鹿瓜多肽注射液对去势大鼠骨密度和骨力学性能的影响

目的研究鹿瓜多肽注射液对去卵巢大鼠骨骼生物力学性能的影响。方法 3个月龄清洁级雌性Wistar大鼠27只,随机分为假手术（sham group,SHAM）组、去势（ovariectomized,OVX）组、去势＋鹿瓜多肽（cervus and cu-cumis polypeptide,CCP）组,每组9只。OVX＋CCP组大鼠于术后第1天开始按0.6 mL/（kg.d）肌注鹿瓜多肽注射液,术后12周处死所有大鼠,取出股骨及腰椎标本,双能X线吸收仪测量各组大鼠股骨近端、股骨干及全腰椎的骨密度。应用INSTRON 3367电子拉伸试验机检测股骨近端、股骨干和L5的生物力学性能。结果 a）OVX组与SHAM组相比较,大鼠股骨和腰椎最大载荷无明显下降（P〉0.05）,但极限强度明显下降（P〈0.01）;与OVX组相比,OVX＋CCP组的最大载荷无明显增加（P〉0.05）,但极限强度显著高于去势组（P〈0.01）;OVX＋CCP组与SHAM组比,上述检测指标间无统计学差异（P〉0.05）;b）与SHAM组相比,OVX组股骨近端、股骨干及全腰椎的骨密度明显降低（P〈0.01）;与OVX组相比,OVX＋CCP组各部位骨密度明显高于OVX组（P〈0.01）;OVX＋CCP组与SHAM组比,两者各部位骨密度无明显差异（P〉0.05）。结论鹿瓜多肽注射液能保护去势大鼠骨密度和骨骼内在生物力学性能。     

辅酶Q10对去卵巢大鼠股骨显微结构及生物力学的影响

目的应用骨生物力学和micro-ct技术,探讨Co Q10对去卵巢大鼠的股骨显微结构及生物力学的影响。方法 48只3月龄SPF级SD雌性未孕大鼠,随机分为假手术组(Sham)、去卵巢模型组(OVX)、小麦胚芽油组(WGO)、WGO+辅酶Q10组(高、低剂量)、戊酸雌二醇组(EV),连续给药90d。实验结束后,取右侧股骨进行生物力学检测,然后进行Micro CT扫描及三维重建。结果与Sham组比较,OVX组大鼠股骨的微观参数:骨体积分数、骨小梁数量、骨小梁厚度和骨密度明显减少,骨小梁分离度和结构模型指数明显增高;而股骨的骨生物力学参数:最大载荷、断裂载荷及弹性载荷明显减少,刚度明显减少。与OVX组相比,EV组大鼠股骨的骨微观参数均得到了良好地修复,骨生物力学参数中最大载荷、断裂载荷、弹性载荷及刚度得到了明显修复。而小麦胚芽油+低剂量CoQ10组大鼠股骨的微观参数骨小梁数量、骨小梁分离度、结构模型指数及骨密度和骨体积分数则得到一定程度的修复。结论辅酶Q10(15 mg/kg)能够修复OVX大鼠股骨微观结构破坏,辅酶Q10(15 mg/kg)可以预防去卵巢手术导致大鼠股骨松质骨结构破坏和股骨生物力学性能的下降,其他剂量组对此无明显的预防作用。提示辅酶Q10的抗骨质疏松作用具有良好的研究前景。     

