中国骨质疏松杂志

两种糖皮质激素导致骨质疏松过程中骨量、骨转换标志物及雌激素水平的差异

Effect of two kinds of glucocorticoid on the difference of bone mass and the levels of bone turnover markers and estrogen during the process of osteoporosis

DOI：10.3969/j.issn.1006-7108.2015.02.003

中文关键词: 糖皮质激素骨质疏松雌激素骨转换指标骨密度

英文关键词:Glucocorticoid Osteoporosis Estrogen Bone turnover markers Bone mineral density

基金项目:广东省教育厅学科建设专项基金（育苗工程）[2013LYM-0012]；广州中医药大学优秀青年学者科研基金项目(KAB110133K04)

作者	单位
杨志东1 崔健超2 江晓兵1* 任辉2 魏秋实3 梁德1 张顺聪1 林顺鑫2 唐晶晶2 沈耿杨2	1．广州中医药大学第一附属医院二骨科,广州 510405 2．广州中医药大学,广州 510405 3．广州军区广州总医院博士后科研工作站,广州 510000

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中文摘要:

目的对比泼尼松龙（PRE）和地塞米松（DXM）致骨质疏松过程中对大鼠骨量和骨转换标志物、雌激素水平的差异。方法选取3月龄SPF级雌性大鼠46只，随机分成4组：基线组（BL组）6只、年龄对照组（AM组）12只、泼尼松龙组（PRE组）14只、地塞米松组（DXM组）14只。BL组于实验开始时麻醉处死，其余各组分别予常规饲养，PRE组以5mg/kg PRE每天一次皮下注射，DXM组以1mg/kg DXM每周两次皮下注射，于干预后1、2、3个月（M1、M2、M3）分3批麻醉处死取材。每次取材时立即取子宫、肾上腺称重，并收集血清以检测血清内雌激素、PINP及β-CTX水平、收集腰1-3椎体以检测腰椎骨密度（BMD）。结果 PRE组各时间点BMD值[（0.183±0.027、0.230±0.005、0.259±0.014）g/cm2]及DXM组各时间点BMD值[（0.191±0.010、0.208±0.012、0.200±0.004）g/cm2]均较AM组[（0.251±0.014、0.275±0.009、0.281±0.008）g/cm2]明显下降（P＜0.05），其中DXM组下降更为显著（P＜0.01），且在M2及M3，DXM组BMD值明显低于PRE组（M2：P＜0.05；M3：P＜0.01）。PRE组干预初期，其血清雌激素水平（36.54±20.40μg/L）较AM组（148.74±40.33 μg/L）明显降低（P＜0.01），但随着干预时间延长， M3时（130.85±18.95 μg/L）增长至与AM组（126.64±69.12 μg/L）相接近水平（P＞0.05），但在DXM干预下，雌激素水平在各时间点[（93.13±31.27、91.77±33.14、98.83±10.58）μg/L]均低于AM组[（148.74±40.33、140.01±28.46、126.64±69.12）μg/L]（P＜0.05）。两种GC干预下，PINP及β-CTX均显著高于AM组（P＜0.01），且PRE干预后各时间点PINP水平[（1410.33±882.40、2089.23±1623.61、1546.88±644.68）μg/L]显著高于DEX组[（258.70±139.42、220.89±92.82、483.36±225.82）μg/L]（P＜0.05）。结论地塞米松诱导骨量减少的能力明显强于泼尼松龙，这可能与其更大程度地降低血清雌激素水平以及更有效地限制成骨有关。

英文摘要:

Objective To study the difference in the bone mass and the levels of bone turnover markers and estrogen in the prednisolone- and dexamethasone-induced osteoporosis. Methods Forty-six 3-month-old female SD rats were randomly divided to 4 groups, baseline group (BL group, 6 rats), age-matched control group (AM group, 14 rats), prednisolone-treated group (PRE group, 14 rats), and dexamethasone-treated group (DXM group, 14 rats). Rats in BL group were euthanized at the beginning of the experiment. Rats in PRE group and DXM group were injected with PRE 5mg/kg per day and DXM 1mg/kg twice per week, respectively, for 3 months. Rats in AM, PRE, and DXM groups were euthanized in 1 month (M1), 2 months (M2), and 3 months (M3) after the treatment. The uterus and adrenal were collected for weight calculation. Serum estrogen, PINP, and β-CTX were examined. Bone mineral density (BMD) of the lumbar 1-3 were isolated and examined. Results BMD of rats at each time point in PRE (0.183±0.027, 0.230±0.005, 0.259±0.014 g/cm2) and DXM (0.191±0.010, 0.208±0.012, 0.200±0.004 g/cm2) was lower than that of rats in AM (0.251±0.014、0.275±0.009、0.281±0.008 g/cm2, P<0.05), The decrease was more notably in DXM rats (P<0.01). Moreover, BMD in DXM rats decreased significantly compared with PRE rats at M2 and M3 (M2, P<0.05; M3, P<0.01). Estrogen level in PRE rats (36.54±20.40 μg/L) was lower than that in AM rats (148.74±40.33 μg/L) at M1 (P<0.01). However, it increased to the similar level of AM rats at M3 (P>0.05). Estrogen level in DXM rats sustained in the lower level at each time point (93.13±31.27, 91.77±33.14, 98.83±10.58 μg/L) compared with AM rats (148.74±40.33, 140.01±28.46, 126.64±69.12 μg/L, P<0.05). The levels of PINP and β-CTX in two glucocorticoid-treated groups were significantly higher than those in AM rats at each time point (P<0.01). Additionally, the level of PINP in PRE rats (1410.33±882.40, 2089.23±1623.61, 1546.88±644.68μg/L) was higher than that in DEX rats at each time point (258.70±139.42, 220.89±92.82, 483.36±225.82 μg/L, P<0.05). Conclusion The effect of DXM on bone mass loss is more powerful than PRE, which might be caused by more reduction of estrogen level and bone formation activity.

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