中等强度运动训练结合仙灵骨葆胶囊对去势大鼠骨代谢的影响

目的 观察中强度运动训练结合仙灵骨葆胶囊对去卵巢大鼠骨密度（bone mineral density, BMD）、骨代谢及股骨生物力学的影响,为防治骨质疏松提供实验室参考。方法 50只雌性SD大鼠随机分为5组,每组10只。A组为正常对照,B组切除卵巢1周后灌胃给予1 mL生理盐水,C组切除卵巢1周后进行中等强度的运动训练（运动速度为20 m/min,每天持续时间为60 min,连续5 d/周）,D组切除卵巢1周后灌胃给予1 mL仙灵骨葆胶囊［0.4 g/(kg·d)］,E组切除卵巢1周后灌胃给予1 mL仙灵骨葆胶囊+中等强度的运动训练,连续治疗8周后,进行血液生化指标检测,以及股骨、L5椎体BMD、Micro-CT检测与生物力学检测。结果 与B组比较,C～E组的血液生化指标均有不同程度的改善,L5椎体、股骨骨密度升高,股骨（或L5椎体）的骨体积分数、骨小梁数目、骨小梁厚度升高,骨小梁间隙与结构模型指数降低,L5椎体最大载荷、最大挠度及最大应力升高,股骨最大载荷、弹性载荷、弹性挠度、弹性模量、弹性应力、最大应力及弹性挠度升高,其中均以E组效果最明显。结论 中等强度运动训练结合仙灵骨葆胶囊治疗可提升去卵巢大鼠BMD,改善骨代谢与骨微结构,提高骨力学性能,两者具有协同作用。     

仙灵骨葆对骨质疏松性骨折骨痂血管形成的影响

背景：骨质疏松对骨折愈合早期的影响尚存争议,仙灵骨葆对骨质疏松性骨折愈合的影响及其机制尚有待深入研究。 目的：观察骨质疏松对大鼠股骨干骨折愈合的影响,以及仙灵骨葆对骨质疏松性骨折愈合的作用。 方法：将50只雌性12周龄Sprague-Dawley大鼠随机分成5组：假手术组、骨折组、去卵巢组、去卵巢+骨折组及治疗组,后3组切除大鼠双侧卵巢制备去卵巢模型,骨折模型于去卵巢后4周制备,为股骨干中段横行骨折。治疗组在去卵巢及骨折基础上灌胃给予仙灵骨葆250 mg/(kg•d)。给药3周,取去卵巢+骨折组、骨折组和治疗组大鼠骨折侧标本行X射线摄像仪摄片后,测量其骨密度,苏木精-伊红染色观察骨痂组织的病理学改变并计数血管,免疫组织化学染色检测骨痂组织骨形态发生蛋白2的表达。 结果与结论：去卵巢处理后大鼠的骨密度、计算机X射线摄像仪摄片评分显著降低(P < 0.05),仙灵骨葆可在一定程度上提高去卵巢后骨折大鼠的骨密度及X射线摄像仪摄片评分,但差异无显著性意义(P > 0.05);仙灵骨葆可提高去卵巢后骨折大鼠骨痂组织的血管数量(P < 0.05),但对骨形态发生蛋白2的表达无影响。提示,去卵巢后大鼠骨折早期愈合过程延迟,仙灵骨葆可促进骨质疏松大鼠骨折愈合早期血管的形成。     