强筋健骨方对PMOP大鼠骨密度及生物力学影响的实验研究

目的探究强筋健骨方对去势致骨质疏松症大鼠双侧股骨髁骨密度、生物力学特性及骨组织形态学的影响。方法采用经典的去势雌鼠建立绝经后骨质疏松症模型,采用随机数字表随机分为6组,分别为假手术组(Sham)、模型组(OVX)、西药对照组(E2)[12μg/(kg·d)]、"强筋健骨方"低、中、高剂量组(JGG、JGZ、JGD)[5.56 g/(kg·d)、11 g/(kg·d)、22 g/(kg·d)],灌胃给药12周后,观察大鼠股骨生物力学特性、骨矿物含量、双能X线测定双侧股骨髁骨密度,光镜下进行骨组织形态学观察。结果与Sham组相比较,OVX组取材时大鼠股骨矿物含量、股骨髁骨密度、股骨生物力学特性降低,骨组织形态学遭到破坏。与OVX组相比较,E2组及"强筋健骨方"三剂量组均能不同程度改善去势雌鼠的股骨生物力学特性、股骨髁骨密度、骨矿物含量及骨组织微结构。结论强筋健骨方对绝经后骨质疏松大鼠骨密度及生物力学特性破坏有一定改善作用,且在此剂量范围内存在剂量相关性。     

骨质疏松绵羊模型松质骨及皮质骨的微观结构及力学性能变化的研究

目的观察去势手术对绵羊皮质骨和松质骨的骨密度、骨小梁结构及力学性能的影响。方法20只雌性成年绵羊（4±1.5）随机分为去势4个月组（OVX-4months）（4只）、去势12个月组（OVX-12months）（8只）和假手术（Sham）组（8只）。OVX组行双侧卵巢切除术,假手术组仅显露双侧卵巢,术中测定腰椎骨密度。分别与术后4、12个月处死动物,测定股骨颈、股骨干及股骨髁的骨密度,并行MicroCT分析及生物力学测试。结果去势12个月后（OVX-12months）组腰椎、股骨颈及股骨髁的骨密度较对照组显著降低,而皮质骨骨密度无明显降低。其松质骨的相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）较对照组显著降低,表面积体积比（BS/BV）、骨小梁间隙（Tb.Sp）则较对照显著增高。生物力学测试表明,去势12个月后,腰椎松质骨的最大压缩应力分别较Sham组和OVX-12months组下降82.5%和85.9%,力学强度显著下降,而皮质骨的力学强度无显著变化。结论去势12个月后,绵羊腰椎、股骨部的松质骨BMD及骨小梁空间结构参数明显降低,力学强度也显著下降,可以作为骨质疏松的大动物模型。而皮质骨的骨密度和力学强度下降不明显,需要更长的去势时间。     

铁蓄积小鼠去势前后骨吸收活性的差异

目的了解小鼠在去势前与去势后,铁对骨吸收影响的差异。方法建立高铁小鼠模型,将小鼠随机分为假手术组(SHAM组)、高铁去势组(F+OVX组)、去势组(OVX组)。铁剂干预两周后去势。在去势前(雌激素存在)与去势7周后(雌激素缺乏)检测小鼠体重,血清铁蛋白;反转录聚合酶链反应(RT-PCR)检测胫骨内抗酒石酸酸性磷酸酶(TRAP)、降钙素受体(CTR)、基质金属蛋白酶9(MMP9)、组织蛋白酶K(cathepsin K)、雌激素受体α(ERα)、雌激素受体β(ERβ)表达情况,股骨远端Micro-CT三维分析,提取各组小鼠股骨骨髓细胞进行破骨细胞培养,抗酒石酸酸性磷酸酶(TRAP)染色观察破骨细胞分化情况。结果各组小鼠体重无明显差异。F+OVX组铁蛋白含量明显升高(P<0.05)。Micro-CT分析表明:雌激素存在时,正常组与铁干预组骨密度及相关指标无明显差异(P>0.05);雌激素缺乏时,与OVX组比较,F+OVX组骨量下降更为严重(P<0.05)。半定量PCR结果显示:雌激素存在时,两组TRAP、CTR、MMP9、cathepsin K基因表达无统计学差异;雌激素缺乏时,F+OVX组各基因表达水平较OVX组显著升高(P<0.05)。去势后ERβ表达下降(P<0.05),ERα无明显差异。TRAP染色显示去势前各组小鼠破骨细胞数无明显差异(P>0.05);而去势后,F+OVX组破骨细胞数明显高于OVX组(P<0.05)。结论未去势时(有雌激素),FAC对骨吸收影响甚微;去势后(无雌激素),FAC能显著增强破骨活性。     

