己烯雌酚对去卵巢大鼠不同部位骨骼的影响

目的　观察己烯雌酚对去卵巢大鼠不同部位骨骼的影响。方法　己烯雌酚SD大鼠行双侧卵巢去除术后 ,灌喂DES 2 2 5μg/ (kg·d) ,持续 90d。用骨组织形态计量学等方法测量胫骨上段和腰椎松质骨及胫骨中段皮质骨的动态参数和静态参数 ,同时测量血清生化指标及子宫内膜厚度。结果　己烯雌酚可使去卵巢大鼠胫骨上段 (PTM)和腰椎 (LV)松质骨的骨量增加、骨小梁分离度减少 ,骨形成和骨吸收降低。与去卵巢组比较 ,DES组的PTM骨量增加 1 54 8% ,LV骨量增加 2 0 3 % ,胫骨中段 (Tx)皮质骨的变化不明显。己烯雌酚还降低去卵巢大鼠血清总胆固醇含量 ,但增加子宫内膜厚度。结论　己烯雌酚能有效预防去卵巢大鼠的骨丢失 ,但是对不同部位的骨骼的作用不同 ,而且具有刺激子宫的作用。     

何首乌煎剂对去卵巢大鼠骨质丢失的防治作用

目的探讨何首乌煎剂对去卵巢大鼠骨丢失的骨组织形态计量学改变及预防作用。方法大鼠双侧卵巢去除术(OVX)后预防用药90d。骨标本行不脱钙骨制片,骨组织形态计量学测量胫骨近心端松质骨静态和动态参数。结果去卵巢大鼠骨小梁面积百分率(%Tb.Ar)减少(P<0.05),出现高转换型骨质疏松:己烯雌酚可完全对抗去卵巢大鼠的体重增加、骨转换率增高和骨量丢失;何首乌煎剂使去卵巢大鼠的%Tb.Ar增加(P<0.05)、骨吸收减少、骨转换率呈下降趋势,不抑制藕联的骨形成。结论何首乌煎剂对去卵巢大鼠骨丢失有一定的预防作用,且对子宫无明显刺激。     

麦胚提取物对去卵巢大鼠无机盐和骨形成蛋白2的影响

目的　探讨麦胚提取物对去卵巢引起骨质疏松大鼠无机盐和骨形成蛋白 2 (BMP2 )的影响。方法　 2 1只雌性 SD大鼠随机分为假手术组、去卵巢模型组、去卵巢加麦胚提取物组 (麦胚提取物 1 0 0 mg/ kg· d) ,1 0 w后测定血清无机盐钙、磷、钠、钾、AL P含量 ,用 SP免疫组织化学检测骨 BMP2 表达。结果　去卵巢组大鼠试验 1 0 w后血清和尿钙、钠和血清 ALP含量显著升高 ;而血清和尿钾降低 ,骨 BMP2 表达下降 (P<0 .0 5或 P<0 .0 1 )。去卵巢加麦胚后大鼠的尿钙、钠和血清 ALP含量显著降低 ,骨 BMP2 表达增高 (P<0 .0 5)。结论　麦胚提取物可调节去卵巢大鼠血清和尿中钙、钠、钾 ,促进 BMP2 表达 ,预防去卵巢大鼠骨质疏松。     

