Bone mineral content and bone metabolism during physiological GH treatment in GH-deficient adults--an 18-month randomised, placebo-controlled, double blinded trial.
OBJECTIVE
To evaluate the effect of physiological adult growth hormone (GH) replacement on bones.


METHODS
Thirty-six prospective severely growth hormone-deficient (GHD) adults (22 females and 14 males) were randomised to either 18 months of GH (0.03 mU/kg/day) or placebo treatment.


METHODS
Bone mineral density and content (BMD, BMC) and body composition were evaluated by dual energy X-ray absorptiometry at baseline and after 6, 12 and 18 months. Serum concentrations of insulin-like growth factor-I (IGF-I), IGF binding protein 3, osteocalcin, carboxyterminal propeptide of type I collagen, carboxyterminal crosslink telopeptide of type I collagen, amino-terminal propeptide of type III procollagen and urine pyridinolin and deoxypyridinolin were determined.


RESULTS
IGF-I levels increased from 63.2 microg/l (+/-10.1) to 193.6 (+/- 25.8) microg/l (mean (+/-s.e.)) (P<0.001 compared with placebo). Markers of bone turnover increased significantly from 142% to 227% of baseline values (all P<0.001 compared with placebo). Body composition changes were an increase of lean body mass and a decrease of fat mass resulting in a reduction of percentage body fat of +/- 1.8 (+/- 3.8) in the GH-treated group vs an increase of 1.0 (+/-2.9)) in the placebo-treated group (P=0.002).


CONCLUSIONS
No significant difference in BMD or BMC between the GH and placebo groups was found after 18 months. At several sites the variances of changes from baseline were significantly greater in the GH than in the placebo group, indicating an impact of the treatment. From baseline to 6 months an insignificant reduction of total BMD was seen while an increase of BMD was found from 6 to 18 months in the GH group compared with the placebo group. This placebo-controlled trial confirmed the longer term open studies on the effect on bones in patients with GHD, with an initial overrepresentation of bone resorption followed by an increase in BMD which at 18 months had reached baseline level.
Sneppen
Simone Bjerregård
SB
Department of Endocrinology, National University Hospital, Copenhagen, Denmark.
Hoeck
Hans Christian
HC
Kollerup
Gina
G
Sørensen
Ole Helmer
OH
Laurberg
Peter
P
Feldt-Rasmussen
Ulla
U
D000328:Adult; D000596:Amino Acids / Q000652:urine; D001823:Body Composition; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004311:Double-Blind Method; D005260:Female; D019382:Human Growth Hormone / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D010919:Placebos; D011347:Procollagen / Q000097:blood; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D013997:Time Factors
D000596:Amino Acids; D024042:Collagen Type I; D018972:Insulin-Like Growth Factor Binding Protein 3; D010446:Peptide Fragments; D010455:Peptides; D010919:Placebos; D011347:Procollagen; D011498:Protein Precursors; C052929:collagen type I trimeric cross-linked peptide; C032431:preprocollagen; D015675:Osteocalcin; D019382:Human Growth Hormone; C015484:pyridinoline; D007334:Insulin-Like Growth Factor I; C036020:deoxypyridinoline; D003094:Collagen