特立帕肽治疗原发性骨质疏松症的短期疗效观察

目的：观察特立帕肽（ Teriparatide ）治疗原发性骨质疏松症的短期疗效和安全性。方法采用自身前后对照临床研究,纳入2011年12月-2012年12月在解放军第309医院骨内科住院的原发性骨质疏松症患者共10名,所有患者在每天口服补充元素钙600 mg和活性维生素D 0.25μg的同时,分别接受特立帕肽治疗,疗程6个月,具体用法为每日皮下注射特立帕肽20μg。所有患者均于用药前、用药后3、6个月采用双能X线吸收法（DEXA）测定腰椎（L2-4）、股骨颈、Ward’s区和大粗隆骨密度（BMD）,用酶联免疫吸附法（ELISA）测定血清骨钙素（sOC）、骨碱性磷酸酶（sBAP）和Ⅰ型胶原交联C端肽（sCTX）水平。观察患者治疗前后骨密度和骨标志物的变化并进行对比分析,记录患者的不良事件。结果10名患者均完成全疗程治疗。治疗3个月时,腰椎（L2-4）、股骨颈、Ward’s区和大粗隆骨密度改善不明显（P＞0.05）,血清骨钙素（sOC）和骨碱性磷酸酶（sBAP）较治疗前明显升高（P＜0.05）。治疗6个月时,腰椎（L2-4）骨密度较治疗前明显增高（P＜0.05）,而股骨颈、Ward’s区和大粗隆骨密度改善不明显（P＞0.05）。血清骨钙素（sOC）和骨碱性磷酸酶（sBAP）呈持续升高趋势（P＜0.05）,Ⅰ型胶原交联C端肽（sCTX）较治疗前略升高,但差异无统计学意义（P＞0.05）。治疗期间不良事件的发生情况：头晕发生2例,恶心发生1例,上述情况均较轻微,没有给予特殊处理即自行缓解。结论特立帕肽能在3个月内改善患者的骨代谢状况（促进骨形成）,6个月内有效增加原发性骨质疏松症患者的腰椎骨密度,适用于绝经后及老年性骨质疏松症患者的治疗。     

特立帕肽联合微创手术治疗复杂椎体骨折的初步观察

目的评估特立帕肽联合微创手术治疗复杂椎体骨折的近期疗效,探讨特立帕肽治疗严重骨质疏松的适应证和安全性。方法本组共16例患者,均为女性。年龄72~86岁,平均78.5岁。病情特点:患者出现多次椎体骨折或同一椎体一次以上骨折;骨密度检查:均存在严重骨质疏松。本组采用微创手术结合特立帕肽(20ug/日,皮下注射)6个月治疗方案。观察手术前、术后3月、随访6个月时疼痛、骨密度(BMD)和骨代谢指标变化,同时记录不良事件。结果所有患者手术后疼痛均较术前不同程度缓解(P0.01),特立帕肽治疗6个月后本组未再发生椎体新鲜骨折,患者腰椎骨密度较术前明显增加(P0.05),血清骨钙素(OC)及总Ⅰ型前胶原氨基端延长肽(tPINP)较治疗前显著提高(P0.05);Ⅰ型胶原羧基端β降解产物(β-CTX)较治疗前无统计学差异(P0.05)。本组3例患者在注射初期出现肢端疼痛,经对症处理后缓解。未记录到其他严重不良事件。结论对于合并严重骨质疏松的复杂椎体骨折患者,特立帕肽联合微创手术近期疗效满意,明显降低了椎体再发骨折的风险,而且具有较高的安全性。     

