糖皮质激素通过糖皮质激素受体介导骨质疏松症的分子机制

糖皮质激素(GC)诱导的骨质疏松症(GIOP)以患者骨量丢失、骨重建功能减退及骨脆性增加为特征。有证据表明,GIOP主要由于GC通过其受体(GR)影响成骨细胞、破骨细胞及骨细胞的正常生物学功能。本文主要简述GR介导的转录因子在调控特定基因和蛋白的表达及在骨系统相关细胞的增生、分化、凋亡中的作用。糖皮质激素(GC)诱导的骨质疏松症(GIOP)以患者骨量丢失、骨重建功能减退及骨脆性增加为特征。有证据表明,GIOP主要由于GC通过其受体(GR)影响成骨细胞、破骨细胞及骨细胞的正常生物学功能。本文主要简述GR介导的转录因子在调控特定基因和蛋白的表达及在骨系统相关细胞的增生、分化、凋亡中的作用。     

糖皮质激素所致骨质疏松症的研究进展

糖皮质激素 (GC)对骨代谢产生广泛而深刻的影响。骨软化、骨质疏松和骨折等是GC性骨病的常见形式。GC在促进骨吸收的同时 ,主要抑制成骨细胞的功能 ,影响骨重建。GC所致的骨质疏松不仅可以有效地防治 ,而且 ,早期诊断和治疗尚可使病情逆转。目前 ,包括VitD和Ca2 +、骨吸收抑制剂、骨代谢促进因子及GC受体调节剂在内的多种治疗策略对这一疾病有着积极的防治意义。     

糖皮质激素所致骨质疏松症的研究进展

糖皮质激素（GC）对骨代谢产生广泛而深刻的影响。骨软化、骨质疏松和骨折等是GC性骨病的常见形式。GC在促进骨吸收的同时，主要抑制成骨细胞的功能，影响骨重建。GC所致的骨质疏松不仅可以有效地防治，而且，早期诊断和治疗尚可使病情逆转。目前，包括VitD和Ca^2 、骨吸收抑制剂、骨代谢促进因子及GC受体调节剂在内的多种治疗策略对这一疾病有着积极的防治意义。     

糖皮质激素性骨质疏松症的发生机制

本文从对骨组织的作用、对钙吸收的影响、对垂体激素的调控和对肌肉的影响等4个方面论述糖皮质激素性骨质疏松症的发病机制,并进一步探讨其发病的分子机制。     

2020版中国糖皮质激素性骨质疏松症防治专家共识

糖皮质激素性骨质疏松症(GIOP)是临床最常见的继发性骨质疏松症,重视GIOP的防治刻不容缓。2013年中华医学会风湿病学分会制定了我国GIOP诊治专家共识。近年来,GIOP在流行病学、评估体系和防治药物等方面取得了巨大进展。同时,鉴于糖皮质激素临床应用非常广泛,2020年由中国医师协会风湿免疫科医师分会、中华医学会风湿病学分会、中华医学会骨质疏松和骨矿盐疾病分会及国家皮肤与免疫疾病临床医学研究中心组成多学科团队,对既往共识进行了更新,采用推荐意见分级的评估、制订及评价(GRADE)分级体系,对骨折风险的评估体系、分层治疗、药物转换和维持减停,以及特殊人群防治等临床问题,给出了较为详细的循证推荐,旨在进一步加强GIOP防治的规范性,提高以患者为中心的医疗服务质量。     

原发性骨质疏松症防治的进展和趋势

原发性骨质疏松症的防治在短短的近二十年中取得了瞩目的进步,防治观念也大有长进。随着人口的日益老龄化,临床诊疗的需求大幅提高,先前认为骨质疏松是老化过程出现的一般生理现象,而现被看成是一种骨量低下、骨结构破坏导致骨脆性增加、易致骨折为特征的全身性骨病。以骨质疏松命名的专业学术会议和专业团体犹如雨后春笋;无创性骨量检测技术(如单能、双能放射线骨矿含量检测技术、超声骨量诊断技术等)、无创性骨转换检测技术、大系列的随机、对照、前瞻性的临床研究和一批新药的问世犤如双膦酸盐类(BPS)、降钙素(CT)、雌激素受体调节剂(…     

