Effects of short-term insulin-like growth factor-I or growth hormone treatment on bone turnover, renal phosphate reabsorption and 1,25 dihydroxyvitamin D3 production in healthy man

Abstract

Objectives. To find out whether insulin-like growth factor-I (IGF-I) mimics the stimulatory effects of growth hormone (GH) on bone turnover and renal tubular phosphate reabsorption. Design. Randomized, crossover study. Setting. University Hospital, Zurich, Switzerland. Subjects. Seven young healthy male subjects. Interventions. Each subject was studied three times at 2-week intervals, treated with saline 0.9% (S), IGF-I [8 μg kg-1 h-1] by a continuous subcutaneous infusion and finally with GH (6 U. twice daily s.c.) for 5 days. Main outcome measures. 36 h after the start of treatment, IGF-I, biochemical markers of bone turnover, calcium, calcium regulating hormones, kidney function and phosphate reabsorption were measured in serum and in 2 h urine in fasting state. Results. Serum levels of IGF-I were 26.8±7.3 (S), 119.4±11.4 (IGF-I) (P < 0.02) and 58.4±12.9 nmolL-1 (GH) (P < 0.02), respectively. Serum osteocalcin and carboxyterminal propeptide of type E collagen (PICP) as well as the urinary deoxypyridinoline/creatinine and the calcium/ creatinine ratios were all significantly higher after IGF-I (P < 0.02) or GH (P < 0.02) than after saline treatment. PTH levels did not change in response to treatment. Total albumin-corrected calcium increased only after GH treatment (P < 0.05). The free calcitriol index rose from 2.2±0.5 x 10-5 (S) to 2.81±0.25 x 10-5 (IGF-I) (P < 0.03) and 2.45±0.25 x 10-5 (GH), respectively. Serum phosphate and maximal tubular reabsorption divided by glomerular filtration rate (TmP/GFR) were significantly raised by GH (P < 0.03) but not by IGF-I as compared to saline 0.9%. Conclusions. (i) Similar to GH, IGF-I rapidly activates bone turnover. (ii) IGF-I does not mimic the effect of GH on renal phosphate reabsorption in spite of comparable effects on renal blood flow and glomerular filtration rate. (iii) IGF-I increases free calcitriol index in face of unchanged serum levels of calcium, phosphate and PTH, consistent with a direct stimulatory effect on 25-OHD-1a-hydroxylase.