The Effects of Growth Hormone Replacement Therapy on Bone Metabolism in Adult-Onset Growth Hormone Deficiency: A 2-Year Open Randomized Controlled Multicenter Trial
作者:Marie Bex、Roger Abs、Dominique Maiter、Albert Beckers、Gerard Lamberigts、Roger Bouillon
DOI:10.1359/jbmr.2002.17.6.1081
日期:——
Adult hypopituitary patients with growth hormone deficiency (GHD) show a significant decrease in bone mass and an increased fracture rate. Replacement therapy with GH increases bone turnover. Most of the long‐term data on bone mineral content (BMC) and bone mineral density (BMD) have been acquired in open, noncontrolled trials involving limited numbers of patients. To determine whether long‐term GH therapy is beneficial for bone despite the increased bone turnover, 100 patients (59 men and 41 women), aged 25‐65 years (mean, 49.7 years) with adult‐onset GHD were randomized to treatment with GH (40 men and 28 women; mean dose, 0.18 IU/kg per week) or to a nontreated control group (19 men and 13 women) for 24 months. Despite a similar increase in parameters of bone turnover (osteocalcin [OC], procollagen type I carboxy‐terminal propeptide [PICP], and pyridinolines ([PYD]) in male and female GH‐treated patients compared with controls, the effects on BMC and BMD as evaluated by dual‐energy X‐ray absorptiometry were gender specific. A significant increase in spine BMC and BMD and total hip BMD and a decrease in BMD at the ultradistal radius over time was observed in male GH‐treated patients compared with the evolution in controls (mean ± SEM change at 24 months: +6.8 ± 1.1% and p = 0.009, +5.1 ± 0.8% and p = 0.005, +3.5 ± 0.7% and p = 0.02, and −2.6 ± 0.8% and p = 0.008, respectively). No significant treatment effects were observed in female patients. Despite the increase in the total remodeling space induced by GH treatment, prolonged GH therapy in adult‐onset GHD has a positive effect on bone balance, maintaining bone mass in women, and even increasing it in men over a 2 year‐period.
成人生长激素缺乏症(GHD)患者表现出骨量显著减少和骨折率增加。生长激素(GH)替代治疗能够增加骨代谢率。关于骨矿含量(BMC)和骨密度(BMD)的长期数据主要来自于开放式的非对照试验,涉及患者人数有限。为了确定尽管骨代谢率增加但长期GH治疗是否对骨骼有益,研究将100名(59名男性和41名女性),年龄介于25至65岁(平均年龄49.7岁)且具有成年起病GHD的患者随机分配至GH治疗组(40名男性和28名女性;平均剂量为0.18 IU/kg每周)或未治疗对照组(19名男性和13名女性),持续24个月。尽管GH治疗组男性和女性患者的骨代谢参数(骨钙素[OC],I型前胶原羧端前肽[PICP],和吡啶醇[PYD])与对照组相比均有类似的增加,但通过双能X射线吸收测定法评估的BMC和BMD的效果在性别上有所差异。与对照组的变化相比,男性GH治疗组患者的脊柱BMC和BMD及总髋BMD显著增加,超远端桡骨BMD则有所减少(24个月的平均±标准误变化:+6.8 ± 1.1%,p = 0.009;+5.1 ± 0.8%,p = 0.005;+3.5 ± 0.7%,p = 0.02;和−2.6 ± 0.8%,p = 0.008)。在女性患者中未观察到显著的治疗效果。尽管GH治疗导致总重塑空间增加,成年起病GHD的长期GH治疗对骨平衡有积极影响,在两年内能够维持女性的骨量,甚至在男性中增加骨量。