对雌性大鼠切除卵巢后骨质疏松症防治的探讨

目的探讨雌性大鼠切除卵巢后施以不同药物对骨转换率和骨丢失的影响。方法３５只６０周龄雌性ＳＤ大鼠分为假性切除卵巢、单纯切除卵巢、切除卵巢后分别给予雌二醇、氟化钠及羟乙膦酸钠５组。第１４周末处死，胫骨不脱钙切片行形态计量等比较。结果单纯切除卵巢后，小梁骨吸收和形成参数均显著增加（Ｐ＜０．０１），小梁骨体积百分比（ＴＢＶ％，８．６５±３．６２）显著减少（Ｐ＜０．０１），呈高转换率骨质疏松；给予雌二醇或羟乙膦酸钠则抑制骨吸收，降低骨转换率，ＴＢＶ％（分别为１８．５７±７．３１及１６．８２±７．９０）较单纯切除卵巢显著增加（均为Ｐ＜０．０１）；给予氟化钠，骨吸收和骨形成显著增多，骨转换率维持高水平，ＴＢＶ％（１３．２５±３．０３）较单纯切除卵巢增加（Ｐ＜０．０５），丢失也相对较多。结论雌二醇和羟乙膦酸钠可有效抑制骨吸收，降低因切除卵巢而增高的骨转换率，减少骨丢失。     

氯化镓治疗去卵巢大鼠骨质疏松的实验观察

目的 探讨镓对去卵巢大鼠骨质疏松的治疗作用。方法 通过切除大鼠卵巢建立骨质疏松模型，经氯化镓治疗12周后，用单光子法测量骨密度；放免法检测相关血清学指标；测定骨病理形态学指标。结果 氯化镓治疗组血清抗酒石酸酸性磷酸酶、骨小梁间距低于骨质疏松对照组，而骨密度和骨小梁宽度高于骨质疏松对照组。结论 镓对去卵巢所致大鼠的骨质疏松有效。     

新型双膦酸盐（BM210955）对卵巢切除大鼠骨量丢失的疗 …

目的　观察新型双膦酸盐BM2 10 95 5 (Ibandronate)防治卵巢切除大鼠骨量丢失的效果。方法　取 10～ 12月龄SD大鼠 40只 ,分为 4组 ,实验组大鼠作双侧卵巢切除 3个月后 ,再给予BM 2 10 95 5 0 .5mg·kg-1·d-1,用药 3个月。设骨质疏松动物模型 (OP模型 )对照组 ,假手术对照组及OP模型 BM 2 10 95 5及尼尔雌醇组作比较。结果　骨干重、灰重和钙含量及股骨骨密度OP模型对照组低于假手术对照组 ,BM2 10 95 5及尼尔雌醇两用药组高于OP模型对照组且均有显著性意义 (P<0 .0 2或P <0 .0 0 1) ;全身骨密度水平BM 2 10 95 5及尼尔雌醇两用药组较OP模型对照组分别增加8.7%及 0 .9% ;椎骨、胫骨骨小梁面积BM2 10 95 5及尼尔雌醇用药组均高于OP模型对照组且均有显著性意义 (P <0 .0 1) ;尿钙与肌酐 (Ca/Cr)比值BM 2 10 95 5及尼尔雌醇用药组低于OP模型对照组均有显著性意义 (P <0 .0 0 1) ,尿羟脯氨酸与肌酐 (HOP/Cr)比值及血清碱性磷酸酶 (ALP)的水平 ,BM 2 10 95 5及尼尔雌醇用药组较OP模型对照组均有下降趋势。结论　SD大鼠卵巢切除 3个月后出现明显的骨质疏松 ,BM2 10 95 5对卵巢切除骨质疏松动物模型大鼠骨量的丢失有显著治疗作用。     

