密骨胶囊和健脾方对去卵巢大鼠骨结构和力学性能的影响

目的 观察密骨胶囊、健脾方对大鼠骨结构、生物力学性能的影响.探讨补肾、健脾不同功效的中药复方,对骨结构、生物力学性能作用可能存在的差异性.方法 复制切卵巢大鼠骨质疏松模型,随机分为假切组、模型组、密骨胶囊组和健脾方组,术后12周开始灌胃,灌胃12周后取材.测定股骨骨密度、骨生物力学,观察骨组织形态学、骨超微结构.结果 密骨胶囊能提高切卵巢大鼠股骨骨密度(P＜0.05),提高骨生物力学性能(P＜0.05),改善骨的微结构;健脾方能维持大鼠股骨骨密度(P＞0.05),提高骨生物力学性能(P＜0.05),明显改善骨的微结构.结论 补肾中药复方对骨量的提高、生物力学性能改善方面较健脾方显著,而健脾中药复方较之在骨微结构的改善方面更有优势.     

重组人生长激素对摘除卵巢大鼠皮质骨的影响

目的 探讨重组人生长激素对摘除卵巢大鼠股骨和椎体皮质骨的影响。方法 ６个月龄ＳＤ大鼠４０只,摘除卵巢后３个月开始皮下注射高、低２种剂量生长激素。注射８周后处死,取出双侧股骨和Ｌ２椎体,测定股骨中段骨密度值,观测股骨中段和椎体皮质骨厚度的改变,测定股骨生物力学强度,并与雌激素注射组比较。结果 生长激素显著增加摘除卵巢大鼠股骨中段和腰椎体皮质骨尤其是外层皮质的厚度,股骨中段骨密度值和生物力学强度出显著     

补肾中药通过调控Notch1蛋白的表达治疗大鼠骨质疏松性骨折的作用研究

目的探究补肾中药对大鼠骨质疏松骨折的治疗作用和机制。方法选取老年雌性大鼠60只,分为正常组、骨质疏松骨折模型组、高、中、低剂量补肾中药治疗组,各组均摘除卵巢,术后3个月形成骨质疏松模型。随后除正常组外,其余各组均建立股骨骨折模型。骨质疏松骨折模型建立后,每日给予正常组与模型组生理盐水进行灌胃,治疗组分别给予高、中、低剂量补肾中药灌胃12 w进行治疗。末次实验结束后麻醉大鼠,应用双能X射线检测大鼠股骨的骨密度。采取血清样品通过ELISA法测量碱性磷酸酶、骨钙素、TRAP破骨标志物等指标含量,对股骨样品进行病理学检查以及Western blot法检测Notch1蛋白的表达。结果病理组织学切片结果显示,高剂量治疗组在骨折端的成骨细胞数量较多,破骨细胞数量较少,提示补肾中药具有促进骨性愈合的效果。经补肾中药治疗后,高剂量治疗组的骨密度与模型组相比骨密度显著回升。研究发现,strACP经过补肾中药治疗后,治疗组中的碱性磷酸酶与血清抗酒石酸性磷酸酶的含量显著降低,骨钙素含量明显提升,上述指标在高剂量治疗组中与模型组相比差异均具有统计学意义(P0.01),呈明显的剂量依赖性。另外,Western blot法检测结果也显示,Notch1蛋白的表达在模型组中受到显著抑制(与正常组相比,P0.01),而补肾中药具有调节Notch1蛋白表达的作用,成明显剂量相关性,且高剂量治疗组的表达水平与正常组接近。结论补肾中药能够通过调节Notch1蛋白的表达来抑制血清中破骨标志物碱性磷酸酶和TRAP的水平,并提高骨钙素的含量来刺激成骨细胞生成、抑制破骨细胞分化,从而加速骨折的愈合,提高骨密度,对大鼠股骨骨质疏松骨折具有良好的治疗作用。     

