Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as the Wnt/β-catenin pathway have been targeted in the quest for new emerging therapeutic strategies.

Areas covered: This review provides an overview of existing pharmacotherapy for osteoporosis in women and explore state-of–the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects.

Expert opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in bone mineral density (BMD) with no plateau being observed, along with continuous anti-fracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown a significant reduction in fracture incidence; however, concerns have arisen with regard to increased cardiovascular risk.     

基于岗位管理的基层医院专科护士使用及考核的现状调查研究

目的调查四川省基层医院专科护士使用和考核现状,对其使用和考核体系进行探索。方法于2017年9月7-15日,采用问卷调查法对四川省38所二级及三级乙等医疗单位专科护士的使用和发展现状进行调查。结果共有38所医院参与网络问卷调查,其中34.21%的医院未针对专科护士设置岗位,岗位职责不清晰。有73.68%的专科护士未进行资质再认证,60.53%的专科护士学成后未进行专科资质再考核。结论我国对专科护士能力的评价认证体系尚未形成统一标准,对专科护士的培养条件也未形成统一标准。护士岗位管理中设置专科护士岗位能促进专科护士的职业发展规划,有利于专科护士使用和考核。     

Using gas chromatography and mass spectrometry to determine 25-hydroxyvitamin D levels for clinical assessment of vitamin D deficiency

Vitamin D is responsible for multiple metabolic functions in humans. Rickets are the most common disease caused by vitamin D deficiency. It is caused by poor calcium intake resulting in poor serum-ionized calcium. The purpose of this study is to develop a rapid, sensitive, and feasible method to determine the 25-hydroxy-vitamin D3 (25(OH)D3) levels in blood samples for clinical assessment. In this study, gas chromatography coupled mass spectrometry with trimethylsilyl derivatization (TMS-GC-MS) is the most suitable protocol for quantitative analyses of 25(OH)D3. Performance of method was evaluated and compared with liquid chromatography and immunoassay. Method validation has been carried out with plasma specimens. The limit of quantitation of TMS-GC-MS method is 1.5 ppb with good linear correlation. Furthermore, the dietary intake and nutritional status of vegetarian and non-vegetarians in Taiwan were assessed by our validated method. As a result, this vitamin D nutrition survey demonstrates that most Taiwanese people have insufficient vitamin D. Due to dietary habits; the male vegans may have the highest risk of vitamin D deficiency.     

骨质疏松相关基因的研究进展

骨质疏松(osteoporosis,OP)在很大程度上受基因的影响。在OP的相关基因中,维生素D受体(VDR)基因、雌激素受体(ER)基因、Ⅰ型胶原基因及转化生长因子基因都是重要的候选基因。VDR基因中BB基因型者比Bb及bb基因型者的腰椎骨密度(bone mineral density,BMD)低,骨丢失率高。FokⅠ基因型与腰椎BMD降低有明显相关性,ff基因型者腰椎BMDXx基因型者>xx基因型者。Ⅰ型胶原基因与骨量呈显著相关性,COLIA1基因突变可致低骨量、骨脆性增加。转化生长因子β(TGF-β)基因对调节骨形成和骨吸收有重要作用,TGF-β基因中可发生碱基丢失,这种变异多见于OP患者。     

大黄素和小剂量雌激素合用对去卵巢大鼠骨质疏松的预防作用

目的观察大黄素和小剂量雌激素联合应用对去卵巢大鼠骨质疏松的预防作用.方法3月龄大鼠双侧卵巢去除术后预防用药90 d.用骨组织形态计量学方法,测定大鼠胫骨近端松质骨静态参数和动态参数,观察骨物理生长指标、血清生化指标和器官指数.结果大黄素90 mg·kg-1·d-1和己烯雌酚5 μg·kg-1·d-1联合应用可抑制去卵巢大鼠的破骨细胞活性,完全对抗其骨转化率增高和骨量丢失的骨质疏松症状,与己烯雌酚30 μg·kg-1·d-1的作用相当,且降低己烯雌酚对子宫和肝脏的刺激作用.结论大黄素和小剂量己烯雌酚联合应用可预防去卵巢大鼠骨质疏松.     

降钙素防治骨质疏松模型兔的人工假体无菌性松动的实验研究

[目的]探讨降钙素对已行人工假体植入骨质疏松模型免的假体无菌性松动防治作用的实验研究。[方法]将30只假体植入模型的骨质疏松症兔随机分成实验组和对照组，各15只。实验组给予鲑鱼降钙素治疗（6U／kg，肌注，隔日1次），而对照组给予等量的生理盐水肌注，持续治疗半年。两组均分别于术前、术后4、8、12和24周检测假体周围感应区（ROI）骨密度（BMD）；于术前及术后4、12、24周行血清骨代谢指标检测：骨特异性碱性磷酸酶（BALP）、骨钙素（BGP）、抗酒石酸酸性磷酸酶-5b（TRAP-5b）；所有动物于术后24周处死，分别行假体拔出实验与扭转实验测定和假体周围骨组织形态计量学分析。[结果]术后24周，实验组假体周围局部感兴趣区BMD增加近5％，而对照组假体周围局部感兴趣区BMD下降了6％，两组比较有显著性差异（P〈0．01）；骨代谢指标中，术后24周实验组的BALP、BGP稍有下降，但组内无显著性差异（P〉0．05），而TRAP-5b有明显下降（P〈0．05），这些指标与对照组比较差异显著（P〈0．05或P〈0．01）；生物力学检测显示，实验组的假体拔出实验较对照组提高了约50％，扭转实验提高近1倍，且两组比较差异显著（P〈0．01）；骨组织形态计量学显示，实验组中反映骨吸收的Oc．No／Tb．Pm、ES／BS明显减少；反映骨量和微结构的％Tb．Ar、Tb．N明显增多，而Tb．Sp明显变窄：反映骨形成与骨矿化的OS／BS、MAR、BFR／TV及％L．Pm也均明显增多；这些指标与对照组比较差异显著（P〈0．01或P〈0．05）。[结论]鲑鱼降钙素能明显减少人工假体周围骨量的丢失和抑制骨溶解；并加快假体周围的骨形成，提高骨密度，促进生理性骨矿化；还能改善骨质量，促进骨微结构改变，提高骨的生物力学特性并增加假体四周的支撑力。其对骨质疏松症兔的假体松动有明显的预防和治疗作用。这对临床预防和治疗人工关节的无菌性松动有很好的指导意义。     