药物治疗老龄骨质疏松大鼠骨显微结构与骨组织形态学指标的变化

目的确定各种药物治疗动物骨质疏松的效果。方法以去卵巢法复制动物骨质疏松模型,以中药、西药、VK,钙剂进行治疗,饲养15 w后处死大鼠、取大鼠胫骨,采用德国蔡司公司生产的扫描电子显微镜观察各组大鼠胫骨纵断面的骨显微结构(骨小梁排列情况),采用成都泰盟公司BI-2000医学图像分析系统观察各组大鼠胫骨切片骨形态计量学指标。结果模型组骨小梁周长、骨小梁面积、骨小梁相对体积、骨小梁平均厚度、骨小梁平均间距小于正常对照组、中药组、西药组、维生素K(VK)组(P<0.05)。模型组与钙剂组各项指标差异不显著(P>0.05),模型组胫骨骨小梁排列稀疏,孔隙较大,正常对照组骨小梁细密,中药组、西药组,通过治疗骨小梁修复较好,钙剂组和VK组骨小梁排列有一定稀疏,有一定孔隙。结论模型组骨纤维结构发生改变,骨组织形态计量学指标发生改变;中药、西药治疗骨组骨组织形态计量学指标与正常对照组接近,中药、西药对治疗骨质疏松都具有一定效果。     

运动加中药对骨质疏松大鼠骨计量学的影响

目的 观察运动与中药联合作用对骨质疏松大鼠骨组织形态计量学的影响.方法 雌性SD大鼠随机分为正常对照组、去卵巢手术组、雌激素对照组、运动组、中药组、运动+中药组.正常对照组行假手术,其余各组行双侧卵巢切除术,术后3个月开始为期3个月的治疗.雌激素对照组用尼尔雌醇治疗, 中药组和运动+中药组应用中药治疗,运动组和运动+中药组按要求进行运动.治疗结束后对腰椎骨作骨组织形态计量学分析.结果 运动+中药组骨小梁的数目在治疗各组中最多,骨小梁分离度在各治疗组中最小,矿化沉积率在各组最高.结论 运动与中药联合治疗方法对骨质疏松大鼠腰椎骨,具有促进骨形成和抑制骨吸收的双重作用.     

硝酸镓治疗骨质疏松大鼠血清IL-6、骨钙素水平及骨结构的研究

目的探讨硝酸镓对雌性大鼠切除卵巢后所致骨质疏松的作用机制。方法 8月龄的雌性SD大鼠随机分为实验组和正常对照组。实验组切除双侧卵巢建立骨质疏松动物模型,实验组分为硝酸镓治疗组和骨质疏松组。硝酸镓治疗组:建模成功后,给予1mg/kg硝酸镓腹腔注射,3次/周。骨质疏松组给予生理盐水腹腔注射。正常对照组给予生理盐水腹腔注射。干预3个月后,分别观察各组大鼠胫骨上段结构和检测血清IL-6、骨钙素水平。结果硝酸镓治疗组胫骨上段骨小梁宽度和骨皮质厚度明显高于骨质疏松组(P<0.05),血清IL-6和骨钙素水平与骨质疏松组及正常对照组比较显著增加(P<0.05)。结论硝酸镓对卵巢切除所致的骨质疏松症有明显的治疗作用,其机制可能是通过降低IL-6表达、增加成骨细胞活性,从而达到治疗骨质疏松的作用。     

选择性雌激素受体调节剂雷洛昔芬阻止去卵巢大鼠骨丢失的机制

目的　了解选择性雌激素受体调节剂雷洛昔芬 (RLX)阻止去卵巢大鼠骨丢失的机制。对骨质疏松症模型大鼠进行雌激素及选择性雌激素受体调节剂类药物RLX治疗 ,观察其对去卵巢大鼠骨组织光镜、电镜及骨密度 (BMD)等各种指标的影响。　方法　用 3月龄雌性SD大鼠 32只 ,随机分为卵巢未切除组、卵巢切除组、雌激素治疗组、RLX治疗组 ,5个月后处死 ,检测股骨、腰椎及全身BMD、子宫重量、骨形态。　结果　卵巢切除组经RLX治疗 3个月后腰椎、股骨、全身BMD增加35 %、4 0 %、2 1% ,分别为 (0 2 5 6± 0 0 2 2 ) g/cm2 、(0 2 93± 0 0 15 ) g/cm2 和 (0 36 8± 0 0 2 5 ) g/cm2 ;RLX组大鼠骨小梁表面的破骨细胞数比卵巢切除组减少 ;与卵巢切除组相比 ,雌激素治疗组的子宫重量增加了 5 5 % ,而RLX组则对子宫无明显刺激作用。　结论　RLX及雌激素都具有防治骨质疏松的作用 ,RLX能阻止去卵巢所造成的骨丢失。     

