Recent developments in in vivo neutron activation analysis facilities

Two new facilities for in vivo activation analysis of patients have been designed, developed, and constructed at Toronto General Hospital. One of these is for the determination of body calcium for the diagnosis of osteoporosis and other diseases associated with bone loss. The other is for the measurement of total body nitrogen for the determination of protein status. These facilities replace old university facilities and take into account the comfort and management of patients. In addition, in the case of the calcium facility, the precision of the measurements has been improved because of larger detector volume and increased neutron source strength. Both the facilities are now in routine hospital clinical use.     

Managing Bone Health in Breast Cancer

ObjectiveOsteoporosis is a common condition that can be caused or exacerbated by estrogen deficiency.MethodsThis narrative review will discuss optimizing bone health in the setting of adjuvant endocrine treatments for hormone receptor–positive breast cancer and the current use of antiresorptive agents as adjuvant therapy and as bone modifying agents.ResultsAdjuvant endocrine treatments for hormone receptor–positive breast cancer (tamoxifen and aromatase inhibitors) affect bone health. The exact effect depends on the agent used and the menopausal state of the woman. Antiresorptive medications for osteoporosis, bisphosphonates and denosumab, lower the risk of bone loss from aromatase inhibitors. Use of bisphosphonates as adjuvant treatment in breast cancer, regardless of hormone receptor status, is increasing because of benefits seen to cancer relapse and survival.ConclusionOptimizing bone health in women with breast cancer during and after cancer treatment is informed by an understanding of breast cancer treatment and its skeletal effect.     

水菠菜叶乙醇提取物对MG-63骨质疏松相关基因表达的影响

为探讨水菠菜叶乙醇提取物与抗骨质疏松作用的关系及其作用机制,用水菠菜叶乙醇提取物处理人成骨样细胞MG-63 48 h后,提取水菠菜叶乙醇提取处理组和对照组细胞的总RNA,将两组RNA纯化为mRNA,逆转录成cDNA,用Cy3和Cy5两种不同的荧光染料进行线性扩增标记,然后与骨质疏松相关基因表达谱芯片杂交,扫描后对获得的数据用LuxScan 3.0软件分析.研究发现经水菠菜叶乙醇提取物诱导后MG-63细胞的244个骨质疏松相关基因中,有c-Fos、JNK、ODF、c-src、OSCAR、RANKL、Samd4、Samd6、Samd7 9个基因表达明显上调,LRP5、Dkk1、TGFB、OPG 4个基因明显下调.结果表明水菠菜叶乙醇提取物能改变骨质疏松相关基因的表达,抗骨质疏松作用机制可能与Wnt/β-catenin蛋白信号传导途径和骨保护素/核因子受体激活信号传导途径有关,与雌激素内分泌途径无关.     

Gentiopicroside promotes the osteogenesis of bone mesenchymal stem cells by modulation of β-catenin-BMP2 signalling pathway

Osteoporosis is characterized by increased bone fragility, and the drugs used at present to treat osteoporosis can cause adverse reactions. Gentiopicroside (GEN), a class of natural compounds with numerous biological activities such as anti-resorptive properties and protective effects against bone loss. Therefore, the aim of this work was to explore the effect of GEN on bone mesenchymal stem cells (BMSCs) osteogenesis for a potential osteoporosis therapy. In vitro, BMSCs were exposed to GEN at different doses for 2 weeks, whereas in vivo, ovariectomized osteoporosis was established in mice and the therapeutic effect of GEN was evaluated for 3 months. Our results in vitro showed that GEN promoted the activity of alkaline phosphatase, increased the calcified nodules in BMSCs and up-regulated the osteogenic factors (Runx2, OSX, OCN, OPN and BMP2). In vivo, GEN promoted the expression of Runx2, OCN and BMP2, increased the level of osteogenic parameters, and accelerated the osteogenesis of BMSCs by activating the BMP pathway and Wnt/β-catenin pathway, effect that was inhibited using the BMP inhibitor Noggin and Wnt/β-catenin inhibitor DKK1. Silencing the β-catenin gene and BMP2 gene blocked the osteogenic differentiation induced by GEN in BMSCs. This block was also observed when only β-catenin was silenced, although the knockout of BMP2 did not affect β-catenin expression induced by GEN. Therefore, GEN promotes BMSC osteogenesis by regulating β-catenin-BMP signalling, providing a novel strategy in the treatment of osteoporosis.     