鹿瓜多肽对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响

目的鹿瓜多肽（松梅乐）注射液肌注对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响。方法将8月龄未经产雌性二级SD大鼠30只，随机分为假手术组（SHAM）组、去势组（OVX）、去势＋鹿瓜多肽（OVX＋CCP）组。OVX＋CCP组大鼠术后第1天开始给药，术后20周处死各组大鼠．应用双能X线吸收仪（DEXA）测量各组大鼠股骨粗隆、股骨干中点及第3～5腰椎中点的骨密度（BMD）；应用INSTRON1195电子拉伸试验机检测股骨生物力学性能；利用免疫组织化学染色及图像分析方法对各组大鼠松质骨切片图像进行灰度分析，观察鹿瓜多肽注射液对OVX大鼠松质骨中BMP2表达的影响。结果（1）OVX与SHAM组比较，灰度值降低明显（P〈0．01），而OVX＋CCP组灰度值较去势组降低（P〈0．01），表明OVX大鼠松质骨中骨小梁周围及髓腔中BMP2表达阳性细胞数明显多于SHAM组；而OVX＋CCP组骨小梁周围及髓腔内BMP2表达阳性细胞数多于去势组，且染色加深。（2）与SHAM组相比，OVX组股骨近端、股骨干、腰椎BMD明显降低（P〈0．01）；OVX＋CCP各部位BMD高于去势组（P〈0．01），但未达到SHAM组水平（P〈0．01）；（3）与SHAM比较，去势组大鼠股骨最大载荷、桡度、最大应力、弹性模量均明显下降（P〈0．01），治疗组上述指标高于去势组（P〈0．01），接近对照组水平（P〉0．05）。结论鹿瓜多肽注射液可以抑制和延缓骨质疏松的形成，对雌激素缺乏引起的骨质疏松具有预防作用。     

骨量、微结构及受力方向对去卵巢大鼠骨生物力学的影响

目的观察骨质疏松模型大鼠骨量、骨微结构和骨的受力方向与生物力学变化的关系。方法6～7月龄Wistar大鼠50只,随机分为正常对照组25只,去势模型组25只,12周后处死全部大鼠,测定大鼠全身、股骨和腰椎(L4～L6)骨密度,对左侧股骨进行三点弯曲试验,右侧股骨沿载荷倾斜20°角进行压力试验,对椎体(L4)进行压缩试验,把部分股骨和腰椎(L5)制成切片进行免疫组化染色,观察它们的形态计量学变化。结果去势组大鼠的全身、股骨和腰椎(L4～L6)骨密度比对照组明显减少(P<0.05),去势组大鼠右侧股骨沿载荷倾斜20°角后的结构力学性能和椎体的最大压缩力较正常对照组明显降低(P<0.05),但两者左侧股骨的结构力学性能差异无显著性(P>0.05),去势后大鼠股骨的材料力学性能较对照组明显下降(P<0.05),组化染色显示去势组大鼠的骨小梁较正常组稀疏减少,尤以松质骨明显。结论大鼠去势后松质骨的骨量、骨微结构较皮质骨变化明显,且骨量、骨微结构和骨的受力方向对骨的生物力学都有着重要影响。     

