The authors state that they have no conflicts of interest.
Article first published online: 12 MAR 2007
Copyright © 2007 ASBMR
Journal of Bone and Mineral Research
Volume 22, Issue 6, pages 799–807, June 2007
How to Cite
Amin, S., Riggs, B. L., Melton, L. J., Achenbach, S. J., Atkinson, E. J. and Khosla, S. (2007), High Serum IGFBP-2 Is Predictive of Increased Bone Turnover in Aging Men and Women. J Bone Miner Res, 22: 799–807. doi: 10.1359/jbmr.070306
Published online on March 12, 2007;
- Issue published online: 4 DEC 2009
- Article first published online: 12 MAR 2007
- Manuscript Received: 9 OCT 2007
- Manuscript Accepted: 5 MAR 2007
- Manuscript Revised: 18 JAN 2007
- insulin-like growth factors;
- insulin-like growth factor binding protein-2;
- bone resorption;
- bone formation;
- bone turnover markers;
Elevated serum IGFBP-2 is associated with lower BMD in men and women. It is unknown whether IGFBP-2 serves as a negative regulator of bone metabolism by decreasing bone formation or increasing bone resorption. Studying an age-stratified community-based sample of 344 men and 276 women, IGFBP-2 was the strongest predictor of increased bone resorption among the IGF/IGFBPs studied.
Introduction: Serum insulin-like growth factor binding protein-2 (IGFBP-2), which increases with age, is a predictor of low BMD among aging men and women. However, it is unknown whether IGFBP-2 negatively influences bone metabolism by decreasing bone formation or increasing bone resorption. Few have examined the relation between the insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) with bone turnover markers.
Materials and Methods: In an age-stratified, random sample of the community, we examined the association between serum IGF-I, IGF-II, IGFBP-1, −2, and −3, and bone turnover markers before and after adjustment for potential confounders (age, body mass index, bioavailable estradiol and testosterone, and sex hormone binding globulin). Analyses were stratified by sex and menopausal status.
Results: We studied 344 men (age range, 23–90 yr) and 276 women (age range, 21–93 yr; 166 postmenopausal) not on oral contraceptives or hormone replacement. Among the IGF/IGFBPs assessed, IGFBP-2 was the strongest and most consistent predictor of bone turnover in men and women. After adjustment for potential confounders, IGFBP-2 was positively associated with osteocalcin (OC) and urine and serum N-teleopeptide (NTX) in men (r = 0.20, 0.26, and 0.23, respectively; p < 0.001), serum C-telopeptide (CTX) in premenopausal women (r = 0.28; p < 0.01), and OC, urine NTX, and serum CTX in postmenopausal women (r = 0.24, 0.33, and 0.19, respectively; p < 0.05).
Conclusions: Higher serum IGFBP-2, which is predictive of lower BMD, is associated with increased markers of bone resorption, independent of age, body mass, and sex hormones. The association between IGFBP-2 and markers of bone formation may reflect coupling with increased bone resorption, which is not adequate to maintain BMD.