Biomechanical properties across trabeculae from the proximal femur of normal and ovariectomised sheep

The elastic behaviour of trabecular bone is a function not only of bone volume and architecture, but also of tissue material properties. Variation in tissue modulus can have a substantial effect on the biomechanical properties of trabecular bone. However, the nature of tissue property variation within a single trabecula is poorly understood. This study uses nanoindentation to determine the mechanical properties of bone tissue in individual trabeculae. Using an ovariectomised ovine model, the modulus and hardness distribution across trabeculae were measured. In both normal and ovariectomised bone, the modulus and hardness were found to increase towards the core of the trabeculae. Across the width of the trabeculae, the modulus was significantly less in the ovariectomised bone than in the control bone. However, in contrast to this hardness was found not to differ significantly between the two groups. This study provides valuable information on the variation of mechanical material properties in healthy and diseased trabecular bone tissue. The results of the current study will be useful in finite element modelling where more accurate values of trabecular bone modulus will enable the prediction of the macroscale behaviour of trabecular bone.     

仙灵骨葆对骨质疏松大鼠OPG/RANK/RANKL 表达的影响

目的:观察仙灵骨葆治疗骨质疏松模型大鼠后,对大鼠体内OPG/RANKL/RANK表达的影响。方法:卵巢摘除法建立SD大鼠骨质疏松模型,设立假手术组、对照组(单纯去卵巢组)、雌激素组(给予17β-雌二醇)和治疗组(给予仙灵骨葆)。术后1周开始给药,给药12周后检测各组大鼠股骨骨密度,ELISA法检测血清中OPG/RANKL含量,RT-PCR检测骨组织中OPG/RANK/RAN-KL mRNA表达,免疫组化检测骨组织中RANK的表达。结果:对照组大鼠骨密度显著低于假手术组;治疗组和雌激素组大鼠O-PG表达显著高于对照组,RANK及RANKL的表达显著低于对照组。结论:采用卵巢摘除法成功建立大鼠骨质疏松模型;仙灵骨葆可促进骨质疏松大鼠OPG的表达,并抑制RANK及RANKL的表达,对骨质疏松模型大鼠有治疗作用。     

Binding of radiolabelled luteinizing hormone to intact and ovariectomised rat uterus.

Binding of ovine LH to uterine tissue preparation from intact and ovariectomised rat clearly indicates that uterus possesses specific binding sites for LH. Binding characteristics of LH to uterine tissue preparation from intact rat showed saturability with high affinity and low capacity. Scatchard plot analysis showed dissociation constant of the specific binding site to be 0.12 x 10(-9) mol/l and the number of binding sites was 2.31 +/- 0.05 f mol/mg protein. Ovariectomy did not change the binding affinity but effected a decrease in the number of binding sites (1.7 +/- 0.08 f mol/mg protein). LH treatment of ovariectomized (ovx) rat had no effect on binding affinity but significantly increased the number of binding sites (3.23 +/- 0.1 f mol/mg protein). Reduction of uterine weight due to ovariectomy and marked increase of ovx rat uterine weight by LH administration indicate a source of estrogen in ovx rat. An in vitro uterine tissue slice (from intact and ovx rat) incubation showed depletion of 17 beta-estradiol (E2) content in ovx rat which significantly elevated on LH addition. Data suggest that LH binding to rat uterine tissue has biological relevance.     

Zoledronic Acid,Bevacizumab and Dexamethasone-Induced Apoptosis,Mitochondrial Oxidative Stress,and Calcium Signaling Are Decreased in Human Osteoblast-Like Cell Line by Selenium Treatment

