GH replacement therapy increases plasma osteoprotegerin levels in GH-deficient adults.
OBJECTIVE
Osteoprotegerin (OPG), a glycoprotein belonging to the tumor necrosis factor receptor family, is an endogenous inhibitor of osteoclastogenesis produced by cells of the osteoblast lineage. OPG is a key cytokine involved in the regulation of osteoblast/osteoclast cross-talk. Since GH replacement therapy in GH deficiency (GHD) activates bone remodeling and increases bone mass, we investigated if short-term GH replacement therapy affects plasma OPG levels.


METHODS
Eighteen adults with GHD, ranging from 17 to 51 Years (nine childhood-onset and nine adult-onset) were enrolled in the study. All subjects were on stable replacement therapy, especially sex hormones. The starting dose of GH replacement therapy was 4 microg/kg per day x 7 days/week, and was progressively increased according to the serum IGF-I values. Biochemical parameters of bone and mineral metabolism were measured before and after 6 Months of GH replacement therapy. Bone mass density (BMD) was monitored at three skeletal sites (lumbar vertebrae, femur, radius) by dual-energy X-ray absorptiometry.


RESULTS
After 6 Months of therapy, ionized calcium, parathyroid hormone and 25-OH vitamin D did not change, whereas total serum calcium and urinary calcium excretion increased significantly (P<0.01). Also osteocalcin and urinary deoxypyridinoline/24 h increased significantly (P<0.02, P<0.05 respectively). Mean basal T-scores of BMD values showed an osteopenic state, which remained unchanged after GH therapy. Plasma OPG increased significantly after 6 Months of therapy (P<0.02) and this increase was significantly correlated with the increase of osteocalcin (r=-0.52; P=0.04) and deoxypyridinoline values (r=-0.64; P=0.011).


CONCLUSIONS
Our results suggest that the bone anabolic effect of GH replacement therapy could in part be mediated by a positive bone balance at each remodeling unit due to the inhibitory action of OPG on osteoclastogenesis.
Lanzi
Roberto
R
Unita di Diabetologia, Endocrinologia e Malattie Metaboliche, Universitá Vita e Salute, Istituto Scientifico H San Raffaele, Milan, Italy.
Losa
Marco
M
Villa
Isabella
I
Gatti
Elisa
E
Sirtori
Marcella
M
Dal Fiume
Chiara
C
Rubinacci
Alessandro
A
D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000652:urine; D002118:Calcium / Q000097:blood / Q000652:urine; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D013006:Growth Hormone / Q000627:therapeutic use*; D019382:Human Growth Hormone / Q000172:deficiency*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor
D000596:Amino Acids; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D015675:Osteocalcin; D019382:Human Growth Hormone; D013006:Growth Hormone; C036020:deoxypyridinoline; D002118:Calcium