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. Design and 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 μg/kg per day × 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.
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