PM 2.5对去卵巢骨质疏松症大鼠骨密度和生物力学性能的影响

目的 探讨PM 2.5对去势致骨质疏松症大鼠腰椎（L3~5）、右侧股骨骨密度及左侧股骨骨生物力学特性的影响。方法 将3周龄雌性SD大鼠（SPF级）适应生长一周后随机分为假手术组、模型对照组和PM 2.5低、中、高剂量组,行气道滴注PM 2.5混悬液或生理盐水,滴注5个月后将模型对照组和PM 2.5各剂量组通过切除大鼠双侧卵巢建立绝经后骨质疏松症模型,假手术组仅切除卵巢周围约1 g的脂肪组织。继续气管滴注至第9个月末,其间分别测定去势后滴注第7、9个月末各组腰椎（L3~5）、右侧股骨骨密度(bone mineral density,BMD)数值,处死大鼠后取左侧股骨进行三点弯曲试验。结果 气管滴注7个月后, 各组大鼠腰椎（L3~5）及右侧股骨 BMD 比较差异无统计学意义 (P>0.05)。滴注9个月后, PM 2.5各剂量组大鼠腰椎及右侧股骨 BMD 明显低于模型对照组,且PM 2.5各剂量组之间呈现一定的剂量关联趋势,中、高剂量组BMD降低趋势明显,差异有统计学意义 (P<0.05)。此外,从骨生物力学角度分析,与假手术组相比,模型对照组、PM 2.5低剂量组的弹性载荷、极限载荷、弹性模量均下降,且差异有统计学意义( P＜0.05) ;与模型对照组比较,PM 2.5各剂量组的股骨弹性载荷、极限载荷和弹性模量降低( P＜0. 05),下降趋势与BMD一致,高剂量组下降最为显著。结论 PM 2.5加速了去势大鼠的骨密度降低,造成骨生物力学破坏,与PMOP的严重程度相关,具体机制有待探讨。     

川牛膝在去卵巢大鼠体内的骨保护作用

目的 观察川牛膝在去卵巢大鼠体内的抗骨质疏松作用。方法 3月龄雌性SD大鼠50只随机分为5组:假手术组 (SHAM)、单纯去卵巢组（OVX)、己烯雌酚组（ERT组,22.5μg/kg? d,ig)、高剂量川牛膝组（CH,14 g/kg? d,ig)、低剂量川牛膝 组(CL,7 g/kg? d,ig)。其中,40只大鼠切除双侧卵巢,SHAM组仅切除卵巢周围等量脂肪组织,术后第8天开始给药,给药12 周后处死所有大鼠,测定腰椎骨密度（L-BMD)、股骨骨密度（F-BMD)及骨生物力学性能：弹性模量（ELASTIC)、刚度 (STIFFNESS)、最大应力（M-STRESS)及最大承载力（M-LORD),并测定血清钙（Ca)、磷（P)、碱性磷酸酶(ALP)、尿羟脯氨酸 (HOP )、肌酐(Cr)值。结果 高剂量川牛膝组及己烯雌酚组大鼠腰椎和股骨的骨密度及骨生物力学性能均高于OVX组（P <0. 05),而尿羟脯氨酸/肌酐值及血清Ca、P含量低于OVX组（P <0.05)。结论 川牛膝在去卵巢大鼠体内能抑制骨量丢失、改善骨生物力学性能,预防骨质疏松的发生。     

联合运用重组人生长激素和雌激素对去势大鼠骨密度及生物力学的影响

目的研究重组人生长激素和雌激素联合用药对去势大鼠股骨、下颌骨骨密度及生物力学的影响。方法选4月龄SD雌性大鼠,随机分为5组:假手术组(sham-OVX)、骨质疏松组(OVX)、雌激素组(E2)、重组人生长激素组(rh-GH)、联合用药组(E2 rh-GH),于去势后8w,各组分别腹腔给予相应的药物,4w末及8w末分两批处死各组大鼠,取股骨和下颌骨新鲜标本,进行骨密度(BMD)与最大载荷的实验研究。结果用药4w末及8w末,OVX组下颌骨和股骨BMD均显著低于其他4组。E2 rh-GH组下颌骨BMD较E2组和rh-GH组高,但是差异均无统计学意义(P>0.05)。用药4w末及8w末,OVX组下颌骨和股骨最大载荷均显著低于sham-OVX组和用药组。E2 rh-GH组下颌骨及股骨最大载荷比E2组、rh-GH组高,用药4w末联合用药组与单一用药组最大载荷的差异有统计学意义;而用药后8w末差异均无统计学意义。结论雌激素、重组人生长激素及两者联合用药都能有效的抑制骨质疏松大鼠颌骨及股骨骨量的丢失,提高骨强度。联合用药与单一用药对下颌骨骨密度的影响没有明显的差异,可能与测量的方法和测量部位结构有关。联合用药对股骨骨密度、最大载荷及颌骨最大载荷的作用与用药时间有关,短期内效果优于单独用药。     

