重组人甲状旁腺素1-34治疗绝经后骨质疏松症的临床研究

目的观察重组人甲状旁腺素1-34(recombinant human parathyroid hormone 1-34)应用于绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)患者的临床疗效。方法筛选出68例绝经后骨质疏松症患者,所有患者入组后均口服元素钙500 mg/d和维生素D 200 U/d,连续服用26周后加用皮下注射重组人甲状旁腺素1-34(特立帕肽)20μg/d,再连续治疗26周,于应用特立帕肽治疗前及治疗后的13和26周测定腰椎(L_(1-4))和股骨近端骨密度(BMD),采静脉血测定血清骨钙素(OC)、碱性磷酸酶(AKP)水平,应用疼痛视觉模拟评分法(VAS评分)评价患者的疼痛程度,并记录不良反应情况。结果 68位患者均完成全疗程治疗。应用特立帕肽治疗13周时,腰椎L_(1-4)、股骨颈、大粗隆和股骨干骨密度改善不明显(P0.05),血清骨钙素和碱性磷酸酶较治疗前升高(P0.05),疼痛缓解明显(P0.05);治疗26周时,腰椎L_(1-4)和股骨颈骨密度较治疗前明显增高(P0.05),而大粗隆和股骨干骨密度改善不明显(P0.05),血清骨钙素和碱性磷酸酶呈持续升高趋势(P0.05),疼痛明显减轻(P0.05)。治疗期间不良反应的情况均较轻微,没有给予特殊处理即自行缓解。结论连续26周使用重组人甲状旁腺素1-34能有效地促进患者骨形成,缓解骨质疏松症患者疼痛症状,提高患者腰椎、股骨骨密度。     

重组人甲状旁腺素（1-34）治疗原发性骨质疏松症疗效观察

目的 观察重组人甲状旁腺素(1-34)[PTH(1-34)]治疗前后骨密度、骨代谢指标变化,以评价该药治疗原发性骨质疏松症疗效。方法 20例原发性骨质疏松症患者皮下注射PTH(1-34) 20μg 每天1次,每日口服钙尔奇D 600mg,连续治疗6个月。所有患者于治疗前、治疗后第3月、第6月检测腰椎(L2-L4)及股骨颈骨密度、血清骨特异性碱性磷酸酶（BSAP）、血清I型胶原交基C端肽(CTX)。结果 治疗后腰椎(L2-L4)骨密度较治疗前均显著升高,差异有统计学意义（P<0.05或P<0.01）。治疗后股骨颈骨密度较治疗前无明显改善(P>0. 05)。治疗后第3月、第6月BSAP较治疗前显著升高,差异有统计学意义（P<0.01）,治疗后第6月CTX较治疗前显著升高,差异有统计学意义（P<0.01）。结论 PTH(1-34)能显著提高腰椎（L2-L4）骨密度,对原发性骨质疏松症治疗有效。     

甲状旁腺激素（1-34)治疗绝经后骨质疏松症疗效的系统评价

目的 评价甲状旁腺激素(1-34)治疗绝经后骨质疏松症的疗效和安全性.方法 计算机检索MEDLINE(1966～2008.7)、EMBASE (1974～2008.7)、Cochrane图书馆临床试验资料库(2008年第二期)、Current Controlled Trials、The National Reseach Register、中国生物医学文献数据库(1983～2008.7)、中国期刊全文数据库(1994～2008.7),并手工检索相关领域其他杂志.检索不受语种限制,时间截止至2008年7月.纳入以患绝经后骨质疏松症的女性为研究对象、比较甲状旁腺激素(1-34)与其他疗法疗效的随机对照试验,评价纳入研究的质量,并用RevMan 5.0软件进行Meta分析.结果 纳入8个随机对照试验,包括2513例患者. PTH(1-34)(单用或与其他药物联用)增加腰椎和髋部等部位的骨密度优于对照组;减少椎体骨折风险达68%(RR=0.32,95% CI: 0.23～0.45,P＜0.00001),减少非椎体骨折风险为43%(RR=0.57,95% CI: 0.39～0.85,P=0.005).因副作用导致的退出和失访在PTH(1-34)组多于对照组[Peto-OR=1.56,95%CI 1.15～2.12,P=0.004].结论 PTH(1-34)治疗绝经后骨质疏松症疗效肯定,能提高腰椎及髋部等部位的骨密度,降低椎体和非椎体骨折的风险.骨量严重低下和有骨质疏松性骨折的绝经后女性是PTH(1-34)较适合的人群.     