硒对饮茶型氟中毒大鼠抗氟能力的影响和骨保护作用

目的探讨硒对饮茶型氟中毒鼠抗氟能力和骨的保护作用。方法将雄性Wistar大鼠按体质量随机分成6组:对照组、氟化钠组、茶氟组、高硒对照组、高硒氟化钠组和高硒茶氟组。对照组饮用自来水,氟化钠组饮用含氟100mg/L自来水,茶氟组饮用含氟100mg/L的砖茶浸出液,高硒组在饲料中加硒2.97mg/kg。3个月后处死实验动物,测定全血谷胱甘肽过氧化物酶(GSH-Px)活力,分离血清测定血氟,检测氟斑牙发生情况,取股骨干骺端进行骨小梁面密度分析。结果高硒氟化钠组血氟同氟化钠组比较明显降低(t=2.12,P<0.05),有统计学意义,同茶氟组比较无统计学意义。茶氟组和氟化钠组不论是否加硒,两组间氟斑牙和骨小梁面密度比较,差异无统计学意义。结论高硒可以降低氟化钠组大鼠的血氟浓度,但不能明显减轻大鼠氟中毒的病理损伤。     

骨碎补总黄酮对去卵巢大鼠组织蛋白酶K的影响

目的观察骨碎补总黄酮对去卵巢大鼠骨质疏松模型组织蛋白酶K(Cathepsin K)的血清浓度和左胫骨干骺端基因表达的影响,探讨骨碎补总黄酮防治骨质疏松的机制。方法选取3月龄雌性SD大鼠72只,随机分为6组:高剂量骨碎补总黄酮组[治疗组1,12只大鼠,切除双侧卵巢,给药剂量0.216 g/(kg·d)];中剂量骨碎补总黄酮组[治疗组2,12只大鼠,切除双侧卵巢,给药剂量0.108 g/(kg·d)];低剂量骨碎补总黄酮组[治疗组3,12只大鼠,给药剂量0.054 g/(kg·d)];雌激素组(12只大鼠,切除双侧卵巢,给予结合雌激素片0.1 mg/kg);假手术组(12只大鼠,仅切除腹腔少量脂肪和软组织,以5 mL蒸馏水灌胃);正常组(12只大鼠,不做特殊处理,以5 mL蒸馏水灌胃)。各组均在去卵巢造模成功后开始灌胃,并于造模成功后即刻、3个月、6个月每组处死4只大鼠,无菌条件下抽取静脉血,检测血清Cathepsin K浓度。取左胫骨近端干骺端标本,荧光定量PCR测定Cathepsin K mRNA表达量,用SPSS13.0软件进行数据分析。结果各治疗组、正常组与雌激素组大鼠血清Cathepsin K浓度间差异均有统计学意义(P0.05)。各治疗组与雌激素组左胫骨干骺端Cathepsin K mRNA表达量相比有统计学意义(P0.05)。各治疗组、假手术组与正常组左胫骨干骺端Cathepsin K mRNA表达量相比均有统计学意义(P0.01)。结论骨碎补总黄酮抑制去卵巢大鼠血清Cathepsin K浓度、降低左胫骨干骺端Cathepsin K mRNA表达量的作用,可能是其治疗骨质疏松症的机制之一。     

