摘要目的：了解维持性血液透析患者骨组织学改变特点及各型骨病的发生率。方法：观察49例维持性血液透析患者骨活检组织学标本，并进行骨形态学计量分析，测定骨铝含量，检测部分血生化指标。结果：本组患者均存在不同程度的骨组织学异常改变。高转化型骨病（High turnoverbonedisease，又称Predominant hyperparathyroid bone disease，PHBD）24例（49.0％），以骨转化明显增加为特点，标本中见大量破骨细胞，典型吸收腔及棕色瘤等。低转化型骨病（Low turnover bone disease，LTBD）19例（38.8％），骨“重建”部位减少，成骨细胞及破骨细胞活性明显下降。LTBD又分为骨软化（Osteomalacia，LTOM）4例，占本组骨病的8.2％，其组织学特点为大量类骨质生成，矿化骨明显减少；骨再生不良（adynamic renal bone disease，ABD）15例，占本组骨病的30.6％，以骨量下降、少量类骨质为特征。混合性尿毒症性骨病（Mixeduremicosteodystrophy，MUO）6例（12.2％），患者具有PHBD和MUO共同的组织学特点。骨组织形态学计量分析证实，与LTBD相比，PHBD患者校正矿化率升高（P＞0.05），矿化时间缩短(P＜0.01)、骨形成率增加，破骨细胞数增多，较多吸收腔（P＜0.001）；LTBD则相反，骨形成较低，矿化时间延长，破骨细胞消失，无吸收腔。本组骨铝染色阳性≥30％者占63.3％，以LTBD患者骨铝阳性居首，占84.2％，而PHBD者骨铝阳性亦为54.2％，其确切机制不清，MUO骨铝阳性者33.3％，血生化检查证实，与LTBD比较，PHBD及MUO组AKP，iPTH水平均升高（P＜0.01），但PHBD及MUO组相比，血AKP及iPTH水平无统计学差异。结论：本组患者均存在不同程度骨病的组织学改变，骨病分型以PHBD为主（49.0％）。骨铝总阳性率63.3％，其中LTBD组骨铝阳性为84.2％，血生化检查不能明确骨病类型，骨活检为诊断骨病类型的可靠方法。

MORPHOMETRIC ANALYSIS OF THE HISTOLOGICAL CHANGES IN PATIENTS ON CHRONIC MAINTENANCE HEMODIALYSIS

CHEN Huiping，JI Daxi，XIE Honglang，ZENG Caihong，LIU Hong，XU Bing，LI Leishi，

（Research Institute of Nephrology，Jinling Hospital，Nanjing University Clinical School of Medicine，Nanjing 210002）

ZHU Jianmin，W．E． Huffer，P．Ruegg

（Department of Pathology，University of Colorado Health Sciences Center，4200 East Ninth Avenue，Denver，Colorado，USA）

OBJECTIVE To investigate the histological characters and classification of bone diseases in maintenance hemodialysis patients．METHODOLOGY Quantitative evaluation of bone biopsy tissue，measurement of bone aluminum content and serum biochemical parameters were performed in 49 patients on chronic maintenance hemodialysis．RESULTS Variant bone histological lesions were observed in all the patients and were classified into 3 groups：predominant hyperparathyroid bone disease（PHBD）in 24 cases（49.0％），low turnover bone disease（LTBD）in 19 cases（38.8％）（including 4 cases of osteomalacia，15 cases of adynamic renal bone disease），and mixed uremic osteodystrophy（MUO）in 6 cases（12.2％）．The PHBD is characterized by a marked increase in bone turnover，with a large amount of enlarged osteoclasts and deep irregular eroded cavities．Representing the other end of the spectrum from PHBD，LTBD is marked by a profound decrease in active remodeling sites．This features underlined a marked decrease in osteoblastic activity and in the number of osteoclasts or osteoblasts．LTBD can be further sub-grouped into osteomalacia（LTOM）and adynamic renal bone disease（ABD）．We identified four cases of LTOM that was characterized by accumulated un-mineralized matrix or pronounced inhibition of collagen deposition．We identified 19 cases of ABD whose bone volume was frequently reduced．However there was few osteoid seams in patients with ABD．The histological features of MUO shared those of PHBD and LTBD，and various in different patients depending on the dominant underline pathogenesis．The morphometric analysis showed that adjusted apposition rate was higher in PHBD group than in LTBD and MUO groups．However the bone formation rate，the number of osteoclasts and eroded cavities surface were increased in PHBD group while decreased in PTLD group（P＜0.001）．The mineralization lag time was decreased in PHBD group and increased in PTLD group（P＜0.01）．Overall，63.3％ of the patients exhibited positive aluminium stain at more than 30％ of the trabecular surface．The positive aluminum deposition in bone was observed in 84.2％ of patients with LTBD，in 54.2％ of patients with PHBD and 33.3％ of patients with MUO．Serum AKP and intact parathyroid hormone (iPTH) levels were increased in PHBD and MUO groups as compared to those in MUO group，while no significant difference of neither of the parameters was found between PHBD group and MUO group．CONCLUSION Patients on chronic maintenance hemodialysis are inevitably complicated with histology evidenced bone diseases（of those PHBD is the commonest type），and are frequently complicated with aluminum deposition（in 63.3％ of the total patients）．Bone biopsy is more informative in the classification of renal osteodystrophy than serum AKP and iPTH．