Increased intracellular free calcium ion (Ca²⁺) concentration induces excessive oxidative stress and apoptosis. Medical procedures such as zoledronic acid (Zol), bevacizumab (Bev), and dexamethasone (Dex) are usually used in the treatment of bone diseases (osteoporosis, Paget’s disease, etc.) and to prevent metastasis in the bone although the procedures induce osteonecrosis of the jaw through excessive production of reactive oxygen species (ROS). Recently, we observed regulator roles of selenium (Se) on apoptosis and Ca²⁺ entry through transient receptor potential vanilloid 1 (TRPV1) channels in the cancer cell lines. Therefore, Se may modulate Zol, Bev, and Dex-induced oxidative stress and apoptosis through regulation of TRPV1 channel. In the current study, we investigated the protective effects of Se on apoptosis and oxidative stress through TRPV1 in Zol, Bev, and Dex-induced osteoblast-like cell line. We used human osteoblast-like cell line (Saos-2), and the cells were divided into 12 groups as control, Zol, Bev, Dex, Se, Zol+Se, Bev+Se, Dex+Se, Zol+Dex, Zol+Dex+Se, Zol+Bev, and Zol+Bev+Se which were incubated with drugs (Zol, Bev, Dex, and Se) for 24 h. The cytosolic free Ca²⁺ concentration was increased by Zol, Bev, Dex, Zol+Bev, and Zol+Dex, although it was reduced by Se treatment. However, Zol, Bev, and Dex-induced increase in apoptosis, caspase 3, caspase 9, poly (ADP-ribose) polymerase 1 expression levels, and intracellular ROS production values in the cells were decreased by Se treatments. In conclusion, we observed that Zol, Bev, and Dex-induced apoptosis, mitochondrial oxidative stress, and calcium signaling are decreased in human osteoblast-like cell line by the Se treatment. Our findings may be relevant to the etiology and treatment of Zol, Bev, and Dex-induced osteonecrosis by Se.     

Effects of ovariectomy on duodenal calcium transport in the rat: altered ability to adapt to low-calcium diet

Studies were undertaken to determine whether ovariectomy (ovx) would alter the ability of female rats to adapt to low dietary Ca intake by exhibiting an in duodenal active Ca transport. Intact and ovx female rats were fed diets containing 1.5, 0.50, or 0.02% Ca prior to measuring active Ca transport using everted duodenal sacs in vitro. In some experiments, ovx animals were pair-fed to intact animals of the same age consuming the same diet. When ovx animals were allowed to eat ad lib, we found that both growth rate and duodenal active Ca transport increased relative to age-matched, intact controls. However, when growth of ovx animals was maintained at the control rate by pair-feeding, ovx per se did not affect intestinal active Ca transport. Ovx did not alter circulating levels of 1,25-dihydroxyvitamin D (1,25(OH)2D). We found that intact females responded to the low-Ca (0.02%) diet with increased circulating 1,25(OH)2D levels and increased intestinal active Ca transport. Ovx animals exhibited the same increase in circulating concentrations of 1,25(OH)2D in response to low-Ca diet, but did not demonstrate increased duodenal active Ca transport. When ovx animals consumed the diet ad lib, they became larger and exhibited higher Ca transport rates than intact animals fed the high-Ca diet, but there was no difference in Ca transport between ovx animals fed diets containing different Ca contents. The results of these experiments demonstrate that in female rats, the ability to adapt to altered dietary Ca intake is dependent on intact ovarian function and is not necessarily directly related to circulating concentrations of 1,25(OH)2D.     

Protective effect of polysaccharides from morinda officinalis on bone loss in ovariectomized rats

In order to examine the effect of polysaccharides from morinda officinalis (MOP) on bone quality of osteoporosis rats. The osteoporosis in rats was induced by ovariectomy, and MOP (100 or 300mg/kg) was orally administrated once daily. The animals were assessed 30 days after the operation for bone mineral density, serum cytokines level and mineral element concentration. MOP administration in rats resulted in an increase in bone mineral density and mineral element concentration, a decrease in serum cytokines level, which indicated that MOP administration may play an important role in the development of osteoporosis.     

