少儿地方性氟骨症骨损害的X线表现及改水降氟后变化

目的了解少儿氟骨症骨损害X线表现、特点,与成人氟骨症X线改变的异同以及脱离高氟影响后的X线变化,为地方性氟骨症的诊断、防治效果评价及发病和转归机理研究提供参考。方法在水氟含量较高(4.3～16.0 mg/L)的地方性氟中毒病区,借助X线检查方法筛选出30例儿童氟骨症病例,对其出现的各种X线征象、特点进行观察和分析,追踪观察并统计了8例儿童氟骨症病例改水前、后X线表现及诊断结果的变化。结果 30名患者中,轻度22例,中度4例,重度4例。硬化型改变26例,软化型2例,混合型2例。所有患者都有骨纹X线征象异常,表现为骨小梁增多、增密(密集),粗大、模糊、紊乱、融合。严重紊乱和融合的骨纹使骨密度增高,骨质硬化。前臂、小腿、骨盆骨软化变形。与成人氟骨症不同,骨周软组织和关节无异常所见。结论少儿地方性氟骨症主要发生在氟含量更高的氟中毒病区,X线表现为骨质方面的损害,骨周软组织和关节不受波及。在改换水源降低饮水氟含量5年后,原有异常骨X线征象即可出现相当明显的逆转或恢复正常影像。部分改水前骨硬化患者在改水后出现了骨质疏松征象,机制有待研究。     

单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白及联合甲氨蝶呤对胶原诱导性关节炎大鼠关节骨破坏影响的实验研究

目的 通过建立胶原诱导性关节炎(CIA)大鼠模型,评价单用重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(rhTNFR:Fc)及其联合甲氨蝶呤在抑制CIA大鼠关节骨破坏方面的作用及机制.方法 利用皮下注射牛Ⅱ型胶原诱导Wistar大鼠发病,建立CIA大鼠模型.将造模成功,炎症评分≥2分的CIA大鼠随机分为生理盐水组(0.4 ml/周,腹腔注射)、甲氨蝶呤治疗组(1 mg周,腹腔注射)、rhTN FR:Fc治疗组(0.8 mg,每周2次,腹腔注射)、甲氨蝶呤+rhTN FR:Fc治疗组(甲氨蝶呤1 mg/周+rhTNFR:Fc 0.8mg,每周2次,腹腔注射).治疗8周后,处死大鼠,取踝关节拍摄X线片,胫骨上段行微计算机断层扫描技术扫描和制作硬组织切片,观察各组踝关节骨破坏情况,评价胫骨上段骨小梁变化及骨量变化.统计学处理采用SNK-q检验.结果 治疗8周后,rhTN FR:Fc组,甲氨蝶呤+rhTNFR:Fc组骨小梁面积百分数[(29.1±0.3)％,(26.7±0.6)％]及骨小梁数量(4.4±0.5)/mm,( 4.0±0.6 )/mm]明显高于0.9％氯化钠注射液组和甲氨蝶呤组[(12.9±0.5)％,( 13.2±0.4)％与(2.0±0.3 )/mm,(2.2±0.2)/mm](P＜0.01);rhTNFR:Fc组、甲氨蝶呤+rhTNFR:Fc组骨小梁分离度明显小于0.9％氯化钠注射液组和甲氨蝶呤组(P＜0.01).结论 单用rhTNFR:Fc及联合甲氨蝶呤均具有明显抑制关节骨破坏的作用,且其抑制炎症关节周围骨量减少的作用与抑制局部骨小梁数量减少及骨小梁分离度的增大相关.     