注射甲状旁腺素相关肽6个月后停药18个月骨密度随访

目的研究重组人甲状旁腺素相关肽注射6个月治疗绝经后骨质疏松,随后停药18个月时,对于骨密度是否仍存在作用。方法以采用甲状旁腺素相关肽注射6个月的32例绝经后骨质疏松患者作为研究对象,同时选取年龄匹配的绝经后骨质疏松患者26例作为对照组。比较治疗组和对照组在治疗6个月及停药18个月时的骨密度变化。结果 6个月后治疗组腰椎骨密度平均增加(1.115±3.711)%,全髋骨密度下降(0.498±2.871)%,股骨颈骨密度增加(0.127±4.912)%;对照组在腰椎下降(1.773±2.626)%,全髋下降(1.255±3.02)%,股骨颈增加(1.959±4.065)%;除腰椎外,两组比较差异均无统计学意义(P0.05);停止治疗18个月时,治疗组腰椎骨密度增加(2.210±8.171)%,全髋下降(0.734±4.266)%,股骨颈下降(1.854±4.184)%;对照组腰椎下降(2.004±5.065)%,全髋下降(3.271±3.003)%,与治疗组比较差异有统计学意义(P0.05),股骨颈下降(2.704±2.659)%,与治疗组比较差异无统计学意义(P0.05)。两组人群均未出现严重的不良反应。结论对于绝经后骨质疏松妇女应用甲状旁腺相关肽6个月,随后停药18个月时,对腰椎和全髋骨密度仍有一定的保护作用。     

甲状旁腺激素(1-34)和阿仑膦酸钠治疗骨质疏松症合并类风湿关节炎疗效的对比研究

目的比较甲状旁腺激素(parathyroid hormone,PTH)(1-34)和阿仑膦酸钠(alendronate,ALN)治疗骨质疏松症合并类风湿关节炎(rheumatoid arthritis,RA)女性患者的疗效。方法选取98例于2017年2月至2017年11月在我院就诊诊断为骨质疏松症合并RA的绝经后女性患者。按照治疗方案将患者分为PTH组和ALN组,两组患者分别接受特立帕肽或阿仑膦酸钠治疗,观察治疗6个月后两组患者骨密度和骨代谢指标的改变。结果在两组治疗6个月后,腰椎的骨密度较治疗前均有显著增加(P0.05)。与ALN组相比,PTH组治疗6个月腰椎骨密度的平均变化百分比显然更高;而股骨颈骨密度仅在PTH组显著增加。结论甲状旁腺激素(1-34)在短期治疗骨质疏松症合并类风湿女性患者时,效果较阿仑膦酸钠更佳。     

重组人甲状旁腺激素1-34治疗绝经后骨质疏松症疗效的临床观察

绝经后骨质疏松症(postmenopausal osteoporosis,PMOP)属于原发性骨质疏松的一种,是一种全身性骨代谢疾病,一旦发生骨折,就会给家庭和社会造成极大的负担.目前用于治疗PMOP的药物大多主要通过抑制骨吸收来提高骨密度(bone mineral density,BMD),而甲状旁腺激素(parathyroid hormone,PTH)却是通过促进骨形成来提高BMD,临床和试验研究证实,单独小剂量间断给药能提高BMD、改善骨质量、降低骨折的发生率;联合雌激素、雌激素受体调节剂、降钙素、膦酸盐同样能增加腰椎及全髋骨密度、降低骨折发生率.本文着重介绍重组人甲状旁腺激素(1-34)及其联合用药对PMOP的临床疗效.     

