Effects of IGF-I combined with GH on glucocorticoid-induced changes of bone and connective tissue turnover in man

Chronic glucocorticoid therapy results in negative bone and connective tiss ue balance. To assess the effects of GH and a combination of IGF-I and GH, 24 healthy male volunteers received in a double blind fashion either recomb inant human GH (0.3 IU/kg per day s.c.), or a combination of GH (0.3 IU/kg per day s.c.) and IGF-I (80 mu g/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0.5 mg/kg per day) treatment. Methylpr ednisolone decreased serum osteocalcin concentrations during placebo treatm ent from 32.9 +/- 2.1 to 9.0 +/- 1.4 mu g/l (P<0.0001), indicating diminish ed osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0.005), indicating d iminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased d uring treatment with methylprednisolone alone, indicating increased bone re sorption (P<0.05 or less). The combination of GH and IGF-I resulted in a si gnificant blunting of the methylprednisolone effect on serum PICP and PIIIN P concentrations (P<0.005 or less vs placebo); this effect was in part due to IGF-I, since serum PICP concentrations decreased less in the combination group than during GH treatment alone (P<0.05). In the groups receiving GH and GH combined with IGF-I, urinary hydroxyproline excretion increased more when compared with methylprednisolone alone (P<0.05 or less). These findings demonstrate that only the combination of GH and IGF-I, but n ot GH alone, markedly counteracts diminished bone and body collagen synthes is caused by glucocorticoids, whereas connective tissue resorption is enhan ced during treatment with GH alone and in combination with IGF-I.