骨康防治去势大鼠骨质疏松的实验研究

目的探讨补肾活血类中药骨康口服液对去势大鼠所造成的骨质疏松的影响。方法通过切除大鼠卵巢造成绝经后骨质疏松模型,观察了中药骨康口服液不同剂量对造模大鼠骨质疏松的防治作用及其对去势大鼠股骨骨生物力学的影响,并与尼尔雌醇作阳性对照。结果中药骨康中、低剂量的去势大鼠股骨扭转试验最大扭矩高于模型组（Ｐ＜０．０５）,中、低剂量组股骨ＢＭＤ、ＢＭＣ高于模型组（Ｐ＜０．０５）。股骨ＢＭＤ值与股骨最大扭矩值呈直线相关（ｒ＝０．７４１５,Ｐ＜０．０１）。结论推测骨康可能能提高去势大鼠骨的骨矿含量及骨密度,并促进去势大鼠骨结构的再建,改善骨的内部构造,从而提高大鼠骨的机械性能。     

雷尼酸锶对局部肌麻痹大鼠的骨量丢失及微结构退变的影响

目的 研究雷尼酸锶对局部肌肉麻痹大鼠的骨量丢失及微结构退变的影响。方法 21只3.5月龄的雌性SD大鼠随机分三组,每组各7只：肉毒素组(BTX组),右侧股四头肌肌注肉毒素建立局部肌肉麻痹废用模型;肉毒素+雷尼酸锶组(BTX+SR组),肌注肉毒素并予以雷尼酸锶灌胃处理;对照组。所有大鼠干预9周后处死,取双侧股骨,行显微CT扫描分析。结果 BTX组与对照组相比较,废用侧的股骨皮质骨矿物盐含量、皮质骨骨密度、皮质骨面积和截面总面积以及松质骨的骨体积分数、骨小梁厚度、骨小梁数量和骨小梁联接密度均明显下降;骨小梁面积分数、骨小梁间隔和结构模型指数显著增加(P＜0.05)。BTX+SR组与BTX组相比较,皮质骨骨密度、皮质骨面积和截面总面积以及松质骨的组织骨密度、骨体积分数、骨小梁厚度、骨小梁数量和骨小梁联接密度明显增加,骨小梁面积分数、骨小梁间隔和结构模型指数显著下降(P＜0.05)。BTX+SR组与BTX组和对照组比较,健侧松质骨的表观骨密度、组织骨密度、骨体积分数和骨小梁厚度均明显增加(P＜0.05)。结论 雷尼酸锶可阻止因局部肌肉麻痹导致的大鼠骨量丢失和微结构的退变。     

纳米压痕技术观察骨微观力学特性变化的实验研究

目的 探讨骨质疏松皮质骨和松质骨微观力学特性的动态变化.方法 20只10月龄雌性SD大鼠随机分为5组:假手术对照组,去势3月组,去势6月组,去势9月组,去势12月组,每组4只.分别于去势不同时间点,取双侧股骨和腰3、4椎体标本,测量骨密度值.采用纳米压痕技术分别测量各组皮质骨和松质骨的微观硬度和弹性模量.结果 随去势时间的增加,皮质骨和松质骨的硬度和弹性模量均呈递减趋势(P＜0.05).各去势组皮质骨内骨板的弹性模量和硬度均比同组的外骨板高,而皮质骨硬度均高于松质骨,假手术对照组和去势3月组皮质骨的弹性模量高于松质骨,去势6月、9月、12月组松质骨的弹性模量高于皮质骨.结论 骨质疏松症皮质骨和松质骨的微观硬度、弹性模量同步降低,这是导致骨骼力学强度下降的重要因素.     

中药复方护骨胶囊对糖皮质激素诱导骨质疏松大鼠骨密度和骨形态计量学的研究

目的 探讨中药复方护骨胶囊(主要由制何首乌、淫羊藿、熟地黄等多味中药加工而成的复方制剂)对糖皮质激素诱导骨质疏松大鼠骨丢失的影响。方法 3月龄SPF级雄性SD大鼠30只,随机平均分为3组：正常对照组(Nrm)、激素组(Met)和中药组(CH)。Met组：皮下注射甲强龙(Met)5 mg/kg/d,每周5次;CH组：在Met组基础上给予中药复方护骨胶囊(150mg/kg/d)灌胃,实验期12w。大鼠右侧股骨和L5行骨密度(BMD)测定,右侧胫骨行骨形态计量学分析。结果 Met组L5和股骨BMD显著低于Nrm组;CH组L5和股骨BMD显著高于Met组。Met组Tb.N、%Tb.Ar、MS/BS、MAR和BFRs显著低于Nrm组,Tb.Sp、ES/BS显著高于Nrm组;中药组Tb.N、%Tb.Ar、MS/BS、MAR和BFRs显著高于Met组,Tb.Sp,ES/BS显著低于Met组。结论 中药复方护骨胶囊在提高激素诱导骨质疏松大鼠的骨密度,促进骨形成,降低骨吸收,延缓骨丢失方面有积极作用,对继发性骨质疏松的预防和治疗有一定前景。     