特立帕肽与阿仑膦酸盐对比治疗骨质疏松症有效性及安全性的Meta分析

目的评价特立帕肽与阿仑膦酸盐对比治疗骨质疏松症有效性和安全性的差异。方法荟萃分析。采用Cochrane系统评价的方法,检索Medline(1966～2011年)、EMbase(1966～2010年)、Cochrane图书馆(2010年)及中国生物医学文献数据库CBM(1979～2010年)有关采用特立帕肽或阿仑膦酸盐治疗骨质疏松症的临床对照研究文献资料,按照纳入和排除标准限定研究对象,通过Jadad评分量表进行文献质量评估后,使用Cochrane协作网提供的RevMan 4.2统计软件进行Meta分析,以获得二者治疗骨质疏松症的疗效和安全性是否有差异的相关证据。结果共纳入使用特立帕肽或阿仑膦酸盐治疗骨质疏松症的临床对照研究6项(760例)。各项研究中腰椎BMD的升高幅度存在异质性,采用随机效应模型进行Meta分析,特立帕肽治疗组在随访期间腰椎BMD的升高幅度比阿仑膦酸盐组高5.16%(95%CI,4.07%～6.26%),P<0.01,差异具有显著的统计学意义。随访期内发生的不良反应包括高钙血症(2.84%,特立帕肽组),背痛(3.98%,阿仑膦酸盐组)等。采用固定效应模型进行Mete分析,合并OR值为0.75(95%CI,0.51～1.11),P=0.15,两组间差异无统计学意义。结论特立帕肽对骨质疏松症患者腰椎BMD的升高幅度高于阿仑膦酸盐,二者的安全性近似,但尚需更多高质量的前瞻性临床对照研究进一步证实。     

联合使用甲状旁腺激素和辛伐他汀对去卵巢大鼠骨质疏松症的治疗有叠加效应

目的探索联合使用甲状旁腺激素(PTH)和辛伐他汀(SIM)对去势大鼠骨质疏松的防治作用。方法 50只健康雌性SD大鼠随机行假手术(Sham,N=10)和切除双侧卵巢(OVX,N=40)手术后,OVX大鼠随机的分成4组:OVX组、SIM组、PTH组、PTH+SIM组。术后第1天开始给予药物治疗,SIM组:SIM灌胃(剂量5 mg/kg,每天1次),PTH组:PTH皮下注射(剂量60μg/kg,每周3次),PTH+SIM组:SIM灌胃和PTH皮下注射,剂量和用药频率和SIM组、PTH组相同,直至手术后12周为止,12时所有大鼠处死取胫骨行Micro-CT检测。结果结果表明SIM组、PTH组、PTH+SIM组和OVX组相比,胫骨近端都有较高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D和较低的Tb.Sp,其中PTH+SIM组大鼠胫骨近端有最高的BMD、BV/TV、Tb.Th、Tb.N、Conn.D和最低Tb.Sp。SIM和PTH单独使用的效果明显低于他们联合使用对去卵巢大鼠骨质疏松的防治作用。结论联合使用甲状旁腺激素和辛伐他汀对去势大鼠骨质疏松的防治有叠加作用     

