Effect and safety of intermittent weekly administration of human parathyroid hormone 1-34 in patients with primary osteoporosis evaluated by histomorphometry and microstructural analysis of iliac trabecular bone before and after 1 year of treatment
Effect and safety of intermittent weekly administration of human parathyroid hormone 1-34 in patients with primary osteoporosis evaluated by histomorphometry and microstructural analysis of iliac trabecular bone before and after 1 year of treatment
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DOI：
10.1007/s00774-004-0525-z
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发表时间：
2004-11-01
影响因子：
3.3
通讯作者：
Nishizawa, Y
中科院分区：
文献类型：
--
作者：
Miki, T;Nakatsuka, K;Nishizawa, Y
为评价间歇性皮下注射人甲状旁腺激素1-34N端肽(hPTH1-34)的疗效和安全性，对10例(男1例，女9例)原发性骨质疏松症患者，每周皮下注射hPTH1-34 100单位，1次/周，疗程1年。获得患者对参与研究的书面同意。与之前的临床研究一致，hPTH治疗12、24和48周后，平均腰椎骨密度(LBMD)明显增加，分别增加1.8%、3.4%和4.6%。在排除了因与试验药物无关的不良事件或拒绝继续治疗而退出的患者后，对6名患者(1名男性和5名女性)进行了双四环素标记后的组织形态计量学分析。薄层硬组织切片检查未发现骨组织或骨髓腔的质地异常，如骨软化、编织骨或纤维性骨炎，排除了质地异常的组织元素对hPTH1-34治疗后LBMD变化的贡献。第二次活检的组织形态计量学测量显示，与给药前相比，骨体积有增加的趋势，类骨质表面有显著增加的趋势，骨形成的其他参数有增加的趋势。微焦点计算机断层扫描(CT)获得的二维显微结构指标和结节-支柱分析结果表明，骨小梁的连续性得到改善。分析三维重建图像的5例患者中，骨体积和骨小梁厚度显著增加，而与连续性相关的骨小梁模式因子显著降低，提示三维小梁结构得到改善。每周间歇性皮下注射hPTH(1-34)48周，可增加骨小梁体积，改善骨微结构，而不会导致原发性骨质疏松症患者出现异常的骨元素。
In order to evaluate the efficacy and safety of intermittent subcutaneous administration of 1-34 N-terminal peptide of human parathyroid hormone (hPTH 1-34), 100 units of hPTH 1-34 was subcutaneously injected once a week for 1 year in ten patients with primary osteoporsis (one male and nine females) with no qualitative abnormality of the bone according to the results of iliac crest biopsy performed previously, followed by a second biopsy after the end of the 1-year administration. Written consent of the patients for participation in the study was obtained. The mean lumbar bone mineral density (LBMD) definitely increased, by 1.8%, 3.4%, and 4.6% after 12, 24, and 48 weeks of hPTH administration, in accordance with previous clinical studies. Histomorphometric analysis after double-tetracycline labeling was completed in six patients (one male and five females) after the exclusion of those who dropped out because of adverse events unrelated to the test drug, or refusal of continuation. Examination of thin hard-tissue sections revealed no qualitative abnormalities of bone tissue or bone marrow cavity, such as osteomalacia, woven bone, or osteitis fibrosa, precluding the contribution of qualitatively abnormal tissue elements to any changes of LBMD in response to hPTH 1-34 administration. Histomorphometric measurement in the second biopsy revealed a tendency for an increase of bone volume, a significant increase of osteoid surface, and a tendency for an increase in other parameters of bone formation, compared with values obtained in the preadministration biopsy. Indices of two-dimensional microstructure obtained by microfocus computed tomography (CT) and results of node-strut analysis indicated improvement of trabecular continuity. In five patients in whom three-dimensional reconstruction images were analyzed, there were significant increases of bone volume and trabecular thickness, and a significant decrease in the trabecular bone pattern factor, a parameter related to the continuity, suggesting an improvement of the three-dimensional trabcular microstructure. Intermittent weekly subcutaneous injections of hPTH (1-34) for 48 weeks increased trabecular bone volume and improved microstructure, without causing the appearance of abnormal bone elements in primary osteoporosis.