Vitamin D receptor genotype and risk of osteoporotic hip fracture in elderly women of Utah: an effect modified by parity

Introduction The associations between vitamin D receptor (VDR) Bsm I and Fok I genotypes, parity, and risk of osteoporotic hip fracture were evaluated in a statewide population-based case-control study in Utah.Methods Women age 50–89 years with hip fracture (n=882) were ascertained via surveillance of 18 Utah hospitals from 1997 to 2001. Age-matched controls were randomly selected (n=897). Participants were interviewed in their homes, and blood samples were collected for genotyping.Results In logistic regression analyses that controlled for multiple confounders, Bsm I VDR genotype but not Fok I genotype was associated with risk of osteoporotic hip fracture (OR bb vs. BB genotype: 0.68; 95% CI: 0.50, 0.95). In similar analyses, no overall association was observed between parity status and risk of osteoporotic hip fracture. However, the effect of VDR genotype was modified by parity status. Among nulliparous women (n=140), Bsm I genotype was not associated with risk of hip fracture (OR bb vs. BB: 0.82; 95% CI: 0.28, 2.4); among primiparous women (n=133), bb genotype was associated with increased risk of hip fracture (OR bb vs. BB: 3.30; 95% CI: 0.96, 11.29); among multiparous women (n=1,400), bb genotype was associated with decreased risk of hip fracture (OR bb vs. BB: 0.59; 95% CI: 0.42, 0.84).Conclusion VDR Bsm I genotype was associated with risk of hip fracture in Utah women, and this effect was modified by parity status. Hormonal or lifestyle factors related to parity may underlie this interaction.     

不同病理类型原发性甲状旁腺功能亢进症临床表现的比较分析

目的 分析不同病理类型甲状旁腺功能亢进（PHPT）的临床表现特点。方法 回顾性分析1958-2005年北京协和医院收治经手术病理证实的280例PHPT患者的临床资料。按病理类型分为甲状旁腺腺瘤组208例，甲状旁腺增生组52例及甲状旁腺腺癌组20例。结果 腺癌组中男性高于另外2组（P〈0．05）。增生及腺癌组中骨畸形、骨软化比例较低，增生组骨吸收、病理性骨折比例低于腺瘤组；胃肠道症状、多饮多尿及泌尿系统病变在腺癌组中高于另外2组（P均〈0．05）。血总钙（TCa）、血游离钙离子（ICa）及24h尿Ca在腺癌组显著高于腺瘤组及增生组（P均〈0．01），在腺瘤组与增生组间差异无统计学意义（P〉0．05）。出现高钙危象的比例在腺癌组显著高于另外2组（P〈0．01）。腺癌组病灶重量高于增生组，腺瘤组病灶直径小于增生组（P均〈0．05）。结论 在本组病例中，腺癌组男性比例较高，泌尿系统病变更为多见，出现高钙危象的比例显著增高，术后复发的比例较高。增生组骨骼系统病变相对较轻，其病变甲状旁腺重量低于腺癌与腺瘤组。     

Development and validation of a food frequency questionnaire for assessing dietary calcium intake in the general population

The aim of this study was to develop and evaluate a food frequency questionnaire (FFQ) for assessing dietary calcium intake in the general population, since all available questionnaires at present are age- and/or gender-specific. A total of 1001 individuals (including children, adults, and elderly people of both genders) were randomly recruited throughout Greece. Estimates of calcium intake from the 30-item FFQ were compared with those from a multi-pass 24-h recall. The FFQ underestimated mean calcium intake compared to the 24-h recall by (mean±SD) –133±333 mg/day or –5.4±47.6% (P<0.001). The two methods were strongly correlated (r=0.639, P<0.001), but the 95% limits of agreement for individual assessment were rather wide, as the FFQ could provide estimates of calcium intake from 533 mg/day above to 799 mg/day below the 24-h recall. Actual values for surrogate FFQ quartiles manifested a progressive increase, with significant differences between mean calcium intakes (P<0.001). The FFQ could identify individuals who consumed less calcium than 800 mg/day or less than the age-specific adequate intake with a relatively high sensitivity (82.8 and 95.5%, respectively), but low specificity (54.9 and 34.1%, respectively). Cross-classification analysis indicated that only 17 subjects (1.7%) were grossly misclassified (lowest quartile for one method and highest quartile for the other), while 827 subjects (82.6%) were correctly classified (into the same or adjacent quartiles). The FFQ could be used in population-based epidemiological studies or screening programs involving individuals of all ages and both genders, where the discrimination of subjects with relatively low (<500 mg/day) and relatively high (>1000 mg/day) calcium intakes is of primary interest. Results, however, do not support its use for the quantitative assessment of individual calcium intakes.