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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Authors: | T Yamaguchi M Kanatani M Yamauchi H Kaji T Sugishita D J Baylink S Mohan K Chihara T Sugimoto |
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Institution: | (1) Division of Endocrinology/Metabolism and Hematology/Oncology, Department of Medicine, Shimane University Faculty of Medicine, Shimane, 693-8501, Japan;(2) Division of Endocrinology/Metabolism, Neurology and Hematology/Oncology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, 650-0017, Japan;(3) Musculoskeletal Diseases Center (151), Jerry L. Pettis V.A. Medical Center, Loma Linda, CA, USA |
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Abstract: | 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, and P = 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. |
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Keywords: | Insulin-like growth factor-binding protein Insulin-like growth factor Bone mineral density Vertebral fracture Postmenopausal women |
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