Evaluation of the optimum dose of growth hormone (GH) for restoring bone mass in adult-onset GH deficiency: results from two 12-month randomized studies.
OBJECTIVE
To establish the optimum GH dose for restoring bone mineral density (BMD) in adult-onset GH deficiency (GHDA).


METHODS
Two separate randomized, controlled clinical trials.


METHODS
Fifty-eight adults aged 45.1 (20-64) years with severe GHDA were followed in two 12-month studies. In the first study, patients were randomized to placebo or GH 1.7 IU/m2/day and in the second study GH 0.5 IU/m2/day or 1.0 IU/m2/day.


METHODS
BMD of the spine, hip, forearm and whole body was measured at 0 and 12 months. Alkaline phosphatase (AP) and collagen markers serum C-terminal propeptide of type I collagen (PICP), type I collagen telopeptide (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured at baseline and every 3 months.


RESULTS
Biochemical markers of skeletal and soft tissue collagen increased significantly and remained elevated throughout the study period. BMD changes depended on site, dose and gender. In placebo-treated patients, spinal BMD declined by 2.5%. At the low and medium doses, BMD increased by 2.4 and 3.1%, respectively, while a nonsignificant 0.2% decrease was seen with high dose. Forearm BMD decreased by 4.9% (P < 0.05) with high-dose treatment but remained unchanged at lower doses. Males showed larger gains in BMD, but the dose-response relationship was similar in males and females.


CONCLUSIONS
A GH dose of 0.5-1.0 IU/m2/day (4-9 micro g/kg/day) stimulated bone remodelling and increased BMD over 12 months in patients with severe GHDA, irrespective of gender. A higher dose (1.7 IU/m2/day congruent with 15 micro g/kg/day) was associated with initial declines in forearm and whole-body BMD.
Abrahamsen
B
B
Departments of Endocrinology, Odense University Hospital, Odense, Denamark. b.abrahamsen@dadlnet.dk
Hangaard
J
J
Horn
H C
HC
Hansen
T B
TB
Gregersen
G
G
Hansen-Nord
M
M
Vahl
N
N
Junker
P
P
Andersen
M
M
Hagen
C
C
D000236:Adenoma / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D010911:Pituitary Neoplasms / Q000097:blood / Q000188:drug therapy*; D011347:Procollagen / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C041876:procollagen Type III-N-terminal peptide; C042813:procollagen type I carboxy terminal peptide; D013006:Growth Hormone; D003094:Collagen; D000469:Alkaline Phosphatase