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

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 mu g/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 mu g/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 92.9U/l during GH therapy in male patients (p < 0.0001), whereas liver-derived alkaline phosphatase was unaltered by GK. In the females, the increase in bone alkaline phosphatase did not reach statistical significance (19.1 vs 40.0U/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.