加强骨质疏松症三级预防对策的落实

骨质疏松症(Osteoporosis)是以骨组织显微结构受损，骨矿成分和骨基质等比例地不断减少，骨质变薄，骨小梁数量减少，骨脆性增加，机械强度减弱和骨折危险性增加的一种全身骨代谢障碍的疾病。中老年人的骨质疏松症绝大多数是属于退行性骨质疏松症。     

氟对大鼠腰椎骨组织形态计量学的影响

目的 观察氟对大鼠腰椎的骨组织形态计量学影响.方法 90只2月龄SPF级SD大鼠,雌雄各半,按体质量随机分成9组,其中对照组分为幼年(CS)、成年(AS)、长期(NS)组,用药组分为幼年高氟(CHS)、幼年低氟(CIS)、成年高氟(AHS)、成年低氟(ALS)、幼年长期高氟(CLHS)、幼年长期低氟(CLLS)组.对照组生理盐水灌胃,用药组分别按相应时间给予不同剂量的氟化钠灌胃.实验验结束后,取腰椎制成不脱钙骨切片,行骨组织形态计量学测量.包括骨小粱面积百分数(Tb.Ar)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、骨小梁分离度(Tb.Sp)、单位骨小梁面积破骨细胞数(Oc.N)、破骨细胞周长百分数(%Oc.Pm)、荧光周长百分率(%L.Pm)、骨矿化沉积率(MAR)、骨小梁周长形成率(BFR/BS)、骨小梁面积形成率(BFR/BV)、骨组织总面积形成率(BFR/TV)、成骨细胞周长(Ob.PM).结果 [1]CHS组的%Tb.Ar、Tb.Th、Tb.N、%L.Pm、MAR、BFR/BS、BFR/BV、和BFR/TV[(50.63±7.44)%,(150.26±27.51)μm,(3.44±0.47)N/mm,(50.63±7.44)%,(0.85±0.03)μm/d、(8.45±2.36)μm/d×100、(381.16±41.62)%/year、(75.07±4.81)%/year]均高于CS组[(29.71±9.32%)、(1 10.93±28.19)μm、(2.68±0.34)N/mm、(24.00±1.22)%、(0.65±0.03)μm/d、(5.43±0.18)μm/d×100、(141.32±9.29)%/year、(58.14±2.3)%/year,P<0.05].CLS组的%Tb.A、Tb.Th、%L.Pm、MAR、BFR/BS、BFR/BV、BFR/TV和Ob.PM[(40.76±6.43)%、(164.25±45.65)μm、(42.02±6.12)%、(0.85±0.04)μm/d、(8.95±3.73)μm/d×100、(378.73±35.39)%/year、(73.52±8.71)%/year、(1.41±0.05)μm]均高于CS组(P均<0.05).[2]AHS组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(50.62±5.76)%、(0.51±0.05)N/mm、(1.13±0.05)%、(42.3±7.02)%、(1.28±0.09)μm/d、(12.91±1.52)μm/d×100、(390.12±43.56)%/year、(65.21±22.13)%/year]均高于AS组[(42.73±5.22)%、(0.41±0.17)N/mm、(0.77±0.52)%、(28.43±6.93)%、(0.80±0.03)μm/d、(9.83±1.44)μm/d ×100、(324.43±53.44)%/year和(48.35±9.36)%/year,P均<0.05].A15组的%Tb.Ar、Oc.N、%Oc.Pm、%L.Pm、MAR、BFR/BS、BFR/BV和BFR/TV[(51.14±6.22)%、(O.49±0.61)N/mm、(1.17±0.11)%、(45.06±6.92)%、(1.39 ±0.08)μm/d、(12.87±1.35)μm/d × 100、(394.6±50.23)%/year和(66.31±18.93)%/year]均高于AS组(P均<0.05).[3]CLHS组的Ob.PM、Oc.N和%Oc.Pm[(1.47±0.27)μm、(0.58±0.13)N/mm、(1.14±0.07)%]均高于NS组[(0.82±1.2)μm、(0.42±0.25)N/mm和(0.75±0.64)%,P均<0.05)].结论 短期染氟导致幼年、成年大鼠的腰椎成骨活动增强;长期染氟虽然增加成骨细胞数目,但是腰椎骨量增加不明显,有促进骨吸收,降低骨质量的可能,随着氟化钠使用时间的延长,逐渐表现出对生长期大鼠骨代谢和骨质量的负作用.     