去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律及相关性

背景：目前对去卵巢大鼠的研究较多,而对不同时间点大鼠骨量、骨转换指标、雌激素水平的变化规律及各因素的相关性研究报道较少。 目的：分析去卵巢大鼠不同时期骨量、骨转换指标、雌激素水平的变化规律并探讨其相关性。 方法：34只3月龄雌性SD大鼠,随机分为基线组、假手术组和去卵巢组。实验开始先将基线组处死,假手术组及去卵巢组于术后第4,8,12周分次处死。双能X射线吸收法(DXA)测定L1-3及股骨不同分区(头颈部R1区、转子部R2区、股骨干R3区、股骨整体R4区)的骨矿含量、骨密度、骨面积;酶联免疫吸附法(ELISA)检测血清Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽及雌激素水平。对大鼠体质量、离体骨密度、Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽、雌激素水平、月龄间的相关性进行分析。 结果与结论：①去卵巢后4周去卵巢组离体腰椎及股骨骨矿含量、骨密度均较基线组、假手术组明显降低(P < 0.05),第8,12周时均显著改善(P < 0.05),腰椎、股骨各区域骨量丢失幅度最大的为L1及股骨转子区。       ②去卵巢后4周去卵巢组血清Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽水平较基线组、假手术组均显著升高(P < 0.05),第8,12周差异无显著性意义。③去卵巢组第8,12周血清雌激素较假手术组及基线组明显降低(P < 0.01,P < 0.05)。④月龄与大鼠体质量、腰椎及股骨骨密度呈正相关,Ⅰ型前胶原氨基端原肽、Ⅰ型胶原羧基端肽与腰椎及股骨骨密度呈负相关(P < 0.01)。提示去卵巢后大鼠腰椎、股骨骨量变化呈先快速降低、再缓慢回升的趋势,其中L1及股骨转子部受影响最大;骨转换指标在去卵巢后显著加快、后期逐渐回归正常;雌激素水平变化规律为第1个月先升高、后期快速降低;体质量、骨转换指标及雌激素水平与骨量密切相关。  中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

大鼠皮质骨上机械性显微损伤的修复机制研究

目的研究大鼠皮质骨上植入物造成的机械性显微损伤的修复机制。方法 30只SD大鼠随机分为两组,一组行卵巢切除术,另一组行假手术。3个月后在右侧胫骨行钻孔术,分别于钻孔后1、2、4周后处死,处死前注射四环素和钙黄绿素进行标记。将含有钻孔的骨段(1 cm)应用大块碱性品红染色,甲基丙烯酸甲酯包埋后切成约50μm厚的切片。应用Bioquant图象分析系统对切片进行骨形态计量学分析。结果去卵巢大鼠和假手术大鼠都出现了与显微损伤有关的骨吸收腔,其中去卵巢组的孔隙率和骨吸收腔明显高于假手术组(P<0.05);随着术后时间的延长,吸收腔的数目逐渐增加,各时间点之间的差异有明显的统计学意义(P<0.05)。结论去卵巢大鼠的孔隙率和骨吸收腔数明显高于假手术大鼠,反映了在雌激素缺乏和较多裂纹形成两种因素刺激下,去卵巢大鼠皮质骨内的重建更为活跃,这会降低骨的强度从而增加骨折的危险性。     

活性维生素D对卵巢切除大鼠骨转换与骨质量的影响

目的　研究１αＯＨＤ３ 对骨质疏松的预防治疗效果和作用机理。　方法　将４０ 只雌性Ｗｉｓｔａｒ大鼠分为４组,以切除卵巢大鼠为模型,分别用０．０４ μｇ／ｋｇ·ｄ 和０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 灌胃给药１２周。测定各组大鼠的血、尿生化指标,骨密度,生物力学和形态计量学等参数,以及骨粘连蛋白基因的表达水平。　结果　切除卵巢大鼠骨吸收和骨形成显著加强,骨密度明显降低,骨小梁结构恶化,骨生物力学性质显著降低。１αＯＨＤ３ 使大鼠骨量恢复,骨密度提高,骨小梁相对体积（ＴＢＶ）增大,并使骨生物力学性质明显提高。０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 对骨生物力学的效果优于０．０４ μｇ／ｋｇ·ｄ １αＯＨＤ３ 的给药量。不同浓度１αＯＨＤ３ 对骨形成与骨吸收的作用不同：０．５ μｇ／ｋｇ·ｄ１αＯＨＤ３ 明显抑制骨转换;０．０４ μｇ／ｋｇ·ｄ １αＯＨＤ３ 则促进骨转换。１αＯＨＤ３ 的浓度对骨的矿化速率无显著影响。大鼠去卵巢后,骨粘连蛋白（ｏｓｔｅｏｎｅｃｔｉｎ, ＯＮ）ｍ ＲＮＡ表达水平降低,０．５ μｇ／ｋｇ·ｄ １αＯＨＤ３ 处理可恢复并促进ＯＮｍ ＲＮＡ 表达。　结论　１αＯＨＤ３ 有明显增加骨密度和骨强度的作用。高浓度１αＯＨ     

