Combination of anabolic and antiresorptive agents for the treatment of osteoporosis

Combination therapy strategies for osteoporosis are reviewed in this article. Regimens including two antiresorptives agents increase BMD more than single therapy alone, but they have not proved to reduce fracture risk. The alternative of combining antiresorptives together with anabolics has gained more interest. There are, however, many questions still pending, as which antiresorptive should be used, and the appropriate sequence of the treatments. It seems that bisphosphonates can blunt the anabolic effect of parathyroid hormone (PTH) when given simultaneously. Instead, when PTH follows the antiresorptive treatment the anabolic effect seems not to be blunted. Finally, other possible approach would be to initiate therapy with an anabolic agent and maintain the effect with any antiresorptive if necessary.     

Vascular and cellular targeting for photodynamic therapy

Photodynamic therapy (PDT) involves the combination of photosensitizers (PS) with light as a treatment, and has been an established medical practice for about 10 years. Current primary applications of PDT are age-related macular degeneration (AMD) and several types of cancer and precancer. Tumor vasculature and parenchyma cells are both potential targets of PDT damage. The preference of vascular versus cellular targeting is highly dependent upon the relative distribution of photosensitizers in each compartment, which is governed by the photosensitizer pharmacokinetic properties and can be effectively manipulated by the photosensitizer drug administration and light illumination interval (drug-light interval) during PDT treatment, or by the modification of photosensitizer molecular structure. PDT using shorter PS-light intervals mainly targets tumor vasculature by confining photosensitizer localization within blood vessels, whereas if the sensitizer has a reasonably long pharmacokinetic lifetime, then PDT at longer PS-light intervals can induce more tumor cellular damage, because the photosensitizer has then distributed into the tumor cellular compartment. This passive targeting mechanism is regulated by the innate photosensitizer physicochemical properties. In addition to the passive targeting approach, active targeting of various tumor endothelial and cellular markers has been studied extensively. The tumor cellular markers that have been explored for active photodynamic targeting are mainly tumor surface markers, including growth factor receptors, low-density lipoprotein (LDL) receptors, transferrin receptors, folic acid receptors, glucose transporters, integrin receptors, and insulin receptors. In addition to tumor surface proteins, nuclear receptors are targeted, as well. A limited number of studies have been performed to actively target tumor endothelial markers (ED-B domain of fibronectin, VEGF receptor-2, and neuropilin-1). Intracellular targeting is a challenge due to the difficulty in achieving sufficient penetration into the target cell, but significant progress has been made in this area. In this review, we summarize current studies of vascular and cellular targeting of PDT after more than 30 years of intensive efforts.     

Study on static morphometric parameters for a diagnostic approach of osteoporosis

The diagnostic value of the morphometric parameters Vv,Sv, dtrab of cancellous bone and relations between them were examined. Iliac bone biopsies of osteoporotic and spasmophilic subjects were studied by means of a Mop 1 semi automatic digitizer tablet joint to a C B M 3032 microprocessor. Both the average Sv and Vv values were significantly different between the two groups. Concordance of Sv values with the radiological diagnosis was closer than Vv ones. The global estimation of mean trabecular thickness is discussed. In conclusion the confrontation of experimental data shows that simple global measure of Sv completes and precise the knowledge of skeleton state.     

The clinical significance of mediators of cellular immunity

This paper reviews experimental and clinical evidence for the existence of soluble mediators of cellular immune responses. Clinical appraisal of this field is now emerging from the stage of biological definition and technical development to the stage at which acceptable standards of mediator activity will now be required. The biological significance of these mediators may lie in amplification and regulation of the immunological response. The clinical significance of this field lies in the detection, assay and repair of genetic or non-genetic disorders of cell-mediated immunity. Development of this field will be much assisted by parallel studies of cell-mediator function in both animals and man; and, with some optimism, may yield a predictive basis for control of the cellular immune response.     

