Insulin-like growth factor-1 increases bone calcium accumulation only during rapid growth in female rats.

Q Zhang
M E. Wastney
C J. Rosen
W G. Beamer
C M. Weaver


Calcium retention varies with developmental state, which may be partially under the control of insulin-like growth factor 1 (IGF-1). IGF-1 levels can be manipulated through dietary and therapeutic interventions. We investigated the relationship between IGF-1 endogenous production and calcium utilization and bone accretion during growth as well as the effects of IGF-1 treatment on calcium utilization during rapid and slowed growth in intact female Sprague-Dawley rats. In 33 rats killed at 11 time points (n = 3 each) from age 4 to 24 wk, femoral and vertebral bone mass were paralleled by plasma IGF-1 up to 9 wk. Fractional calcium absorption was maximal at 9 wk, reduced by one-half at 12 wk, and there was no further change at 20 wk. From this study, we selected 2 stages of growth, rapid and slow, for a subsequent intervention study. A 4-wk intervention was initiated at 6 or 8 wk when rats (n = 15/group) received either continuous rhIGF-1/IGF binding protein 3 (IGFBP3) infusion (0.3 mg/d) or vehicle (control) by osmotic mini-pumps. In rapidly growing IGF-1/IGFBP3-treated rats compared to controls, but not in slowly growing treated compared to control rats, IGF-1 treatment increased (P < 0.05) calcium absorption (35 vs. 21%), bone calcium balance (0.55 vs. 0.3 mmol/d), and femoral calcium content (31 vs. 24% of dry weight). Exogenous IGF-1/IGFBP3 treatment increased calcium accretion during rapid growth, but rats past rapid growth were no longer as sensitive to this dose of IGF-1/IGFBP3. Thus, interventions designed to improve bone mass through increased IGF-1 will have the greatest impact during rapid growth.