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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 IGFs¹

Departments of Internal Medicine I (T.S., B.S., H.B, G.S., R.Z., J.P.), Gynecology (I.D.), and Pathology (B.K.) University of Heidelberg; Rehabilitation Center Berchtesgadener Land (S.S.), Schönau am. Königssee; and Lilly Deutschland GmbH (W.F.B.), Bad Homburg, Germany

Address all correspondence and requests for reprints to: T. Seck, Department of Internal Medicine I, University of Heidelberg, Luisenstraße 5, D-69115 Heidelberg, Germany.

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.

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