糖皮质激素性骨质疏松机制的研究进展

糖皮质激素在临床上应用广泛,其长期应用可引起骨质疏松等严重并发症,目前尚无有效的防治手段。因此,研究糖皮质激素性骨质疏松的机制对于寻找有效的干预措施具有重要意义。骨吸收增加是糖皮质激素性骨质疏松的机制之一,但近年来的研究证实糖皮质激素导致骨质疏松主要与其抑制骨形成有关。本文主要对糖皮质激素抑制骨形成的机制研究进展进行综述。     

糖皮质激素诱导骨质疏松的细胞及分子学机制

长期大剂量使用糖皮搏击激素会诱导骨质疏松,其机制为糖皮质激素抑制成骨细胞的增殖及分化,促进成骨细胞的凋亡,并降低其功能,使骨形成延迟并减少。它可抑制破骨细胞的产生,但是否影响破骨细胞的活性则尚不清楚;此外,它也可促进破骨细胞凋亡。     

糖皮质激素诱导骨质疏松的细胞及分子学机制

长期大剂量使用糖皮质激素会诱发骨质疏松 ,其机制为糖皮质激素抑制成骨细胞的增殖及分化 ,促进成骨细胞的凋亡 ,并降低其功能 ,使骨形成延迟并减少。它可抑制破骨细胞的产生 ,但是否影响破骨细胞的活性则尚不清楚 ;此外 ,它也可促进破骨细胞凋亡。     

糖皮质激素引起骨质疏松的发病机制及防治

糖皮质激素可直接作用于成骨细胞和破骨细胞,并在分子水平调节骨微环境局部因子,导致骨吸收大于骨形成而发生骨质疏松。随着对其发病机制的深入研究,的药物不断一切研制,有力地促进了临床治疗。     

糖皮质激素诱导的骨质疏松

1932年Ｃｕｓｈｉｎｇ描述了由于垂体肿瘤产生ＡＣＴＨ而引起双侧肾上腺皮质增生症中 ,有骨骼脱钙现象。这是糖皮质激素诱导的骨质疏松的最早的描述。 50年代以后 ,由于使用糖皮质激素治疗 ,有出现脊柱压缩性骨折的报道。现在糖皮质激素已广泛应用于临床 ,它所引起的骨质疏松症的发病率 ,仅次于绝经后及老年性骨质疏松症而居第 3位。因此 ,日益受到医学界的关注。糖皮质激素诱导的骨质疏松有其特殊性 ,临床上分为内源性 (柯兴病或柯兴综合征 )和外源性 (长期应用糖皮质激素治疗 )。1　流行病学我国王家池等统计过 77例柯兴综合征中 ,4 6例有…     

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。     

氟化物对骨形成中成骨细胞的影响及机制

氟化物作为促骨形成药物之一 ,最早被推荐应用于骨质疏松症的临床治疗 ,目前仍是唯一可供临床使用的有效的促骨形成的药物。近年来由于成骨细胞 (osteoblast OB)培养技术及基因工程技术的发展 ,对氟化物刺激骨形成作用有了更进一步的认识 ,有助于我们对氟中毒时氟骨症机制的探讨。1　氟化物对成骨细胞的直接作用　　氟是一种已知可影响骨形成的非激素因子。具有双相调节作用。长期小剂量氟可促进骨形成 ;大剂量可引起骨质疏松或骨硬化。在人体和动物实验研究中 ,较多学者报道氟中毒时骨量增多是由于 OB数增多 ,活性增加 ,生命周期延长 [1 …     

糖皮质激素性骨质疏松防治进展

糖皮质激素由于其强大的抗炎及免疫抑制作用,在多种疾病的诊断和治疗上得以广泛应用,其在风湿性疾病中的应用更为普遍。糖皮质激素诱导的骨质疏松（GIOP）是长期应用激素的主要副作用之一,也是继发性骨质疏松的最主要原因。因此,近年来受到临床医生的重视。     

糖皮质激素所致骨质疏松的研究现状及治疗

糖皮质激素 (ｇｌｕｃｏｃｏｒｔｉｃｏｉｄ ,ＧＣ)在肾脏疾病、风湿性疾病、器官移植等领域应用广泛 ,但其长程治疗相关的骨质疏松也逐渐成为肾脏科医师关注的重要问题。 1932年Ｃｕｓｈｉｎｇ最早报道垂体嗜碱细胞腺瘤患者出现激素相关性骨病 ,骨组织定量形态学分析也显示Ｃｕｓｈｉｎｇ综合征患者骨形成受抑而骨吸收增加[1] 。一系列的临床研究也表明 ,器官移植术后接受大量免疫抑制剂的患者易于发生骨折 ,大体解剖和组织形态学分析均证实 ,这部分患者术后丢失大量骨质成分。在应用ＧＣ的同时 ,如何预防和治疗骨质疏松都是临床研究的重点…     