Anti-tumour and anti-angiogenetic effects of zoledronic acid on human non-small-cell lung cancer cell line

Objectives: Although emerging data suggest that zoledronic acid (Zol) may have different anti‐tumour activities against a broad range of cancers, its effects on lung cancer remain largely unknown. The aim of this study was to evaluate in vitro the anti‐tumoural and anti‐angiogenetic effect of zoledronic acid in non‐small‐cell lung cancer (NSCLC) cells. Material and methods: We treated A549 NSCLC cells with zoledronic acid to investigate survival, cell cycle activity, anti‐angiogenic activity and apoptotic responses to it. Results: We observed that highest Zol concentration (100 μm ) caused arrest in G1 phase of the cell cycle and also induced different percentages of apoptosis in presence (0.9% versus 4.4%) or absence (2.4% versus 28.5%) of serum (P = 0.0001). Zol concentration from 5 to 100 μm for 2 days induced significant concentration‐dependent cell death in adherent cells. Furthermore, Zol (10–100 μm ) induced dose‐dependent reduction both of mRNA and protein expression of VEGF associated with parallel decrease in VEGF secretion in the culture medium. Conclusion: Taken together, these results support a possible anti‐cancer and anti‐angiogenetic activity of Zol. Our data may not only provide a basis for the clinical use of this drug as preventive agent of bone metastases but also suggest that Zol deserves attention as an anti‐cancer agent in non‐small‐cell lung cancer.     

唑来膦酸治疗原发性骨质疏松症的效果观察

目的：研究唑来膦酸在治疗原发性骨质疏松症过程中患者骨密度及疼痛的变化。方法：设计为期两年的随机、前瞻性研究,通过Achilles定量超声（QUS）系统测量骨密度（BMD）,进行问卷调查、疼痛评估,共入选60例原发性骨质疏松症患者。随机分为唑来膦酸组和对照组,唑来膦酸组使用唑来膦酸及元素钙治疗;对照组使用元素钙治疗。治疗前后分别进行骨密度测定及疼痛评估,进行对比研究。结果：治疗两年后.与治疗前比较,唑来膦酸组BMD上升（P〈0.05）;对照组BMD无明显变化（P〉0.05）。两组临床获益率分别为73.33%和46.67%,无显著差别（P〉0.05）。结论：唑来膦酸治疗原发性骨质疏松症有良好作用,能提高骨密度,对骨质疏松的治疗及预防骨折具有重要的意义。     

In vivo anti-osteoporotic activity of isotaxiresinol, a lignan from wood of Taxus yunnanensis

Isotaxiresinol, the main lignan isolated from the water extract of wood of Taxus yunnanensis, was investigated for its effect on bone loss, on serum biochemical markers for bone remodeling and on uterine tissue, using ovariectomized (OVX) rats as the model of postmenopausal osteoporosis. After oral administration of isotaxiresinol (50 and 100mg/kg/d) for 6 weeks, bone mineral content (BMC) and bone mineral density (BMD) in total and cortical bones were increased as compared to those of OVX control rats, and decreases of three bone strength indexes induced by OVX surgery were prevented. Serum biochemical markers for bone remodeling revealed that isotaxiresinol slightly increased bone formation and significantly inhibited bone resorption without side effect on uterine tissue. These results suggest that isotaxiresinol may be useful for treatment of postmenopausal osteoporosis, especially for prevention of bone fracture induced by estrogen deficiency.     

Estrogen modulates the mechanical homeostasis of mouse arterial vessels through nitric oxide