二膦酸盐长期服用可造成去势大鼠成骨矿化障碍

目的　观察羟乙膦酸钠 (二膦酸盐 )长期服药与间歇服药对去卵巢大鼠实验模型股骨骺板及骺板下骨小梁结构的骨组织形态计量学变化 ,为指导二膦酸盐药物的用药方式 ,探讨膦酸盐类对骨质疏松的疗效机制提供依据。方法　 5 0只SD雌性大鼠分 5组 ,假手术A组、去卵巢B组、去卵巢服用雌激素C组 (尼尔雌醇 0 1mg·kg-1·d-1)与去卵巢间歇服用羟乙膦酸钠D组(10mg·kg-1·d-1,用药 2周 ,停药 5周 ,重复 1次 )和连续服用羟乙膦酸钠E组 (10mg·kg-1·d-1,连续用药 10 0d)。各组均在服药 10 0d后处死 ,进行全股骨骨密度测量及股骨下端不脱钙切片的骨计量学观察。结果　大鼠模型的离体全股骨骨密度测定发现 ,间歇给药组能明显增加股骨的BMC和BMD矿物含量且去势对照组差异显著。间歇组BMD值为 (4 1 8± 8 4)mg/cm2 ,去势组 (31 6± 7 0 )mg/cm2 ,假手术对照组 (4 7 6± 2 7)mg/cm2 ,而连续给药组仅为 (2 9 4± 9 4)mg/cm2 ,与间歇组比较差异具有显著性 (P <0 0 1)。骨组织形态计量学研究发现 ,间歇用药组骨体积值 (5 0 2± 2 5 ) % ,连续用药组仅为(38 2± 3 4) %与去势对照组相似 (34 0± 2 9) % ,连续组与间歇组两者之间差异具有显著性 (P <0 0 0 1)。两组间最大差别在于类骨质量的多少与四环素标记率所体现     

丹参酮对去卵巢大鼠牙槽骨丢失的抑制作用

目的探讨丹参酮对去卵巢大鼠牙槽骨丢失的抑制作用。方法 SD大鼠随机分为对照组、去卵巢组和丹参酮治疗组。实验90 d后取大鼠牙槽骨,测量牙槽骨组织形态计量学参数、牙槽骨组织中碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(TRAP)活性。结果与去卵巢组相比,丹参酮治疗组牙槽骨骨量明显增多,%Tb.Ar升高33.33%(P<0.05);牙槽骨组织中ALP阳性的成骨细胞数升高了51.38%(P<0.05);TRAP阳性的破骨细胞数减少27.27%(P>0.05)。结论丹参酮能促进牙槽骨骨形成和抑制骨吸收,防治牙槽骨骨质疏松。     

红花水提液对老年去卵巢大鼠骨生物力学状况的改善作用

目的观察红花水提液对老年去卵巢大鼠骨丢失的治疗作用。方法 10月龄SD大鼠行双侧卵巢切除术,术后2个月开始用红花进行治疗,用药2个月后用骨组织形态计量学方法测定第4腰椎松质骨静态参数,应用骨生物力学方法对第5腰椎体作压缩试验。结果红花水提液使去卵巢大鼠骨小梁面积(%Tb.Ar)增加不明显,与去卵巢组相比,差异无统计学意义;但红花水提液可改善去卵巢大鼠椎骨的生物力学状况,表现为能使去卵巢大鼠的破坏荷载、弹性模量和破坏应力增加。结论红花水提液对老年去卵巢大鼠椎骨的生物力学状况有改善作用。     

人参皂甙与己烯雌酚联用对去卵巢大鼠骨丢失作用的观察

目的　探讨人参皂甙单用或与己烯雌酚合用对去卵巢大鼠骨丢失的预防作用。方法　 4.5月龄 SD雌性大鼠 ,按体重随机分为正常对照组、去卵巢组、己烯雌酚组、人参皂甙组和人参皂甙与己烯雌酚联用组。采用双侧卵巢摘除术 ,体内双荧光标记法 ,胫骨上段硬组织包埋切片 ,全自动图像分析及松质骨形态计量学软件处理 ,观察药物对骨形态计量参数的影响。结果　去卵巢 1 0 w后骨量丢失和破骨细胞活性、骨形成率及骨转换率增加 ,子宫重量减轻 ,子宫内膜厚度变薄 ,存在显著性差异 (P<0 .0 1或 P<0 .0 5)。人参皂甙与己烯雌酚合用能使骨量增加 ,骨形成增多 ,骨吸收和骨转换率下降并有显著性差异 (P<0 .0 1或 P<0 .0 5) ,子宫重量和子宫内膜厚度均下降。结论　去卵巢大鼠骨量丢失 ,骨转换率增高 ,出现明显的骨质疏松 ;己烯雌酚 (1 0μg· kg- 1· d- 1 )能抑制骨吸收 ,也抑制骨形成。与 1 0 0 mg/ kg人参皂甙合用 ,能增加骨量 ,增加骨形成 ,并减轻己烯雌酚导致的子宫重量增加和内膜增厚的危险性 ,能完全预防去卵巢大鼠的骨丢失     