Isoflavones with supplemental calcium provide greater protection against the loss of bone mass and strength after ovariectomy compared to isoflavones alone

Although hormone replacement therapy (HRT) and calcium (Ca) supplementation preserve bone mass more when combined, there is a growing concern over the safety of HRT that necessitates thorough investigation of effective, alternative treatments for bone loss. While plant-derived estrogen-like compounds such as isoflavones preserve bone, it is not known whether isoflavones and Ca supplementation attenuate losses in bone mass and strength to a greater extent when combined. This study compared the effects of an isoflavone extract + high Ca to isoflavone extract or high Ca alone on preservation of bone mineral density (BMD) and biomechanical strength in ovariectomized (ovx) rats. Rats were sham-operated (n = 10) or ovx (n = 40). Shams were fed a 0.2% Ca diet. Ovx rats were randomized to a 0.2% Ca diet alone (OVX) or with isoflavone extract (IE; 1.6 g/kg diet) or to a high Ca diet (Ca; 2.5%) alone or a high Ca diet with the isoflavone extract (IE + Ca) for 8 weeks. BMD of femur and lumbar spine were measured by dual-energy X-ray absorptiometry. The biomechanical strength of femurs and individual vertebra was measured by three-point bending and compression testing, respectively. The average food intake was lowest (P < 0.05) among sham and IE groups and greatest (P < 0.05) among the OVX group. Final body weight was lowest (P < 0.05) among shams and highest (P < 0.05) among the OVX group while IE + Ca were lighter (P < 0.05) than all ovx groups. Femur and vertebra BMD was greater (P < 0.05) among IE + Ca and sham rats compared to IE, Ca, or OVX rats. Although there were differences in femur BMD among groups, biomechanical properties at the femur midpoint did not differ among groups, possibly due to the lack of cortical bone loss at this site. Conversely, vertebra biomechanical strength was greater (P < 0.05) among IE + Ca and Ca alone groups compared to IE alone. Uterine weight was higher (P < 0.05) among shams than OVX and IE with no difference among shams, Ca, or IE + Ca rats, suggesting that the isoflavones did not have an uterotrophic effect. In conclusion, isoflavones combined with high Ca are more protective against the loss of femur and vertebra BMD than isoflavones or high Ca diet alone.     

维生素K2对去卵巢大鼠股骨干骨折愈合影响的实验研究

目的探讨维生素K2能否促进卵巢切除骨质疏松(OVX)大鼠骨折愈合。方法将30只雌性大鼠随机分为3组(每组10只):假手术组(SHAM)、去卵巢组(OVX)、OVX+维生素K2组。大鼠卵巢切除术后3个月,在右侧股骨干制作单侧股骨干骨折。然后在通过维生素K2治疗8周后处死动物,行X线片检测;对骨折的股骨进行生物力学检测并观察血清骨钙素(BGLAP)、碱性磷酸酶(ALP)、抗酒石酸酸性磷酸酶(TRACP)和雌二醇水平的变化。结果与OVX组相比,OVX+维生素K2组观察到更多骨痂组织形成和更好的骨愈合,并且BGLAP、ALP和TRACP水平降低,但是血液雌二醇水平没有观察到显著增加。与OVX组相比,OVX+维生素K2组显示出骨强度、最大负荷和弹性显著增加。结论维生素K2具有作为绝经后骨质疏松症骨折愈合新型替代治疗剂的潜力。     

Comparable Effects of Alendronate and Strontium Ranelate on Femur in Ovariectomized Rats