We have recently shown that estrogen causes vessel dilation through receptor-mediated stimulation of nitric oxide (NO) production. Here, we hypothesize that estrogen modulates the mechanical homeostasis in the blood vessel wall through NO production. The mechanical properties of female ovariectomized (ovx) mice, female mice lacking the gene for endothelial NO synthase (eNOS(-/-)), and control female and male mice were studied to test the hypothesis. The femoral and carotid arteries and aorta were cannulated in situ and mechanically distended. The stress, strain, elastic modulus, and wall thickness of vessels in ovx and eNOS(-/-) mice, as well as intact female and male mice, were determined. Western blot and immunohistochemistry were used to assess eNOS protein expression in the aorta. Moreover, NO by-products of the femoral and carotid artery were determined by measuring the levels of nitrite and nitrate. Our results show that ovariectomy and eNOS(-/-) significantly decrease the strain in all arteries. Furthermore, the eNOS protein was significantly reduced in ovx mice. Finally, the NO metabolites were significantly decreased both in ovx and eNOS(-/-) mice. We found statistically significant correlations between the structural (wall thickness), mechanical (stress, strain, and elastic modulus), and biochemical parameters (NO by-products). These novel results connect NO to the structural and mechanical properties of the vessel wall. Hence, the effect of endogenous estrogen on the arterial mechanical properties is mediated by the regulation of NO derived from eNOS.     

Use of biochemical markers to monitor changes in bone turnover in cynomolgus monkeys.

The ovariectomized old cynomolgus monkey is a recognized model of human osteoporosis, and the same species can be used for the assessment of the efficacy and potential toxicity of agents intended to prevent or treat osteoporosis. Several assays have been developed that can measure the same biochemical markers of bone turnover as are used in human patients for the diagnosis and treatment follow-up of bone-related diseases, including osteoporosis. The aim of the present study was to describe the results obtained with these assays in normal control monkeys, their variations with age and sex, and their sensitivity in monitoring the bone turnover induced by ovariectomy in old skeletally mature cynomolgus monkeys. Seven old cynomolgus monkeys were bilaterally ovariectomized and 13 age-matched monkeys were sham-operated. Bone mineral density and biochemical markers were measured before and at regular intervals after surgery for up to 20 months. Total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase isoenzyme (bone ALP) and osteocalcin (OC) were highly correlated to the decrease in bone mineral density (BMD) induced by ovariectomy. Deoxypyridinoline (DPD) measured by enzyme-linked immunoassay was insensitive to the bone resorption induced by ovariectomy, but cross-linked N-telopeptide (NTX-I) was higher in ovariectomized monkeys than in control monkeys. These results demonstrate that reliable biochemical parameters are available to adequately monitor and provide insight into osteoclastic bone resorption and osteoblastic bone formation, the two components of bone turnover in this animal model, and can thus be used to assess the efficacy and toxicity of potential therapeutic agents.     

Use of biochemical markers to monitor changes in bone turnover in cynomolgus monkeys

The ovariectomized old cynomolgus monkey is a recognized model of human osteoporosis, and the same species can be used for the assessment of the efficacy and potential toxicity of agents intended to prevent or treat osteoporosis. Several assays have been developed that can measure the same biochemical markers of bone turnover as are used in human patients for the diagnosis and treatment follow-up of bone-related diseases, including osteoporosis. The aim of the present study was to describe the results obtained with these assays in normal control monkeys, their variations with age and sex, and their sensitivity in monitoring the bone turnover induced by ovariectomy in old skeletally mature cynomolgus monkeys. Seven old cynomolgus monkeys were bilaterally ovariectomized and 13 age-matched monkeys were sham-operated. Bone mineral density and biochemical markers were measured before and at regular intervals after surgery for up to 20 months. Total alkaline phosphatase (total ALP), bone-specific alkaline phosphatase isoenzyme (bone ALP) and osteocalcin (OC) were highly correlated to the decrease in bone mineral density (BMD) induced by ovariectomy. Deoxypyridinoline (DPD) measured by enzyme-linked immunoassay was insensitive to the bone resorption induced by ovariectomy, but cross-linked N-telopeptide (NTX-I) was higher in ovariectomized monkeys than in control monkeys. These results demonstrate that reliable biochemical parameters are available to adequately monitor and provide insight into osteoclastic bone resorption and osteoblastic bone formation, the two components of bone turnover in this animal model, and can thus be used to assess the efficacy and toxicity of potential therapeutic agents.     