金匮肾气丸联合葡萄糖酸钙对去势大鼠骨微结构的影响

目的观察金匮肾气丸联合葡萄糖酸钙对去卵巢大鼠骨微结构的影响,探究其对骨质疏松(OP)的防治作用。方法将75只雌性大鼠随机分成假手术组,模型组,葡萄糖酸钙组,金匮肾气丸组,金匮肾气丸及葡萄糖酸钙联合用药组共5组,采用卵巢切除的方法制成OP动物模型,灌胃给药3个月后处死,取同侧股骨上段,进行骨形态计量学检测及扫描电镜观察。结果金匮肾气丸及葡萄糖酸钙均可增加骨小梁的百分面积,增加骨小梁数目,减轻骨吸收程度,改善骨胶原的排列及骨小梁立体网状结构,且联合组作用明显优于单纯金匮肾气丸组及葡萄糖酸钙组。结论金匮肾气丸联合葡萄糖酸钙能显著改善骨微结构,提高骨生物力学性能,增加骨强度,从而有效地防治OP。     

Bone anabolic effects of basic fibroblast growth factor in ovariectomized rats

The purpose of this study was to characterize the bone anabolic effects of basic fibroblast growth factor (bFGF) in ovariectomized (OVX) rats. Female Sprague Dawley rats were subjected to ovariectomy or sham surgery at 3 months of age and maintained untreated for 2 months post surgery. Groups of OVX rats were then treated iv with bFGF at doses of 100 or 200 microg/kg day for 7 or 14 days. Another group of OVX rats and a group of sham-operated control rats were treated iv with vehicle alone for 14 days. Certain groups of bFGF-treated OVX rats were killed at 7 or 14 days after withdrawal of treatment. The right tibiae were processed undecalcified for quantitative bone histomorphometry. Vehicle-treated OVX rats were characterized by decreased cancellous bone volume associated with increased bone turnover. Treatment of OVX rats with bFGF strongly stimulated bone formation, as indicated by marked increases of at least a factor of 10 in osteoblast surface, osteoid surface, and osteoid volume. Furthermore, new osteoid spicules were observed within the marrow cavity of these animals. Osteoclast surface was markedly decreased in bFGF-treated OVX rats, but this finding may be secondary to the extensive osteoid surface. The strongest bone anabolic effects occurred in OVX rats treated with the higher dose of bFGF for 14 days, but these animals exhibited a bone mineralization defect, as evidenced by abundant osteoid and a lack of double fluorochrome labeling, despite markedly increased osteoblast surface. However, the newly-formed osteoid rapidly calcified after withdrawal of bFGF treatment. The data indicate that bFGF not only stimulates bone formation on pre-existing bone surfaces but also induces de novo formation of bone spicules within the marrow cavity, which results in partial restoration of lost cancellous bone mass in osteopenic OVX rats after only 14 days of treatment with the growth factor. These findings suggest that bFGF merits consideration for development as a potential treatment for patients with severe osteopenia who are unresponsive to conventional osteoporosis therapies.     

四环素-雌酮对去卵巢山羊髂骨的有利作用

目的　山羊双侧卵巢切除 (OVX)建立绝经后骨质疏松 (PMO)动物模型 ,应用骨组织形态计量学方法观察OVX山羊对四环素 雌酮 (XW 63 0 )的治疗反应。方法　 3 1只雌性山羊随机分成 4组 ,即正常对照组、假手术组、OVX术后 6个月组、XW 63 0治疗 6个月组。在处死前第 2 1天和第 9天 ,给山羊口服四环素以标记骨组织和进行动力学研究。制备山羊髂骨不脱钙骨切片 ,应用骨组织形态计量学方法 ,观察各组髂骨骨计量学参数的变化。结果　与正常对照组和假手术组比较 ,OVX术后 6个月组的骨小梁体积比全部骨组织体积 (TBV/TTV)、骨小梁体积比海绵骨体积 (TBV/SBV)、平均骨小梁板厚度 (MTPT)、四环素双标线距离 (DDL)、平均类骨质宽度 (MOSW )、骨矿化沉积率 (MiAR)和组织水平的骨形成速率 (Svf)显著减少 (Svf:P <0 .0 5 ,其余各参数 :均P <0 .0 1) ,骨小梁表面比体积 (S/V)则显著增加 (P <0 .0 1) ,说明OVX山羊骨量丢失 ,骨小梁体积明显减小 ,骨小梁厚度下降、连接性降低 ,骨转换率降低 ,激活频率减慢 ,骨形成明显减少 ,表现为低转化骨质疏松的骨代谢特征。以上结果提示 ,骨质疏松山羊模型复制成功。与OVX术后 6个月组相比 ,XW63 0治疗 6个月组的TBV/TTV ,TBV/SBV ,MTPT ,DDL ,MOSW ,MiAR和Svf显著增加 (均P <0 .0 1)     