己烯雌酚对去卵巢大鼠不同部位骨骼的影响

目的　观察己烯雌酚对去卵巢大鼠不同部位骨骼的影响。方法　己烯雌酚SD大鼠行双侧卵巢去除术后 ,灌喂DES 2 2 5μg/ (kg·d) ,持续 90d。用骨组织形态计量学等方法测量胫骨上段和腰椎松质骨及胫骨中段皮质骨的动态参数和静态参数 ,同时测量血清生化指标及子宫内膜厚度。结果　己烯雌酚可使去卵巢大鼠胫骨上段 (PTM)和腰椎 (LV)松质骨的骨量增加、骨小梁分离度减少 ,骨形成和骨吸收降低。与去卵巢组比较 ,DES组的PTM骨量增加 1 54 8% ,LV骨量增加 2 0 3 % ,胫骨中段 (Tx)皮质骨的变化不明显。己烯雌酚还降低去卵巢大鼠血清总胆固醇含量 ,但增加子宫内膜厚度。结论　己烯雌酚能有效预防去卵巢大鼠的骨丢失 ,但是对不同部位的骨骼的作用不同 ,而且具有刺激子宫的作用。     

甲状腺机能亢进症与骨质疏松症

骨质疏松症是以骨组织显微结构破坏,骨矿成分和骨基质等比例地不断减少,骨皮质变薄伴骨小梁数量减少,导致骨脆性增加和骨折危险度升高的一种全身骨代谢障碍性疾病。目前我国骨质疏松患者（包括骨量减少）占总人口6．6％,老年男性患病率为60．72％,女性为90．47％。     

去卵巢大鼠不同时期皮质骨与松质骨变化的显微CT观察

目的 应用显微CT观察去卵巢大鼠胫骨近端皮质骨与松质骨骨密度和骨微结构差异. 方法40只7月龄SD大鼠,随机分为去卵巢(OVX)组和假手术(SHAM)组,每组20只,于手术后第3周及第15周处死.处死后剥离左侧胫骨,行显微CT三维扫描,扫描完成后选取距生长板远端2.5 mm、层厚0.4 mm骨组织为皮质骨感兴趣区域,选取距生长板远端0.7 mm、层厚1.2 mm骨组织为松质骨感兴趣区域行三维重建.获取二维最大密度投射图像及三维结构图像,并对感兴趣区的皮质骨和松质骨进行定量分析. 结果 3周时,OVX和SHAM组大鼠皮质骨面积分别为(0.43±0.13)、(0.31±0.06)mm2;骨髓腔面积(10.31±1.98)、(8.44±1.25)mm2,截面总面积(10.74±2.05)、(8.75±1.26)mm2,截面惯性矩(4.10±0.73)、(3.49±0.37)mm4,两组比较差异有统计学意义(均为P＜0.05).第15周时,除OVX组皮质骨平均厚度低于SHAM组外(P＜0.05),其余各参数两组比较差异无统计学意义.15周OVX组大鼠左侧胫骨骨丢失敏感区域内皮质骨平均厚度和皮质骨面积较3周OVX组大鼠下降(P＜0.05).SHAM组15周大鼠骨内径周长、骨外径周长和截面惯性矩增大,与3周比较,差异有统计学意义(P＜0.05).3周时,OVX和SHAM组体积骨密度分别为(288.2±48.2)mg/mm3和(408.4±51.6)mg/mm3、组织骨密度(604.5±45.3)mg/mm3和(686.7±40.0)mg/mm3、骨体积分数(25.1±5.1)%和(33.6±4.1)%、骨小梁数量(6.04±2.94)个/mm和(9.85±2.83)个/mm,两组比较差异有统计学意义(均为P＜0.05),结构模型指数(分别为3.11±0.36)和2.58±0.36),小梁间隔为(0.37±0.22)mm和(0.14±0.10)mm,明显高于SHAM组(P＜0.05).第15周时,OVX组体积骨密度、骨体积分数、骨小梁数量、结构模型指数和骨小梁间隔改变与SHAM组比较,差异有统计学意义(均为P＜0.05),但组织骨密度差别消失.OVX组大鼠15周较3周组织骨密度增加、骨小梁厚度增厚、骨小梁数量减少和骨小梁间隔增宽(P＜0.05). 结论 大鼠去卵巢后,胫骨近端皮质骨与松质骨具有不同的骨量丢失方式和不同的微结构改变.早期松质骨骨密度明显下降,骨微结构发生退变;皮质骨厚度减少,其微结构改变则先于骨密度的下降,骨量在去卵巢后15周变化不大.     