Trabecular bone's mechanical properties are affected by its non-uniform mineral distribution

The bone remodeling process takes place at the surface of trabeculae and results in a non-uniform mineral distribution. This will affect the mechanical properties of cancellous bone, because the properties of bone tissue depend on its mineral content. We investigated how large this effect is by simulating several non-uniform mineral distributions in 3D finite element models of human trabecular bone and calculating the apparent stiffness of these models. In the ‘linear model’ we assumed a linear relation between mineral content and Young's modulus of the tissue. In the ‘exponential model’ we included an empirical exponential relation in the model. When the linear model was used the mineral distribution slightly changed the apparent stiffness, the difference varied between an 8% decrease and a 4% increase compared to the uniform model with the same BMD. The exponential model resulted in up to 20% increased apparent stiffness in the main load-bearing direction. A thin less mineralized surface layer (28 μm) and highly mineralized interstitial bone (mimicking mineralization resulting from anti-resorptive treatment) resulted in the highest stiffness. This could explain large reductions in fracture risk resulting from small increases in BMD. The non-uniform mineral distribution could also explain why bone tissue stiffness determined using nano-indentation is usually higher than finite element (FE)-determined stiffness. We conclude that the non-uniform mineral distribution in trabeculae does affect the mechanical properties of cancellous bone and that the tissue stiffness determined using FE-modeling could be improved by including detailed information about mineral distribution in trabeculae in the models.     

Effect of hormone replacement therapy on the elemental contents of uterine tissue

For the past years, different therapies based on steroid hormone supplementation or modulators of estrogen receptors have been used after menopause to prevent or manage osteoporosis. Although these treatments seem to be beneficial, they have some negative effects in the uterus and breast. The objective of this study was to assess variations for the concentrations of K, Ca, Mn, Fe, Cu, Zn, and Se in uterine tissue of Wistar rats. Ovriectomized rats were subjected to estrogen, progesterone, raloxifene, and tibolone supplementation and compared with nonovariectomized control animals. Elemental contents determined by the particle-induced X-ray emission (PIXE) technique revealed major alterations in Fe, Ca, Mn, and Se in the uterus of ovariectomized rats relative to control animals. After ovariectomy, a significant increase in Ca and Fe and a significant decrease in Mn and Se contents were determined in the uterus. For the ovariectomized groups in which animals, received raloxifene, tibolone, estrogen, and estrogen combined with progesterone supplementation, an overall recovery in Mn, Fe, and Se contents was verified. Elemental concentration in the progesterone-supplemented group did not significantly differ from ovariectomized animals receiving placebo. The alterations found for ovariectomized animals receiving placebo and progesterone suggest tissue impairment and trace element imbalance, contrasting with the remaining supplemented groups where an enhancement of tissue activity might justify similar concentration levels relative to controls, because most of the elemental contents altered after ovariectomy.     

Gender dependent effects of testosterone and 17β-estradiol on bone growth and modelling in young mice