电针对去卵巢大鼠骨组织形态学影响

目的观察电针对去卵巢大鼠骨组织形态的影响,探讨针灸防治绝经后骨质疏松的可能机制。方法 60只3月龄SD健康雌性大鼠,随机分为手术组(切除双侧卵巢)和假手术组,3月造模成功后将手术组随机分为:模型组、电针组、雌激素组。干预治疗12周后,处死大鼠,取右侧股骨进行骨组织形态分析。结果去卵巢大鼠经电针治疗后,与模型组相比骨小梁面积百分数、骨小梁宽度、荧光标记百分率、矿化沉积率升高,矿化延迟时间显著升高,骨小梁分离度、骨吸收周长百分率降低(P<0.05或P<0.01),骨小梁数目、类骨质周长百分率及骨形成率无明显改变。结论电针能够改善去卵巢大鼠的骨形态计量学指标,增加去卵巢大鼠股骨下段的骨量,具有促进骨形成和抑制骨吸收的双重作用。     

尼尔雌醇对去卵巢大鼠骨代谢影响的定量研究

实验用３月龄雌ＳＤ大鼠，分基础对照组、年龄对照组、去卵巢组及去卵巢加尼尔雌醇治疗组（ＣＥＥ１ｍｇ·ｋｇ－１，每周ｉｇ１次），１２ｗ后，对各组大鼠胫骨近端不脱钙骨进行骨组织形态计量学分析。结果表明：去卵巢大鼠骨形成和骨吸收均明显增加，但骨吸收大于骨形成，出现高转换型骨质疏松。尼尔雌醇通过明显抑制去卵巢大鼠的骨吸收和骨形成，阻止骨高转换，保持骨量的正常。     

骨质疏松合并动脉粥样硬化大鼠实验模型的建立

目的 建立绝经后骨质疏松合并动脉粥样硬化大鼠实验模型.方法 在去势的基础上3次大剂量肌肉注射维生素D与高脂灌胃相结合处理大鼠,90天后观察血脂,胸主动脉的形态学变化,取左侧胫骨行骨组织形态计量学测量,右侧股骨进行骨密度的测定,测定后行三点弯曲试验,左侧股骨行骨矿物元素测定.结果 在去卵巢的基础上3次大剂量肌肉注射维生素D与高脂灌胃后,大鼠血清TC、LDLC均明显升高(P<0.01);HDLC明显下降(P<0.01);主动脉形成较成熟的动脉粥样斑块;大鼠骨骨小梁面积百分率、骨小梁厚度、骨小梁数量均显著下降(P<0.01)、骨小梁分离度明显升高(P<0.05),骨密度、最大载荷、弹性载荷、弹性挠度、断裂载荷、骨钙、骨镁、骨磷、骨羟脯氨酸含量均显著下降(P<0.05).结论 采用在去卵巢的基础上3次大剂量肌肉注射维生素D与高脂灌胃相结合的方法可以成功建立骨质疏松并发AS大鼠模型.     

IGF-1对去卵巢大鼠骨密度及骨力学强度的影响

目的 研究外源性胰岛素样生长因子-1(IGF-1)对去卵巢(OVX)骨质疏松大鼠骨密度、骨转换率、骨力学强度等方面的影响.方法 对大鼠施行双侧卵巢摘除术,术后3个月以骨密度测定证实骨质疏松的存在后,随机分为5组,分别以生理盐水、甲状旁腺激素1-34及3种不同剂量IGF-1进行干预.同时设立生理盐水干预的假手术大鼠作为对照.8周后检测血清钙、磷、骨钙素水平及碱性磷酸酶活性;测定腰椎骨密度、股骨力学强度;组织学染色测定股骨远端骨皮质厚度.结果 IGF-1虽未提高OVX大鼠腰椎骨密度却可以显著提高其股骨力学强度.血清学检测结果表明,IGF-1可降低血清钙、磷、骨钙素水平及碱性磷酸酶活性;组织学染色显示IGF-1可显著提高OVX大鼠股骨骨皮质厚度.结论 IGF-1可增加OVX大鼠股骨的力学强度,此作用可能是通过改善骨结构而非提高骨密度所实现的.     

