DEXAMETHASONE-INDUCED ABNORMALITIES IN GROWTH AND BONE METABOLISM IN PIGLETS ARE PARTIALLY ATTENUATED BY GROWTH-HORMONE WITH NO SYNERGISTICEFFECT OF INSULIN-LIKE GROWTH-FACTOR-I

Dexamethasone (DEX) therapy improves pulmonary compliance in premature infants with chronic lung disease; however, normal growth and bone de velopment are impaired. Because DEX may mediate its effects by alterin g the GH-IGF-I axis, we investigated whether adjunctive therapy with G H or GH + IGF-I during DEX therapy could attenuate these DEX-induced e ffects. Piglets were randomized to placebo, oral tapered DEX (0.5, 0.3 , and 0.2 mg kg(-1) d(-1) over 14 d), DEX + GH (0.1 mg kg(-1) d(-1)) o r DEX + GH + IGF-I (0.1 mg kg(-1) d(-1)). Final whole body weight and length were improved with GH or GH + IGF-I compared with the DEX alone group. Plasma GH and IGF-I were not influenced by DEX, but infusion o f IGF-I resulted in higher (p < 0.05) plasma IGF-I compared with all o ther groups at d 15. DEX reduced (p < 0.05) circulating IGFBP-2 and IG FBP-3 and liver IGFBP-2 and IGFBP-4 mRNA expression compared with cont rols. Treatment with DEX alone resulted in lower (p < 0.05) plasma ost eocalcin, urinary N-telopeptide, and whole body and femur bone mineral density compared with controls, whereas results with piglets receivin g adjunctive GH or GH + IGF-I were similar to those of controls. Given adjunctively, GH alone appears to partially counter the abnormalities in growth and bone metabolism associated with DEX therapy; however, t his improvement cannot be attributed to higher circulating IGF-I, beca use combined therapy did not further improve growth or bone homeostasi s compared with DEX + GH treatment. Growth hormone therapy has the pot ential to stimulate growth in infants exposed to steroid treatment.