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Effects of 12 Months of GH Treatment on Cortical and Trabecular Bone Content of IGFs and OPG in Adults with Acquired GH Deficiency: A Double-Blind, Randomized, Placebo-Controlled Study

Department of Endocrinology (T.U., J.B.), National University Hospital, N-0027 Oslo, Norway; Medical Research Laboratory M (A.F.), Aarhus University Hospital, DK-8000 Aarhus, Denmark; Department of Endocrinology (T.B.H.), Odense University Hospital, DK-5000 Odense, Denmark; Department of Internal Medicine and Endocrinology (N.V.), Aarhus Kommunehospital, DK-8000 Aarhus, Denmark; and Department of Cell Biology (L.M.), University of Aarhus, DK-8000 Aarhus, Denmark

Address all correspondence and requests for reprints to: Thor Ueland, Department of Endocrinology, National University Hospital, N-0027 Oslo, Norway. E-mail: . thor.ueland{at}klinmed.uio.no

Abstract

To investigate the effects of 12 months of GH treatment on cortical and trabecular bone content of IGFs, iliac crest bone biopsies were obtained from 25 patients with GH deficiency (9 women and 16 men; ages, 21–61 yr; mean, 46 yr) who were randomized to sc injections with GH (2 IU/m²·d) or placebo for 12 months. Levels of IGF-I, IGF-II, IGF binding protein (IGFBP)-3, IGFBP-5, osteocalcin, OPG, RANKL, and total protein were determined in extracts obtained after EDTA and guanidine hydrochloride extraction. Calcium was determined after HCl hydrolysis. Comparing changes during GH or placebo treatment, significant increases were observed during GH substitution for cortical and trabecular bone content of IGF-I [mean difference vs. placebo (mean ± SEM), 97 ± 30 and 72 ± 38%] and OPG (mean difference vs. placebo, 109 ± 59 and 51 ± 19%). Also, a significant decline was found for cortical osteocalcin (mean difference vs. placebo, -49 ± 22%) during GH treatment. In conclusion, our results indicate that long-term GH treatment increases the accumulation of IGF-I and OPG in cortical and trabecular bone in patients with GH deficiency, and this may in turn lead to an increase in bone mass and improved skeletal biomechanical competence.

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