Bone effects of hexarelin,a GH-releasing peptide,in female rats: influence of estrogen milieu

OBJECTIVE: The present study was performed to evaluate the potential influence of the estrogen milieu in modulating the effects of GH/IGF stimulation by a GH-releasing peptide, hexarelin (HEXA), on bone metabolism and mineral density in middle-aged female rats. METHODS: HEXA was administered for 60 days (50 microg/kg s.c. twice a day) to intact and ovariectomized (OVX) 11-month-old female rats and changes in bone parameters were evaluated with respect to those of the same rats under baseline conditions and with those of control rats (intact and OVX) administered isovolumetric amounts of physiological saline. Serum total alkaline phosphatase (ALP) and urinary deoxypyridinoline (Dpd) were measured before and at various times during HEXA treatment. Bone mineral content (BMC) and density of lumbar vertebrae and femoral mid-diaphyses were measured by dual energy X-ray absorptiometry before and after treatment. In all groups, serum IGF-I levels were determined before and during treatment and the GH secretory response to HEXA was assessed at the end of the experiment. RESULTS: In intact rats, HEXA did not modify Dpd urinary excretion, induced a trend toward an increase of serum ALP activity and significantly increased BMC (+6.5%) and bone area (+4.1%) only at lumbar vertebrae. In OVX rats, HEXA did not modify the OVX-induced increase in bone turnover markers (Dpd and ALP) and did not affect the OVX-induced vertebral bone loss, but significantly increased BMC (+7.2%) and bone area (+5.3%) at femoral mid-diaphyses. HEXA significantly increased serum IGF-I levels at day 14, but not at day 60, in both intact and OVX rats, whereas the GH secretory response to HEXA was higher in the former than in the latter. CONCLUSIONS: Overall, the present data demonstrate that chronic HEXA treatment increases BMC and bone area at lumbar vertebrae in intact rats and at femoral diaphyses in OVX rats. The different sensitivity to HEXA of the skeletal districts examined is related to the estrogen milieu and may reflect a complex interplay between estrogens and GH/IGF function.     

叶酸对去卵巢大鼠骨质疏松的保护作用

目的 探讨叶酸对去卵巢大鼠骨质疏松的保护作用.方法 40只3月龄雌性SD大鼠随机分为5组:假手术组、去卵巢组、乙烯雌酚组(乙烯雌酚0.03 mg·kg-1·d-1)、低剂量叶酸组(叶酸5 mg·kg-1·d-1)、高剂量叶酸组(叶酸20 mg·kg-1·d-1).各组大鼠于术后1周开始灌胃给药,治疗10周,假手术组和去卵巢组给予溶媒灌胃.测定大鼠血浆总同型半胱氨酸(tHcy)浓度,骨匀浆中碱性磷酸酶(ALP)和抗酒石酸酸性磷酸酶(TRACP)的水平;取右股骨和腰5椎体进行骨密度和骨生物力学测定,取腰6椎体和左股骨制备HE切片,观察骨组织的形态学变化.结果 与假手术组比较,去卵巢大鼠血浆tHcy浓度明显升高,腰椎和股骨骨密度显著减低(均P＜0.01),血浆tHcy浓度与腰椎骨密度呈负相关(r=-0.359,P=0.040).叶酸显著降低去卵巢大鼠血浆tHcy浓度(均P＜0.01).大剂量叶酸显著增加去卵巢大鼠骨匀浆ALP水平,降低TRACP水平,增加腰椎和股骨骨密度(均P＜0.01),改善腰椎和股骨的生物力学性能.结论 去卵巢大鼠存在高同型半胱氨酸血症,高同型半胱氨酸参与了去卵巢大鼠骨质疏松的发生.叶酸对去卵巢大鼠骨质疏松具有保护作用,其机制可能与改善同型半胱氨酸的代谢作用有关.