This study examined the effects of estrogen (17β-estradiol) and testosterone on the growth of long bones in male and female mice, with and without gonadectomy. Weight and nose-to-tail length were determined at 3 weeks of age at time of gonadectomy, 7 days later at the onset of hormone therapy, and throughout the treatment period. Gonadectomized mice exhibited an initial weight gain during the pretreatment period but length was unaffected. Hormone treatment altered weight gain in surgical and intact animals in a gender- and hormone-dependent manner. Estradiol enhanced weight gain in intact mice, but inhibited weight gain in ovariectomized mice. Lower doses of estradiol increased weight gain in orchiectomized mice at early time points. Testosterone increased weight in intact females and males, but not in gonadectomized mice. Estradiol increased nose-to-tail length in intact females at early time points, but inhibited length in ovariectomized females at later times, and it decreased length in intact males. Testosterone increased length in normal females and normal males. Serum Ca was unaffected by ovariectomy, but orchiectomy resulted in decreased levels. Estradiol reduced serum Ca in gonadectomized animals; serum Ca was increased by estradiol treatment in intact females. Changes in tibial bone weight, ash weight and mineral composition, and relative sizes of epiphyseal and metaphyseal bone were gender-, gonadectomy- and hormone-specific. Bone weight was greater in ovariectomized mice. Ash weight per bone was comparable, but there was an increase in Ca and P content with ovariectomy. Estradiol increased bone weight, ash content, and bone Ca and P in ovariectomized and intact females. Orchiectomy alone did not alter bone weight, ash content, or Ca and P, but orchiectomized mice were sensitive to estradiol; all parameters were increased in the orchiectomized animals treated with estradiol. Analysis of the ash content and Ca and P per mg bone, rather than per bone, demonstrated estradiol and testosterone alter net bone formation, but not the amount of mineral per unit bone. Ovariectomy increased hypertrophic cartilage. While estradiol did not alter tibial area in ovariectomized mice, it caused an increase in intact females. The total amount of growth plate cartilage in ovariectomized animals was decreased by estradiol to levels typical of intact animals due to a greater decrease in the hypertrophic cartilage in the ovariectomized mice, as well as a greater increase in metaphyseal bone area. Testosterone had no effect on these parameters in the females. Orchiectomy decreased the amount of growth plate cartilage, but increased the hypertrophic zone. Estradiol increased growth plate cartilage in intact male mice, but decreased it in orchiectomized mice. This difference was also seen in the hypertrophic zone. Total growth plate cartilage and hypertrophic cartilage were increased by testosterone in intact males, whereas metaphyseal and epiphyseal bone area were decreased. The results show for the first time that there is a gender-specific response in both male and female mice to both estradiol and testosterone, whether or not the animals have been gonadectomized. For many parameters, orchiectomized mice behave like females in response to both sex steroids, indicating that the male gonad is needed for mouse bone to exhibit the male phenotypic response to estradiol and testosterone.     

Shear strength and toughness of trabecular bone are more sensitive to density than damage

Microdamage occurs in trabecular bone under normal loading, which impairs the mechanical properties. Architectural degradation associated with osteoporosis increases damage susceptibility, resulting in a cumulative negative effect on the mechanical properties. Treatments for osteoporosis could be targeted toward increased bone mineral density, improved architecture, or repair and prevention of microdamage. Delineating the relative roles of damage and architectural degradation on trabecular bone strength will provide insight into the most beneficial targets. In this study, damage was induced in bovine trabecular bone samples by axial compression, and the effects on the mechanical properties in shear were assessed. The damaged shear modulus, shear yield stress, ultimate shear stress, and energy to failure all depended on induced damage and decreased as the architecture became more rod-like. The changes in ultimate shear strength and toughness were proportional to the decrease in shear modulus, consistent with an effective decrease in the cross-section of trabeculae based on cellular solid analysis. For typical ranges of bone volume fraction in human bone, the strength and toughness were much more sensitive to decreased volume fraction than to induced mechanical damage. While ultimately repairing or avoiding damage to the bone structure and increasing bone density both improve mechanical properties, increasing bone density is the more important contributor to bone strength.     

Microstructural,Densitometric and Metabolic Variations in Bones from Rats with Normal or Altered Skeletal States

Background

High resolution μCT, and combined μPET/CT have emerged as non-invasive techniques to enhance or even replace dual energy X-ray absorptiometry (DXA) as the current preferred approach for fragility fracture risk assessment. The aim of this study was to assess the ability of µPET/CT imaging to differentiate changes in rat bone tissue density and microstructure induced by metabolic bone diseases more accurately than current available methods.

Methods

Thirty three rats were divided into three groups of control, ovariectomy and vitamin-D deficiency. At the conclusion of the study, animals were subjected to glucose (¹⁸FDG) and sodium fluoride (Na¹⁸F) PET/CT scanning. Then, specimens were subjected to µCT imaging and tensile mechanical testing.