Effect of alendronate on glucocorticoid-induced osteoporosis in Japanese women with systemic autoimmune diseases: versus alfacalcidol

Glucocorticoids-induced osteoporosis is a serious problem for patients with systemic autoimmune disease requiring relatively long-term glucocorticoid treatment. Effectiveness of alendronate for the prevention of glucocorticoids-induced osteoporosis was evaluated in comparison with that of alfacalcidol in Japanese women with autoimmune disease excluding rheumatoid arthritis. Loss of bone mass was evaluated with bone mineral density (BMD) of lumber vertebrae, bone resorption was with urinary N-telopeptide for type I collagen (NTX), and bone formation was with serum bone-specific alkaline phosphatase (B-ALP). A total of 33 patients who were treated with oral glucocorticoids (>/=5 mg/day of prednisolone equivalence) for more than 6 months were randomized into two groups; alendronate group (n = 17) received 5 mg/day of alendronate, and alfacalcidol group (n = 16) received 1.0 mug/day of alfacalcidol for 24 months with glucocorticoids. The dose of alendronate was the maximal dose approved in Japan. BMD had tendency to decrease with alfacalcidol, while increase with alendronate. The difference in BMD change between the two groups was significant by 4.3% at 18 months and by 4.2% at 24 months (both P < 0.05). Bone resorption was significantly reduced only with alendronate; NTX was decreased by 28 to 35% at 6 to 24 months (P < 0.05), but not changed with alfacalcidol at 24 months. The bone formation was found to be unchanged according to the B-ALP measured between the two groups. In conclusion, the treatment of 5 mg alendronate daily is more effective than alfacalcidol for preventing the glucocorticoid-induced osteoporosis by the mechanism of reducing bone resorption in Japanese women with systemic autoimmune disease.     

甲状旁腺激素及其拟似剂治疗骨质疏松症的研究进展

甲状旁腺激素(PTH)目前已作为一种促骨合成药物,用于骨质疏松症的临床治疗。它所发挥的生物学效应取决于其作用模式和剂量,即间断小剂量使用能增加骨形成,而大剂量持续使用则加速骨吸收使骨量减少。PTH对骨代谢调节的确切机制尚未阐明,大量研究工作力图从各个层面寻找PTH治疗骨质疏松的效应模式及机制,以便使其更安全有效地应用于临床,本文对目前的研究进展作综述。     

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.     

血管生成在骨代谢及骨质疏松症中的作用研究进展

目前,骨质疏松症(OP)的防治主要集中于抑制骨吸收,但其局限性已显现。近年文献报道,血管生成与OP关系密切,而且发现血管生成与骨代谢间存在特定的"耦合"关系。血管生成,尤其是H型血管,可能通过影响骨形成、骨吸收及骨重塑进程的方式,在OP发生、发展及防治过程中发挥着重要的调节作用。本文重点梳理血管生成与骨代谢和OP之间的...     

辛伐他汀对骨质疏松大鼠骨形成作用研究

目的　探讨他汀类药物对绝经后骨质疏松症骨形成的刺激作用和药理机制。方法　 54只 SD雌鼠随机分为 3组 :去势后给药实验组 ,去势组和对照组 ,观察术后 4、1 0和 1 6 w骨形成指标 :骨钙素 (BGP) ,骨特异碱性磷酸酶 (骨 AKP)和总碱性磷酸酶 (总 AKP) ;骨吸收指标 :尿呲啶醚 (PYD)和脱氧呲啶醚 (DPD)。同步用 IBAS计算机全自动图像分析系统对不脱钙骨组织动态观测骨形态计量学参数。结果　给药实验组在去势后 4～ 1 6 w BGP和骨 AKP明显高于单纯去势组 (分别为 P<0 .0 0 1和 P<0 .0 5) ,而尿 PYD和 DPD两组间无显著差异 (P>0 .0 5)。骨形成表面(FS)和骨小梁体积 (TBV) ,骨小梁平均厚度 (MTT)较去势组明显升高 ,尤其是 TBV和 FS(分别为 P<0 .0 0 1和 P<0 .0 1 ) ,这种差异在第 1 0周最为显著。随着给药时间的延长 (第 1 6周 ) MAR逐渐增加 (P<0 .0 0 1 )。 RS与去势组比较在所有实验周均无差异。结论　辛伐他汀可刺激骨质疏松大鼠成骨细胞活跃增生 ,促进骨形成与骨转换速率 ,并可使骨质疏松症骨组织形态改善。     

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.     