Abstract：

Objective To investigate the protective effect of folic acid(FA) on osteoporosis in ovariectomized(OVX) rats.Methods Forty three-month-old female SD Rats were divided into 5 groups, sham operation group, OVX group, diethylstilbestrol group(0.03mg·kg-1·d-1),low dose FA Group (5 mg·kg-1·d-1),and high dose FA group (20 mg·kg-1·d-1).Gastric gavage in each group was started from one week after being ovariectomized and lasted 10 weeks. Sham operation group and OVX group were treated with solvent. The rats were sacrificed at the end of 10th week after treatment. The total homocysteine(tHcy) in plasma, alkaline phosphatase(ALP), and tartrate-resistant acid phosphatase(TRACP) activity of bone homogenates were measured. The bone mineral density(BMD) and bone biomechanics were determined using L5 vertebrae and right femur. The bone tissue slices were made with L6 vertebrae and left femur and HE stained, and then the histomorphology was observed. Results Compared with sham operation group, plasma tHcy level was significantly increased(P＜0.01), BMD of lumbar vertebrae and femur was remarkedly decreased in OVX group(all P＜0.01). Plasma tHcy concentration was negatively correlated with lumbar BMD(r=-0.359, P=0.040). Plasma tHcy level in both groups treated with folic acid was significantly reduced(all P＜0.01). The ALP concentration in bone homogenates was higher, the TRACP concentration in bone homogenates was lower, and BMD and bone biomechanics of lumbar vertebrae and femur were increased in high dose FA group than those in OVX group(all P ＜0.01). Conclusions In OVX rats hyperhomocysteinemia existed and was involved in the development of osteoporosis. Folic acid could protect OVX rats from osteoporosis, due probably to improved homocysteine metabolism.     

硝酸甘油治疗大鼠骨质疏松症血清NO、NOS的变化

目的初步探讨用硝酸甘油治疗骨质疏松症(OP)及其与一氧化氮(NO)、一氧化氮合酶(NOS)的关系。方法将40只6月龄雌性大鼠随机分成假手术组(15只)和OP模型组(25只),其中OP模型组去卵巢造成骨质疏松模型,从其中随机选5只大鼠测定血清NO、NOS的变化,并与5只假手术组大鼠比较。剩余OP模型组大鼠随机分为OP对照组(10只)与硝酸甘油治疗组(10只),硝酸甘油治疗组经硝酸甘油治疗骨密度升高后,测其血清NO、NOS的变化,并与OP对照组及假手术组比较。结果OP模型组血清NO、NOS低于假手术组(P<0.01,P<0.05)。硝酸甘油治疗组大鼠骨密度升高后,其血清NO、NOS高于OP对照组(P<0.01,P<0.05),而与假手术组差异无显著意义(P>0.05)。结论NO、NOS参与了骨质疏松症的病理生理过程,硝酸甘油治疗骨质疏松症可能与NO、NOS有关。     

淫羊藿总黄酮对去卵巢大鼠骨组织细胞凋亡的影响

目的 观察淫羊藿总黄酮(HEF)对去卵巢大鼠骨组织中细胞凋亡的影响.方法 54只雌性SD大鼠随机分成6组:假手术组,去卵巢组,尼尔雌醇组(0.1 mg·kg-1·d-1)和HEF低、中、高剂量组(40,80和160 mg·kg-1·d-1),治疗12周,测定大鼠令身骨密度及雌二醇水平,采用3'-OH末端DNA原位标记技术和透射电镜检测细胞凋亡,并用免疫组化方法观察骨转化生长因子β1(TGF-β1)、成纤维细胞生长因子(FGF-2)和凋亡相关基因Fas的蛋白表达.结果 HEF增加去卵巢大鼠的全身骨密度,中、高剂量组与去卵巢组差异有统计学意义(均P<0.01),但不增加血清雌二醇水平(P>0.05).去卵巢组骨细胞、成骨细胞凋亡较假手术组明显增高(P<0.01),HEr组明显降低(P<0.01).与去卵巢组相比,HEF组Fas的表达明显降低(P<0.01),TGF-β1、FGF-2表达明显增加,尤以中、高剂量组为显著(P<0.01).结论 HEF对去卵巢大鼠骨丢失具有防治作用,其部分机制可能与促进TGF-β1、FGF-2,抑制Fas蛋白的表达和抑制骨细胞、成骨细胞凋亡有关.     