中药复方护骨胶囊对糖皮质激素诱导骨质疏松 大鼠骨密度和骨形态计量学的研究

目的 探讨中药复方护骨胶囊(主要由制何首乌、淫羊藿、熟地黄等多味中药加工而成的复方制剂)对糖皮质激素诱导骨质疏松大鼠骨丢失的影响.方法 3月龄SPF级雄性SD大鼠30只,随机平均分为3组:正常对照组(Nrm)、激素组(Met)和中药组(CH).Met组:皮下注射甲强龙(Met)5mg/kg/d,每周5次;CH组:在Met组基础上给予中药复方护骨胶囊(150 mg/kg/d)灌胃,实验期12w.大鼠右侧股骨和腰椎行骨密度(BMD)测定,右侧胫骨行骨形态计量学分析.结果 Met组腰椎和股骨BMD显著低于Nrm组;CH组腰椎和股骨BMD显著高于Met组.Met组Tb.N、%Tb.Ar、MS/BS、MAR和BFRs显著低于Nrm组,Tb.Sp、ES/BS显著高于Nrm组;中药组Tb.N、%Tb.Ar、MS/BS、MAR和BFRs显著高于Met组,Tb.Sp,ES/BS显著低于Met组.结论 中药复方护骨胶囊在提高激素诱导骨质疏松大鼠的骨密度,促进骨形成,降低骨吸收,延缓骨丢失方面有积极作用,对继发性骨质疏松的预防和治疗有一定前景.     

补肾中药对骨质疏松大鼠性激素影响的实验研究

目的　探讨补肾中药骨康对去势所造成骨质疏松大鼠性激素及骨密度的影响及性激素水平在骨质疏松发病中的作用。方法　通过切除大鼠睾丸和卵巢造成骨质疏松模型,观察中药骨康不同剂量对骨质疏松大鼠血睾酮（Ｔ）、血清雌二醇（Ｅ２）、ＢＭＤ 和ＢＭＣ的影响,并与特乐定、尼尔雌醇作阳性对照。结果　中药骨康高、中剂量防治的去势大鼠Ｔ 含量高于模型组（Ｐ＜ ０．０５ 和０．０１）,高、中、低剂量组的Ｅ２、全身及左、右股骨ＢＭＤ、ＢＭＣ高于模型组（Ｐ＜ ０．０５）。结论　骨康能提高去势大鼠血性激素含量、骨的骨矿含量及骨密度,其提高骨矿含量及骨密度的作用可能与其提高性激素水平有关。     

慢性肾衰竭大鼠股骨cbfa1表达与骨密度关系的研究

目的探讨股骨核心结合因子-a1(cbfa1)对慢性肾衰竭大鼠股骨密度变化的影响。方法将12只大鼠随机分为空白对照组、慢性肾衰竭模型组。造模成功后测量各组大鼠股骨的整体骨密度(Whole-bone mineral density,W-BMD)、松质骨骨密度(Trabecular-bone mineral density,T-BMD)、皮质骨骨密度(Cortical-bone mineral density,C-BMD),留取血清测定钙、磷等生化参数,采用免疫组织化学和HE染色的方法分别检测大鼠股骨中Cbfa1蛋白的表达及松质骨和皮质骨的形态学改变。结果与空白对照组比较,慢性肾衰竭模型组W-BMD、C-BMD降低,T-BMD升高(P0.001);股骨松质骨Cbfa1表达增多,皮质骨Cbfa1表达减少(P0.001);相关分析显示W-BMD与皮质骨Cbfa1蛋白表达呈正相关(r=0.979,P0.001),与松质骨Cbfa1蛋白表达呈负相关(r=-0.974,P0.001),与血清钙浓度呈正相关(r=0.730,P0.001),与血清磷浓度呈负相关(r=-0.652,P0.001)。结论 Cbfa1是肾性骨病导致的骨密度改变的预测因素,可能是Cbfa1对骨形态的影响而导致骨密度的改变。     

Three-dimensional microstructure of the bone in a hamster model of senile osteoporosis

