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

Abstract

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 microg/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.

Consensus Statement on the Use of Gonadotropin-Releasing Hormone Analogs in Children

“…[117][118][119] Three prospective studies that reported near-AH or AH have shown an ϳ1-SD height gain, [120][121][122] possibly without detrimental effect on BMD. 123 Conclusions: Routine use of combined therapy with GnRH and GH in GH-deficient children with low predicted AH at onset of puberty cannot be suggested (CIII).…”

The associations between serum trace elements and bone mineral density in children under 3 years of age

“…Osteoporosis is associated with many primary and secondary paediatric diseases 16 , 17 . Studies have shown that low BMD during adolescence can result in permanent low BMD in adulthood 18 . The vital period for the growth and development of children is between zero and 3 years of age.…”

Effect of Testosterone on Bone Mineral Gain: Observations of Male Patients with Growth Hormone Deficiency and Normal Gonadotropin Secretion

“…Patients with central precocious puberty or GH-deficient children who are diagnosed late in childhood often have a decreased height potential, and a strategy to increase their adult height is to use GnRH analogues or add GnRH analogues to the GH treatment regimen, thereby delaying puberty and slowing skeletal maturation. These treatments raise concern that the suppression of puberty with GnRH analogues might have an adverse effect on bone mineral acquisition during puberty, although this strategy has recently been demonstrated to have no adverse effect on bone mineralization (9,10,11). From our observations, however, we propose that the build-up of bone mass in boys as a result of the effects of testosterone should not be neglected, and this issue remains to be further clarified.…”