雌激素对运动防治骨质疏松效果的影响

目的 探讨雌激素对运动防治骨质疏松效果的影响.方法 48只5个月龄SD雌性大鼠随机分为假手术组(Sham组)、假手术加运动组(Sham+run组)、单纯去卵巢组(Ovx组)、去卵巢加运动组(Ovx+run组)、去卵巢加运动加1/4雌激素组(Ovx+run+e1组)和去卵巢加运动加雌激素组(Ovx+run+e2组).其中Ovx+run+e1组和Ovx+run+e2组于术后1周开始皮下注射不同剂量的己烯雌酚,Ovx+run+e1组剂量为0.025mg/kg,1次/4d;Ovx+run+e2组为0.025mg/kg,1次/d,持续12周.Sham+run组、Ovx+run组、Ovx+run+e1组、Ovx+run+e2组于术后1周开始采用大鼠专用跑笼进行运动训练12周.术后13周行股骨远端骨密度和生物力学测量,并对胫骨近端进行骨组织计量学测量.结果 (1)Ovx组股骨远端骨密度值最低[(0.10±0.01)g/cm2],与其他各组相比差异有统计学意义(均P＜0.05);Ovx+run+e2组与Sham+run组骨密度值相当[分别为(0.14±0.02)g/cm2和(0.13±0.02)r/cm2],均显著高于其他各组(均P＜0.05);Sham组、Ovx+run组和Ovx+run+e1组之间骨密度值差异无统计学意义[(0.11±0.01)g/cm2比(0.12±0.01)g/cm2比(0.12±0.01)g/cm2,均P＞0.05].(2)Sham组骨小梁的厚度、骨小梁面积百分比和骨小梁数量与Ovx+run+e2组、Sham+run组差异无统计学意义,且均高于Ovx+run+e1组、Ovx+run组和Ovx组(均P＜0.05);而骨小梁分离度在Sham组、Ovx+run+e2组和Sham+run组之间差异也无统计学意义,但低于Ovx+run+e1组、Ovx+run组和Ovx组(均P＜0.05).骨小梁面积百分比和骨小梁数量:Ovx组＜Ovx+run组＜Ovx+run+e1组(均P＜0.05);骨小梁分离度:Ovx组＞Ovx+run组＞Ovx+run+e1组(均P＜0.05);骨小梁厚度在3组间差异无统计学意义.(3)Ovx组极限剪切载荷、剪切强度极限、最大剪应变、剪切弹性模量明显低于其他各组(均P＜0.05).Ovx+run+e2组的极限剪切载荷、剪切强度极限、最大剪应变与Sham+run组相当,均高于其他各组(均P＜0.05);剪切弹性模量则与Sham+run组、Ovx+run组相当,均高于Sham组、Ovx组、Ovx+run+e1组(均P＜0.05).Sham组、Ovx+run+e1组与Ovx+run组极限剪切载荷、剪切强度极限、最大剪应变之间差异均无统计学意义.Sham组剪切弹性模量小于Ovx+run组(P＜0.05),但Sham组与Ovx+run+e1组、Ovx+run+e1组与Ovx+run组之间差异无统计学意义.结论 雌激素水平对运动防治骨质疏松的效果有显著影响.雌激素充足,对运动防治骨质疏松效果起协同作用;雌激素不足,则对运动防治骨质疏松效果无协同作用.     

失用性骨质疏松症的发病机制及预防治疗进展

背景：失用性骨质疏松较为常见,因其特殊的病因,预防治疗缺乏有效手段,给社会和家庭带来了巨大的负担。 目的：分析失用性骨质疏松的病因、发病机制及预防治疗方法,为失用性骨质疏松的有效预防提供参考。 方法：检索CNKI和PUBMED数据库,2002年1月至2012年9月收录的失用性骨质疏松症的相关文献,中文检索词为“废用性骨质疏松或失用性骨质疏松”,共检索到中文67篇;英文检索词为“disuse osteoporosis AND English”检索到111篇相关文献,对文章进行初审,纳入文献主题与此文联系密切,原创、论点论据可靠的文章,观点明确,分析全面的文章;排除内容陈旧或重复文献及试验设计不是随机对照试验的文章。 结果与结论：共纳入符合标准的文献50篇(中文25篇,英文25篇)。目前对失用性骨质疏松症的病因大致归为3大类,即机械负重的减少、微重力状态、脊髓及神经损伤。失用性骨质疏松的预防和治疗主要有：药物预防治疗,包括降钙素、中草药、双膦酸盐、维生素、钙、锶盐及神经生长因子等;物理治疗：脉冲电磁场、超声波、共振波、被动运动及电针治疗。目前临床上对失用性骨质疏松症没有理想的预防治疗措施,近年来研究者们开始试图从遗传学角度探讨其发病机制,在一些信号通道蛋白、特异性基因位点的研究中取得了一定进展。     

