Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures
Increased RANKL/OPG mRNA ratio in iliac bone biopsies from women with hip fractures
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DOI：
10.1007/s00223-004-0074-4
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发表时间：
2005-02-01
影响因子：
4.2
通讯作者：
Abrahamsen, B
中科院分区：
文献类型：
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作者：
Abdallah, BM;Stilgren, LS;Abrahamsen, B
RANKL（NF-κ B受体激活剂）是破骨细胞生成的有效生理诱导剂。其作用被诱骗受体骨保护素（OPG）阻断，用OPG治疗可阻断绝经后妇女的骨吸收。血清OPG和骨密度（BMD）之间的正相关和负相关已在文献中报道。我们假设骨内OPG相对于RANKL的产生减少可能导致骨质疏松性骨折的风险增加。我们纳入了10名髋部骨折妇女（年龄76.3 ± 8.0岁，NS髋部BMD 0.686 ± 1.3 g/cm 2，p < 0.05）和24名髋部骨关节病妇女（年龄72.8 ± 7.2岁，髋部BMD 0.832 ± 1.1 g/cm 2）。手术时进行了经髂骨活检。从活检组织中提取总RNA并进行逆转录。用SYBR绿色I真实的时间PCR分析进行mRNA的实时定量，用0肌动蛋白mRNA结果的标准化计算相对基因表达。骨折患者中OPG和白细胞介素（IL）-6的肌动蛋白标准化mRNA水平显著较低，骨折患者中RANKL/OPG比值显著较高。肿瘤坏死因子（TNF）、IL-1、IL-1 ra或IL-7表达无显著差异。骨折组IL-6 mRNA水平明显低于对照组（P < 0.05）。Logistic回归分析显示，RANKL/OPG比值升高（Z = 2.08，P < 0.05）与髋部BMD T评分（Z =-1.95，P < 0.05）对骨折风险的影响是相加的。髋部骨折的老年妇女髂骨RANKI_（10）PG mRNA含量增加。这与骨折易感性增加有关，这本身不能用低BMD解释。
RANKL (receptor activator of NF-kappaB) is a potent physiological inducer of osteoclastogenesis. Its actions are blocked by the decoy receptor osteoprotegerin (OPG), and treatment with OPG blocks bone resorption in postmenopausal women. Both positive and negative associations between serum OPG and bone mineral density (BMD) have been reported in the literature. We hypothesized that decreased OPG production relative to RANKL within bone itself could lead to increased risk of osteoporotic fracture. We included ten women with hip fracture (age 76.3 +/- 8.0 years, NS hip BMD 0.686 +/- 1.3 g/cm(2), p < 0.05) and 24 women with osteoarthrosis of the hip (age 72.8 +/- 7.2 years, hip BMD 0.832 +/- 1.1 g/cm(2)). Transiliac biopsies were obtained at the time of surgery. Total RNA was extracted from biopsies and reverse-transcribed. Real-time quantification of rnRNA was performed with a SYBR Green I real time PCR assay, calculating relative gene expession with normalization of results for 0 actin mRNA. Actin normalized mRNA levels for OPG and interleukin (IL)-6 were significantly lower in fracture patients, with a significantly higher RANKL/OPG ratio in patients with Fractures. There was no significant difference in tumor necrosis factor (TNF), IL-1, IL-1ra, or IL-7 expression. IL-6 mRNA levels were lower in fracture patients (P < 0.05). The effect of increased RANKL/OPG ratio (Z = 2.08, P < 0.05) on fracture risk was additive to that of hip BMD T score (Z = -1.95, P < 0.05) when assessed using logistic regression. Elderly women with hip fractures exhibit an increased RANKI_/0PG rnRNA content of iliac bone. This is associated with increased fracture susceptibility, which is not in itself explained by low BMD.