Age-related bone loss, which is poorly characterized, is a major underlying cause of osteoporotic fractures in the elderly. In order to identify the morphological feature of age-related bone loss, we investigated sex and site (tibia, femur and vertebra) dependence of bone microstructure in aging hamsters from 3 to 24 months of age using micro-CT. In the proximal tibia and distal femur, trabecular bone volume (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and bone mineral density (BMD) increased to a maximum at 6 or 12 months and then declined progressively from 12 to 24 months of age. Trabecular separation (Tb.Sp), trabecular bone pattern factor (TBPf) and structure model index (SMI) increased with age. As compared with male hamsters, BV/TV and Tb.N were significantly lower in females at 18 and 24 months of age. Age-related decrease of trabecular BV/TV in the vertebral body was less than that of the femoral and tibial metaphyses. In the mid-femoral diaphysis, cortical bone area remained constant from 3 to 24 months of age. Cortical thickness decreased from 12 to 24 months and cortical BMD declined significantly from 18 to 24 months of age. These findings indicate that skeletal site and sex differences exist in hamster bone structure. Age-related bone changes in hamsters resemble those in humans. We conclude that hamster may be a useful model to study at least some aspects of bone loss during human aging.     

去卵巢后大鼠不同部位的骨组织计量学与骨密度研究

目的 观察大鼠去除卵巢后不同部位骨的骨组织计量学参数与骨密度以及两之间的相关性。方法 分别进行卵巢去除和伪手术，56d时处死大鼠，取离体胫骨，股骨测量骨密度与组织学参数%Tb.Ar,Tb.Th,Tb.N。结果 OVX后5d时，股骨远端和胫胫骨近端大部分骨组织计量学参数下降；全股骨和股骨远端1/3处骨密度降低；股骨部分骨组织计量学参数与骨密度测量值之间存在正相关性且差异有显性。结论 切除大鼠卵巢56d时，大鼠骨组织计量学参数下降显，骨密度测量以股骨较为敏感，骨组织计量学与骨密度测量值之间的相关性以股骨明显。     

Daily Treatment of Aged Ovariectomized Rats with Human Parathyroid Hormone (1-84) for 12 Months Reverses Bone Loss and Enhances Trabecular and Cortical Bone Strength

Most studies that have investigated the anabolic effects of parathyroid hormone (1-84) (PTH) or PTH fragments on the skeleton of ovariectomized (OVX) rats have evaluated the short-term effects of high-dose PTH(1-34) in young animals. This study used densitometry, histomorphometry, and biomechanical testing to evaluate the effects of 12-month daily treatment with low-dose PTH (15 or 30 μg/kg) in rats that were 10 months old at baseline, 4 months after OVX. Bone mineral density (BMD) and bone strength were reduced substantially in control OVX rats. The 15 μg/kg dose of PTH restored BMD to levels similar to those in sham animals within 6 months at the lumbar spine, distal and central femur, and whole body and maintained the BMD gain from 6 to 12 months. The 30 μg/kg dose produced greater effects. Both PTH doses normalized the trabecular bone volume-to-total volume ratio (BV/TV) at lumbar vertebra 3 but not at the proximal tibia (where baseline BV/TV was very low), solely by increasing trabecular thickness. PTH dose-dependently increased bone formation by increasing the mineralizing surface, but only the 30 μg/kg dose increased resorption. PTH increased cortical BMD, area, and thickness, primarily by increasing endocortical bone formation, and restored all measures of bone strength to levels similar to those in sham animals at all skeletal sites. PTH increased bone mass safely; there was no osteoid accumulation, mineralization defect, or marrow fibrosis and there were no abnormal cells. Thus, long-term PTH therapy normalized bone strength in the aged OVX rat, a model of postmenopausal osteoporosis, through increased bone turnover and enhanced formation of both trabecular and cortical bone.     