Results

Compared to control, those allocated to ovariectomy and vitamin D deficiency groups showed 4% and 22% (significant) increase in ¹⁸FDG uptake values, respectively. DXA-based bone mineral density was higher in the vitamin D deficiency group when compared to the other groups (cortical bone), yet μCT-based apparent and mineral density results were not different between groups. DXA-based bone mineral density was lower in the ovariectomy group when compared to the other groups (cancellous bone); yet μCT-based mineral density results were not different between groups, and the μCT-based apparent density results were lower in the ovariectomy group compared to the other groups.

Conclusion

PET and micro-CT provide an accurate three-dimensional measurement of the changes in bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity. As osteomalacia is characterized by impaired bone mineralization, the use of densitometric analyses may lead to misinterpretation of the condition as osteoporosis. In contrast, µCT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity.     

Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation

Generalized osteoporosis in postmenopausal rheumatoid arthritis (RA) is caused both by estrogen deficiency and by the inflammatory disease. The relative importance of each of these factors is unknown. The aim of this study was to establish a murine model of osteoporosis in postmenopausal RA, and to evaluate the relative importance and mechanisms of menopause and arthritis-related osteoporosis. To mimic postmenopausal RA, DBA/1 mice were ovariectomized, followed by the induction of type II collagen-induced arthritis. After the mice had been killed, paws were collected for histology, one femur for bone mineral density (BMD) and sera for analyses of markers of bone resorption (RatLaps; type I collagen cross-links, bone formation (osteocalcin) and cartilage destruction (cartilage oligomeric matrix protein), and for the evaluation of antigen-specific and innate immune responsiveness. Ovariectomized mice displayed more severe arthritis than sham-operated controls. At termination of the experiment, arthritic control mice and non-arthritic ovariectomized mice displayed trabecular bone losses of 26% and 22%, respectively. Ovariectomized mice with arthritis had as much as 58% decrease in trabecular BMD. Interestingly, cortical BMD was decreased by arthritis but was not affected by hormonal status. In addition, markers of bone resorption and cartilage destruction were increased in arthritic mice, whereas markers of bone formation were increased in ovariectomized mice. This study demonstrates that the loss of endogenous estrogen and inflammation contribute additively and equally to osteoporosis in experimental postmenopausal polyarthritis. Markers of bone remodeling and bone marrow lymphocyte phenotypes indicate different mechanisms for the development of osteoporosis caused by ovariectomy and arthritis in this model.     

唑来膦酸注射液联合骨肽注射液治疗绝经后骨质疏松症的临床疗效及安全性分析

目的:研究唑来膦酸注射液联合骨肽注射液治疗绝经后骨质疏松症的临床效果以及安全性。方法:选择2014年1月～2018年1月我院收治的100例绝经后骨质疏松症患者,将其随机分为两组。对照组采用静脉滴注唑来膦酸注射液5 mg一次,观察组在对照组基础上静脉注射骨肽注射液,每次30 mg,每天1次。治疗6个月后,检测并比较两组治疗前后的骨代谢指标(血清骨特异性碱性磷酸酶(BAP)、甲状旁腺素(PTH)、血磷(P)、血钙(Ca)和碱性磷酸酶(ALP))以及骨转换指标(骨钙素(OC)和Ⅰ型胶原交联C-末端肽(CTX-1))的变化及不良反应的发生情况。结果:治疗后,观察组总有效率明显高于对照组(P0.05);两组血清ALP、PTH以及BAP等骨代谢指标均较治疗前明显降低(P0.05),且观察组以上指标明显低于对照组(P0.05);两组的OC均较治疗前明显升高(P0.05),CTX-1均较治疗前明显降低(P0.05),且观察组的骨转换指标改善的程度较对照组更为明显(P0.05)。观察组的不良反应发生率为8.00%(4/50),明显低于对照组[18.00%(9/50)](P0.05)。结论:唑来膦酸注射液联合骨肽注射液治疗绝经后骨质疏松症的效果明显优于单独使用唑来膦酸注射液,其可以显著改善患者的骨代谢及骨转换状态,且安全性更高。