This study compared the effects of alendronate (ALN) and strontium ranelate (SR) on bone mineral density (BMD), bone histomorphometry, and biomechanics in ovariectomized (OVX) rats. We randomly assigned 48 3-month-old female Sprague–Dawley rats to four groups: sham, OVX, ALN, and SR. Rats in the OVX, ALN, and SR groups received bilateral OVX. Rats in the ALN and SR groups were orally administrated ALN (7 mg/kg/week) and SR (500 mg/kg/day). Rats in the sham and OVX groups were treated with saline. All treatments continued for 12 weeks. Femoral BMD examination, distal femoral bone histomorphometry analysis, and biomechanical tests at the femoral diaphysis and metaphysis were performed to evaluate the effects of treatments in OVX rats. Results showed that both ALN and SR significantly increased femoral BMD (total femur, diaphyseal BMD, and distal metaphyseal BMD), distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral biomechanical parameters (maximum load, failure load, stiffness) compared with the OVX group (P < 0.05). No differences were found between ALN and SR in increasing femoral BMD, distal femoral bone histomorphometric parameters (BV/TV, Tb.N, and Tb.Th), and femoral diaphysis biomechanical parameters (maximum load, failure load, stiffness) (P > 0.05). The SR group was inferior to the ALN group in femoral metaphysis biomechanical parameters (P < 0.05). In conclusion, ALN (7 mg/kg/week) and SR (500 mg/kg/day) have similar effects by increasing BMD, distal femoral bone histomorphometric parameters, and femoral metaphysis biomechanical properties. Although ALN has greater effects than SR on distal femoral metaphysis biomechanical properties, in general, ALN and SR have comparable effects on the femur in OVX rats.     

Daidzein together with high calcium preserve bone mass and biomechanical strength at multiple sites in ovariectomized mice

As the prevalence of osteoporosis is increasing, and the adverse effects of hormone replacement therapy are evident, women are searching for natural alternatives such as soy isoflavones to help prevent postmenopausal osteoporosis. Daidzein is one of the most abundant isoflavones present in soy and it is unique as it can be further metabolized to equol, a compound with greater estrogenic activity than other isoflavones. The objective of this study was to determine the effects of purified daidzein in combination with high calcium (Ca) on preserving femur and lumbar vertebrae (LV1-LV4) bone mineral density (BMD) and biomechanical bone strength at three different sites (femur midpoint, femur neck and LV3) in ovariectomized mice. Sham (SH) mice (n = 12) received control diet (AIN93G) containing 2 g Ca/kg diet and ovariectomized mice were randomized to 1 of 6 groups (n = 12/group): OVX (2 g Ca/kg diet), HCa (25 g Ca/kg diet), HD (2 g Ca + 200 mg daidzein/kg diet), HDCa (25 g Ca + 200 mg daidzein/kg diet), LD (2 g Ca + 100 mg daidzein/kg diet) or LDCa (25 g Ca + 100 mg daidzein/kg diet) for 12 weeks. HDCa preserved femur and vertebrae BMD and biomechanical bone strength (at all three sites) compared to the OVX group, however, only femur yield load (at midpoint) was preserved to a level that was greater (P < 0.05) than HCa alone. Mice fed HD diet had greater (P < 0.05) femur BMD than OVX group, however, daidzein alone (HD) did not appear to preserve trabecular bone (i.e., vertebrae BMD and vertebra peak load). All mice fed daidzein produced equol and there were no uterotrophic effects of daidzein at either dose. Both daidzein and Ca attenuated the increase in serum IL-1beta observed in the OVX group. The results from this study suggest that the combination of daidzein and high Ca favorably affect cortical and trabecular bone as indicated by femur and lumbar vertebrae BMD and biomechanical strength but much of this effect is mediated by the high Ca diet. Further investigation is required to determine optimal dietary levels of daidzein and Ca with the long-term goal of developing a dietary strategy to prevent postmenopausal osteoporosis and related fragility fractures.     