骨质疏松症治疗新进展

骨转换失衡是骨质疏松症发病的重要病理机制,骨质疏松症的治疗靶点主要集中在抑制破骨细胞活性及增强成骨细胞活性.新型骨吸收抑制剂包括核因子-kB受体活化因子配体(RANKL)的单克隆抗体、组织蛋白酶K抑制剂、新型选择性雌激素受体调节剂、口服降钙素等;新型骨形成促进剂有骨硬化素单克隆抗体、Dickkopf-1单克隆抗体、甲状旁腺激素(PTH)制剂及钙敏感受体拮抗剂等.此外,含有维生素D的复方制剂也是很有应用前景的骨质疏松治疗新药.     

骨质疏松症治疗新进展

骨转换失衡是骨质疏松症发病的重要病理机制,骨质疏松症的治疗靶点主要集中在抑制破骨细胞活性及增强成骨细胞活性。新型骨吸收抑制剂包括核因子-κB受体活化因子配体（RANKL）的单克隆抗体、组织蛋白酶K抑制剂、新型选择性雌激素受体调节剂、口服降钙素等;新型骨形成促进剂有骨硬化素单克隆抗体、Dickkopf-1单克隆抗体、甲状旁腺激素（PTH）制剂及钙敏感受体拈抗剂等。此外,含有维生素D的复方制剂也是很有应用前景的骨质疏松治疗新药。     

Prevention and treatment strategies for glucocorticoid-induced osteoporotic fractures

Glucocorticoids are the most common cause of drug-related osteoporosis. We reviewed current evidence on risk factors for glucocorticoid-induced osteoporosis (GIOP) and prevention and treatment of GIOP-related fractures. Guidelines for GIOP management published since 2000 were also reviewed. Significant bone loss and increased fracture risk is seen with daily prednisone doses as low as 5 mg. Alternate-day glucocorticoid therapy can lead to similar bone loss. No conclusive evidence exists for a safe minimum dose or duration of glucocorticoid exposure. Physicians should consider risk factors for involutional osteoporosis such as older age, postmenopausal status, and baseline bone density measurements as they assess patients for prevention or treatment of GIOP. Bisphosphonates were reported to reduce GIOP-related vertebral fractures, but inconclusive data exist for hip fractures associated with glucocorticoid use. Hormone replacement therapy and parathyroid hormone analogs are effective in preserving bone density in GIOP. The risk of osteoporosis and fractures should be routinely assessed in patients receiving glucocorticoid therapy. Effective prevention and treatment options are available and can result in meaningful reduction of GIOP-related morbidity and mortality. Current guidelines for GIOP management recommend bisphosphonates, especially alendronate and risedronate, as first-line agents for GIOP, and these guidelines propose the preventive use of bisphosphonates early in the course of glucocorticoid therapy in high-risk patient subgroups.     

阿伦膦酸盐预防激素相关性骨量丢失的前瞻性研究

目的 研究阿伦膦酸盐预防激素相关性骨质疏松的作用.方法 将21例需要长期服用糖皮质激素的风湿病患者随机分为治疗组和对照组.对照组在应用糖皮质激素治疗同时给予乐力(氨基酸鳌合钙加维生素D)1粒,每天2次,口服;治疗组在对照组药物的基础上,加用阿伦膦酸盐10 mg,每天1次或70 mg,每周1次,口服.所有患者在治疗前和治疗后3、6、12月,应用双能X线吸收法测定腰椎及股骨颈的骨密度(BMD).结果 对照组在糖皮质激素治疗后3、6、12个月BMD与自身治疗前比较明显下降(P<0.01);治疗组腰椎的BMD与自身治疗前比较有上升趋势(12个月时有统计学差异,P<0.05),股骨颈的BMD治疗后3、6个月与自身治疗前比无变化(P>0.05),12个月有轻度降低(P<0.05).结论 单予钙剂加维生素D不能有效预防糖皮质激素相关性骨质疏松的发生,加用阿伦膦酸盐则可有效延缓糖皮质激素相关性骨量丢失.