多代连续饮用四种饮水的雌性大鼠骨生物力学性能和骨代谢水平的比较

目的观察雌性SD大鼠多代连续单纯饮用自来水、纯净水、矿物质水和天然水,对其骨质密度、骨生物力学性能及骨代谢的影响。方法取前期实验暴露于四种饮水条件下的F2代断乳健康雌性SD大鼠,各组30只,饮用与F1代相同饮水,除饮水外其他条件完全相同。饲养10个月后处死,腹主动脉取血并分离血清检测大鼠骨碱性磷酸酶（BALP）、骨钙素（BGP）、血清I型前胶原羧基端前肽（PICP）、I型胶原交联羧基末端肽（ICTP）,同时取右侧股骨,进行骨密度和骨生物力学检测。结果血清中BGP含量天然水组高于自来水组（P〈0.05）;PICP含量纯净水组和天然水组低于自来水组（P〈0.01）;ICTP含量天然水组低于自来水组（P〈0.01）。拉伸试验显示：自来水组大鼠股骨最大桡度高于天然水组、矿物质水组和纯净水组（P〈0.01）;自来水组弹性桡度高于天然水组（P〈0.01）和矿物质水组（P〈0.05）。自来水组大鼠股骨最大应变高于天然水组、矿物质水组和纯净水组（P〈0.01）;断裂应变自来水组高于矿物质水组和天然水组（P〈0.01）。杨氏模量自来水组低于天然水组（P〈0.05）。结论长期饮用不同水质的水,可能对大鼠骨骼的生长发育会造成一定的影响。     

降钙素促进骨质疏松骨床中植入体的骨整合

背景：降钙素具有提高骨量、骨质量,降低骨折发生的效果。 目的：评价鲑鱼降钙素对羟基磷灰石植入体骨整合的影响,及其在治疗骨质疏松症同时促进植入体生物学固定的能力。 方法：将SD大鼠随机分为假手术+羟基磷灰石棒组、卵巢切除+羟基磷灰石棒组、卵巢切除+降钙素+羟基磷灰石棒组,后2组建立绝经后骨质疏松动物模型。建模后分别在3组大鼠的胫骨平台处开孔植入多孔羟基磷灰石假体,卵巢切除+降钙素+羟基磷灰石棒组大鼠皮下注射鲑鱼降钙素12周。 结果与结论：卵巢切除后,大鼠的腰椎骨密度降低,而持续皮下注射鲑鱼降钙素后,大鼠的腰椎骨密度逐渐改善。应用降钙素处理后的大鼠,其骨结合率较卵巢切除+羟基磷灰石棒组提高了22.0%(P < 0.05)。结果证实,全身给予鲑鱼降钙素能提高骨质疏松大鼠骨床和植入体周围骨量、促进主体骨-植入体的骨整合。     

去势大鼠骨形态计量学、生物性能变化

目的 通过观察大鼠血清学、骨形态计量学测定、骨生物性能等方法研究去卵巢大鼠骨变化.方法 采用7-12月龄SD雌性大鼠30只,随机分为对照组、模型组和尼尔雌醇组.模型组和尼尔雌醇组大鼠切除双侧卵巢进行造模.尼尔雌醇组大鼠造模后45天开始灌服尼尔雌醇,连续90天;对照组和模型组大鼠手术后第45天开始灌服去离子水,连续90天.所有大鼠给药第80、87天时两次ip四环素20mg/kg进行骨荧光标记.实验结束时,取出大鼠股骨及第四腰椎骨进行股骨形态计量学测定、股骨骨密度测量、股骨三点弯曲实验及椎骨压缩实验,同时测定血清碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(StrACP)水平.结果 大鼠去双侧卵巢后,股骨骨密度、骨最大载荷、最大应力、弹性模量、刚度水平和骨小梁体积显著性提高;椎体压缩性能、股骨形态计量学、股骨弯曲性能有明显改变;而雌激素对以上变化有不同程度改善作用.结论 骨组织形态、骨生物性能是评价骨质疏松模型或药物疗效的重要指标;发生骨质疏松时,骨组织形态学变化先于骨生物性能变化.     