新型骨质疏松大鼠骨生物力学测试方法:股骨干骺端弯曲试验

 目的 建立一种新的骨生物力学测试方法用以评价去卵巢骨质疏松大鼠股骨干骺端生物力学的变化。方法 20只 5月龄雌性 SD大鼠随机分为去卵巢组和假手术组。术后 12周, 对全部大 鼠进行股骨骨密度和股骨远端骨组织计量学测定。所有大鼠取一侧股骨行中段三点弯曲试验, 另一侧 股骨行干骺端弯曲试验, 测定生物力学指标(最大载荷、屈服载荷、刚度)。对各生物力学指标和骨密度 及骨组织计量学指标行 Pearson相关分析。结果 去卵巢组股骨骨密度、骨组织计量学指标(骨小梁面 积百分比、骨小梁数量、骨小梁厚度)和生物力学参数(最大载荷、屈服载荷、刚度)较假手术组均明显降 低。在股骨干骺端弯曲试验中, 两组最大载荷和屈服载荷的差值明显大于三点弯曲试验所得的相应差值。 Pearson相关分析显示骨生物力学各参数与骨密度、骨组织计量学指标均呈正相关, 且股骨干骺端 弯曲试验的生物力学参数与骨密度、骨组织计量学指标的相关性明显强于股骨干三点弯曲试验。结论 建立了新型骨质疏松大鼠骨生物力学测试方法, 即股骨干骺端弯曲试验, 可用来评估去卵巢骨质疏松 大鼠股骨干骺端生物力学性能, 与股骨干三点弯曲试验相比, 其敏感度更高, 与骨密度和骨组织计量学 参数的相关性更强。     

Correlation among geometric,densitometric, and mechanical properties in mandible and femur of osteoporotic rats

We have previously demonstrated bone loss of the mandible and femur in experimental osteoporotic rats and its prevention by medication, using peripheral quantitative computed tomography (pQCT). In the present study, the mechanical properties of the mandible and femur and the correlation to their geometric and densitometric properties were studied in ovariectomized rats with or without etidronate treatment. Fifty-four Wistar strain SPF female rats, 26 weeks old, were randomly assigned to four groups: (1) Basal group (12 rats, 1.0% Ca diet); (2) Sham group (Sham-operated, 12 rats, 0.1% Ca diet); (3) OVX group (ovariectomized, 15 rats, 0.1% Ca diet); (4) Treated group (OVX + etidronate, 15 rats, 0.1% Ca diet). Total bone mineral density (BMD), cortical BMD, cross-sectional cortical bone area, cross-sectional cortical bone thickness, crosssectional moment of inertia (CSMI), and polar strength index (SSI) of the mandible and femur were measured by pQCT. The failure load of mandible and femur was evaluated by three-point bending. The failure load of both bones was significantly lower in the Sham group compared with the Basal group. The OVX group further had a 8% and 7% decrease in the failure load for mandible and femur, respectively, compared to the Sham group. Treatment with etidronate led to an increase in the failure load compared with the OVX group. The failure load was related to the pQCT-assessed variables, especially with cortical bone area and total BMD. Moreover, the geometric and densitometric properties and failure load in the mandible showed a correlation to those in the femur.     

Effects of Different Dosages of Parathyroid Hormone-Related Protein 1–34 on the Bone Metabolism of the Ovariectomized Rat Model of Osteoporosis