特立帕肽联合双膦酸盐对老年性椎体压缩骨折术后骨质疏松患者PINP和CTX-1的影响

目的探究特立帕肽联合双膦酸盐对老年性椎体压缩骨折术后骨质疏松患者I型前胶原N末端前肽（PINP）、I型胶原C末端肽（CTX-1）的影响。 方法前瞻性收集2017年9月至2018年3月在河北北方学院附属第二医院骨科就诊的老年性椎体压缩骨折术后骨质疏松患者,共44例,依据随机数字表将患者分为A组（24例）,B组（20例）,另取因无法耐受术后药物治疗等而未进行治疗的患者为C组（20例）,给予A组：特立帕肽+双膦酸盐（唑来膦酸）+钙剂（钙尔奇D咀嚼片）治疗,给予B组维生素D+钙尔奇D咀嚼片治疗,治疗后随访12个月。记录3组随访情况及手术情况,观察并比较3组不同时间点视觉模拟疼痛评分（VAS）、Oswestry功能障碍指数（ODI）、骨密度（BMD）、（腰椎L1-4）、PINP、CTX-1、不良反应和再次骨折发生率。 结果64例患者均获得完整随访,随访率100%,随访时间12~22个月,平均（13.82±1.24）个月。64例患者平均手术时间（17.63±2.04）min,骨水泥灌注量3~7 mL,平均（3.32±0.46）mL,术后发生骨水泥渗漏12例（18.75%）,其中A组5例,B组4例,C组3例。A组在治疗后3个月、6个月、9个月、12个月的VAS评分[（3.06±1.12、1.82±0.74、1.52±0.54、1.41±0.49）分]和ODI指数（28.42±5.16、21.64±4.92、18.76±4.52、17.59±4.38）均小于B组[VAS：（3.81±1.28、3.19±1.13、2.76±0.97、2.53±0.85）分;ODI：34.58±6.13、31.27±5.86、28.48±5.34、27.94±5.17）和C组[VAS：（4.51±1.42、4.16±1.49、3.98±1.31、3.59±1.24）分;ODI：37.71±6.54、35.48±6.07、33.97±5.87、33.61±5.80）（均P<0.05）,B组在治疗后3个月时,与C组比较,差异无统计学意义（P>0.05）,在治疗后6个月、9个月、12个月时,均小于C组（P<0.05）。A组在治疗后3个月时,BMD、PINP和CTX-1水平[（0.835±0.103）g/cm²,（134.08±27.29）ng/mL,（216.85±26.63）μg/L]高于B组[（0.774±0.076）g/cm²,（93.57±19.85）ng/mL,（216.85±26.63）μg/L]和C组的[（0.706±0.051）g/cm²,（49.74±10.59）ng/mL,（161.05±15.42）μg/L],且B组各指标水平均高于C组（均P<0.05）。随访期间,A组无再次骨折患者,B组再次骨折发生率5.00%,C组发生率15.00%,但3组骨折再发率差异无统计学意义（P>0.05）。 结论特立帕肽联合双膦酸盐对老年性椎体压缩骨折术后骨质疏松患者临床疗效显著,可有效提高BMD,改善骨合成、骨吸收指标水平,显著降低疼痛及相关功能障碍程度,安全性高,值得推广。     

狄诺塞麦对去卵巢大鼠股骨干骺端骨缺损修复影响的实验研究

目的研究狄诺塞麦(DMAb)对去卵巢大鼠股骨干骺端骨缺损修复的影响。方法 40只健康雌性SD大鼠随机行假手术(Sham,n=15)和切除双侧卵巢(OVX,n=25)手术,术后12 w每组各取5只大鼠处死取股骨行双能X线骨密度仪检测来确定骨质疏松的建立情况,随后各组大鼠在双侧股骨干骺端建立3 mm圆形缺损,术后随机分成3组:Sham、OVX组及DMAb组。术后第一天DMAb组给予DMAb皮下注射一次,剂量为60 mg,正常饲养12 w后所有大鼠处死取股骨行Micro-CT、骨生物力学、组织切片检测。结果和OVX组、Sham组股骨干骺端缺损愈合相比,DMAb组大鼠股骨干骺端缺损区域有较高的最大载荷、骨密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小粱数量(Tb.N)、连接密度(Conn.D)、骨矿化沉积率(MAR)和较低的骨小粱分离度(Tb.Sp),且各组之间比较差异有统计学意义(P0.05)。结论 DMAb通过增加骨量,促进骨组织矿化及提高骨骼强度来加速去势大鼠股骨干骺端骨缺损的修复。     

特立帕肽预防骨质疏松患者腰椎融合术后椎弓根螺钉 松动的前瞻性研究

目的观察特立帕肽在预防绝经后骨质疏松患者腰椎融合术后椎弓根螺钉松动治疗中的作用。方法 72名绝经后骨质疏松患者,诊断为腰椎退行性滑脱,随机分为3组:特立帕肽组(n=24,每日行皮下注射20μg teriparatide),双磷酸盐组(n=24,每日口服2.5mg利塞膦酸risedronate),空白对照组(n=24)。所有患者均接受腰椎管减压及1个节段后外侧融合手术,术后12月运用摄片、CT、临床体检等方法判断椎弓根螺钉松动及临床疗效。结果术后12月随访时,特立帕肽组螺钉松动率:X线摄片为7%,CT为12%;利塞膦酸组分别为13%和25%;空白对照组为14%和25%。特立帕肽组椎弓根螺钉松动率明显低于利塞膦酸组及空白对照组(P0.05),而利塞膦酸组椎弓根螺钉松动率与空白对照组无明显差别(P0.05)。末次随访时三组间临床评分无显著差异(P0.05)。结论特立帕肽能够增强腰椎椎体松质骨及椎弓根皮质骨强度,降低螺钉松动发生率。     