强骨康疏胶囊对去卵巢骨质疏松大鼠骨细微结构及骨代谢的影响

目的:观察强骨康疏胶囊对去卵巢骨质疏松大鼠的骨密度、OPG及RANKL蛋白表达、骨组织形态计量学参数及骨组织细微结构的影响。方法:制备去卵巢骨质疏松大鼠模型后,分组:正常对照组、模型空白组、中药低剂量预防组、中药高剂量预防组、雌激素预防组。给药1月后,检测各组股骨骨密度值,显微镜下观察股骨骨小梁的结构变化,并检测骨组织形态计量学参数。采用免疫组织化学染色法检测大鼠股骨OPG及RANKL蛋白表达。结果:模型空白组大鼠股骨骨密度减少,骨小梁厚度、面积、面积百分数均减少,骨小梁间距增大,股骨OPG蛋白平均光密度值显著降低,RANKL蛋白平均光密度值明显增高;雌激素预防组、中药低剂量组、中药高剂量组对上述指标均有明显改善。结论:强骨康疏胶囊能有效提高骨量,维持骨小梁立体空间结构,改善大鼠股骨远端松质骨的显微结构,能够提高骨OPG蛋白表达及抑制RANKL蛋白表达。     

大豆异黄酮对去卵巢大鼠抗氧化及骨形态学影响的研究

目的 研究大豆异黄酮(SI)对去卵巢大鼠抗氧化及骨形态学的影响.方法 70只雌性SD大鼠按血清总胆固醇水平随机分为7组:高脂、雌激素,低、中、高剂量SI干预、假手术及正常对照组.对前5组摘除双侧卵巢后恢复1周开始干预,实验周期为12周,灌胃给药,每周称重1次,分别在去卵巢及处死时(12周)抽取尾静脉血,实验结束后取内脏及骨骼标本,分别测定血清碱性磷酸酶(AKP)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶活性(GSH-Px)及骨密度等指标,共63只大鼠完成实验.结果 SI干预组股骨重量高于高脂与正常对照组,干预可提高AKP、GSH-Px酶活性.高剂量干预对维持大鼠股骨密度的作用与雌激素相似.SI干预可缓解因去卵巢造成的骨丢失.结论 大豆异黄酮对去卵巢大鼠的抗氧化、骨代谢酶活性及骨转化存在一定影响,适量干预能逆转因去势造成的骨密度下降.考虑到植物雌激素与哺乳动物的雌激素受体(ER)结合能力低下,采用SI在临床开展干预的剂量与远期效果尚待进一步研究.     

不同剂量糖皮质激素对大鼠骨密度和生物力学性能的影响

目的通过双能X射线骨密度仪(dual energy X-ray absorptiometry,DXA)、骨生物力学测试及骨组织计量学等方法研究不同剂量糖皮质激素摄入对正常3月龄大鼠骨骼的影响。方法 31只SPF级3月龄SD雌性大鼠,随机分为正常对照组、地塞米松(Dex)1、2.5、5 mg/kg组,每周尾静脉注射给药2次,共8周,对照组给予生理盐水对照。给药结束后,离体股骨和第3腰椎通过DXA进行骨矿含量(bone mineral content,BMC)、骨矿密度(bone mineral density,BMD)测定,全股骨和第5腰椎分别进行三点弯曲和压缩力学实验,并通过骨组织病理切片观察胫骨近端骨小梁的显微结构并定量分析。结果与正常组相比,所有激素组大鼠体重均明显降低,腰椎BMC、BMD及最大压缩载荷均未明显下降,全股骨BMC均有所降低,但只有Dex 1 mg组全股骨和股骨远端、近端BMD降低;Dex 1 mg组三点弯曲实验断裂载荷、最大载荷和弹性载荷都明显降低,而Dex 2.5 mg、Dex 5 mg组只有弹性载荷仍低于正常对照组。激素组骨小梁有空间密度分布不均现象,骨代谢处于低转换。结论应用糖皮质激素8周对3月龄大鼠骨骼的不利影响股骨较腰椎明显,股骨骨量丢失,力学性能下降,两者均无剂量依赖性。更高剂量Dex并没有增加骨量丢失和力学性能改变。力学性能特别是弹性载荷下降以及骨小梁密度分布不均,提示糖皮质激素更多的是引起骨质量下降。临床上应用糖皮质激素时,应使用多种方法评价其对骨骼的副作用。     

Bone anabolic effects of separate and combined therapy with growth hormone and parathyroid hormone on femoral neck in aged ovariectomized osteopenic rats

