Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs.
Insulin-like growth factor-I (IGF-I) and -II are important local regulators of bone metabolism, but their role as determinants of human bone mass is still unclear. In the present study, we analyzed the concentration of IGF-I and -II in the bone matrix of 533 human biopsies from the iliac crest that were obtained during surgery for early breast cancer. There was an inverse association of bone matrix IGF-I concentration with age that was unaffected by menopause. Bone matrix IGF-I was positively associated with histomorphometric and biochemical parameters of bone formation and bone resorption and with cancellous bone volume. Based on the estimates of the linear regression analysis, women with a bone matrix IGF-I concentration 2 SD above the mean had a 20% higher bone volume than women with a bone matrix IGF-I concentration 2 SD below the mean. In contrast, serum IGF-I was neither correlated with bone turnover nor with bone volume and was only weakly associated with bone matrix IGF-I when adjusted for the serum concentration of IGF binding protein-3. Bone matrix IGF-II was positively associated with the osteoblast surface, but in contrast to IGF-I, tended to be positively associated with age and was unrelated to cancellous bone volume. In summary, our study suggests the following. 1) The concentration of IGF-I in cancellous bone undergoes age-related decreases that are similar to those of circulating IGF-I. 2) Menopause has no effect on this age-related decline. 3) Physiological differences in bone matrix IGF-I are associated with differences in iliac crest cancellous bone volume. 4) Bone matrix IGF-I is a better predictor of cancellous bone volume than circulating IGF-I. 5) The role of IGF-II in human bone tissue is clearly distinct from that of IGF-I.
Seck
T
T
Department of Internal Medicine, University of Heidelberg, Germany.
Scheppach
B
B
Scharla
S
S
Diel
I
I
Blum
W F
WF
Bismar
H
H
Schmid
G
G
Krempien
B
B
Ziegler
R
R
Pfeilschifter
J
J
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism; D001706:Biopsy; D001857:Bone Matrix / Q000378:metabolism*; D016723:Bone Remodeling / Q000502:physiology; D001842:Bone and Bones / Q000473:pathology; D005260:Female; D006801:Humans; D007085:Ilium / Q000378:metabolism* / Q000648:ultrastructure; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D016014:Linear Models; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D017697:Premenopause / Q000378:metabolism*; D011446:Prospective Studies
D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II