Key words hemodialysis osteodystrophy bone biopsy

终末期肾功能衰竭可以产生一系列的代谢变化，其中矿物质代谢紊乱所致的骨结构、骨转化的异常直接影响患者的生活质量^［1］。因此，早期诊断、预防骨病是长期替代治疗患者需要正视的问题。本文报告49例国人慢性肾功能衰竭（chronicrenalfailure，CRF）维持性血液透析患者骨活检组织学改变及形态学计量分析，旨在提高对肾性骨病的诊断、分型认识。

1对象和方法

1．1病例选择49例维持性血液透析患者均来自南京军区南京总医院解放军肾脏病研究所血液净化中心，其中男性38例，女性11例，平均年龄53.8±11.4（33～78）岁，平均透析时间92.3±43.4（30～206）个月，血液透析时间≥5年者12例，5～10年者25例，12例患者血透时间＞10年，透析时间最长者达206个月余。原发病因为：慢性肾小球肾炎29例，慢性间质性肾炎4例，糖尿病肾病3例，紫癜性肾炎、慢性肾盂肾炎、遗传性肾炎、肾结核及庆大霉素中毒引起的肾损害各1例，8例患者原发病因不明。

1．2骨活检方法患者在第1～3天，每次口服四环素150mg，3次／d，第16～19天每次口服土霉素0.25g，4次／d，第22日在局部麻醉下，采用Jamshidi针行髂后嵴穿刺活检。将Jamshidi针垂直刺入骨组织约2cm，轻轻摇动拆断基部，拔针后用针芯将所取骨组织（直径约2mm，长约1.5～2cm）推入盛有冷纯乙醇的小瓶中固定，0℃放置2h(不能冰冻)以上^［2，3］。

1．3骨组织处理和染色(1)固定及包埋：取出纯乙醇固定的骨组织，置丙酮30min以上，再将其放入甲基丙烯酸酯（Glycolmelhaerylate）中浸透，置冷室震荡，24h更换甲基丙烯酸酯液，3天后取出骨组织，包埋，置4℃冰箱4h以上，以Jung切片机连续切片，切片厚5μm。（2）染色：全部标本采用不脱钙染色，包括：A、改良的VonKossa染色：测定类骨质和矿化骨；B、酸性磷酸酶（Tartrateresistantacidphosphatase）染色：计算破骨细胞数；C、酸性铬兰（acidicsolochromeazurine）染色：骨组织中铝含量；D、碱性磷酸酶（alkalinephosphatase）染色：计算成骨细胞；E、未染色切片：测定四环素标记线距离，计算骨矿化率和矿化时间；F、其它：包括铁离子染色及SiriusRed染色^［3～5］。

1．4骨组织形态计量分析采用黑白图象分析系统，对49例国人维持性血液透析患者骨组织标本进行测量，计算出类骨质面积（OsteoidArea，％）；类骨质宽度（Osteoidwidth，μm）；骨小梁面积（TrabecularArea，％）；骨校正矿化率（Adjustedappositionrate，Aj．Ar，μm／d）、矿化时间（Mineralizationlagtime，天）、破骨细胞（Osteoclast）及成骨细胞（Osteoblast）数（个／mm²）；吸收腔面积（Erodedarea，％）；观察骨铝沉积状况^［6］，当骨小梁表面铝沉积≥30％时，则提示骨铝阳性^［7］。

1．5血生化检查全部患者均在骨活检前一周透析前取血，查钙、磷、碱性磷酸酶等；并用放射免疫法测定全段甲状旁腺素（intactparathyroidhormone，iPTH）水平（正常值9～55μg／L）。

1．6统计学分析对各组数据采用t检验和χ²检验。

2结果