辛伐他汀联合雌二醇对去卵巢大鼠骨质疏松的影响

目的探讨辛伐他汀联合雌二醇对大鼠骨质疏松的影响。方法 75只雌性SD大鼠随机分为5组:假手术组、去势组、辛伐他汀组、雌二醇组、联合药物组,15只/组,构建去卵巢大鼠骨质疏松模型,给予不同药物干预。检测骨代谢相关生化指标及骨生物力学指标,测定骨组织骨密度(bone mineral density,BMD)和骨矿物含量(bone mineral content,BMC),HE染色观察骨组织形态结构。结果去势组血清骨代谢相关生化指标(ALP、BGP、PICP、TRAP)水平较假手术组均显著增高(P0.05),辛伐他汀组、雌二醇组、联合药物组较去势组均降低,尤以联合用药组降低最显著(P0.05)。去势组骨组织BMD和BMC、骨生物力学指标(最大载荷、最大应力、最大位移和刚度)较假手术组显著降低(P0.05),辛伐他汀组、雌二醇组、联合药物组较去势组均增高,尤以联合药物组增高最显著(P0.05)。去势组骨组织骨小梁减少稀疏,排列紊乱,网状结构破坏,大量纤维组织,髓腔内大量空泡状脂肪细胞。联合药物组骨组织结构较完整,骨小梁数目增多,致密均匀粗壮,连接成网状结构,脂肪细胞明显减少。结论辛伐他汀联合雌二醇可调节大鼠骨代谢,增加骨密度和骨矿物质,改善骨生物力学和骨组织形态学,起到抗骨质疏松疗效和骨保护作用。     

低强度脉冲电磁场对去卵巢大鼠不同部位骨密度的影响

目的 探讨低强度脉冲电磁场(PEMFs)对去势雌性大鼠不同部位骨密度的影响.方法 30只10月龄雌性SD大鼠随机分为3组:一组去势造模(造模组),另一组行假手术(空白组),第三组去势造模后暴露于50 Hz、0.16 mT的磁场环境下60 min/d,共90天(磁疗组).实验期间动态观察大鼠全身及颅骨骨密度,期满处死后测定血清雌二醇水平及骨密度.结果 ①空白组雌激素水平和子宫系数均显著高于其他两组(P<0.01);②至60天时,空白组、磁疗组的颅骨骨密度显著高于造模组(P<0.05),全身骨密度在90天时才出现统计学意义(P<0.05);③与空白组和磁疗组相比,造模组椎体骨密度(P<0.01)比腰椎骨密度(P<0.05)差异更显著,磁疗组股骨骨密度虽较造模组有所上升但差异未达到统计学意义.结论 全身骨密度与颅骨骨密度结合可有效评估大鼠活体骨密度动态变化;PEMFs对因去势造成的骨密度下降有明显抑制作用,且对不同部位骨密度影响程度不同;采用去椎弓的单一椎体为骨密度衡量点能更为敏感的反映治疗效果.     

唑来膦酸与特立帕肽对骨质疏松患者腰椎椎间融合影响的对比分析

目的：比较唑来膦酸与特立帕肽对骨质疏松患者腰椎间融合的影响。方法：前瞻性纳入2016年3月至2018年10月行后路腰椎间融合术合并骨质疏松患者91例,根据患者自行选择接受的治疗方式分为基础对照组22例、唑来膦酸组39例和特立帕肽组30例,分别采用基础抗骨质疏松治疗、辅助唑来膦酸或者特立帕肽抗骨质疏松治疗促进椎间骨融合。术后1年、2年随访时采用双能X线骨密度仪测量髋部骨密度,采用CT检查评估椎间融合情况,同时记录腰腿痛视觉模拟量表（VAS）评分和下肢Oswestry功能障碍指数（ODI）评分以评估临床效果。结果：最终基础对照组21例、唑来膦酸组37例及特立帕肽组26例完成2年随访。三组患者术前一般临床资料差异无统计学意义（P>0.05）,具有可比性。术后1年,特立帕肽组、唑来膦酸组患者髋部骨密度均较术前提高（P<0.05）;特立帕肽组患者椎间融合率均高于基础对照组及唑来膦酸组患者（P<0.05）。术后2年,特立帕肽组、唑来膦酸组患者髋部骨密度均高于基础对照组患者（P<0.05）,且特立帕肽组患者髋部骨密度高于唑来膦酸组患者（P<0.05）;特立帕肽组、唑来膦...     