2111例上海健康女性骨密度值测定与年龄相关骨丢失的研究

目的　建立上海市健康女性骨密度 (BMD)参考值数据库 ,为骨质疏松症的诊断及防治效果评估提供依据。方法　选取健康女性 2 111例 ,为上海市区的居民 ,汉族 ,年龄 2 0～ 84岁 ,分为13组。研究对象均详细填写健康调查表格 ,排除因继发性骨病或服用影响骨代谢药物 ,以及一些特殊职业者。用双能X线吸收仪 (HologicQDR - 2 0 0 0型 )测定所有对象的腰椎 (L1 - 4)、股骨颈 (Neck)、大转子 (Troch)、粗隆间 (Inter)及Ward’s三角区部位的BMD值。结果　峰值骨量 (PBM)出现的年龄段如下 :腰椎为 30～ 34岁 ,股骨近端为 2 0～ 2 4岁。此后 ,随年龄增长而BMD值下降 ,但在 4 0～ 4 4岁时BMD值均有较明显回升 (但低于各部位峰值 ) ,呈“沟壑状”。绝经后妇女在绝经后头 10年及 2 6～30年时有两个骨量快速丢失期 ,前者见于腰椎和股骨上端 ,年丢失率为 1 4 %～ 3 2 % ,后者仅见于股骨上端 ,年丢失率为 1 1%～ 1 4 %。腰椎部位BMD值在 75～ 79岁组略有回升。各部位骨量累积丢失率随年龄增长而增加。到 80岁时 ,各部位的骨量累积丢失为 2 8%～ 5 8% (比PBM)。骨质疏松症检出率在腰椎和Ward’s两部位最高 ,在 6 0～ 6 4岁组分别达 4 8%和 4 3% (以WHO诊断标准 ,T score<2 5SD)。 75岁以后 ,Ward’s部位检出率达 83%。结论     

Age-related changes in bone mineral content and density in intact male F344 rats.

This study was undertaken to determine whether age-related bone loss occurs in intact male F344 rats. Bone loss was assessed in male F344 rats aged 3 to 27 months by scanning different bones using peripheral quantitative computed tomography (pQCT) densitometry. Cancellous and cortical bones were analyzed at the vertebra, proximal tibial metaphysis (PTM), and the neck of the femur. Cortical bone was also analyzed at the tibial and femoral diaphysis and at the tibio-fibula junction. In the vertebra, cancellous bone mineral content (Cn. BMC) did not change significantly with age. Cancellous bone mineral density (Cn. BMD) gradually decreased from 9 months onwards; and at 27 months of age, there was a 29% (p < 0.0001) decrease, when compared with 9-month-old animals. No significant change was observed in cortical bone mineral content (Ct. BMC) and cortical bone mineral density (Ct. BMD) with age. In the PTM, bone loss started to occur after 18 months of age. At 27 months of age, Cn. BMC decreased by 58% (p < 0.0001) and Cn. BMD also decreased by 58% (p < 0.0001). Ct. BMC decreased by 28% (p < 0.0001) in 27-month-old animals, whereas Ct. BMD was not affected by aging. At the tibio-fibula junction, Ct. BMC and Ct. BMD decreased after 18 months of age. At 27 months, Ct. BMC and Ct. BMD had decreased by 8% (p < 0.001) and 3% (p < 0.0001), respectively. Ct. BMC in the tibial diaphysis did not change significantly with age, whereas Ct. BMD decreased by 1% (p < 0.05) at 27 months. In the neck of the femur, Cn. BMC increased up to 24 months of age. Cn. BMD increased up to 18 months of age and decreased by 9% (p < 0.05) at 24 months and 11% (p < 0.001) at 27 months of age when compared with 18-month-old animals. Ct. BMC and Ct. BMD increased with age. In conclusion, although some components of the PTM decreased appreciably with age, in this study, most of the bone parameters analyzed either increased or did not change significantly with age. We conclude that unlike male Sprague Dawley rats, male F344 rats appear not to be a good model for studying age-related bone loss as occurs in aging men.     

Effects of endurance exercise on three-dimensional trabecular bone microarchitecture in young growing rats