骨细胞密度对骨生物力学性能的影响

目的 探讨骨细胞密度是否为衡量骨生物力学性能的指标. 方法 40只7月龄雌性SD大鼠随机分为去卵巢组(OVX)、OVX+金雀异黄酮(GEN,5 mg·kg-1·d-1)和OVX+1713雌二醇(EST,10 μg·kg-1·d-1)组及假手术组(SHAM),每组lO只.手术后15周第5腰椎(L5)椎体进行压缩试验,L6椎体先行显微CT扫描测量三维骨密度和骨微结构参数,然后进行疲劳损伤试验,最后行大块组织品红染色、塑料包埋和磨片.磨片标本用于微损伤、骨细胞密度检测. 结果 去卵巢后15周时,OVX组骨细胞密度为(1268.1±191.2)个/mm2,较SHAM组(1760.8±376.6)个/mm2及EST组(1550.9±202.2)个/mm2降低(F=3.531,P<0.05);OVX组最大应力为(84.4±16.9)N,较SHAM(110.3±25.6)N、EST(103.9±15.8)N及GEN组(110.1±4.9)N降低(F=9.561,P<0.05);OVX组骨小梁连接密度为(47.4±7.4)mm-3,较SHAM(71.8±16.0)mm-3及EST组(74.0±12.7)mm-3降低(F=7.635,P<0.05);OVX组骨矿含量为(6.5±2.2)g,较SHAM组(7.9±1.2)g降低(F=2.489,P<0.05);OVX组微破裂平均长度(58.1±6.8)μm,较SHAM(24.2±8.1)/Lm、EST(36.5±9.7)μm及GEN组(28.5±7.5)μm增加(F=3.179,P<0.05);OVX组骨小梁间隔(315.0±32.7)μm,较SHAM(222.5±21.7)μm及EST组(273.3±50.O)μm增加(F=7.007,P<0.05).骨细胞密度与最大应力(R2=0.7874,P<0.05)、骨小梁连接密度(R2=0.1153,P<0.05)、骨矿含量(R2=0.1309,P<0.05)呈正相关,与微破裂平均长度(R2=0.5738,P<0.05)、骨小梁分离度(R2=0.3964,P<0.05)负相关. 结论 骨细胞在维持骨力学性能中起重要作用,骨细胞密度可能是潜在的评价骨力学性能的重要指标.     

四环素-雌酮对去卵巢山羊髂骨的有利作用

目的　山羊双侧卵巢切除 (OVX)建立绝经后骨质疏松 (PMO)动物模型 ,应用骨组织形态计量学方法观察OVX山羊对四环素 雌酮 (XW 63 0 )的治疗反应。方法　 3 1只雌性山羊随机分成 4组 ,即正常对照组、假手术组、OVX术后 6个月组、XW 63 0治疗 6个月组。在处死前第 2 1天和第 9天 ,给山羊口服四环素以标记骨组织和进行动力学研究。制备山羊髂骨不脱钙骨切片 ,应用骨组织形态计量学方法 ,观察各组髂骨骨计量学参数的变化。结果　与正常对照组和假手术组比较 ,OVX术后 6个月组的骨小梁体积比全部骨组织体积 (TBV/TTV)、骨小梁体积比海绵骨体积 (TBV/SBV)、平均骨小梁板厚度 (MTPT)、四环素双标线距离 (DDL)、平均类骨质宽度 (MOSW )、骨矿化沉积率 (MiAR)和组织水平的骨形成速率 (Svf)显著减少 (Svf:P <0 .0 5 ,其余各参数 :均P <0 .0 1) ,骨小梁表面比体积 (S/V)则显著增加 (P <0 .0 1) ,说明OVX山羊骨量丢失 ,骨小梁体积明显减小 ,骨小梁厚度下降、连接性降低 ,骨转换率降低 ,激活频率减慢 ,骨形成明显减少 ,表现为低转化骨质疏松的骨代谢特征。以上结果提示 ,骨质疏松山羊模型复制成功。与OVX术后 6个月组相比 ,XW63 0治疗 6个月组的TBV/TTV ,TBV/SBV ,MTPT ,DDL ,MOSW ,MiAR和Svf显著增加 (均P <0 .0 1)     

