Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

Juul A, Pedersen SA, Sørensen S, Winkler K, Jørgensen JOL, Christiansen JS, Skakkebæk NE. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein- bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset. Eur J Endocrinol 1994;131:41–9. ISSN 0804–4643 Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4 months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 μg/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 μg/l after 4 months of GH treatment (p < 0.0001). In addition, the molar ratio between IGF-I and IGFBP-3 increased significantly from 0.22 to 0.33 after GH treatment (p < 0.0001), Bone alkaline phosphatase increased significantly from 38.6 to 92.9 U/l during GH therapy in male patients (p < 0.0001), whereas liver-derived alkaline phosphatase was unaltered by GH. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0 U/l, p = 0.06). The GH-induced increase in bone alkaline phosphatase correlated significantly with the increase in serum IGFBP-3 (r = 0.46, p = 0.04) but not with the increase in serum IGF-I (p = 0.16). Liver function as assessed by the galactose elimination capacity was within the normal range for healthy adults and did not change after GH treatment. Bone mineral content increased significantly between 7 and 14 months of GH treatment (mean increase in bone mineral content Z score = 0.24 sd/ 7 months), but remained low even after 14 months of GH treatment (Z score = –2.2 ± 0.24 (mean ± sem)). We conclude that GH administration increases serum levels of bone-derived alkaline phosphatase in male patients and has a potentially beneficial impact on bone mineral content in young adults with GH deficiency of childhood onset. Anders Juul, Department of Growth and Reproduction, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark