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

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.

Ameloblastin, an Extracellular Matrix Protein, Affects Long Bone Growth and Mineralization

“…A PCR array employed during our quest for an explanation of the unexpected growth reduction in AMBN mice identified IGF1 as the second most deregulated gene product and possible candidate for changes in osteoblast proliferation and overall growth rate. IGF1 is the most abundant growth factor produced by osteoblasts (36,37) and is thought to be responsible for the maintenance of a physiological pace of proliferation in the skeletal system. (38)(39)(40) Low levels of IGF1 have been associated with dwarfism and Laron syndrome, and Igf1 null mice exhibit impaired postnatal growth and defects in longitudinal bone growth.…”

Relationship between IGF-I and skeletal aging

“…It is conceivable that skeletal IGF-I activity differs greatly from that of circulating IGF-I because of the complex IGF regulatory system in bone tissue. In fact, data from our laboratory suggest that, despite age-associated decreases in both human cancellous bone matrix and serum, IGF-I concentrations between the two compartments hardly correlate with each other at all (11). Of possibly even greater significance, only bone matrix IGF-I was significantly associated with trabecular bone volume in these samples, indicating that measuring circulating IGF-I levels may underestimate the impact of IGF-I on bone metabolism.…”

“…Even the weak association between circulating IGF-I and bone mass in the elderly may be reminiscent of the beneficial effects of IGF-I on peak bone mass, as individual differences in IGF-I activity may persist throughout life. Compatible with such an hypothesis of a waning anabolic effect of IGF-I on bone, circulating IGF parameters in the 50-80-year-old men and women from the Heidelberg cohort of the European Vertebral Osteoporosis Study study were weakly positively correlated with baseline BMD values (5), but not with longitudinal changes in BMD over a 2-3 year observation period (11).…”

Microarray Analysis of Human Dental Follicle Cells in Osteogenic Differentiation

“…However, the molecular mechanisms for osteogenic differentiation of hDFC are not well known. In this study, we investigated the changes of gene expressions in hDFC during the osteogenic differentiation using 15) , and is suggested to be an important growth-promoting factor for human bone cells in vivo and in vitro; therefore, we focused on IGF-II.…”