SKELETAL RESPONSE TO RECOMBINANT HUMAN GROWTH-HORMONE (RHGH) IN CHILDREN TREATED WITH LONG-TERM CORTICOSTEROIDS

Corticosteroid therapy causes osteopenia and growth retardation in chi ldren; such changes are associated with diminished rates of bone forma tion and turnover. Since growth hormone activates bone remodeling, the biochemical and skeletal responses to rhGH were evaluated in four ped iatric patients, aged 12.8 +/- 3 years, with long-term corticosteroid use (5 +/- 2 years). Recombinant human growth hormone (rhGH), 0.125 mg /kg, was given 3 times/week by subcutaneous injection for 12 months. I liac crest bone biopsies were obtained after double tetracycline label ing before and at the end of rhGH therapy; serum levels of calcium, ph osphorus, alkaline phosphatase, parathyroid hormone (intact), 25-hydro xyvitamin D, 1,25-dihydroxyvitamin D-3, osteocalcin (BGP), and insulin -like growth factor-1 (IGF-1) were measured every 3 months during the treatment period. The average dose of prednisone was 0.24 +/- 0.05 mg/ kg/day initially, and this did not change during the study. Serum calc ium, phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, 1,25-dihyd roxyvitamin D-3, and BGP were unchanged during the rhGH therapy, but t he serum IGF-1 level increased by 71%, p < 0.01. Eroded bone perimeter and cancellous bone area did not change significantly during rhGH the rapy. Bone formation rates rose from 423 +/- 475 to 781 +/- 407 mu m(2 )/mm(2)/day, p < 0.05, and the length of double tetracycline-labeled b one perimeter increased by 85%, p < 0.05. The bone formation rate in t he growth hormone group exceeded the values of an age-matched referenc e group (14.3 +/- 3 years), 780 +/- 407 mu m(2)/mm(2)/day versus 411 /- 479 mu m(2)/mm(2)/day,p < 0.05. Thus, rhGH therapy increases osteob lastic activity, bone formation, and possibly bone turnover despite co ntinued and prolonged corticosteroid administration in children.