Finite element analysis of Stryker Xia pedicle screw in artificial bone samples with and without supplemental cement augmentation

A validated, using in vitro biomechanical testing, finite element model was used to evaluate the affects of (1) cement augmentation and (2) an intact posterior cortex in osteoporotic bone. The presence of augmentation and/or a posterior cortical cortex increased the stabilization of the pedicle screw 2–5 fold. Placement of cement influenced failure load and toggle; with distal placement having the largest increase in failure load and decrease in cephalad–caudad toggle. The presence of posterior cortex caused a decrease in the amount of toggle, a proximal shift of the center of rotation and an increase in the maximum failure force.     

Role of phytoestrogenic oils in alleviating osteoporosis associated with ovariectomy in rats

The objective of this study was to elucidate the effect of soybean oil (SbO) and sesame oil (SO) supplemented diets on bone biomarkers changes in OVX (ovariectomized) rats. The current data exhibited significant decrease in BMD (bone mineral density), accompanied with marked depletion in the level of Ca, P and Mg in both serum and bone of OVX rats. Also, serum estrogen, total protein, HDL-C (high density lipoprotein cholesterol), bone NO levels were decreased in OVX rats. However, a significant increase in the level of serum TL (total lipids), TC (total cholesterol), TG (triglycerides), LDL-C (low density lipoprotein cholesterol), VLDL-C (very low density lipoprotein cholesterol), urine minerals (Ca, P, Mg), as well as serum, bone and urine ALP (alkaline phosphatase) and ACP (acid phosphatase) activity were recorded in OVX rats. Further changes were also detected by the increased level of urine hydroxyproline, serum parathyroid hormone and osteocalcin, as well as urea and creatinine level in both serum and urine. On the other hand, when OVX rats were fed on SbO (soy bean oil) (15 % w/w) or SO (sesame oil) (10 % w/w) supplemented diets, the data recorded a significant improvement in all the above mentioned parameters. So, it can be concluded that consumption of SbO or SO supplemented diets might be considered as a functional food for retarding risks of osteoporosis associated with estrogen deficiency in OVX states.     

Glutamine Metabolism Regulates Proliferation and Lineage Allocation in Skeletal Stem Cells

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Estrogen inhibits osteoclasts formation and bone resorption via microRNA-27a targeting PPARγ and APC

Inhibition of osteoclasts formation and bone resorption by estrogen is very important in the etiology of postmenopausal osteoporosis. The mechanisms of this process are still not fully understood. Recent studies implicated an important role of microRNAs in estrogen-mediated responses in various cellular processes, including cell differentiation and proliferation. Thus, we hypothesized that these regulatory molecules might be implicated in the process of estrogen-decreased osteoclasts formation and bone resorption. Western blot, quantitative real-time polymerase chain reaction, tartrate-resistant acid phosphatase staining, pit formation assay and luciferase assay were used to investigate the role of microRNAs in estrogen-inhibited osteoclast differentiation and bone resorption. We found that estrogen could directly suppress receptor activator of nuclear factor B ligand/macrophage colony-stimulating factor-induced differentiation of bone marrow-derived macrophages into osteoclasts in the absence of stromal cell. MicroRNA-27a was significantly increased during the process of estrogen-decreased osteoclast differentiation. Overexpressing of microRNA-27a remarkably enhanced the inhibitory effect of estrogen on osteoclast differentiation and bone resorption, whereas which were alleviated by microRNA-27a depletion. Mechanistic studies showed that microRNA-27a inhibited peroxisome proliferator-activated receptor gamma (PPARγ) and adenomatous polyposis coli (APC) expression in osteoclasts through a microRNA-27a binding site within the 3′-untranslational region of PPARγ and APC. PPARγ and APC respectively contributed to microRNA-27a-decreased osteoclast differentiation and bone resorption. Taken together, these results showed that microRNA-27a may play a significant role in the process of estrogen-inhibited osteoclast differentiation and function.