吸入糖皮质激素治疗支气管哮喘与骨质疏松的研究进展

糖皮质激素性骨质疏松症是糖皮质激素治疗支气管哮喘的严重并发症之一,尤其是支气管哮喘患者长期应用糖皮质激素越来越受到人们的关注。糖皮质激素通过多种机制干扰骨质的形成和吸收,从而导致糖皮质激素性骨质疏松症,对糖皮质激素治疗支气管哮喘与骨质疏松的研究具有重要的临床意义,故本文从糖皮质激素及不同给药途径引发骨质疏松机制、临床特点、诊断和防治几方面作一综述。     

吸入糖皮质激素治疗支气管哮喘与骨质疏松的研究进展

糖皮质激素性骨质疏松症是糖皮质激素治疗支气管哮喘的严重并发症之一,尤其是支气管哮喘患者长期应用糖皮质激素越来越受到人们的关注.糖皮质激素通过多种机制干扰骨质的形成和吸收,从而导致糖皮质激素性骨质疏松症,对糖皮质激素治疗支气管哮喘与骨质疏松的研究具有重要的临床意义,故本文从糖皮质激素及不同给药途径引发骨质疏松机制、临床特...     

老年人骨质疏松症的防治

年龄是骨质疏松症患病的重要危险因素,老年人骨质疏松患病率和骨质疏松性骨折发生率高.死亡率增加、功能下降、长期照料需要增加、生活质量下降和医疗资源消耗增加与老年人骨质疏松性骨折密切相关.为此,我们简要介绍老年人骨质疏松和骨质疏松性骨折的流行趋势和防治要点.     

Update on glucocorticoid-induced osteoporosis

Glucocorticoid-induced osteoporosis (GIOP) is the most common form of secondary osteoporosis, and fractures are the most frequent adverse effects of this medication. Glucocorticoids have several direct and indirect adverse effects on bone, primarily through reduction in osteoblasts and osteocyte activity, and life span. Recent advances in the pathophysiology and prevention of this complication of therapy provide hope for its amelioration in patients being treated with glucocorticoids. Several effective pharmacologic agents are now available, and guidelines for the prevention and treatment of GIOP have been published. Despite these advances, many patients still do not receive proper prevention or therapy.     

中药对糖皮质激素所致大鼠骨质疏松的影响

目的研究中药对强的松所致大鼠骨质疏松（OP）的保护治疗作用。方法将4月龄的SD大鼠随机分3组,即正常对照组、激素组和激素＋用药组。激素组每次喂强的松5mg／kg,每周2次,激素＋用药组除喂强的松外,还同时喂中药,剂量为3ml／kg·d。3个月后用双能X光骨密度仪测量小鼠股骨骨密度（BMD）变化。采血测定其血清骨钙素（BGP）的变化。结果激素组与对照组比较,股骨的骨密度及血清骨钙素都明显低于对照组（P〈0．05）;而治疗组的骨密度值及血清骨钙素都有明显的改善（P〈0．05）。结论本实验所用的中药能减轻激素所致的骨质疏松。     

糖皮质激素所致骨质疏松与维生素D受体基因型相关性的初步研究

目的　利用聚合酶链反应 限制性片段长度多态性方法 (PCR RFLP)研究长期接受糖皮质激素治疗患者的维生素D受体 (VDR)基因型与骨密度 (BMD)之间的关系。方法　收集 71例长期服用糖皮质激素的风湿性疾病患者的临床资料及静脉血 ,双能X线骨密度仪测定其BMD。提取基因组DNA行PCR扩增出约 185 0bp的VDR基因片段 ,用限制性内切酶BsmI进行酶切 ,根据酶切后片段长度不同判定基因型 ,并统计分析基因型与BMD及Z值之间的关系。结果　 71例患者中检测出的基因型为Bb和bb两种 ,分布频率分别为 11 3%、88 7% ,其等位基因分布频率符合遗传平衡定律 (Hardy Weinberg定律 )。两种基因型间年龄、性别比、体重指数 (BMI)、病程、病种构成比、服用激素时间及激素累积量之间差异无显著性 (P >0 0 5 )。Bb及bb基因型患者的骨质疏松发生率分别为 37 5 %和 33 3% ,差异无显著性 (χ2 =0 0 5 ,P =0 8)。两种基因型患者间腰椎、髋部的BMD和Z值有一定的差异 ,但无统计学意义。结论　①我国汉族人群VDR基因型以bb为主 ,Bb其次 ,BB基因型分布频率最低。②长期接受糖皮质激素治疗的患者中 ,Bb和bb两种基因型间骨密度差异无显著性 ,VDR基因型不能预测糖皮质激素相关性骨质疏松发生的危险性 ,但该结论有待于加大样本量后进一步确证     

