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

Abstract

Chronic glucocorticoid therapy results in negative bone and connective tissue 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 recombinant 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 µg/kg per day s.c.) or placebo (saline s.c.) during 6 days of methylprednisolone (0·5 mg/kg per day) treatment. Methylprednisolone decreased serum osteocalcin concentrations during placebo treatment from 32·9 2·1 to 9·0 1·4 µg/l (P<0·0001), indicating diminished osteoblast activity, and procollagen type I (PICP) and procollagen type III (PIIINP) to 46 and 70% of baseline respectively (P<0·005), indicating diminished bone (PICP) and soft tissue collagen synthesis (PIIINP). Urinary excretion of pyridinoline, deoxypyridinoline and hydroxyproline increased during treatment with methylprednisolone alone, indicating increased bone resorption (P<0·05 or less). The combination of GH and IGF-I resulted in a significant blunting of the methylprednisolone effect on serum PICP and PIIINP 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 not GH alone, markedly counteracts diminished bone and body collagen synthesis caused by glucocorticoids, whereas connective tissue resorption is enhanced during treatment with GH alone and in combination with IGF-I.

Effect of Carnitine on Cutaneous Wound Healing in Immunosuppressed Rats

“…Despite the well known fact that glucocorticoids decrease hydroxyproline levels and increase connective tissue turnover [16,17], it was shown in the 1990s that they also increase matrix protein production and matrix maturation. In a study by Del Monaco et al, glucocorticoids were shown to induce up-regulation of human elastin promoter activity and regulate gene expression at the transcriptional level [11].…”

Skeletal effects of growth hormone and insulin-like growth factor-I therapy

“…On the whole, IGF-I therapy resulted in significantly increased bone turnover and improved bone formation, with no significant adverse effects reported (Locatelli and Bianchi, 2014). IGF-I administration has been studied in healthy subjects (Bianda et al, 1997; Ghiron et al, 1995; Mauras et al, 1996), fasting subjects (Grinspoon et al, 1995), anorexic/osteopenic subjects (Grinspoon et al, 2002, 1996; Misra et al, 2009), postmenopausal women with and without osteoporosis (Ebeling et al, 1993; Friedlander et al, 2001), osteopenic men (Johansson et al, 1996, 1992), subjects with osteoporosis secondary to Werner syndrome (Rubin et al, 1994), and subjects with glucocorticoid-induced osteoporosis (Berneis et al, 1999). The only study which did not find any differences between IGF-I treatment and placebo (Friedlander et al, 2001) was a relatively long-term study in which negative feedback from exogenous IGF-I could have suppressed GH secretion.…”

Glucocorticoid-Induced osteoporosis: clinical and therapeutic aspects

“…An increase in serum osteocalcin, carboxy-terminal propeptide of type I procollagen and carboxy-terminal telopeptide of type I collagen was observed following shortterm recombinant human (rh)GH treatment in a selected population of patients receiving chronic corticosteroid treatment for non-endocrine diseases (27). Moreover, combined therapy of rhGH and rhIGF-I counteracted selected negative effects of glucocorticoids on bone in healthy volunteers who received short-term glucocorticoid therapy (29). Observational and controlled studies in children receiving glucocorticoid therapy for juvenile idiopathic arthritis showed that rhGH restored normal height velocity with a concomitant improvement of bone mineralization (30)(31)(32)(33).…”