血清骨钙素和骨保护素在燃煤型氟骨症患者中的表达

目的 观察血清骨钙素(BGP)、骨保护素(OPG)在燃煤型地方性氟中毒(简称地氟病)人群中的表达,为深入认识氟骨症发病机制以及评价和监测除氟效果提供基础依据.方法 选择贵州省6个燃煤型地氟病病区村居民作为观察对象,进行临床氟骨症检查,按病情分度分为正常、轻度、中度、重度4种,按不同分型分为正常、硬化型、疏松型、混合型4种,并根据氟骨症病情分度情况,将观察病区村分为轻、中、重病区村.分别用放射免疫法和酶联免疫法检测观察对象血清BGP、OPG.结果 重度氟骨症患者血清BGP[(6.78±4.43)μg/L]与正常[(3.58±1.53)μg/L],轻、中度患者[(3.44±2.66)、(3.41±2.20)μg/L]比较均明显增高(P<0.05);轻、中、重度患者血清OPG[(1251.55±998.31)、(1265.94±931.77)、(1560.55±858.07)ng/L]与正常[(520.81±385.05)ng/L]比较明显增高(P<0.05).混合型氟骨症患者血清BGP[(6.09±2.62)μg/L]与正常,硬化、疏松型患者[(3.97±1.53)、(3.20±2.12)μg/L]比较均明显增高(P<0.05);硬化、疏松、混合型氟骨症患者血清OPG[(1321.63±1017.00)、(1205.42±852.22)、(1529.01±402.83)ng/L]与正常比较明显增高(P<0.05).轻病区村人群血清OPG[(452.06±338.10)ng/L]与中、重病区村[(1266.30±899.14)、(1851.80±956.08)ng/L]比较明显降低(P<0.05),重病区村与中病区村比较则明显增高(P<0.05).结论 血清OPG可作为燃煤型氟中毒骨病变的一个早期生物学指标.重度氟骨症患者的骨代谢(骨再建)处于活跃状态,并随着氟中毒的严重程度加重而加重.     

Effects of high doses of corticosteroids on bone metabolism

The effects of a chronic treatment with corticosteroids on bone are well known, but few data are available regarding the acute effect of these drugs on bone turnover. This study was aimed at evaluating the effects of high doses of corticosteroids administered for a short period on bone metabolism. We assessed 23 subjects (15 women and 8 men) suffering from multiple sclerosis and treated with methylprednisolone (1 g i.v. for 10 days) followed by oral prednisone for 9 days; patients affected by diseases involving bone or treated during the previous 6 months with drugs influencing bone metabolism were excluded. We observed a significant decrease of ALP and bone glia protein (BGP), in these subjects, and a significant sudden increase of urinary calcium/creatinine and urinary cross-laps after 3 days of treatment. All of these parameters, except urinary calcium/creatinine, returned to basal levels after 30 days from the beginning of treatment (11 days after the interruption of corticosteroids administration). Serum phosphorus showed a significant decrease after 3 days of treatment, but returned to basal levels after 10 days. These data suggest that high doses of corticosteroids administered for a short period are able to induce an increase of bone resorption and a decrease of bone formation; moreover, bone turnover returns to basal levels when the treatment is stopped.     

