title: Serum levels of insulin-like growth factor binding proteins (IGFBP)-4 and -5 correlate with bone mineral density in growth hormone (GH)-deficient adults and increase with GH replacement therapy.
abstract: Adults with growth hormone deficiency (GHD) exhibit low bone mineral density (BMD) which improves by growth hormone (GH) replacement therapy. The insulin-like growth factor (IGF) system has an established role in mediating the effects of GH on bone and IGF binding proteins (IGFBP)-4 and IGFBP-5 have been shown to modulate the effects of IGFs in bone. Therefore, we studied serum levels of IGFBP-4 and IGFBP-5 and their relationship to serum levels of bone biochemical markers and BMD in adults with GH deficiency (GHD) before and during GH therapy. Serum levels of IGFBP-5 and IGFBP-4 were measured on samples from 20 patients (11 males) 22-57 years of age. All had IGF-I serum values below -2 standard deviation score. The first 6 months were placebo controlled and all received 3 years of active treatment with the mean dose 0.23 +/- 0.01 IU/kg/week divided into daily subcutaneous injections. Serum IGFBP-5 levels in GHD adults were low at baseline and positively related to total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.471, 0.549, 0.462, and 0.470, respectively, p < 0.05). The mean serum IGFBP-5 level increased by about 2-fold within 3 months after the initiation of GH therapy and was correlated with serum IGF-I (r = 0.719, 0.801, and 0.722 before and after 18 and 36 months, respectively,p < 0.001). A positive correlation between serum IGFBP-5 levels and lumbar spine BMD was found during GH treatment but not before. The percentage increase of serum IGFBP-5 after GH therapy showed a positive correlation with the percentage increase of total alkaline phosphate activity (r = 0.347 p < 0.05). In contrast to IGFBP-5, serum IGFBP-4 levels were positively related to body mass index (r = 0.607, p < 0.01). Baseline serum IGFBP-4 levels also correlated with total body, femoral neck, trochanter, and Ward's triangle BMD (r = 0.502, 0.590, 0.612, and 0.471, respectively,p < 0.05). The mean serum IGFBP-4 level was increased by 25% within 3 months after initiation of GH therapy and did not correlate with serum IGF-I levels. Although the above findings are consistent with the idea that GH-induced changes in serum IGFBP-5 and IGFBP-4 levels may in part mediate the anabolic effects of GH on bone tissue in adults with GHD, further studies are needed to establish the cause and effect relationship.
authors.affiliation: Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Thorén
authors.forename: A
authors.initials: A
authors.lastname: Hilding
authors.forename: T
authors.initials: T
authors.lastname: Brismar
authors.forename: P
authors.initials: P
authors.lastname: Magnusson
authors.forename: M
authors.initials: M
authors.lastname: Degerblad
authors.forename: L
authors.initials: L
authors.lastname: Larsson
authors.forename: M
authors.initials: M
authors.lastname: Sääf
authors.forename: D J
authors.initials: DJ
authors.lastname: Baylink
authors.forename: S
authors.initials: S
authors.lastname: Mohan
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D019382:Human Growth Hormone / Q000008:administration & dosage / Q000172:deficiency* / Q000627:therapeutic use*; D006801:Humans; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood*; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged
chemical_list: D018974:Insulin-Like Growth Factor Binding Protein 4; D018975:Insulin-Like Growth Factor Binding Protein 5; D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I; D000469:Alkaline Phosphatase