Thorén M, Hilding A, Brismar T, Magnusson P, Degerblad M, Larsson L, Sääf M, Baylink D J, Mohan S
Department of Endocrinology and Diabetology, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden.
J Bone Miner Res. 1998 May;13(5):891-9. doi: 10.1359/jbmr.1998.13.5.891.
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.
患有生长激素缺乏症（GHD）的成年人表现出低骨矿物质密度（BMD），而生长激素（GH）替代疗法可使其改善。胰岛素样生长因子（IGF）系统在介导GH对骨骼的作用方面已确立其作用，并且胰岛素样生长因子结合蛋白（IGFBP）-4和IGFBP-5已被证明可调节IGF在骨骼中的作用。因此，我们研究了患有GH缺乏症（GHD）的成年人在GH治疗前和治疗期间血清IGFBP-4和IGFBP-5水平及其与血清骨生化标志物水平和BMD的关系。对20名年龄在22至57岁之间的患者（11名男性）的样本进行了IGFBP-5和IGFBP-4血清水平检测。所有人的IGF-I血清值均低于-2标准差评分。前6个月为安慰剂对照，所有人均接受了3年的积极治疗，平均剂量为0.23±0.01 IU/kg/周，分为每日皮下注射。GHD成年人的血清IGFBP-5水平在基线时较低，与全身、股骨颈、大转子和沃德三角区的BMD呈正相关（分别为r = 0.471、0.549、0.462和0.470，p < 0.05）。GH治疗开始后3个月内，血清IGFBP-5平均水平增加了约2倍，并且与血清IGF-I相关（分别在18个月和36个月前后，r = 0.719、0.801和0.722，p < 0.001）。在GH治疗期间发现血清IGFBP-5水平与腰椎BMD呈正相关，但治疗前未发现。GH治疗后血清IGFBP-5的增加百分比与总碱性磷酸酶活性的增加百分比呈正相关（r = 0.347，p < 0.05）。与IGFBP-5相反，血清IGFBP-4水平与体重指数呈正相关（r = 0.607，p < 0.01）。基线血清IGFBP-4水平也与全身、股骨颈、大转子和沃德三角区的BMD相关（分别为r = 0.502、0.590、0.612和0.471，p < 0.05）。GH治疗开始后3个月内，血清IGFBP-4平均水平增加了25%，并且与血清IGF-I水平不相关。尽管上述发现与GH诱导的血清IGFBP-5和IGFBP-4水平变化可能部分介导GH对GHD成年人骨组织的合成代谢作用这一观点一致，但仍需要进一步研究来确立因果关系。