替勃龙对去势大鼠骨强度的影响研究

目的探讨替勃龙对切除卵巢大鼠骨强度的影响。方法选用6月龄未交配健康雌性Sprague-Dawley大鼠共40只,随机分为4组(每组10只)①正常对照组或假手术组(Sham),②空白对照组即骨质疏松组(OVX),③OVX加戊酸雌二醇(ValerateEstriolVE)组(0.8mg/kg),④OVX加替勃龙(Tibolone)组(0.25mg/kg);行去势手术3周后开始按分组设计喂药(灌胃),共治疗3个月后处死。取大鼠右股骨及第3腰椎进行骨密度测定;之后对右股骨标本进行中段三点弯曲试验,测定股骨干强度指标;取大鼠第4、5腰椎制作不脱钙病理切片后进行图像分析计量。统计学处理P<0.05为具有统计学意义。结果①骨密度椎骨及股骨干骺端骨密度OVX组明显下降,使用戊酸雌二醇能够提升骨密度;但股骨干骨密度各组间差异无显著性。②骨强度三点弯曲实验结果显示OVX组股骨干强度较假手术组明显下降,替勃龙组骨干强度较OVX组提升30%(P<0.05)。③椎骨形态计量结果OVX组与假手术组、戊酸雌二醇组及替勃龙组间差异均有显著性。结论短期小剂量替勃龙治疗能阻止卵巢切除导致的成熟雌性大鼠股骨干强度受损。     

Shock wave treatment shows dose-dependent enhancement of bone mass and bone strength after fracture of the femur

Shock wave treatment is believed to improve bone healing after fracture. The purpose of this study was to evaluate the effect of shock wave treatment on bone mass and bone strength after fracture of the femur in a rabbit model. A standardized closed fracture of the right femur was created with a three-point bending method in 24 New Zealand white rabbits. Animals were randomly divided into three groups: (1) control (no shock wave treatment), (2) low-energy (shock wave treatment at 0.18 mJ/mm2 energy flux density with 2000 impulses), and (3) high-energy (shock wave treatment at 0.47 mJ/mm2 energy flux density with 4000 impulses). Bone mass (bone mineral density (BMD), callus formation, ash and calcium contents) and bone strength (peak load, peak stress and modulus of elasticity) were assessed at 12 and 24 weeks after shock wave treatment. While the BMD values of the high-energy group were significantly higher than the control group (P = 0.021), the BMD values between the low-energy and control groups were not statistically significant (P = 0.358). The high-energy group showed significantly more callus formation (P < 0.001), higher ash content (P < 0.001) and calcium content (P = 0.003) than the control and low-energy groups. With regard to bone strength, the high-energy group showed significantly higher peak load (P = 0.012), peak stress (P = 0.015) and modulus of elasticity (P = 0.011) than the low-energy and control groups. Overall, the effect of shock wave treatment on bone mass and bone strength appears to be dose dependent in acute fracture healing in rabbits.     

