Janssen Y J, Hamdy N A, Frölich M, Roelfsema F
Department of Endocrinology, Leiden University Medical Center, The Netherlands.
J Clin Endocrinol Metab. 1998 Jun;83(6):2143-8. doi: 10.1210/jcem.83.6.4851.
A low bone mass in adults with childhood-onset GH deficiency (GHD) is likely to be caused by deficient bone accretion during childhood and early adulthood, whereas a decreased bone mass in patients with adult-onset GHD is likely to be caused by an imbalance in bone remodeling. Data on bone mineral density (BMD) and biochemical parameters of bone metabolism and data on response of these parameters to treatment with GH are scarce in patients with adult-onset GHD. It has been suggested that in patients with GHD, GH at the relatively high dose originally used may have beneficial effects on the skeleton. To address the question as whether lower, more physiological doses would have similar effects on the skeleton, we studied 47 patients with adult-onset GHD (27 women and 20 men, range 26-70 yr) randomized to receive one of three recombinant human GH (rhGH) dose regimens: 0.6 IU/day, 1.2 IU/day, or 1.8 IU/day as part of a study examining optimal GH dose replacement therapy. After 24 weeks of treatment, the dose of rhGH was individually adjusted to maintain the concentration of serum insulin growth factor-I within the normal laboratory reference range. Biochemical parameters of bone metabolism were measured at baseline and after 24 and 52 weeks and 2 yr of treatment. BMD of the lumbar spine was measured at baseline and after 52 weeks and 2 yr of treatment. Parameters of bone metabolism generally fell within the low-normal range and increased in a dose-dependent manner at 24 weeks of treatment. Between 24 and 52 weeks of rhGH treatment, mean serum osteocalcin levels and alkaline phosphatase activity further increased, whereas mean 24-h urine hydroxyproline/creatinine and N-telopeptide/creatinine excretion remained unchanged. After 52 weeks of treatment, serum alkaline phosphatase activity and 24-h urine hydroxyproline/ creatinine excretion decreased, although not to pretreatment levels. Mean BMD at the lumbar spine (Z-score) was normal at baseline (-0.20 +/- 0.16) and increased during treatment (at 2 yr of treatment: 0 +/- 0.20; P < 0.005). Our data suggest that a low physiological dose of rhGH, individually adjusted to maintain serum insulin-like growth factor I levels within the normal laboratory reference range, increased bone turnover in favor of bone formation, as suggested by the significant, albeit small increase in BMD observed after 2 yr of treatment. Further studies are required to establish whether in patients with adult-onset GHD the preservation and/or increase in bone mass observed with the use of physiological doses of rhGH could be maintained with longer-term treatment.
儿童期起病的生长激素缺乏症（GHD）成人患者骨量低，可能是由于儿童期和成年早期骨量积累不足所致，而成人期起病的GHD患者骨量减少，可能是由于骨重塑失衡所致。成人期起病的GHD患者中，关于骨矿物质密度（BMD）和骨代谢生化参数的数据，以及这些参数对生长激素治疗反应的数据都很缺乏。有人提出，在GHD患者中，最初使用的相对高剂量的生长激素可能对骨骼有有益作用。为了解决较低、更接近生理剂量的生长激素是否对骨骼有类似作用的问题，我们研究了47例成人期起病的GHD患者（27名女性和20名男性，年龄范围26 - 70岁），这些患者被随机分配接受三种重组人生长激素（rhGH）剂量方案之一：0.6 IU/天、1.2 IU/天或1.8 IU/天，这是一项研究最佳生长激素剂量替代疗法的一部分。治疗24周后，rhGH剂量进行个体化调整，以维持血清胰岛素样生长因子-I浓度在正常实验室参考范围内。在基线、治疗24周、52周和2年后测量骨代谢生化参数。在基线、治疗52周和2年后测量腰椎的BMD。骨代谢参数一般在低正常范围内，在治疗24周时呈剂量依赖性增加。在rhGH治疗的24至52周期间，血清骨钙素平均水平和碱性磷酸酶活性进一步升高，而24小时尿羟脯氨酸/肌酐和N-端肽/肌酐排泄量保持不变。治疗52周后，血清碱性磷酸酶活性和24小时尿羟脯氨酸/肌酐排泄量下降，尽管未降至治疗前水平。腰椎的平均BMD（Z评分）在基线时正常（-0.20±0.16），在治疗期间升高（治疗2年后：0±0.20；P<0.005）。我们的数据表明，将rhGH的生理剂量个体化调整以维持血清胰岛素样生长因子I水平在正常实验室参考范围内，可增加骨转换，有利于骨形成，这从治疗2年后观察到的BMD虽小但显著增加可以看出。需要进一步研究以确定在成人期起病的GHD患者中，使用生理剂量的rhGH观察到的骨量保存和/或增加是否能通过长期治疗得以维持。
