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

Shreyasee Amin, B. Lawrence Riggs, L. Joseph Melton, Sara J. Achenbach, Elizabeth J. Atkinson, Sundeep Khosla

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)799-807
Number of pages9
JournalJournal of Bone and Mineral Research
Volume22
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Insulin-Like Growth Factor Binding Protein 2
Bone Remodeling
Bone Resorption
Serum
Insulin-Like Growth Factor Binding Proteins
Osteogenesis
Osteocalcin
Somatomedins
Urine
Insulin-Like Growth Factor Binding Protein 1
Bone and Bones
Sex Hormone-Binding Globulin
Insulin-Like Growth Factor II
Gonadal Steroid Hormones
Oral Contraceptives
Insulin-Like Growth Factor I
Testosterone
Estradiol
Body Mass Index
Hormones

Keywords

  • BMD
  • Bone formation
  • Bone resorption
  • Bone turnover markers
  • Insulin-like growth factor binding protein-2
  • Insulin-like growth factors

ASJC Scopus subject areas

  • Surgery

Cite this

High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. / Amin, Shreyasee; Riggs, B. Lawrence; Melton, L. Joseph; Achenbach, Sara J.; Atkinson, Elizabeth J.; Khosla, Sundeep.

In: Journal of Bone and Mineral Research, Vol. 22, No. 6, 06.2007, p. 799-807.

Research output: Contribution to journalArticle

Amin, Shreyasee ; Riggs, B. Lawrence ; Melton, L. Joseph ; Achenbach, Sara J. ; Atkinson, Elizabeth J. ; Khosla, Sundeep. / High serum IGFBP-2 is predictive of increased bone turnover in aging men and women. In: Journal of Bone and Mineral Research. 2007 ; Vol. 22, No. 6. pp. 799-807.
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abstract = "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.",
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AU - Amin, Shreyasee

AU - Riggs, B. Lawrence

AU - Melton, L. Joseph

AU - Achenbach, Sara J.

AU - Atkinson, Elizabeth J.

AU - Khosla, Sundeep

PY - 2007/6

Y1 - 2007/6

N2 - 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.

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KW - Bone formation

KW - Bone resorption

KW - Bone turnover markers

KW - Insulin-like growth factor binding protein-2

KW - Insulin-like growth factors

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