Superiority of alfacalcidol over plain vitamin D in the treatment of glucocorticoid-induced osteoporosis

Supplementation therapy with plain vitamin D plus calcium is in general regarded as effective prevention or first-step treatment of glucocorticoid-induced osteoporosis (GIOP). The aim of our study was to compare the therapeutic efficacy of the D-hormone analog alfacalcidol with plain vitamin D in patients with established GIOP with or without vertebral fractures. Patients on long-term glucocorticoid (GC) therapy were included as matched pairs to receive randomly either 1 microg alfacalcidol plus 500 mg calcium per day (group A, n=103) or 1000 IU vitamin D3 plus 500 mg calcium (group B, n=101). The two groups were well matched in terms of mean age, sex ratio, mean height and weight, daily dosage, and duration of GC therapy, and the percentages of the three underlying diseases included chronic obstructive pulmonary disease, rheumatoid arthritis, and polymyalgia rheumatica. The baseline mean bone mineral density (BMD) values at the lumbar spine for the two groups were -3.26 (alfacalcidol) and -3.25 (vitamin D(3)) and, at the femoral neck, -2.81 and -2.84, respectively (T scores). Rates of prevalent vertebral and nonvertebral fractures did not differ between groups. During the 3-year study, we observed a median percentage increase of BMD at the lumbar spine of 2.4% in group A and a loss of 0.8% in group B ( P<0.0001). There also was a larger median increase at the femoral neck in group A (1.2%) than in group B (0.8%) ( P<0.006). The 3-year rates of patients with at least one new vertebral fracture were 9.7% among those assigned to the alfacalcidol group and 24.8% in the vitamin D group (risk reduction 0.61, 95% CI 0.24-0.81, P=0.005). The 3-year rates of patients with at least one new nonvertebral fracture were 15% in the alfacalcidol group and 25% in the vitamin D group (risk reduction 0.41, 95% CI 0.06-0.68, P=0.081). The 3-year rates of patients with at least one new fracture of any kind were 19.4% among those treated with alfacalcidol and 40.65% with vitamin D (risk reduction 0.52, 95% CI 0.25-0.71, P=0.001). In accordance with the observed fracture rates, the alfacalcidol group showed a substantially larger decrease in back pain than the plain vitamin D group ( P<0.0001). Generally, side effects in both groups were mild, and only three patients in the alfacalcidol group and two in the vitamin D group had moderate hypercalcemia. We conclude that alfacalcidol plus calcium is highly superior to plain vitamin D3 plus calcium in the treatment of established GIOP.     

阿仑膦酸钠对糖皮质激素导致骨质疏松防治作用的Meta分析

目的 评价阿仑膦酸钠防治糖皮质激素导致的骨质疏松(GIOP)的有效性和安全性.方法 检索PubMed、EMBASE、Cochrane Library、Web of Science、中国生物医学文献数据库(CBM)、万方数据库,收集有关阿仑膦酸钠与安慰剂比较防治GIOP的随机对照试验(RCT),依据Jadad评分评价纳入RCT的质量,采用RevMan 5.1进行统计分析.结果 纳入7篇文献,共1111例患者.Meta分析显示,与安慰剂相比,阿仑膦酸钠治疗12个月可增加腰椎和股骨颈的骨密度(BMD)[均数差(MD)＝3.35,95％ CI(2.67 ～4.02),P=0.000;MD=1.90,95％ CI(0.89 ～2.92),P=0.000],治疗24个月增加腰椎BMD[MD＝3.91,95％ CI(2.37 ～5.45),P＜0.000],但没有增加股骨颈BMD[MD=1.91,95％ CI(-1.15 ～5.02),P＝0.22].在降低椎骨和非椎骨骨折风险方面与安慰剂相比差异无统计学意义[RR＝1.00,95％ CI (0.49 ～2.07),P=0.99;RR=1.02,95％ CI (0.49～2.14),P=0.95].阿仑膦酸钠与安慰剂相比不良事件发生率的差异无统计学意义[RR =0.97,95％CI (0.90～1.05),P＝0.47].结论 阿仑膦酸钠能增加患者腰椎和股骨颈BMD,且不良反应低,还没有证据表明可以降低骨折风险.今后,尚需要开展大样本RCT观察阿仑膦酸钠对股骨BMD的影响是否与用药时间有关以及进一步探索其能否降低骨折发生率.     