山茶籽联合乌圆口服液对去卵巢大鼠血液和骨组织的影响

目的观察乌圆口服液及山茶籽联合乌圆口服液对去卵巢大鼠骨组织及血液的影响。方法选取5月龄雌性SPF级大鼠80只,随机抽样分入4个组。对照组、切除卵巢(OVX)组、乌圆口服液+OVX(W+OVX)组和山茶籽+乌圆口服液+OVX组(H+W+OVX)。8 w后,大鼠麻醉状态下开胸取2 ml心血,失血致处死后分离取股骨近端0.8 cm。取得骨样本经常规固定、酸液脱钙、梯度乙醇脱水、包埋切片,最后染色放大200倍镜下观察骨切片形态结构,并对血清中的磷、钙、碱性磷酸酶和雌二醇进行检测。结果 OVX组镜下有骨质疏松病理改变,血钙磷下降,碱性磷酸酶升高及红细胞计数减少,血红蛋白和雌二醇下降。W+OVX组骨质疏松病理改变无明显改善、血磷钙、和碱性磷酸酶和雌二醇与OVX组无明显差异(P>0.05),但红细胞计数和血红蛋白明显升高(P<0.05);与OVX组比较,H+W+OVX组骨质疏松病理改变明显改善,血磷钙明显升高,碱性磷酸酶降低红细胞计数和血红蛋白明显升高(P<0.01),雌二醇显著升高(P<0.01)。与W+OVX组比较,H+W+OVX组红细胞计数和血红蛋白明显升高(P<0.05)。结论 OVX也会引起红细胞和血红蛋白下降;乌圆口服液可以提高OVX贫血指标,但不能减轻骨质疏松;山茶籽联合乌圆口服液既增强乌圆口服液治疗贫血效果,也可以拮抗骨质疏松。     

大鼠骨基质形态增龄性改变及其与骨代谢指标的相关性研究

目的　研究大鼠增龄过程中骨基质形态计量改变规律及与骨代谢指标相关性。　方法　 3、9、15个月龄雌性SD大鼠各 10只。第 4腰椎及右侧胫骨上段作形态计量学分析。物理密度法测定股骨及腰椎骨密度 (BMD)。第 3腰椎作抗压缩试验。自动分析仪测定血清钙、磷 ,放免法测定1,2 5 (OH) 2 D3 。　结果　与 3月龄组比较 ,15月龄组第 4腰椎骨小梁体积减小 4 3 3% (P <0 0 1) ,胫骨上段骨小梁体积减小 2 8 0 % (P <0 0 1) ,骨形成表面降低 17 2 % (P <0 0 5 ) ,骨吸收表面增加39 8% (P <0 0 1) ,腰椎、股骨BMD分别下降 7 7% (P <0 0 1)和 7 3% (P <0 0 1)。骨小梁体积与腰椎BMD、最大载荷、血清 1,2 5 (OH) 2 D3 呈明显正相关 (r =0 6 84、0 972及 0 86 6 ,P <0 0 0 1)。血清 1,2 5 (OH) 2 D3 与胫骨骨形成表面及矿化沉积率呈明显正相关 (r =0 5 87,r =0 6 2 8,P <0 0 1)。　结论　 15月龄雌性SD大鼠骨形成减弱 ,骨吸收增加 ,骨量减少 ,骨结构改变 ,生物力学性能降低。骨形态计量学指标与腰椎BMD和骨生物力学指标有明显的相关性。     

Recombinant human insulin-like growth factor-binding protein-5 stimulates bone formation parameters in vitro and in vivo.