甲状旁腺激素相关蛋白羧基端片段对去卵巢大鼠骨代谢的影响

目的 研究甲状旁腺激素相关蛋白(PTHrP)羧基端107-139(PTHrP107-139)对去卵巢大鼠骨代谢的影响.方法 4月龄健康雌性未孕Wistar大鼠40只,随机分为四组.假手术组(Sham组)和卵巢切除+安慰剂组(Placebo组)给予生理盐水0.2 ml/只;卵巢切除PTHrPC治疗组给予PTHrP107-139 40μg/Kg;卵巢切除+鲑鱼降钙素治疗组(CT组),给予鲑鱼降钙素15 U/kg.术后5周给药,隔日注射.治疗3个月,比较股骨、腰椎骨密度(BMD)、骨生物力学参数及骨组织形态计量学指标.结果 ①PTHrPC组和CT组大鼠股骨、腰椎BMD及骨生物力学性能明显高于Placebo组(P<0.05).②与Placebo组相比,PTHrPC和CT组的平均骨体积(TBV/TTV)明显升高,骨重建时间明显延长,而骨小梁类骨质表面(TOS)、平均类骨质宽度(MOSW)、成骨细胞表面(ObS)、骨吸收表面(OcS)、四环素单标记线占骨小梁表面的百分比(STS)、四环素双标记线占骨小梁表面的百分比(DTS)、纠正骨矿化沉积率(iMAR)较Placebo组明显下降.结论 PTHrP羧基端107-139片段主要通过降低OVX大鼠骨转换,抑制骨吸收,增加OVX大鼠的骨量,提高骨强度.     

缺碘大鼠的骨发育障碍

目的　研究碘缺乏对大鼠骨发育和骨转换的影响。方法　复制生长发育期碘缺乏大鼠动物模型 ,测定血清中TT3 、TT4、FT4含量 ,对股骨远端 2 /3进行骨计量学测定。结果　碘缺乏大鼠血清TT4、FT4含量显著下降 ,TT3 含量代偿性增加。碘缺乏大鼠骨小梁骨量较正常大鼠明显减少 ,骨小梁体积(TBV) /全部骨组织体积减少约 47% ,TBV/海绵骨体积减少约 3 5 % ,平均骨小梁板厚度减少约 3 6% ,骨小梁表面 /TBV较正常大鼠增加约 3 4% (P <0 .0 1) ,骨皮质平均厚度较正常组减少了 16% (P <0 .0 5 )。碘缺乏大鼠四环素单标记线占全部骨小梁表面的百分比、四环素双标记线占全部骨小梁表面的百分比、平均类骨质宽度、骨小梁类骨质表面占骨小梁表面的百分比、矿化沉积率和组织水平骨形成率均低于正常对照组 (P <0 .0 5或P <0 .0 1) ,矿化延迟时间 (P <0 .0 5 )和类骨质成熟时间 (P <0 .0 1)大于正常大鼠。结论发育期的骨骼对T4的缺乏非常敏感。T4降低时骨骼发育不良 ,骨小梁骨量减少 ,皮质骨的生长也受到影响。碘缺乏组大鼠成骨细胞活性降低和类骨质矿化障碍     

