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

Abstract

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.

In vivo characterization of 3D-printed polycaprolactone-hydroxyapatite scaffolds with Voronoi design to advance the concept of scaffold-guided bone regeneration

“…Specifically-although this was not the hypothesis of this work-we showed that utilizing bone chips, bone marrow, or a combination of both was associated with superior bone volume compared to bone marrow alone. This is in line with previous literature (Laubach et al, 2023a) where the bone matrix is host to various growth factors such as insulin-like growth factor 1 (Seck et al, 1998), bone morphogenetic protein (BMP)-2 and BMP-4 (Sipe et al, 2004;Dimitriou et al, 2005;Pecina and Vukicevic, 2007), and transforming growth factor-ß1 (Perez et al, 2018) that are deeply embedded in the bone matrix and thus sustainably released over time as the matrix is degraded and remodeled (Canalis et al, 1988;Joyce et al, 1990). Such controlled release of growth factors is not possible with bone marrow, which is rapidly resorbed by the body, thus limiting sustained bone regeneration.…”

Bone remodeling: an operational process ensuring survival and bone mechanical competence

“…IGF-1 is the most abundant growth factor deposited in the bone ECM. 212 Osteocytes in particular secrete large amounts of IGF1, which is incorporated in the bone matrix. 213 Since IGF-1 is produced under loading, it might contribute to the mechanotransduction process.…”

The Potential Role of Serum IGF-1 and Leptin as Biomarkers: Towards Screening for and Diagnosing Postmenopausal Osteoporosis

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