Appropriate endurance exercise is capable of increasing bone mass and strength in both animals and humans. We examined the skeletal changes induced by treadmill running exercise in young growing rats with a particular emphasis on three-dimensional trabecular bone microarchitecture. Fourteen male Wistar rats were divided into sedentary (CON; n = 7) and exercised (RUN; n = 7) groups at the age of 4 weeks. The rats in the RUN group performed the treadmill running exercise of 30 m/min for 60 min, 5 times a week. After 10 weeks of exercise, bone mineral density (BMD), cortical geometry, diaphyseal breaking force, and trabecular bone microarchitecture in the femur were measured. Three-dimensional trabecular bone microarchitecture was evaluated at the distal femoral metaphysis using microcomputed tomography. The running exercise significantly increased BMD, bone volume, bone volume fraction, trabecular thickness, and trabecular number, whereas trabecular bone pattern factor, the parameter associated with decreased trabecular connectivity, was significantly lower in the RUN group than the CON group. On the other hand, no significant difference in the degree of anisotropy and structure model index was observed between the two groups. At the femoral diaphysis, running exercise significantly increased cortical bone area, width, and maximum load without affecting bending stress, implying that the material properties of bone had not changed in the exercised rats. These results suggest that the increase in bone strength induced by endurance exercise is mediated by changes in trabecular bone microarchitecture as well as density and cortical geometry.     

老年大鼠松质骨骨重建的组织形态计量学研究

目的：研究老年大鼠及在促骨合成药前列腺素E2（PGE2）作用下松质骨骨重建和骨建造的形态计量学改变，探讨动物骨重建形态学新参数测量方法及其意义。方法：50只20月龄雄性Wistar大鼠随机分成5组，年龄对照组（基础组、10d和30d年龄对照组），PGE2给药组（分别10d和30d给予3mg/kg/d处理组）。用体内双荧光标记，不脱钙组织切片，粘合线（cement line）染色，骨组织形态计量学方法，测定骨重建和骨建造参数。结果：20月龄雄性大鼠胫骨近端松质骨的形成表面大多数为骨重建单位（占63．3％），少部分为骨建造单位（占26．7％）；PGE2用药后骨重建单位增加1．5倍，骨建造单位增加4倍，比值倒置，成骨细胞10d时明显增多。说明PGE2通过刺激成骨细胞骨合成而介民导骨建造性骨增加和骨重建性骨量增加，并以前为主。结论：老年雄性大鼠 松质骨以骨重建活动为主，仍有骨建造活动。PGE2主要通过刺激成骨细胞骨建造而增加骨量。     

Male rodent model of age-related bone loss in men

Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the left proximal tibia using peripheral quantitative computed tomography (pQCT) densitometry. In the L-4 vertebra of the male SD rats, cortical bone mineral content (BMC), cortical bone mineral density (BMD), and cortical bone thickness (Ct.Th) increased to a maximum at about 4 months of age and then plateaued. Vertebral cortical BMC began to decrease after about 13 months and vertebral Ct.Th began to decrease after about 9 months. By 27 months of age, vertebral cortical BMC decreased by 26.1% (p < 0.0001) and vertebral Ct.Th decreased by 31% (p < 0.0001). Vertebral cancellous BMC and vertebral cancellous BMD increased to a maximum at about 3 months of age and then declined progressively with aging after a short plateau. From 3 to 27 months of age, vertebral cancellous BMC and vertebral cancellous BMD had decreased linearly by 35.4% (p < 0.0001) and 49.4% (p < 0.0001), respectively. Both vertebral periosteal and vertebral endocortical perimeters of the L-4 vertebra of the rats increased with aging. From 9 to 27 months of age, the percent increase of vertebral endocortical perimeter (19.8%, p < 0.0001) was higher than that of vertebral periosteal perimeter (7.4%, p < 0.0001). This process was associated with a decrease with aging in vertebral Ct.Th. In addition, cancellous bone in the femoral neck and the proximal tibia began to be lost at 9 months of age and, by 27 months of age, cancellous BMC and cancellous BMD decreased by 59.7% (p < 0.0001) and 58.4% (p < 0.0001), respectively, in the femoral neck and by 72.2% (p < 0.0001) and 71.4% (p < 0.0001), respectively, in the proximal tibia. To gain further insight into the effects of aging on cancellous bone in the L-4 vertebra, histomorphometry was done on the L-4 vertebral body of animals aged 3, 6, 9, 18, and 24 months after pQCT densitometry. From 3 months of age and thereafter, cancellous bone volume (BV/TV) decreased progressively and, by 24 months, there was a decrease of 35.7% (p < 0.0001). In the L-4 vertebra, single- and double-labeled surfaces, mineral apposition rate (MAR), and bone formation rate (BFR/BS) decreased with aging. In conclusion, age-related bone loss in male SD rats started mostly from 9 months of age when bone growth had been completed. Aging male SD rats experience bone loss comparable to that seen in men. Thus, male SD rats represent an appropriate animal model of age-related bone loss in men. We recommend using male SD rats that are 9 months old as the starting age for age-related bone loss. We also suggest using the L-4 vertebra and femoral neck as the clinically relevant bone sites for determining the cause of the loss of bone, and how and whether therapeutic agents could modulate age-related bone loss in men.     

