Serum Levels of Insulin-Like Growth Factor (IGF); IGF-Binding Proteins-3, -4, and -5; and Their Relationships to Bone Mineral Density and the Risk of Vertebral Fractures in Postmenopausal Women
Serum Levels of Insulin-Like Growth Factor (IGF); IGF-Binding Proteins-3, -4, and -5; and Their Relationships to Bone Mineral Density and the Risk of Vertebral Fractures in Postmenopausal Women
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DOI：
10.1007/s00223-005-0163-z
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发表时间：
2006-01
影响因子：
4.2
通讯作者：
Toru Yamaguchi;M. Kanatani;M. Yamauchi;H. Kaji;T. Sugishita;D. Baylink;S. Mohan;Kazuo Chihara;T. Sugimoto
中科院分区：
文献类型：
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作者：
Toru Yamaguchi;M. Kanatani;M. Yamauchi;H. Kaji;T. Sugishita;D. Baylink;S. Mohan;Kazuo Chihara;T. Sugimoto
我们以前发现，血清胰岛素样生长因子I（IGF-I）和胰岛素样生长因子结合蛋白（IGFBP）-3水平与骨密度（BMD）和椎体骨折风险相关，但与IFGBP-2无关。本研究的目的是调查IGFBP-4和-5在绝经后日本妇女年龄依赖性骨丢失和椎骨骨折风险中的作用，并将其与IGF-I和IGFBP-3进行比较。193名年龄在46-88岁（平均62.5岁）的日本女性参加了这项横断面研究。采用双能X线骨密度仪测量腰椎、股骨颈、桡骨远端（UDR）和全身BMD。采用放射免疫法测定血清IGFBP-4、IGFBP-5、IGF-I、IGFBP-3水平。血清IGF-I、IGFBP-3和IGFBP-5水平随年龄增长而下降，而血清IGFBP-4随年龄增长而增加。对每个骨骼部位的BMD与血清IGF-I和IGFBPs水平进行多元回归分析，调整年龄、体重、身高和血清肌酐。UDR部位的BMD与血清IGF-I和IGFBPs均呈显著正相关（P< 0.01），而股骨颈部位的BMD与血清IGF-I和IGFBPs均无相关性。血清IGF-I水平与除股骨颈外其他部位的BMD均呈显著正相关（P< 0.01），血清IGFBP-3、-4水平仅与桡骨BMD呈显著正相关（P< 0.01）。血清IGFBP-5水平与UDR BMD呈正相关（P< 0.001），与BMD呈负相关（P< 0.05）。血清IGF-I、IGFBP-3和IFGBP-5水平在有脊椎骨折的女性中显著低于无骨折的女性（平均值±标准差：97.1 ± 32.1对比143.9 ± 40.9 ng/dl，P< 0.0001; 2.18 ± 1.02对比3.23 ± 1.07 μg/ml，P< 0.0001; 223.6 ± 63.3对比246.5 ± 71.5 ng/ml，P= 0.0330）。当进行多变量逻辑回归分析时，以椎骨骨折的存在作为因变量，并以年龄、体重、身高、血清肌酐和血清白蛋白校正的IGF-I和IGFBP的血清水平作为自变量，选择IGF-I和IGFBP-3作为影响椎骨骨折存在的指标[比值比（OR）= 0.29，95%置信区间（CI）0.15-0.57/SD增加，P= 0.0003和OR = 0.31，95% CI 0.16-0.61/SD增加，P= 0.0007]。为了比较显著性值，在分析中同时添加IGF-I、IGFBP-3和年龄作为自变量。与IGF-I和年龄相比，IGFBP-3与椎体骨折的发生有更强的相关性（分别为P= 0.0006，P = 0.0148，P = 0.0013）。因此，在综合测量血清IGF-I和IGFBP水平后，似乎血清IGF-I水平与骨量最有效相关，血清IGFBP-3水平与所检查的IGF系统组分中绝经后妇女椎骨骨折的存在最强烈相关。
We previously found that serum levels of insulin-like growth factor I (IGF-I) and IGF-binding protein (IGFBP)-3, but not IFGBP-2, were associated with bone mineral density (BMD) and the risk of vertebral fractures. The aim of the present study was to investigate the roles of IGFBP-4 and -5 in age-dependent bone loss and vertebral fracture risk in postmenopausal Japanese women and to compare them with those of IGF-I and IGFBP-3. One hundred and ninety-three Japanese women aged 46–88 years (mean 62.5) were enrolled in the cross-sectional study. BMD was measured at the lumbar spine, femoral neck, ultradistal radius (UDR), and total body by dual-energy X-ray absorptiometry. Serum levels of IGFBP-4 and -5 as well as IGF-I and IGFBP-3 were measured by radioimmunoassay. Serum levels of IGF-I, IGFBP-3, and IGFBP-5 declined with age, while serum IGFBP-4 increased with age. Multiple regression analysis was performed between BMD at each skeletal site and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, and serum creatinine. BMD at the UDR was significantly and positively correlated with all serum levels of IGF-I and IGFBPs measured (P< 0.01), while BMD at the femoral neck was correlated with none of them. Serum IGF-I level was significantly and positively correlated with BMD at all sites except the femoral neck (P< 0.01), while serum IGFBP-3 and -4 levels were significantly and positively correlated with only radial BMD (P< 0.01). Serum IGFBP-5 level was positively correlated with UDR BMD (P< 0.001) and negatively correlated with total BMD (P< 0.05). Serum IGF-I, IGFBP-3, and IFGBP-5 levels were significantly lower in women with vertebral fractures than in those without fractures (mean ± SD: 97.1 ± 32.1 vs. 143.9 ± 40.9 ng/dl,P< 0.0001; 2.18 ± 1.02 vs. 3.23 ± 1.07 μg/ml,P< 0.0001; 223.6 ± 63.3 vs. 246.5 ± 71.5 ng/ml,P= 0.0330, respectively). When multivariate logistic regression analysis was performed with the presence of vertebral fractures as a dependent variable and serum levels of IGF-I and IGFBPs adjusted for age, body weight, height, serum creatinine, and serum alubumin as independent variables, IGF-I and IGFBP-3 were selected as indices affecting the presence of vertebral fractures [odds ratio (OR) = 0.29, 95% confidential interval (CI) 0.15–0.57 per SD increase,P= 0.0003 and OR = 0.31, 95% CI 0.16–0.61 per SD increase,P= 0.0007, respectively]. To compare the significance values, IGF-I, IGFBP-3, and age were simultaneously added as independent variables in the analysis. IGFBP-3 was more strongly associated with the presence of vertebral fractures than IGF-I and age (P= 0.0006,P= 0.0148, andP= 0.0013, respectively). Thus, after comprehensive measurements of serum levels of IGF-I and IGFBPs, it seems that serum IGF-I level is most efficiently associated with bone mass and that serum IGFBP-3 level is most strongly associated with the presence of vertebral fractures in postmenopausal women among the IGF system components examined.