Efficacy of intravenous alendronate for the treatment of glucocorticoid-induced osteoporosis in children with autoimmune diseases

Our objective was to investigate the efficacy of intravenous alendronate for the treatment of glucocorticoid-induced osteoporosis (GIOP) in children with autoimmune diseases. Five children with autoimmune disease and GIOP were treated with 5 mg intravenous alendronate once every 3 months. After 1 and 2 years, we evaluated the changes in the Z score of the femoral neck bone mineral density (BMD), serum bone alkaline phosphatase, and urinary deoxypyridinoline. Six patients with GIOP, whose BMD could be observed over a 1-year period without alendronate treatment, were defined as controls. After 1 and 2 years of treatment, intravenous treatment significantly inhibited bone loss. The efficacy of alendronate demonstrated a significant correlation with a high level of bone turnover markers before alendronate treatment. Intravenous alendronate is considered to be a good choice for the treatment of GIOP because of its excellent efficacy. In addition, our study suggests that the efficacy of alendronate depends on the bone turnover of patients before treatment. Intervention with bisphosphonates during periods of high bone turnover may be recommended.     

Secondary osteoporosis and glucocorticoid-induced osteoporosis

In order to assess properly the diagnosis of osteoporosis, a short clinical investigation is required to address potential causes for bone loss. Osteoporosis used to be suspected in a patient with vertebral demineralization, but nowadays it is often diagnosed in a patient with a low bone mass on a screening dual-energy X-ray absorptiometry (DEXA). In this setting, it is important for the clinician to look for secondary osteoporosis, especially in men in whom secondary osteoporosis is more frequent than in women, before discussing any specific therapy. The major causes are longterm glucocorticoid therapy, endocrine (hypogonadism, primary hyperparathyroidism, hyperthyroidism), or digestive diseases.     

A systematic review and meta-analysis of glucocorticoid-induced osteoporosis in children

Objective

To summarize the published effects of systemic glucocorticoid therapy on bone mineral density (BMD) and fractures in children.

Methods

We performed a systematic review and meta-analysis of existing literature, using Medline, CINAHL, and Cochrane databases to identify studies of BMD or fractures in children ≤18 years taking systemic glucocorticoid therapy. We excluded studies of inhaled glucocorticoids, chemotherapy, and organ transplantation. Two authors reviewed abstracts for inclusion, read full-text articles to extract data, and rated each study using the Downs–Black scale.

Results

A total of 16 studies met eligibility criteria, including 10 BMD (287 children) and six fracture (37,819 children) studies. Spine BMD was significantly lower (−0.18; 95% CI = −0.25; −0.10 g/cm²) in children taking glucocorticoid therapy, compared to age- and gender-matched healthy controls. Spine BMD was also lower (−0.14; 95% CI = −0.27; 0.00 g/cm²) in children taking glucocorticoids, compared to children with the same disease not taking glucocorticoids. Incident clinical fracture rates varied from 2% to 33%. Morphometric vertebral fracture incidence ranged from 6% to 10%, and prevalence was 29–45%.

Conclusion

Published data suggest that children treated with glucocorticoid therapy have lower spine BMD compared to healthy children. Whether children receiving glucocorticoid therapy have lower spine BMD compared to children with milder disease not requiring such therapy is not certain. Clinical and morphometric vertebral fractures are common, although only one study assessed fracture rates in healthy controls. Additional well-designed, prospective studies are needed to evaluate the skeletal effects of glucocorticoid therapy in children.     

An update on glucocorticoid-induced osteoporosis

PURPOSE OF REVIEW: Glucocorticoids are widely used, often long term, and a major side effect is osteoporosis and increased risk of fracture. This review considers how common is the problem, the patients who are most at risk, our current understanding of mechanisms, and how to prevent and effectively treat glucocorticoid-induced osteoporosis. The actions currently being undertaken in clinical practice are reviewed. RECENT FINDINGS: Glucocorticoid-induced osteoporosis is an increasing problem that occurs not only in those on high-dose therapy. Advances in our knowledge of the cellular and cytokine mechanisms of bone turnover and glucocorticoid mechanisms of action are leading to a better understanding of how glucocorticoids affect bone cells and novel ways of prevention. Although there are effective treatments to prevent and control glucocorticoid-induced osteoporosis as well as guidelines for their use, they are still not being applied in routine clinical practice. SUMMARY: Glucocorticoid-induced osteoporosis is a significant problem. Although our understanding of effective prevention and treatment strategies is improving, there needs to be better implementation of these strategies.