Previous studies have demonstrated that growth hormone (GH) has a marked anabolic effect on cortical bone and parathyroid hormone (PTH) has been shown to increase cancellous bone and cortical bone markedly in ovariectomized (OVX) rats. Most previous combination therapies used the bone anabolic agent (PTH) and the anti-resorptive agents. In this study, two bone anabolic hormones, GH and PTH, were used in rebuilding bone following loss due to ovariectomy in the femoral neck, which contains both cortical and cancellous bones. Twelve-month-old female F344 rats were divided into five groups: Sham+solvent vehicle, OVX+solvent vehicle, OVX+GH (2.5 mg/kg/day), OVX+PTH (80 microg/kg/day), and OVX+GH (2.5 mg/kg/day)+PTH (80 microg/kg/day). Following surgery, the animals were left for 4 months to become osteopenic before the beginning of hormone therapies. Hormone administrations were given 5 days per week for 2 months and the animals sacrificed. The right femurs were removed and the femoral necks were examined by pQCT densitometry and by histomorphometry. There was a 12.3% decrease in total bone mineral content (BMC) (P<0.01), a 6.2% decrease in total bone mineral density (BMD) (P<0.01), a 12.8% decrease in cortical BMC (P<0.05), a 25.9% decrease in cancellous BMC (P<0.0001), a 20.4% decrease in cancellous BMD (P<0.01), and a 34.2% decrease in cancellous bone volume (BV/TV) (P<0.0001) in vehicle-treated OVX rats. Growth hormone, PTH and GH+PTH treatment increased total BMC of the OVX rats by 14.4% (P<0.01), 23.5% (P<0.0001) and 30.6% (P<0.0001), respectively; increased total BMD by 7.0% (P<0.01), 9% (P<0.001) and 14.8% (P<0.0001), respectively; increased cortical BMC by 15.9% (P<0.05), 25.5% (P<0.001) and 29% (P<0.001), respectively; increased cancellous BMC by 40.9% (P<0.0001), 61.9% (P<0.0001) and 86.8% (P<0.0001), respectively; increased cancellous BMD by 31% (P<0.001), 41.8% (P<0.0001) and 61.8% (P<0.0001), respectively; increased cancellous BV/TV by 30.6% (P<0.05), 76.3% (P<0.0001) and 94.9% (P<0.0001), respectively; and increased trabecular thickness by 26.4% (P<0.05), 41.5% (P<0.001) and 43.2% (P<0.001), respectively, compared to the age-matched vehicle-treated OVX controls. In conclusion, both GH and PTH increased cortical and cancellous bone mass at the osteopenic femoral neck. Using two techniques, it was observed that the effects of PTH were mostly more marked than those of GH. Combined therapy with GH+PTH was more effective in rebuilding cortical bone and cancellous bone than either therapy alone in the aged ovariectomized osteopenic rats, which is in line with our hypothesis.     

运动联合福善美对去卵巢大鼠骨密度和神经传导的影响

目的: 观察运动是否可增强福善美对卵巢切除大鼠骨质疏松的治疗作用。方法: 将90只6月龄雌性SD大鼠随机分为假手术组(sham,18只)和卵巢切除模型组(OVX,72只)。大鼠卵巢切除8周后,测定大鼠第4腰椎骨密度(BMD)和血清雌二醇含量。随后,存活的OVX大鼠分为模型组(OVX)、福善美治疗组(OVX+FOX)、运动治疗组(OVX+EX)和福善美与运动联合治疗组(OVX+FOX+EX),分别给予1 mg·kg^-1·d^-1福善美灌胃和(或)跑台运动干预治疗12周后,双能X线骨密度仪测定各组大鼠第4腰椎BMD;肌电图机检测大鼠左侧股神经传导速度(MCV)、运动末端潜伏期(ML)和复合肌肉动作电位(CMAP);ELISA法测定大鼠血清Ⅰ型前胶原羧基端前肽(PICP)及Ⅰ型胶原羧基端交联端肽(ICTP)含量。结果: 卵巢切除大鼠福善美和(或)运动干预治疗12周后,OVX组与sham组相比,BMD显著降低(P<0.05),血清PICP和ICTP明显增高(P<0.05),左侧股神经ML未见明显改变。福善美和运动均可显著提高骨质疏松大鼠BMD,降低ICTP;福善美可显著降低骨质疏松大鼠ICTP,而运动对ICTP无明显影响。运动可明显缩短模型组左侧ML(P<0.05),福善美对ML无显著改善作用。运动与福善美联合对BMD、PICP、ICTP及ML的改善作用较两者单用效果显著(P<0.05);福善美与运动两治疗组间未见明显差异。各组大鼠左侧股神经MCV和CMAP未见明显差异。2×2析因设计的方差分析显示,福善美与运动2种处理方式之间不存在交互作用(P>0.05)。结论: 福善美和运动可能通过抑制破骨细胞的骨吸收而抑制大鼠卵巢切除对骨密度的影响。     

