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Effects of Treatment with GH Alone or in Combination with LHRH Analog on Bone Mineral Density in Pubertal GH-Deficient Patients

Institute of Maternal and Child Research, University of Chile, Santiago, Chile

Address all correspondence and requests for reprints to: Fernando Cassorla, IDIMI, University of Chile, Casilla 226-3, Santiago, Chile. E-mail: fcassorl{at}machi.med.uchile.cl

The aim of the present study was to assess the impact of treatment with GH with or without LHRH analog (LHRH-A) on bone mineralization of GH-deficient adolescents. We studied 17 pubertal, treatment-naive, GH-deficient patients (10 girls and 7 boys) in a prospective, randomized trial. Mean chronological age and mean bone age were 14.1 ± 0.4 and 11.3 ± 0.3 yr, respectively, at the beginning of the study. Treatment with GH + LHRH-A (n = 7) or GH alone (n = 10) started simultaneously. Nutropin was administered at a dose of 0.1 U/kg per day sc until patients reached near final height (NFH), defined as a bone age of 14 yr in girls and 16 yr in boys. Mean time of GH therapy in the patients treated with GH+LHRH-A was 4.8 ± 0.5 yr and in the patients treated with GH alone 2.9 ± 0.7 yr. Lupron was administered at a dose of 300 µg/kg every 28 d im for 3 yr. Bone mineral density (BMD) was assessed yearly by dual-energy x-ray absorptiometry at the lumbar spine (L2-L4) and femoral neck at the beginning of the study, after 3 yr of hormonal therapy, and at NFH. Statistical analysis was performed by t test and ANOVA. We observed a significant increase in lumbar and femoral bone mineral content, BMD, SD score, and bone mineral apparent density, compared with baseline in both groups of patients, regardless of whether they were treated with GH alone or in combination with LHRH-A. The patients treated with GH + LHRH-A had a significantly lower bone mineral content after 3 yr of therapy. This difference, however, did not persist after both groups of patients reached NFH. These results indicate that delaying puberty with LHRH-A in GH-deficient patients treated with GH diminishes transient bone mineralization but does not appear to have a permanent impact on BMD.

This work was supported in part by Fondecyt Grant 1940543 (to F.C.). This work was presented in part at the 82nd Annual Meeting of The Endocrine Society, Toronto, Canada, 2000.

Abbreviations: BMAD, Bone mineral apparent density; BMC, bone mineral content; BMD, bone mineral density; GHD, GH deficiency; IGFBP3, IGF-binding protein-3; LHRH-A, LHRH analog; NFH, near final height.

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