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
Authors: Lanes Roberto , Gunczler Peter , Esaa Sara , Weisinger Jose R. 
Published: March 2003

Objective 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.

Patients and Design 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.

Measurements 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).

Results 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 µg/l, while levels of ICTP increased from 9·6 ± 5·9 to 13·7 ± 2·1 µg/l. After 36 months of GH therapy, PICP and ICTP values had decreased to 303·3 ± 67·2 µg/l and 11·3 ± 3·3 µg/l, respectively, and were no longer significantly different from baseline.

Conclusions 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.