异补骨脂素联合锌治疗对1型糖尿病大鼠骨量、骨密度及骨强度的影响

目的探讨异补骨脂素联合锌治疗对1型糖尿病大鼠骨强度和骨量的影响,并探索可能的机制。方法通过链脲佐菌素注射(60 mg/kg)建立了1型糖尿病大鼠模型;随后1型糖尿病大鼠随机分为1型糖尿病组(Con)、锌治疗组(Zn)、异补骨脂素组(Bgz)以及锌联合异补骨脂素组(Zn+Bgz),每组10只;其中异补骨脂素组和锌治疗组以及联合治疗组大鼠分别接受硫酸锌、异补骨脂素以及两者联合治疗12周;待治疗结束后使用Micro-CT、HE染色切片、骨生物力学检测以及蛋白质印迹观察治疗效果以及可能的机制。结果治疗12周后,与Zn组及Bgz组相比,Zn+Bgz组的大鼠骨小梁数量和骨密度得到明显改善。Zn+Bgz组大鼠BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较Zn组及Bgz组明显改善(P0.05)。治疗12周时,Zn+Bgz组最大负荷、刚度和最大功耗较Zn组及Bgz组显著增加,差异有统计学意义(P0.05)。和Zn组及Bgz组比较,Zn+Bgz组的大鼠Wnt/β-catenin信号通路被激活,Wnt 1、Wnt 5a、p-GSK-3β、GSK-3β、β-catenin水平显著上调,差异有统计学差异(P0.05)。结论异补骨脂素及锌均可以通过Wnt/β-catenin信号通路激活介导对1型糖尿病大鼠骨骼的保护作用,且联合治疗效果更佳。     

The surgical treatment of nonunion of the proximal metaphysis of the femur

Nonunion of the proximal femur is a severe pathology, often provoked by the inopportune or improper use of a therapeutic aid: nonsurgical (primary nonunion), surgical (secondary nonunion). Surgical treatment of this nonunion may thus be characterized by different degrees of difficulty, depending on whether or not it is the sequela of surgery or of nonsurgical treatment. In lax nonunion, with atrophy of the segments and regions of necrotic bone interposed, modeling resection is required to correct the functional axes. The condylar blade-plate may be opposed by a cortical graft--to improve stability of the assembly--protecting the medial wall and providing the screws with excellent hold.     

Individual and combined effects of exercise and alendronate on bone mass and strength in ovariectomized rats

Exercise and bisphosphonate therapies increase bone strength by primarily increasing bone formation and reducing resorption, respectively. Based on these different mechanisms of action, it is possible that combined introduction of exercise and bisphosphonate therapies generates greater improvements in bone mass and strength than either intervention alone. The aim of this study was to examine the individual and combined effects of exercise (treadmill running) and bisphosphonate therapy (alendronate [ALN]) on bone mass and strength in ovariectomized (OVX) rats. Seven-month-old virgin female rats were randomly assigned to either a sham-OVX group (n=13) or one of four OVX groups: vehicle-treated cage-control (VEH-CON, n=10); ALN-treated cage-control (ALN-CON, n=13); vehicle-treated plus treadmill running (VEH-RUN, n=13); and ALN-treated plus treadmill running (ALN-RUN, n=13). ALN-treated groups received twice-weekly ALN (0.015 mg/kg), and exercise groups ran on a motorized treadmill at a 5% incline for 60 min/day, 22-24 m/min, 5 days/week. In vivo measurements included dual-energy X-ray absorptiometry (DXA) of whole-body bone mineral content (BMC), and ex vivo measurements included DXA, micro-computed tomography (muCT), and mechanical testing of the femur and L4 vertebrae. After 14 weeks of intervention, exercise and ALN had additive benefits on whole body and proximal femur BMC, cross-sectional area of the L4 vertebrae, and mechanical properties of the mid-shaft femur. In comparison, for total and mid-shaft femur BMC, L4 vertebrae BMC, and mid-shaft femur cortical thickness and area, there were significant exercise and ALN interactions indicating that the two interventions worked in synergy to enhance bone properties. Supporting the contention that ALN and exercise function via distinct mechanisms of action, ALN successfully reduced medullary canal area suggesting it reduced endocortical bone resorption, whereas exercise augmented periosteal perimeter suggesting it stimulated periosteal bone formation. In summary, we found combined treadmill running and ALN to be more beneficial in preventing declines in bone mass and strength following OVX than the introduction of either intervention alone. These data suggest that a comprehensive program of bisphosphonate therapy and weight-bearing exercise may be an effective method for preventing and treating osteoporosis in post-menopausal women.     