阿仑膦酸钠与激素替代疗法治疗骨质疏松症的比较

文章快速阅读： 文题释义： 激素替代疗法(hormone replacement therapy,HRT)：是指通过补充激素来治疗激素分泌减退或者缺乏所引起的疾病的治疗方法。广义上的HRT涵盖所有的激素。狭义上的HRT多是针对女性激素,特别是指雌激素替代疗法(estrogen replacement therapy,ERT)。美国公布的研究结果显示,虽然激素替代疗法能帮助中老年妇女改善更年期不适症状,但这种疗法也会增加女性患痴呆症的风险。新结果再次表明需要对激素替代疗法的利弊进行重新评估。 骨质疏松症：是由于多种原因导致的骨密度和骨质量下降,骨微结构破坏,造成骨脆性增加,从而容易发生骨折的全身性骨病。绝经后骨质疏松症一般发生在妇女绝经后5-10年内。摘要 背景：研究表明雌激素、双膦酸盐、降钙素等可在一定程度上提高骨密度和降低骨折发生率,其中阿仑膦酸钠作为临床最常用的双膦酸盐类药物得到人们的关注。 目的：对比分析阿仑膦酸钠与激素替代疗法治疗绝经后骨质疏松症的疗效。 方法：绝经后骨质疏松症患者198例随机平均分为2组,每组99例,阿仑膦酸钠组口服阿仑膦酸钠,每周70 mg,连续1年;激素代替疗法组口服替勃龙片2.5 mg/d,连续1年,比较治疗前后2组的骨密度、性激素水平,并比较2组患者的不良发应发病率及对骨代谢标志物的影响,同时进行疼痛改善评价。 结果与结论：①治疗之后2组的股骨颈及L1-4的骨密度均较治疗前有所改善(P < 0.05);②激素代替疗法组治疗后血清雌激素和孕酮浓度均有下降的趋势,皮质醇有升高的趋势(P < 0.05);③目测类比评分阿仑膦酸钠组优于激素代替疗法组(P < 0.05);④阿仑膦酸盐组血清Ⅰ型原骨胶原 N端肽、血清β胶原降解产物治疗后较激素代替疗法组下降明显(P < 0.05)、阿仑膦酸钠组血清骨源性碱性磷酸酶和血清骨钙素较激素代替疗法组上升(P < 0.05);⑤激素替代疗法组的恶心、乏力等不良发应发病率高于阿仑膦酸钠组(P < 0.05);⑥结果说明,阿仑膦酸钠与激素替代疗法治疗绝经后骨质疏松症均可有效的提高骨密度,促进骨形成,阿仑膦酸钠对患者激素水平影响较小且不良反应小,其治疗效果更佳。中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程 ORCID: 0000-0003-1435-913X(苏凡)     

Building your body to survive: the use of anabolic steroids for HIV therapy

The loss of lean body mass (LBM) that is commonly associated with wasting syndrome has been linked to death in HIV disease. Bioelectrical Impedance Analysis (BIA) is a simple, inexpensive and painless technique used to assess body composition. The test gives a good reading of body cell mass, fat mass, and body water, and can be used to detect loss of LBM when it first occurs. BIA is a useful tool in managing and preventing wasting. Other factors that influence LBM include testosterone levels and anabolic steroids. Anabolic steroids, synthetic analogs of testosterone, are a Class III regulated drug. The use of anabolic steroids is controversial, and abuse by athletes led to the drugs being banned for many uses. A list of approved steroids, their actions, and potential problems associated with their use is included. Another table rates the major steroids for their effectiveness in AIDS therapy.     

Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.     

Genetic safety of cellular therapy

This paper presents the main results of the study on chromosome and genome variability of mesenchymal stem cell cultures from bone marrow and adipose tissue carried out in the Laboratory of Mutagenesis, Research Centre for Medical Genetics, over the last three years. Genome stability was assessed from DNA damage using the DNA comet assay, karyotyping and registration of aneuploidy by the FISH method. We found that DNA damage rate in MSC cultures from bone marrow was 3.9% and 3.8% at the early (2-5) passages and the late (10-15) passages respectively. The cultures were characterized by high dispersion of individual values. Karyotyping showed mosaicism in both types of MSC cultures at the early and late stages of cultivation. The fraction of abnormal cells in some cultures amounted to 80-90%. Evaluation of aneuploidy in interphase cells revealed 1.34% of aneuploid cells (on the average) per one "conventional" chromosome; their overall frequency in the genome amounted to 20-40%. The frequency of aneuploid cells was similar at the early and late passages. Cultures with clones of trisomic and monosomic cells were revealed. The probability of occurrence of abnormal cells may increase by virtue of de novo mutations in the culture and as a result of positive selection of the cells existing in the organism that exhibit a higher reproduction rate in culture. Based on the experimental data on mutational process, selection of mutant cells and clone formation, it is concluded that cytogenetic control of stem cells is necessary to ensure the safety of cellular therapy.