甲状旁腺激素(1-34)在治疗胸腰椎骨质疏松性椎体压缩骨折经皮椎体后凸成形术后邻近椎体再骨折中的应用

目的观察甲状旁腺激素(PTH)(1-34)在治疗胸腰椎骨质疏松性椎体压缩骨折(OVCF)经皮椎体后凸成形术(PKP)后邻近椎体再骨折中的效果。方法回顾性分析2014年1月至2018年6月山西白求恩医院骨科收治的43例胸腰椎OVCF PKP术后邻近椎体再骨折患者资料。其中男14例,女29例;年龄平均73.7岁(61~84岁);邻近椎体再骨折部位:T91例,T102例,T117例,T1214例,L112例,L24例,L32例,L41例。根据治疗方式不同分为3组:A组行PKP治疗(22例),B组行PKP+PTH(1-34)治疗(9例),C组行PTH(1-34)治疗(12例)。记录并比较3组患者入院时、术后6个月X线椎体前缘、中线高度及后凸cobb角,入院时及治疗后6、12个月左侧髋部骨密度,入院时、治疗后3、6、12个月视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI)评分。结果3组患者术前一般资料比较差异均无统计学意义(P>0.05),具有可比性。A组中有3例患者再次出现邻近椎体压缩骨折,B、C组中未出现再次OVCF。A、B组治疗后6个月时椎体高度及后凸cobb角均较入院时改善,差异有统计学意义(P<0.05),而C组无改善。B组治疗后6、12个月及C组治疗后12个月时骨密度T值较入院时改善,差异均有统计学意义(P<0.05),而A组无改善。3组患者的VAS、ODI评分较入院时改善,差异均有统计学意义(P<0.05)。结论PTH(1-34)治疗胸腰椎OVCF PKP术后邻近椎体再骨折可明显改善老年骨质疏松患者的骨密度,防止伤椎塌陷并减少PKP术后骨折患者邻近椎体再骨折。PTH(1-34)结合PKP还可以恢复椎体高度,减少椎体后凸畸形,是治疗OVCF PKP再骨折有效的治疗方法。     

血清胃饥饿素水平与绝经后骨质疏松症合并代谢综合征患者骨密度相关性研究

目的探索胃饥饿素与绝经后骨质疏松症合并代谢综合征患者骨密度相关性。方法本研究纳入我院初诊未经治疗的绝经后骨质疏松症患者(T评分<-2.5)参加了研究,共纳入320位绝经后骨质疏松症女性受试者,其中绝经后骨质疏松症合并代谢综合征78位,绝经后骨质疏松症女性不合并代谢综合征242位。采用酶联免疫吸附法测定血清胃饥饿素和骨代谢指标水平。采用双能X线骨密度仪测量各研究对象腰椎(L1-L4)和股骨颈的骨密度。变量间的相关分析采用Pearson相关分析。结果绝经后骨质疏松症组(OP)和绝经后骨质疏松症合并代谢综合征组(OPMS)的身高、体重、BMI、血糖、腰椎(L1-L4)、三酰甘油、血糖、总胆固醇、股骨颈骨密度、Ⅰ型胶原氨基端延长肽和β-I型胶原羧基端肽和胃饥饿素水平比较,差异有统计学意义(P均<0.05)。根据Spearman相关分析显示,血清胃饥饿素水平与腰椎和股骨颈BMD呈负相关;和P1NP和β-CTX水平呈正相关,但与三酰甘油、血糖和总胆固醇不相关。结论血清胃饥饿素水平升高可能是绝经后骨质疏松症合并代谢综合征患者骨密度降低的潜在危险因素。     

甲状旁腺激素(1-34)联合伊班膦酸钠治疗严重骨质疏松症的临床研究

目的甲状旁腺激素(parathyroid hormone,PTH)(1-34)联合伊班膦酸钠治疗严重骨质疏松症效果临床观察。方法98例严重绝经后骨质疏松症合并骨骼疼痛患者随机分为治疗组和对照组,治疗组使用PTH联合伊班膦酸钠治疗,对照组单纯予以伊班膦酸钠治疗,为期12个月。分别检测两组受试者腰椎及髋部骨密度、血清骨代谢指标治疗前后的改变。结果药物治疗6个月后两组患者腰椎L1~4及股骨粗隆、左侧股骨颈、Ward三角区的骨密度明显增加,且12个月后骨密度进一步增加,显著高于对照组(P0.05);药物治疗12个月后两组血清及碱性磷酸酶(ALP)、血清Ⅰ型胶原C末端肽(s-CTX)、血清抗酒石酸酸性磷酸酶-5b(TRACP-5b)、血清骨源性碱性磷酸酶(BAP)及血清骨钙素(OC)水平均显著改变,且治疗组对ALP及s-CTX、BAP、OC及TRACP-5b影响更明显(P0.05),而两组血钙(Ca)及血磷(P)治疗前后无明显差异(P0.05)。结论PTH联合伊班膦酸钠使用能有效提高严重骨质疏松症患者髋部及腰椎骨密度,改善骨代谢。     