Insulin-like growth factor-binding protein-5 (rhIGFBP-5) is stored in bone and stimulates osteoblast cell proliferation in vitro. Bone formation is dependent on the number and activity of osteoblasts. We therefore evaluated the ability of recombinant human (rh) IGFBP-5 to increase osteoblast activity in vitro; both alkaline phosphatase (ALP) activity and osteocalcin levels showed a dose-dependent increase. In in vivo time-course studies, daily s.c. administration of 50 microg rhIGFBP-5/day/mouse significantly increased serum osteocalcin levels by day 7, and these levels were sustained through day 21. We further evaluated whether rhIGFBP-5 was as effective as IGF-I. Daily s.c. administration of rhIGFBP-5 (50 microg/day), IGF-I (13 microg/day), or IGF-I plus rhIGFBP-5 complex for 9 days increased serum osteocalcin levels by 58%, 65%, and 81% (P < 0.001 in all) and femoral bone extract ALP activity by 85% (P < 0.001), 29% (P < 0.05), and 13% (P = NS), respectively, and decreased carboxyl-terminal cross-linked telopeptide of type I collagen by 29% (P < 0.05), 20% (P = NS), and 12.5% (P = NS), respectively. One s.c. injection of rhIGFBP-5 (50 microg/mouse) increased serum osteocalcin and bone ALP activity by 21% (P < 0.05) and 27% (P < 0.02), respectively, after 5 days, but did not significantly increase serum IGF-I (1, 6, or 24 h/postinjection), suggesting that the effects of rhIGFBP-5 on bone are not mediated by increasing circulating IGF-I. Our data demonstrate that systemic administration of rhIGFBP-5, either alone or in combination with IGF-I, increases bone formation parameters in vivo.     

Increased bone formation and bone mass induced by sclerostin antibody is not affected by pretreatment or cotreatment with alendronate in osteopenic, ovariectomized rats

Clinical studies have revealed a blunting of the bone anabolic effects of parathyroid hormone treatment in osteoporotic patients in the setting of pre- or cotreatment with the antiresorptive agent alendronate (ALN). Sclerostin monoclonal antibody (Scl-Ab) is currently under clinical investigation as a new potential anabolic therapy for postmenopausal osteoporosis. The purpose of these experiments was to examine the influence of pretreatment or cotreatment with ALN on the bone anabolic actions of Scl-Ab in ovariectomized (OVX) rats. Ten-month-old osteopenic OVX rats were treated with ALN or vehicle for 6 wk, before the start of Scl-Ab treatment. ALN-pretreated OVX rats were switched to Scl-Ab alone or to a combination of ALN and Scl-Ab for another 6 wk. Vehicle-pretreated OVX rats were switched to Scl-Ab or continued on vehicle to serve as controls. Scl-Ab treatment increased areal bone mineral density, volumetric bone mineral density, trabecular and cortical bone mass, and bone strength similarly in OVX rats pretreated with ALN or vehicle. Serum osteocalcin and bone formation rate on trabecular, endocortical, and periosteal surfaces responded similarly to Scl-Ab in ALN or vehicle-pretreated OVX rats. Furthermore, cotreatment with ALN did not have significant effects on the increased bone formation, bone mass, and bone strength induced by Scl-Ab in the OVX rats that were pretreated with ALN. These results indicate that the increases in bone formation, bone mass, and bone strength with Scl-Ab treatment were not affected by pre- or cotreatment with ALN in OVX rats with established osteopenia.     

Bone metabolism and mass in women with Cushing's syndrome and adrenal incidentaloma

OBJECTIVE: The aim of this study was to compare bone turnover and mass in women with either Cushing's syndrome (CS) or adrenal incidentaloma (AI), which is a possible model for minimal hypersecretion of cortisol. DESIGN AND PATIENTS: We studied 15 patients with CS (seven premenopausal and eight postmenopausal women); 23 patients with AI (five premenopausal and 18 postmenopausal women) and 20 matched controls (seven premenopausal and 13 postmenopausal women). Alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), osteocalcin (BGP), 24-h urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) and serum and 24-h urinary calcium and phosphorus were determined in all subjects. Bone mineral density (BMD) at lumbar spine and proximal femur was measured by dual energy X-ray absorptiometry (DEXA). RESULTS: We found a significant reduction of BGP and serum phosphorus in CS and AI (P < 0.05) vs. controls and significantly lower levels of Pyr only in CS (P < 0.05) vs. AI and controls. Spinal and femoral BMD z-values were significantly lower (P < 0.05) in patients with CS (z-score: lumbar spine -1.44 +/- 1.5 and femoral neck -1.07 +/- 1; mean +/- SD) compared to AI and controls. CONCLUSIONS: Our data show that hypercortisolism reduces osteoblastic function and bone resorption and that osteocalcin can contribute to the precocious diagnosis of silent glucocorticoid excess. Patients with active CS were found to have lower BMD, particularly at vertebral level.