Quantitative histology of myeloma-induced bone changes

S ummary . In order to quantify bone changes which occur in multiple myeloma, undecalcified transiliac bone biopsies from 118 myelomatous patients were analysed by histomorphometric methods. Osteoclastic resorption surfaces were increased compared with controls, and the number of osteoclasts/mm² of bone section was significantly greater in the areas massively invaded by plasma cells than in less invaded areas. The osteoid surfaces were also increased and the percentage of trabeculae that exhibited tetracycline labelling was also greater, indicating increased formation surfaces. However, reduced thickness of the osteoid seams and a low calcification rate, measured after tetracycline double labelling, suggests a reduced activity for each osteoblast. The mean trabecular bone volume was not reduced as compared with controls, but the biopsies showed a heterogeneous distribution of osteolytic and osteosclerotic areas. In the invaded areas, no major histomorphometric difference was found between patients receiving chemotherapy and untreated patients, demonstrating that if usual chemotherapies reduce the tumour mass, they do not improve histological bone lesions in areas still invaded by plasma cells.     

Effects of chronic prednisolone treatment on bone resorption and bone composition in intact and ovariectomized rats and in ovariectomized rats receiving beta-estradiol

To examine the interactions between estrogen deficiency and glucocorticoid excess on bone metabolism the osteopenic effects of a standard dose of prednisolone (2 mg/kg BW.day) were studied in sham-ovariectomized (Sham-OVX), ovariectomized (OVX), and OVX rats given replacement beta-estradiol (OVX + E2). For 12 weeks six groups of female albino rats aged 4 months which had their skeletons labeled with 45Ca were fed matched amounts of low-calcium (0.1% Ca) hydroxyproline-free diet. The six treatment groups were: group 1, Sham-OVX; group 2, Sham-OVX + prednisolone; group 3, OVX; group 4, OVX + prednisolone; group 5, OVX + E2; group 6, OVX + E2 + prednisolone. Bone resorption was estimated by studying the urinary excretion of hydroxyproline and 45Ca. Parathyroid function was assessed indirectly from urinary cAMP excretion. Treatments did not influence parathyroid activity or serum levels of calcium or 1,25-dihydroxyvitamin D. However, ovariectomy increased bone resorption and induced osteopenia whereas prednisolone decreased bone resorption and formation and caused osteopenia. Ovariectomy increased the rate of bone resorption in prednisolone-treated rats; prednisolone lowered the rates of bone resorption and formation in OVX rats. The osteopenic effects of prednisolone and ovariectomy were additive and independent. E2 protected bone from the osteopenic effects of ovariectomy but did not affect bone loss induced by prednisolone. These results suggest prophylactic estrogen should help to avoid bone loss from estrogen deficiency in patients requiring chronic high dose glucocorticoid treatment.     

Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. II: Bone histomorphometry

Histomorphometric analysis of iliac crest biopsies was performed after tetracycline double-labelling in 22 hyperthyroid patients before and after medical antithyroid treatment for an average period of 4 months. The initially increased cortical porosity was normalized during treatment whereas the amount of trabecular bone was unchanged. The osteoclastic resorption in cortical bone decreased but was still elevated. The osteocytic osteolysis remained slightly increased. In trabecular bone, however, the bone turn-over decreased to a subnormal level following treatment and the surfaces were inactive in bone resorption and bone formation. An increase was observed in the amount, extent and width of osteoid seams due to an increase in the lifespan of bone forming sites and a prolongation of the maturity period of osteoid. The observed increased deposition of cortical bone after antithyroid treatment may explain the positive calcium balance in this period.     

Low bone turnover state in primary biliary cirrhosis

To determine whether bone loss in patients with chronic cholestatic liver disease is the consequence of a high or low bone turnover state, 30 female patients with biopsy-proven primary biliary cirrhosis underwent iliac crest biopsy following double tetracycline labeling. The mean trabecular bone volume was decreased as a result of trabecular plate thinning in both the premenopausal (p less than 0.02) and postmenopausal (p less than 0.05) patients, compared to age- and sex-matched controls. Indications that osteoblastic function was impaired included a significantly lower mean wall thickness (p less than 0.01) and mean osteoid seam width (p less than 0.05), and this in association with a decreased mineral appositional rate and prolonged mineralization lag time was suggestive of a defect in matrix synthesis. Further evidence of impaired osteoblastic activity was the significantly lower bone formation rate at both tissue (p less than 0.001) and basic multicellular unit levels (p less than 0.05) in the postmenopausal patients. Total resorption surfaces and fasting urinary calcium/creatinine ratios were significantly increased (p less than 0.005 and 0.05, respectively) in the premenopausal patients and mean interstitial bone thickness reduced in both pre- and postmenopausal patients, suggesting that increased resorption may also contribute to bone loss in primary biliary cirrhosis.     