甲状旁腺素在骨质疏松症及骨科领域应用的研究进展

骨质疏松症(osteoporosis, OP)是一种以骨量低下、骨微结构损坏而导致骨脆性增加、易发生骨折为特征的全身性骨病。骨质疏松症所致的骨折严重影响患者的健康和生活质量,并对社会经济造成沉重的负担。目前骨质疏松症的治疗手段主要是以双膦酸盐类为主的抗骨吸收类药物。这类药物抑制骨吸收,但无法新生成骨组织。以重组人甲状旁腺素（1-34)[PTH(1-34)]为代表的促骨形成类药物作用于成骨细胞,通过刺激骨形成发挥作用,为治疗骨质疏松症提供了新的选择。多项临床研究证明PTH(1-34)可增加骨密度并改善骨结构,长期应用可降低骨质疏松症患者椎体和非椎体骨折发生率。PTH (1-34)巳在中国获批用于治疗有骨折高发风险的绝经后妇女骨质疏松症。骨质疏松症不仅增加了患者发生骨折的风险,也使得骨折愈合更加困难。由于PTH(1-34)特殊的成骨作用机制,近年来其在治疗骨折不愈合和脊柱融合等骨科领域的应用也日益受到重视,并且巳经有一些成功的个案报道。本文回顾了近年来国内外关于PTH( 1-34)在骨质疏松症和骨科领域的临床研究的进展,以期为临床实践提供参考。     

rhPTH(1-34)对骨质疏松大鼠的作用及对sclerostin的影响

[目的]探讨人重组甲状旁腺素1-34(rhPTH1-34)对骨质疏松的治疗作用以及与血钙、磷代谢和生长因子的关系。[方法]用摘除大鼠双侧卵巢的方式制备骨质疏松模型,实验动物分为3个组:模型对照组(OVX组,摘除大鼠双侧卵巢不作任何处理);rhPTH1-34治疗组(PTH组,摘除大鼠双侧卵巢12周后用rhPTH1-34治疗8周);假手术组(sham组,仅切除卵巢周围的脂肪组织约3 g,术后12周纳入实验)。应用第4代双能X线骨密度仪测量大鼠股骨上段骨密度值(BMD);用ELISA法测定血清硬化蛋白(sclerostin)水平及骨钙素(BGP)浓度;用自动生化仪测定血清碱性磷酸酶(ALP)。[结果]rhPTH1-34治疗组、sham组均较OVX组股骨上段骨密度增高,组间比较差异有显著性(P<0.01)。rhPTH1-34治疗组血清BGP浓度值升高及sclerostin值降低,与OVX组比较差异有显著性(P<0.01)。各组血清钙、磷含量无明显变化,与OVX组比较差异无显著性,ALP值治疗组与OVX组无明显差异。[结论]rhPTH1-34能够预防股骨上段骨密度丢失,并且血清BGP浓度值升高及sclerostin值降...     

Comparison of bone formation responses to parathyroid hormone(1-34), (1-31), and (2-34) in mice

In this study we used a mouse model system to compare the in vivo effects of parathyroid hormone(1-34) [PTH(1-34)] with that of PTH(1-31) or PTH(2-34) analogs. Daily subcutaneous administration of PTH(1-34) for 15 days caused a dose-dependent increase in the serum osteocalcin level and bone extract alkaline phosphatase activity, markers of bone formation. PTH(2-34) was much less potent, whereas PTH(1-31) was equipotent in stimulating bone formation parameters in mice. PTH(1-34) caused significant increases in serum calcium (after 4 h) and tartrate-resistant acid phosphatase activity in bone extract (after 4 h), whereas PTH(2-34) and PTH(1-31) were less potent. Because PTH(1-31) caused a smaller increase in bone resorption parameters compared to PTH(1-34), despite similar effects on bone formation parameters, we evaluated the long-term anabolic effects of PTH(1-31) and PTH(1-34) in mice. Weekly evaluations of serum osteocalcin levels demonstrated that daily injections of PTH(1-34) and PTH(1-31) at 80 microg/kg body weight increased serum osteocalcin levels within 1 week of the start of treatment, which were maintained during the entire 22 week treatment. Assessment of bone density at the end of the treatment period with peripheral quantitated computed tomography (pQCT) revealed that PTH(1-34) caused a significantly greater increase in femoral bone density compared to PTH(1-31) at the middiaphysis (18% vs. 9% over vehicle control; p < 0.001). Both PTH(1-34) and PTH(1-31) increased periosteal circumference compared to vehicle (p < 0.01) without a significant difference between the two treatments. In contrast, PTH(1-34) caused a significantly greater reduction in endosteal circumference than PTH(1-31) (p < 0.001). Both analogs significantly increased maximum load and area of moment of inertia over the vehicle group. In conclusion, our findings suggest that PTH(1-34) and PTH(1-31) may exhibit different anabolic effects at the periosteum vs. endosteum in the long bones of mice.     

