女75歲，以“反復(fù)泌尿系結(jié)石10年，發(fā)現(xiàn)血鈣升高一月余”入院患者10年前因無痛血尿就診發(fā)現(xiàn)雙腎結(jié)石，后結(jié)石部分排出后血尿消失，時(shí)有結(jié)石排出，后常查雙腎B超均為多發(fā)性結(jié)石，2013年8月體檢發(fā)現(xiàn)雙腎鈣質(zhì)沉著，后到南京鼓樓醫(yī)院就診查總鈣2.94mmol/L，磷0.63mmol/L，血糖6.343mmol/L，PTH135.6pmol/L ， 為求進(jìn)一步診治來我院門診就診,患者20年以來輕微外傷常有骨折發(fā)生，33歲尾骨骨折，35歲腳部舟狀骨骨折，45歲肋骨骨折、前臂骨折手術(shù)：甲狀旁腺腺瘤 1.2*1.8cm,甲狀旁腺全切除加前臂移植治療腎性繼發(fā)性甲狀旁腺功能亢進(jìn),甲狀旁腺全切除加前臂移植治療腎性繼發(fā)性甲狀旁腺功能亢進(jìn),PTH是維持機(jī)體鈣平衡的重要激素之一，直接作用于骨和腎，促進(jìn)骨鈣動(dòng)員和腎對(duì)鈣的重吸收長(zhǎng)期高濃度的血