The Effect of the Cathepsin K Inhibitor ONO‐5334 on Trabecular and Cortical Bone in Postmenopausal Osteoporosis: The OCEAN Study

ONO‐5334 (Ono Pharmaceutical Co., Ltd., Osaka, Japan) inhibits cathepsin K and has been shown to increase areal bone mineral density (BMD) at the hip and spine in postmenopausal osteoporosis. Quantitative computed tomography (QCT) allows the study of the cortical and trabecular bone separately and provides structural information such as cortical thickness. We investigated the impact of 2 years of cathepsin K inhibition on these different bone compartments with ONO‐5334. The clinical study was a randomized, double‐blind, placebo, and active controlled parallel group study conducted in 13 centers in six European countries. The original study period of 12 months was extended by another 12 months. A total of 147 subjects (age 55–75 years) of the QCT substudy who participated in the extension period were included. Subjects had been randomized into one of five treatment arms: placebo; ONO‐5334 50 mg twice per day (BID); ONO‐5334 100 mg once daily (QD); ONO‐5334 300 mg QD; or alendronate 70 mg once weekly (QW). QCT was obtained to evaluate bone structure at the lumbar spine and proximal femur. After 24 months ONO‐5334 showed statistically significant increases versus placebo for integral, trabecular, and cortical BMD at the spine and the hip (for ONO‐5334 300 mg QD, BMD increases were 10.5%, 7.1%, and 13.4% for integral, cortical, and trabecular BMD at the spine, respectively, and 6.2%, 3.4%, and 14.6% for integral, cortical, and trabecular total femur BMD, respectively). Changes in cortical and trabecular BMD in the spine and hip were similar for alendronate as for ONO‐5334. Integral volume did not demonstrate statistically significant changes under ONO‐5334 treatment, thus there was no evidence of periosteal apposition, neither at the spine nor at the femur. Cortical thickness changes were not statistically significant for ONO‐5334 in the spine and hip, with exception of a 2.1% increase after month 24 in the intertrochanter for ONO‐5334 300 mg QD. Over 2 years ONO‐5334 showed a statistically significant and persistent increase of trabecular and integral BMD at the spine and the hip. Cortical BMD also progressively increased but at a lower rate. Changes in bone size and of periosteal apposition were not observed. © 2014 American Society for Bone and Mineral Research.     

Effects of Treatment of Ovariectomized Adult Rhesus Monkeys with Parathyroid Hormone 1-84 for 16 Months on Trabecular and Cortical Bone Structure and Biomechanical Properties of the Proximal Femur

Treatment of monkeys and humans with parathyroid hormone (PTH) 1-84 stimulates skeletal remodeling, which increases trabecular (Tb) bone mineral density (BMD) but decreases cortical (Ct) BMD at locations where these bone types predominate. We report the effects of daily PTH treatment (5, 10, or 25 μg/kg) of ovariectomized (OVX) rhesus monkeys for 16 months on bone structure and biomechanical properties at the proximal femur, a mixed trabecular and cortical bone site. PTH reversed the OVX-induced decrease in BMD measured by dual-energy X-ray absorptiometry at the proximal femur, femoral neck, and distal femur. Peripheral quantitative computed tomography confirmed a significant decrease in Ct.BMD and an increase in Tb.BMD at the total proximal femur and at the proximal and distal femoral metaphyses. The decrease in Ct.BMD resulted primarily from increased area because cortical bone mineral content was unaffected by PTH. Histomorphometry revealed that PTH significantly increased the trabecular bone formation rate (BFR) as well as trabecular bone volume and number. PTH did not affect periosteal or haversian BFR at the femoral neck, but cortical porosity was increased slightly. PTH had no effects on stiffness or peak load measured using a shear test, whereas work-to-failure, the energy required to fracture, was increased significantly. Thus, PTH treatment induced changes in trabecular and cortical bone at the proximal femur that were similar to those occurring at sites where these bone types predominate. Together, the changes had no effect on stiffness or peak load but increased the energy required to break the proximal femur, thereby making it more resistant to fracture.