rhPTH(1-34)对成骨细胞增殖、Collagen I及Osterix mRNA表达的影响

目的 观察间歇给予重组人甲状旁腺激素(1-34)[rhPTH(1-34)]对体外成骨细胞增殖、I型胶原蛋白(CoHagen I)及Osterix mRNA表达的影响,初步探讨rhPTH(1-34)对体外成骨细胞的作用机制.方法 体外培养新生大鼠成骨细胞,间歇循环给予0、10-11、10-10、10-9、10-8、10-7 M rhPTH(1-34)干预,(24 h为一循环,前12h给药),共2次,用MTT法检测细胞的增殖;RT-PCR法半定量测定成骨细胞Collagen I、Ostefix mRNA的表达.结果 显示rhPTH(1-34)可明显促进成骨细胞的增殖(P<0.05),促进成骨细胞Collagen I和Ostefix mRNA表达(P<0.05),101-9 M增殖、表达最明显,呈剂量依赖关系.结论 rhPTH(1-34)可促进成骨细胞的增殖、分化,可能是通过Collagen I和Ostefix mRNA表达来调节.     

rhPTH(1-34)对成骨细胞增殖、Collagen I及Osterix mRNA表达的影响

目的 观察间歇给予重组人甲状旁腺激素(1-34)[rhPTH(1-34)]对体外成骨细胞增殖、I型胶原蛋白(CoHagen I)及Osterix mRNA表达的影响,初步探讨rhPTH(1-34)对体外成骨细胞的作用机制.方法 体外培养新生大鼠成骨细胞,间歇循环给予0、10-11、10-10、10-9、10-8、10-7 M rhPTH(1-34)干预,(24 h为一循环,前12h给药),共2次,用MTT法检测细胞的增殖;RT-PCR法半定量测定成骨细胞Collagen I、Ostefix mRNA的表达.结果 显示rhPTH(1-34)可明显促进成骨细胞的增殖(P<0.05),促进成骨细胞Collagen I和Ostefix mRNA表达(P<0.05),101-9 M增殖、表达最明显,呈剂量依赖关系.结论 rhPTH(1-34)可促进成骨细胞的增殖、分化,可能是通过Collagen I和Ostefix mRNA表达来调节.     

Separate binding sites for intact PTH 1-84 and synthetic PTH 1-34 in canine kidney

Summary The present studies examine the characteristics of parathyroid hormone (PTH) receptor binding in canine basolateral renal cortical membranes using iodinated preparations of intact bovine PTH 1-84 and [Nle⁸, Nle¹⁸, Tyr³⁴] bPTH 1-34 amide. A solid phase lactoperoxidase technique was used to iodinate the bPTH 1-84. The PTH 1-34 analog was iodinated using chloramine T. Both radioligands were purified by reverse phase high pressure liquid chromatography (HPLC). Specific binding of¹²⁵I PTH 1-84 reached equilibrium at 3 hours whereas binding of the¹²⁵I PTH 1-84 analog reached equilibrium at 45 minutes. Excess bPTH 1-84 resulted in complete inhibition of binding of¹²⁵I bPTH 1-84, whereas 22±1.6% of the bound radioligand remained bound in the presence of excess synthetic bPTH 1-34. These data suggested the possibility of a binding site for the carboxy-terminal region of intact PTH, or binding sites selective for intact hormone. Therefore, additional studies were performed with PTH fragments, PTH 28-53, PTH 35-84, and PTH 53-84. In contrast to previous studies in other systems, these fragments did not result in significant displacement of¹²⁵I PTH 1-84. Analysis of binding of¹²⁵I PTH 1-84 and¹²⁵I [Nle⁸, Nle¹⁸, Tyr³⁴] PTH 1-34 amide, using LIGAND, both indicated a single site model with similar affinities. Thus, the data are consistent either with multiple receptors with similar affinities or a second binding site for bPTH 1-84 on the same receptor. In the canine kidney membranes, bPTH 1-84 and synthetic bPTH 1-34 were equipotent in activating adenylate, although the dose-response curve for bPTH 1-84 was shifted slightly to the right (Kact 2 nm for synthetic bPTH 1-34 versus 5 nm for bPTH 1-84). The present studies suggest that there are binding sites in canine kidney which are selective for the intact hormone and support the existence of more than one class of PTH receptors or a second binding site for intact PTH on a single PTH receptor.     