去卵巢大鼠骨形成参数和血清碱性磷酸酶的相关性研究

目的　观察去卵巢大鼠骨组织形态计量学参数和血清碱性磷酸酶 (ALP)之间的相关性。方法　 4个半月龄 SD大鼠双侧卵巢去除术后预防用药 90 d。用骨组织形态计量学方法测定大鼠胫骨组织近端松质骨形态计量学参数 ,并测定血清 ALP含量。结果　去卵巢组大鼠血清 ALP含量增加 ,骨形成参数增加 (P<0 .0 5)。去卵巢组和预防用药组骨形成参数与 ALP测量值之间有相关性 (P<0 .0 5)。去卵巢组的骨组织形态计量学参数与 ALP测量值之间的相关系数大于预防用药组。结论　去卵巢大鼠血清 ALP与骨形成参数之间存在相关性 ,这种相关性在给药后下降。     

Sequential treatment with basic fibroblast growth factor and PTH is more efficacious than treatment with PTH alone for increasing vertebral bone mass and strength in osteopenic ovariectomized rats

The study was designed 1) to determine whether treatment with basic fibroblast growth factor (bFGF) and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic ovariectomized rats, and 2) to assess whether prior and concurrent administration of the antiresorptive agents estrogen and risedronate suppresses the bone anabolic response to treatment with bFGF alone and sequential treatment with bFGF and PTH. Three-month-old female Sprague Dawley rats were ovariectomized (OVX) or sham-operated (sham) and maintained untreated for 1 yr. Baseline sham and OVX rats were killed at this time (15 months of age). Groups of rats were injected sc with estrogen (10 microg/kg, 4 d/wk), risedronate (5 microg/kg, 2 d/wk), or vehicle. At the end of the second week of antiresorptive treatment, catheters were inserted into the jugular veins of all rats, and vehicle or bFGF at a dose of 250 microg/kg was injected daily for 14 d. Three groups of rats were killed at the end of bFGF treatment. The remaining rats were continued on their respective antiresorptive therapy and injected sc with vehicle or synthetic human PTH-(1-34) at a dose of 80 microg/kg, 5 d/wk, for 8 wk. Lumbar vertebrae were processed for cancellous bone histomorphometry and biomechanical testing. Ovariectomy resulted in a decrease in vertebral bone mass and strength. Treatment of OVX rats for 14 d with bFGF markedly increased osteoblast surface, osteoid surface, and osteoid volume compared with vehicle treatment of sham and OVX rats. Furthermore, osteoid bridges were observed extending between preexisting trabeculae in bFGF-treated OVX rats. Prior and concurrent administration of estrogen and risedronate did not suppress these bone anabolic effects of bFGF. Treatment of OVX rats with PTH alone increased vertebral cancellous bone mass and strength to the level of vehicle-treated sham rats. Sequential treatment of OVX rats with bFGF and PTH further augmented vertebral bone mass and strength to a level above that observed in OVX rats treated with PTH alone. The improvements in bone mass and strength were associated with an increase in trabecular thickness in OVX rats treated with PTH alone and with an increase in trabecular thickness and node to terminus ratio, an index of trabecular connectivity, in OVX rats treated sequentially with bFGF and PTH. Cotreatment with estrogen and risedronate did not suppress the anabolic response of bone to bFGF and PTH. In fact, a trend for an even greater increase in cancellous bone mass and node to terminus ratio was observed in OVX rats treated with risedronate, bFGF, and PTH. These findings indicate that sequential treatment with bFGF and PTH is more efficacious than treatment with PTH alone for increasing bone mass and strength and improving trabecular microarchitecture in osteopenic OVX rats.