Salmon calcitonin prevents cyclosporin-A-induced high turnover bone loss

Cyclosporin-A (CsA) has greatly influenced the outcome of organ transplantation and has also been effective in the treatment of many autoimmune diseases. Unfortunately, it has deleterious effects on bone remodelling, causing a high turnover bone loss, with bone resorption exceeding bone formation. Salmon calcitonin (SCtn) has been shown to inhibit bone resorption in high turnover states such as Paget's disease and postmenopausal osteoporosis. In an attempt to attenuate the high turnover bone remodelling caused by CsA alone, we studied the bone mineral effects of CsA in combination with SCtn in male Sprague-Dawley rats. Group A (n = 20) received vehicle as control, group B (n = 20) received CsA (15 mg/kg BW) by daily gavage and SCtn vehicle sc, group C (n = 20) received SCtn (1.3 IU/kg BW) daily sc and CsA vehicle, and group D (n = 20) received a combination of CsA and Ctn daily, as described above. Rats were bled weekly for determination of circulating biochemical bone parameters. Eight rats from each group were killed on day 14 (short term), and the remaining rats were killed on day 28 (long term). Tibiae were removed for bone histomorphometry after death, which revealed a reduction of trabecular bone volume and an increase in osteoclast number induced by CsA alone. These changes were significantly attenuated by the combination of CsA and SCtn to resemble the histomorphometry of the control group. The inhibition of osteoclast number by SCtn is the most plausible mechanism by which the combination therapy attenuates the high turnover bone loss induced by CsA alone.     

Low vitamin D status, high bone turnover, and bone fractures in centenarians

The oldest olds, including centenarians, are increasing worldwide and, in the near future, will represent a consistent part of the population. We have studied bone status and metabolism in 104 subjects over 98 yr of age to evaluate possible interventions able to avoid fragility fractures and disability. Ninety females and 14 males not affected by any acute disease were considered. After a complete clinical assessment, blood was drawn for evaluating bone turnover markers, and performance tests together with skeletal ultrasonography (either at the phalanges or at the heel) were performed. We found that 38 subjects had sustained a total of 55 fractures throughout their lives, and 75% of these were fragility fractures. Twenty-eight fractures occurred at the proximal femur, with 14 after the age of 94 yr. Serum 25-hydroxyvitamin D was undetectable in 99 of 104 centenarians. PTH and serum C-terminal fragment of collagen type I were elevated in 64 and 90% of centenarians, respectively, with a trend toward hypocalcemia. Bone alkaline phosphatase levels were close to the upper limit. Serum IL-6 was elevated in 81% of centenarians and was positively correlated with PTH and negatively correlated with serum calcium. Serum creatinine was not correlated with PTH. Bone ultrasonography showed that most centenarians had low values, and ultrasonographic parameters were correlated with resorption markers. We conclude that the extreme decades of life are characterized by a pathophysiological sequence of events linking vitamin D deficiency, low serum calcium, and secondary hyperparathyroidism with an increase in bone resorption and severe osteopenia. These data offer a rationale for the possible prevention of elevated bone turnover, bone loss, and consequently the reduction of osteoporotic fractures and fracture-induced disability in the oldest olds through the supplementation with calcium and vitamin D.     

The effect of maternal high sucrose exposure on bone mineral density and serum bone metabolism markers in adult offspring

<正>Objective To study the impact on bone mineral density,serum bone metabolism markers,and the expression of osteoprotegerin(OPG) and receptor activator of NF-κB ligand(RANKL) in the adult offspring exposed     

Transient high grade heart block following autologous bone marrow infusion.

We performed a retrospective analysis of 42 consecutive patients undergoing autologous BMT to determine the incidence of second and third degree heart block following the infusion of cryopreserved autologous bone marrow and to identify any predisposing characteristics. A decrease in heart rate > or = 10 beats/min was observed in 80.5% of patients, with a mean decrement of 27 +/- 7 beats/min. 48.8% of patients developed absolute bradycardia (< or = 60 beats/min). Four of 41 patients (9.7%) experienced high-grade heart block: 9.7% second degree and 4.8% third degree. Heart block patients did not differ from the non-heart block group with respect to age, interval from diagnosis or bone marrow harvest to transplant, cardiac risk factors, pretransplant electrocardiograms or radionuclide angiograms, transplant chemotherapy regimens or serum chemistry values. There was an increased incidence of heart block in patients with prior exposure to cyclophosphamide (p < 0.05) and vinca alkaloids (p < 0.05). There appears to be a high incidence of transient second and third degree heart block following autologous marrow infusion. This may be related to prior chemotherapy, but more likely is an effect of the infusate itself. Predisposing factors were not identified.