High serum IGFBP-2 is predictive of increased bone turnover in aging men and women.
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.


BACKGROUND
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.


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.
Amin
Shreyasee
S
Division of Rheumatology, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. amin.shreyasee@mayo.edu
Riggs
B Lawrence
BL
Melton
L Joseph
LJ
Achenbach
Sara J
SJ
Atkinson
Elizabeth J
EJ
Khosla
Sundeep
S
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000032:analysis / Q000097:blood / Q000652:urine; D001862:Bone Resorption / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism; D001842:Bone and Bones / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood*; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D007335:Insulin-Like Growth Factor II / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000502:physiology; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood / Q000652:urine; D011237:Predictive Value of Tests; D011347:Procollagen / Q000097:blood; D012737:Sex Factors
D015415:Biomarkers; D024042:Collagen Type I; C032231:IGFBP1 protein, human; C515497:IGFBP3 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D000469:Alkaline Phosphatase