牛磺酸治疗通过激活自噬介导对老年大鼠骨量和骨强度的保护作用

目的探讨牛磺酸(NHS)对老年大鼠骨量流失的影响,并探讨可能的机制。方法将30只大鼠随机分为对照组(CON)、模型组(MOD)以及牛磺酸组(NHS),每组10只;其中NHS组大鼠每天接受牛磺酸(2 g/kg)治疗12周;待治疗结束后通过Micro-CT检测、HE染色切片、血清指标、蛋白质印迹观察治疗效果,探讨可能的机制。结果治疗12周后,与MOD组相比,三点弯曲试验、Micro-CT和HE染色切片结果显示NHS组大鼠的骨小梁数量、骨强度和骨密度(bone mineral density,BMD)得到明显改善。NHS组大鼠最大载荷和弹性模量、BMD、TV/BV、Tb.N、Tb.Th和Tb.Sp较OVX组明显改善(P<0.05)。和MOD组比较,NHS治疗后大鼠血清BLAP、P1NP、TRACP-5b和β-CTX水平明显降低,组间差异有统计学意义(P<0.05)。和MOD组比较,NHS组Runx2、BMP2、Beclin-1和LC3Ⅱ/LC3-Ⅰ表达水平明显上调,而P62表达水平显著下调,比较差异有统计学意义(P<0.05)。结论NHS可能通过激活自噬,从而对年龄引起的骨量丢失起到保护作用。     

Effects of combined elcatonin and alendronate treatment on the architecture and strength of bone in ovariectomized rats

We examined the combined effects of elcatonin (ECT) and alendronate (ALN) on bone mass, architecture, and strength in ovariectomized (OVX) rats. Fifty female Sprague Dawley rats, aged 13 weeks, were divided into Sham, OVX, OVX+ECT, OVX+ALN, and OVX+ECT+ALN groups (n = 10). Immediately after ovariectomy, ECT was administered at a dose of 15 units (U)/kg three times a week, and ALN was administered daily at a dose of 2.0 µg/kg, subcutaneously for 12 weeks. The three-dimensional architecture of the bone in the distal femoral metaphysis was analyzed using a microfocus X-ray computed tomography system (µCT), and bone strength was measured using a material-testing machine. Trabe-cular bone volume (BV/TV) and number (Tb.N) were significantly greater in the OVX+ECT and OVX+ALN groups than in the OVX group. In the OVX+ECT+ALN group, BV/TV and Tb.N were significantly greater when compared with those in the OVX+ECT and OVX+ALN groups. Trabecular thickness (Tb.Th) was significantly greater in the OVX+ECT+ALN group than in the OVX+ALN group. With regard to bone strength, the compression strength in the femoral metaphysis was significantly lower in the OVX group than in the Sham group. The reduction of compression strength was slightly lower in the OVX+ECT and OVX+ALN groups. In the OVX+ECT+ALN group, the compression strength in the femoral metaphysis significantly increased when compared with the OVX and OVX+ECT groups. These results suggest that the combined treatment of ECT and ALN does not alter the individual effects of each drug and that it exerts an additive effect on trabecular architecture and bone strength in OVX rats.     

Sclerostin antibody treatment improves bone mass,bone strength,and bone defect regeneration in rats with type 2 diabetes mellitus