多尺度分析骨质疏松大鼠骨微结构变化

目的 多尺度分析骨质疏松大鼠的骨微结构变化。 方法 20只5月龄雌性SD大鼠随机选取12只实施双侧去卵巢(ovariectomy, OVX)手术,术后 8 周形成骨质疏松大鼠模型,另外 8 只作为假手术( SHAM) 对照组。 利用Micro-CT 和 SR-Nano-CT 定量分析骨质疏松大鼠在组织尺度下皮质骨和松质骨以及细胞尺度下骨细胞、骨陷窝小管和细胞外基质的微结构变化。 结果 组织尺度下,OVX 组皮质骨的截面积较 SHAM 组显著增大(P<0. 05),皮质骨骨密度和厚度较 SHAM 组虽有变化,但不显著;OVX 组骨小梁的骨密度、体积分数、厚度和骨小梁数量较 SHAM组显著降低(P<0. 01),骨小梁分离度显著增加(P<0. 01)。 细胞尺度下,OVX 组骨陷窝半轴长较 SHAM 组没有显 著差异,但 OVX 组骨陷窝厚度和骨小管直径较 SHAM 组显著增大(P<0. 05);同时,细胞尺度下 OVX 组皮质骨孔隙率较 SHAM 组显著增大(P<0. 05)。 结论 OVX 大鼠骨在组织和细胞尺度出现不同程度的微结构变化。 其中,组织尺度主要是松质骨丢失,皮质骨变化不大;细胞尺度骨陷窝小管网络孔隙显著增大,将直接影响皮质骨骨密度和强度。 多尺度分析骨质疏松大鼠骨微结构变化对于骨质疏松症的临床诊断及病理分析有潜在的应用价值。     

High physiological prolactin induced by pituitary transplantation decreases BMD and BMC in the femoral metaphysis, but not in the diaphysis of adult female rats

High physiological prolactin (PRL) stimulated intestinal calcium absorption and renal calcium uptake in mammals. Previous histomorphometric study revealed a significant increase in bone turnover in the trabecular part of the PRL-exposed long (cortical) bone; however, whole-bone densitometric analysis was unable to demonstrate such effect. We therefore studied differential changes in bone mineral density (BMD) and contents (BMC) of the femoral diaphysis and metaphysis in adult female rats exposed to high PRL induced by anterior pituitary (AP) transplantation. The estrogen-dependent effects of PRL on the femur were also investigated. We found that chronic exposure to PRL had no effect on BMD or BMC of the femoral diaphysis, which represented the cortical part of the long bone. It is interesting that 7 weeks after an AP transplantation, BMD and BMC of the femoral metaphysis were significantly decreased by 8% and 14%, respectively. Ovariectomy (Ovx) for 2, 5, and 7 weeks also decreased BMD and BMC in the femoral metaphysis, but not in the diaphysis. However, the AP transplantation plus Ovx (AP+Ovx) produced no additive effects. Nevertheless, 2.5 microg/kg 17beta-estradiol (E2) supplementation abolished the osteopenic effects of both Ovx and AP+Ovx on the femur. As for the L5-6 vertebrae, BMD and BMC were not affected by PRL exposure, but were significantly decreased by Ovx and AP+Ovx, and such decreases were completely prevented by E2 supplementation. It could be concluded that high physiological PRL induced a significant osteopenia in the trabecular part, i.e., the metaphysis, of the femora of adult female rats in an estrogen-dependent manner. Since PRL had no detectable effect on the vertebrae, the effects of PRL on bone appeared to be site-specific.     

