The effect of short- and long-term growth hormone treatment on bone mineral density and bone metabolism of prepubertal children with idiopathic short stature: a 3-year study.

Abstract

We recently reported that children with idiopathic short stature (ISS) have decreased lumbar spine bone mineral density (BMD) that increases after 1 year of GH therapy. The aim of this study was to confirm these short-term results and to evaluate the effect of long-term GH therapy on the BMD of children with ISS. We treated a group of 16 short, slow-growing but otherwise healthy non-GH-deficient prepubertal children (8 girls and 8 boys) with a chronological age of 9.5 +/- 0.9 years, a bone age of 8.1 +/- 1.2 years and a height of 124.3 +/- 6.3 cm (height-SDS of -2.1 +/- 0.6) with GH at a dose of 0.1 IU/kg/day for 3 consecutive years. Height was determined at 3-month intervals and annual growth velocities were calculated. Bone ages and BMD were measured every 12 months by dual-energy X-ray absorptiometry, as were serum concentrations of the carboxy-terminal propeptide of type 1 collagen (PICP) and the carboxy-terminal cross-linked telopeptide of type 1 collagen (ICPT). Growth velocity increased from 4.0 +/- 0.8 cm/year to 8.7 +/- 1.5 and 8.0 +/- 1.7 cm/year at 12 and 36 months of GH therapy, respectively, while height-SDS improved from -2.1 +/- 0.6 to -1.6 +/- 0.4 after 36 months of GH (P < 0.0001). Baseline lumbar spine BMD was decreased when compared to that of a control group of healthy children paired for gender, bone age and height (0.640 +/- 0.08 g/cm2vs. 0.730 +/- 0.08 g/cm2; P < 0.003). Lumbar spine BMD increased after 1 year of GH from 0.640 +/- 0.08 to 0.749 +/- 0.08 g/cm2 (P < 0.05), reaching levels similar to that of controls followed for 1 year without therapy (0.749 +/- 0.04 g/cm2vs. 0.760 +/- 0.08 g/cm2). During this period lumbar spine BMD increased 14.5% in the ISS subjects and 3.9% in the controls. Over the following 2 years of GH therapy the lumbar spine BMD of our ISS patients increased at a rate similar to that of the control population, so that after 3 years of consecutive GH therapy the lumbar spine BMD of ISS children was comparable to that of the controls (0.784 +/- 0.12 g/cm2vs. 0.785 +/- 0.09 g/cm2). Femoral neck BMD of our patients was similar to that of the controls at baseline and at 36 months. Following 1 year of GH treatment serum concentrations of PICP increased from 229.6 +/- 63.5 to 358.6 +/- 87.9 micro g/l, while levels of ICTP increased from 9.6 +/- 5.9 to 13.7 +/- 2.1 micro g/l. After 36 months of GH therapy, PICP and ICTP values had decreased to 303.3 +/- 67.2 micro g/l and 11.3 +/- 3.3 micro g/l, respectively, and were no longer significantly different from baseline. Children with ISS have decreased lumbar spine BMD, which normalized after 1 year of GH. Over the next 2 years of therapy lumbar spine BMD increased at a normal rate, so that after 3 consecutive years of GH the lumbar spine BMD of children with ISS was similar to that of controls. Bone turnover increased with treatment as indicated by a rise in bone formation and bone resorption markers.