Intermittent and low-dose parathyroid hormone (PTH) injection to stimulate bone formation has been used in the treatment of osteoporosis. The N-terminal fragment 1–34 of PTH is quite similar in structure and function to N-terminal PTH-related protein (PTHrP). PTH(1–34) and PTHrP also share a coreceptor, the PTH/PTHrP receptor. Therefore, some studies have suggested that PTHrP could effectively stimulate bone formation, similar to PTH. We used an ovariectomized (OVX) rat model of osteoporosis to study the effects of PTHrP(1–34) on bone metabolism by measuring bone mineral density (BMD), bone histomorphometrics, and biomechanical parameters. We found that subcutaneous injection of PTHrP(1–34) (40 or 80 μg/kg body weight every day) in OVX rats increased lumbar and femoral BMD, improved bone biomechanical properties, enhanced bone strength, and promoted bone formation. We selected 40 μg/kg as the preferred therapeutic dose of PTHrP(1–34) and investigated the effects of frequency of treatment (per 1, 2, 3, or 7 days) on bone metabolism in OVX rats. We found that injection of PTHrP(1–34) once per day or every other day significantly improved the BMD and strength of OVX rats. Serum calcium and phosphate levels in all treated rats did not vary significantly from control rats. Based on our results, intermittent low-dose PTHrP(1–34) injection promoted bone formation in OVX rats, suggesting a high potential for therapeutic use in osteoporosis patients.     

Effects of running exercise on the mandible and tibia of ovariectomized rats

To examine the effects of running exercise on the mandible and tibia of ovariectomized (OVX) rats, 26-week-old sham-operated (Sham) and OVX rats 1 week post-ovariectomy were subjected to non-exercise (Sham-Cont and OVX-Cont) and exercise (Sham-Exc and OVX-Exc) for 8 weeks. OVX induced a significant decrease in alkaline phosphatase (ALP) and an increase in tartrate-resistant acid phosphatase (TRAP) activity and a reduction of 17β-estradiol in the serum. In OVX-Cont rats, histology and bone mineral density (BMD) showed bone loss in the proximal tibia, and histology, soft X-ray photographs and bone marrow area (BMA) revealed enlargement of the bone marrow cavity in the neck of the condylar process. In OVX-Exc rats, exercise significantly increased ALP activity, decreased TRAP activity and markedly elevated serum progesterone levels. Histology and BMD in the tibia and histology, X-ray photographs and BMA in the mandible were comparable to those in Sham rats. In Sham-Exc rats, unexpected decreases were observed in serum enzymes and hormones, but the histology and BMD in the tibia and histology, X-ray photographs and BMA in the mandible were very similar to those in Sham-Cont rats, suggesting a decrease of bone turnover with no change of bone mass in the tibia and mandible. We conclude that exercise has a beneficial effect not only on bone loss in the tibia, but also on differential changes in the neck of the condylar process, perhaps by increasing serum levels of progesterone in OVX rats. Received: May 29, 2000 / Accepted: November 6, 2000     

补骨脂盐炙前后对去卵巢大鼠的骨保护作用及其机制

目的 比较补骨脂盐炙前后对去卵巢（OVX）大鼠骨质疏松的治疗作用，并探讨其炮制机理。方法 制备大鼠骨质疏松模型，分别用补骨脂生、盐品灌胃，给药12周后称重，取子宫，测血清中钙（Ca）、磷（P）、碱性磷酸酶（ALP）、骨钙素（OC）以及雌二醇（E2）含量，测骨生物力学强度和骨密度（BMD），观察骨小梁微结构。制备补骨脂生、盐品含药血清，检测含药血清对成骨细胞增殖和分化影响。检测补骨脂生、盐品水煎液和含药血清中主要有效成分含量。结果 补骨脂生、盐品均能有效抑制去卵巢所致的大鼠体重增加和子宫萎缩，升高血清Ca、P含量，降低ALP、OC和E2含量，显著提高BMD、骨生物力学强度，改善骨小梁结构的完整性。补骨脂生、盐品对成骨细胞的增殖和分化均有明显的促进作用，且盐品效果优于生品。此外，补骨脂盐炙后有效成分的煎出和入血成分的含量存在明显差异。结论 补骨脂生、盐品对OVX所致的大鼠骨质疏松症有良好的治疗效果，并且补骨脂盐品的抗骨质疏松作用更强，这与补骨脂盐炙促进补骨脂苷、异补骨脂苷等有效成分煎出和盐炙后补骨脂素、异补骨脂素等入血有效成分增加有关。