The effects of hyaluronan on bone resorption and bone mineral density in a rat model of estrogen deficiency-induced osteopenia

Hyaluronan, or hyaluronic acid (HA), is an essential component of extracellular matrices. HA of appropriate molecular weight and concentration can induce osteoblast differentiation and bone formation in vitro. The aim of our study was to evaluate the effects of HA of different molecular weights on ovariectomy (OVX)-induced bone loss in rats. Adult female Sprague Dawley rats were subjected to bilateral OVX or sham surgical procedure (sham). OVX rats were treated with: HA of molecular weight of 0.75 MDa at a dose of 1 mg/kg/day and with HA of molecular weight of 1.62 MDa at a dose of both 0.5 mg/kg/day and 1 mg/kg/day. HA was applied orally once a day during the 8-week period after ovariectomy. Body weight, urinary pyridinoline (Pyr), deoxypyridinoline (DPyr) corrected for urinary creatinine, serum nitrite/nitrate concentrations and whole body and femoral bone mineral density (BMD) were measured. HA treatment had no effect on the body weight gain in OVX rats. Excretion of urinary Pyr and Dpyr significantly increased in OVX rats compared to sham controls. The higher molecular weight HA (1.62 MDa) significantly reduced urinary Pyr and DPyr concentrations measured on day 28 after ovariectomy (p < 0.001). Serum concentrations of nitric oxide metabolites, nitrite/nitrate significantly decreased in OVX rats in comparison with sham controls (p < 0.001). HA of both 0.75 MDa and 1.62 MDa molecular weights significantly enhanced serum nitrite/nitrate concentrations in OVX rats. There was a clear reduction of whole body and femoral BMD in untreated OVX rats. The higher molecular weight HA decreased both whole body and femoral BMD loss. Our results show that orally applied HA of high molecular weight (1.62 MDa) inhibits bone resorption and provides a protective effect on bone density in ovariectomized rats.     

Triterpenoids from Cimicifugae rhizoma, a novel class of inhibitors on bone resorption and ovariectomy-induced bone loss

OBJECTIVE: Increasing research suggested that Cimicifugae rhizoma might be protective against osteoporosis. In this study, we investigated the effects of three cycloartane-type triterpenoids isolated from Cimicifugae rhizoma, cimicidol-3-O-beta-D-xyloside (1), cimicidanol-3-O-beta-D-xyloside (2) and acetylacteol-3-O-beta-d-xyloside (3) on bone resorption in vitro and bone loss in ovariectomized (OVX) mice. METHODS: The activities of the tested compounds on bone resorption were evaluated using three assays, neonatal mouse parietal bone organ culture, osteoclast-like cells (OCLs) formation and pit formation. The effects on bone mineral density (BMD) and uterine weight were examined using OVX mice. Using LC-MS/MS method, the serum concentrations of the triterpenoids were measured in mice serum collected at 0.5, 1, 3, 6 and 12h following its oral administration. RESULTS: All of the tested compounds exerted the inhibitory effects on bone resorption in bone organ culture, suppressed both of the formation and the resorbing activity of OCLs. Furthermore, a synergistic effect was observed among those compounds. In vivo studies revealed that compounds 1-3 and the mixture of compounds 1-3 prevented the bone loss in OVX mice without affecting uterine weight, and each compound was detected in the mice serum after single oral administration. CONCLUSIONS: The triterpenoids exerted the inhibitory effects on osteoclastic bone resorption through the suppression of both OCLs formation and the resorbing activity of OCLs, and also showed a significant protective effect on BMD in OVX mice. The present results might provide a new pharmacological potential for the treatment of osteoporosis.     

Potent inhibitory effect of Foeniculum vulgare Miller extract on osteoclast differentiation and ovariectomy-induced bone loss

Inhibition of osteoclast differentiation and bone resorption is considered an effective therapeutic approach to the treatment of postmenopausal bone loss. To find natural compounds that may inhibit osteoclastogenesis, we screened herbal extracts on bone marrow cultures. In this study, we found that an aqueous extract of Foeniculum vulgare Miller seed (FvMs) at low concentration, which has traditionally been used as a treatment for a variety of ailments, inhibits the osteoclast differentiation and bone resorptive activity of mature osteoclasts. We further investigated the effects of FvMs on ovariectomy (OVX)-induced bone loss using microcomputed tomography, biomechanical tests and serum marker assays for bone remodeling. Oral administration of FvMs (30 mg or 100 mg/kg/day) for 6 weeks had an intermediary effect on the prevention of femoral bone mineral density (BMD), bone mineral content (BMC), and other parameters compared to OVX controls. In addition, FvMs slightly decreased bone turnover markers that were accelerated by OVX. The bone-protective effects of FvMs may be due to suppression of an OVX-induced increase in bone turnover. Collectively, our findings indicate that FvMs have potential in preventing bone loss in postmenopausal osteoporosis by reducing both osteoclast differentiation and function.