Type 2 diabetes mellitus results in increased risk of fracture and delayed fracture healing. ZDF fa/fa rats are an established model of type 2 diabetes mellitus with low bone mass and delayed bone healing. We tested whether a sclerostin‐neutralizing antibody (Scl‐AbVI) would reverse the skeletal deficits of diabetic ZDF rats. Femoral defects of 3 mm were created in 11‐week‐old diabetic ZDF fa/fa and nondiabetic ZDF +/+ rats and stabilized by an internal plate. Saline or 25 mg/kg Scl‐AbVI was administered subcutaneously (s.c.) twice weekly for 12 weeks (n = 9–10/group). Bone mass and strength were assessed using pQCT, micro–computed tomography (µCT), and biomechanical testing. Bone histomorphometry was used to assess bone formation, and the filling of the bone defect was analyzed by µCT. Diabetic rats displayed lower spinal and femoral bone mass compared to nondiabetic rats, and Scl‐AbVI treatment significantly enhanced bone mass of the femur and the spine of diabetic rats (p < 0.0001). Scl‐AbVI also reversed the deficit in bone strength in the diabetic rats, with 65% and 89% increases in maximum load at the femoral shaft and neck, respectively (p < 0.0001). The lower bone mass in diabetic rats was associated with a 65% decrease in vertebral bone formation rate, which Scl‐AbVI increased by sixfold, consistent with a pronounced anabolic effect. Nondiabetic rats filled 57% of the femoral defect, whereas diabetic rats filled only 21% (p < 0.05). Scl‐AbVI treatment increased defect regeneration by 47% and 74%, respectively (p < 0.05). Sclerostin antibody treatment reverses the adverse effects of type 2 diabetes mellitus on bone mass and strength, and improves bone defect regeneration in rats. © 2013 American Society for Bone and Mineral Research.     

Additive effects of combined treatment with etidronate and alfacalcidol on bone mass and mechanical properties in ovariectomized rats

The present study was undertaken to evaluate the effects of combined treatment with intermittent cyclical etidronate and daily alfacalcidol on the mass and the mechanical properties of bone in ovariectomized rats, and to compare the effects with those of single treatments. Seventy 14-week-old female rats underwent ovariectomy (ovx) or sham operation, and were assigned to seven groups (n = 10 each): sham-operated; ovx; ovx treated with etidronate; ovx treated with 0.1 microg/kg alfacalcidol; ovx treated with 0.2 microg/kg alfacalcidol; ovx treated with etidronate and 0.1 microg/kg alfacalcidol; and ovx treated with etidronate and 0.2 microg/kg alfacalcidol. One week after the operation, etidronate (4 mg/kg per day) was intermittently injected into rats for 2 weeks followed by a 10 week period of no treatment, and alfacalcidol was administered orally every day. After 24 weeks of treatment, all single and combined treatments increased the bone mineral densities (BMDs) of the proximal tibiae, midfemurs, and the fourth and fifth vertebral bodies, which had been decreased by ovx. Combined treatment groups showed higher BMDs than single treatment groups, and the effects were almost equal to the addition of those of respective single treatment groups. The combined treatment also showed additive effects on the mechanical properties of both midfemurs and L4 vertebral bodies. The increases in mechanical properties were proportional to those in BMDs. Analyses of microcomputed tomography images and histology confirmed the strong effects of combined treatments on both trabecular and cortical bone mass without impairment of mineralization or connectivity. We conclude that the combined treatment with etidronate and alfacalcidol additively increases the mass of bone with normal quality, resulting in bone strengthening in ovx rats.     

The influence of combined parathyroid hormone and growth hormone treatment on cortical bone in aged ovariectomized rats.

The influence of combined parathyroid hormone (PTH) and growth hormone (GH) treatment on bone formation and mechanical strength was investigated in femoral middiaphysial cortical bone from 20-month-old ovariectomized (OVX) rats. The animals were OVX at 10 months of age, and at 18 months they were treated daily for 56 days with PTH(1-34) alone (60 microg/kg), recombinant human GH (rhGH) alone (2.7 mg/kg), or a combination of PTH(1-34) plus rhGH. Vehicle was given to OVX control rats. All animals were labeled at day 28 (calcein) and at day 49 (tetracycline) of the treatment period. PTH(1-34) alone gave rise to formation of a new zone of bone at the endocortical surface. rhGH alone caused substantial bone deposition at the periosteal surface without influencing the endocortical surface. Combined PTH(1-34) plus rhGH administration enhanced bone deposition at the periosteal surface to the same extent as that of rhGH alone. However, the combined treatment resulted in a more pronounced formation of new bone at the endocortical surface than was induced by PTH(1-34) alone. Both PTH(1-34) alone and rhGH alone increased the mechanical strength of the femoral diaphysis, and further increase in mechanical strength resulted from combined PTH(1-34) plus rhGH treatment. OVX by itself induced the characteristic increase in medullary cavity cross-sectional area and a minor decrease in the mechanical quality of the osseous tissue.