Comparison of Hypotensive Response following Intravenous Injection of Parathyroid Hormone 1-84 and 1-34 in Conscious Rats

Activation of parathyroid hormone 1 (PTH-1) receptors on vascular smooth muscle cells causes relaxation and decreases blood pressure in rats and humans. However, when PTH(1-84) and PTH(1-34) were injected in anesthetized rats, PTH(1-34) produced a greater decrease in blood pressure. This study quantified the dose-response relationship of the hypotensive response to intravenously injected PTH(1-84) and PTH(1-34) in conscious rats and assessed the role that the C-terminal region of PTH(1-84) played in the differences. Mean arterial pressure (MAP) decreased rapidly following injection of both peptides (0–100 nmol/kg) and reached a nadir at 1–2 minutes before increasing at a rate that was dose- and time-dependent. PTH(1-34) produced a greater hypotensive effect than PTH(1-84) at most doses tested and was significantly different from PTH(1-84) at 1–10 nmol/kg. The greatest difference in MAP decrease between PTH(1-84) and PTH(1-34) (24 and 35 mm Hg, respectively) occurred at 10 nmol/kg. Median effective dose (ED₅₀) values for PTH(1–84) and PTH(1-34) were significantly different (5.9 and 1.3 nmol/kg, respectively). The C-terminal PTH fragments PTH(7–84), PTH(39–84), and PTH(53–84) did not affect MAP when injected alone (10 nmol/kg), nor did they influence the hypotensive response when given at a 10–fold molar excess in combination with PTH(1-84) or PTH(1-34) (1.4 nmol/kg). In conclusion, PTH(1-84) is a less potent but, because it induced the same maximum response, not a less efficacious hypotensive agent than PTH(1-34) when administered by bolus intravenous injection in conscious rats. We found no evidence to support the concept that the C-terminal region of PTH is responsible for this difference in potency.     

甲状旁腺素(1-34)在内固定中的早期作用

目的 :研究甲状旁腺素 ( 1 3 4)在不锈钢螺钉内固定中的早期作用。方法 :48只雄性SD大鼠 ,随机分成 2组 ,每组 2 4只。在动物右侧胫骨中段植入一个不锈钢螺钉。实验组隔日注射甲状旁腺素 ( 1 3 4) 0 6mg/kg ,对照组注射等容量的生理盐水。 2组动物分别在第 1、2、4周后处死。取右侧胫骨 ,用测力计检测螺钉的拔出力。另取 8只雄性SD大鼠为立即处死组同样于右胫骨中段植入一个不锈钢螺钉并立即处死 ,测螺钉的拔出力。结果 :立即处死组螺钉的拔出力平均为 13N ,对照组 1周后螺钉的拔出力是 2 4N ,2周后是 3 5N ,4周后是 46N。而实验组 1周后螺钉的拔出力是 48N ,2周后是 68N ,4周后是 112N。第 1、2、4周的增长具有统计学意义 (P <0 0 0 1)。结论 :周期性应用甲状旁腺素可以促进内固定物的早期固定。     

重组人甲状旁腺激素1-34对骨质疏松性骨折愈合影响的实验研究

目的研究重组人甲状旁腺激素1-34（rhPTH1-34）片段对大鼠骨质疏松性骨折愈合的影响。方法选择6个月龄雌性SD大鼠80只，随机分为rhPTH1-34组、雌激素组、对照组（骨质疏松组）及假手术组，每组20只。前三组切除双侧卵巢，假手术组暴露卵巢而不切除，术后3个月行右侧股骨中段骨折内固定术。术后分别皮下注射rhPTH1-34、苯甲酸雌二醇及等量生理盐水，进行骨密度、X线片组织病理学和生物力学检测，观察骨折愈合情况。结果rhPTH1-34组骨折局部骨密度明显高于对照组，差异有统计学意义（P〈0．05）；rhPTH1-34组比同时期的对照组骨痂生成量多，愈合时间提前。结论rhPTH1-34能促进骨形成，增加骨量，加快骨痂形成，促进骨质疏松性骨折愈合，同时能提高骨生物力学特性和抗骨折能力。     

Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (microCT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a approximately 35% recovery of this loss and a approximately 40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2- and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The Swiss-Webster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.