Välimäki M J, Salmela P I, Salmi J, Viikari J, Kataja M, Turunen H, Soppi E
Department of Medicine, University of Helsinki, Helsinki, Finland, [1]Department of Medicine, University of Oulu, Oulu, Finland.
Eur J Endocrinol. 1999 Jun;140(6):545-54. doi: 10.1530/eje.0.1400545.
To study the effects of GH treatment for up to 42 months on bone mineral density (BMD) and bone turnover.
BMD with dual energy X-ray absorptiometry, serum type I procollagen carboxy-terminal propeptide (PICP), serum type I collagen carboxy-terminal telopeptide (ICTP) and serum IGF-I were assessed in 71 adults with GH deficiency. There were 44 men and 27 women, aged 20 to 59 (median 43) years. Thirty-two patients completed 36 months and 20 patients 42 months of treatment.
The BMD increased for up to 30-36 months and plateaued thereafter. In the whole study group, the maximum increase of BMD was 5.0% in the lumbar spine (P<0. 001), 5.9% (P<0.01) in the femoral neck, 4.9% (NS, P>0.05) in the Ward's triangle and 8.2% (P<0.001) in the trochanter area. The serum concentrations of PICP (202.6+/-11.5 vs 116.3+/-5.4 microg/l; mean+/-s.e.m.) and ICTP (10.5+/-0.6 vs 4.4+/-0.3 microg/l) doubled (P<0.001) during the first 6 months of GH treatment but returned to baseline by the end of the study (130.0+/-10.4 and 5.6+/-0.7 microg/l respectively), despite constantly elevated serum IGF-I levels (39. 6+/-4.1 nmol/l at 42 months vs 11.9+/-0.9 nmol/l at baseline; P<0.001). The responses to GH treatment of serum IGF-I, PICP, ICTP (P<0.001 for all; ANOVA) and of the BMD in the lumbar spine (P<0.05), in the femoral neck and the trochanter (P<0.001 for both) were more marked in men than in women. At the end of the study the BMD had increased at the four measurement sites by 5.7-10.6% (P<0.01-0.001) in patients with at least osteopenia at baseline and by 0.1-5.3% (NS P<0.05) in those with normal bone status (P<0.001 for differences between groups; ANOVA). Among patients who completed 36-42 months of treatment, the number of those with at least osteopenia was reduced to more than a half. The response of BMD to GH treatment was more marked in young than in old patients at three measurement sites (P<0. 05-<0.001; ANOVA). In the multiple regression analysis the gender and the pretreatment bone mass appeared to be independent predictors of three measurement sites, whereas the age independently determined only the vertebral BMD.
GH treatment in GH-deficient adults increased BMD for up to 30-36 months, with a plateau thereafter. Concurrently with the plateau in BMD the bone turnover rate normalized. From the skeletal point of view GH-deficient patients exhibiting osteopenia or osteoporosis should be considered as candidates for GH supplementation of at least 3-4 years.
研究生长激素(GH)治疗长达42个月对骨密度(BMD)和骨转换的影响。
采用双能X线吸收法评估71例生长激素缺乏的成年人的骨密度,检测血清I型前胶原羧基末端前肽(PICP)、血清I型胶原羧基末端端肽(ICTP)和血清胰岛素样生长因子-I(IGF-I)。其中男性44例,女性27例,年龄20至59岁(中位数43岁)。32例患者完成了36个月的治疗,20例患者完成了42个月的治疗。
骨密度在30 - 36个月内持续增加,之后趋于平稳。在整个研究组中,腰椎骨密度最大增加了5.0%(P<0.001),股骨颈增加了5.9%(P<0.01),Ward三角区增加了4.9%(无统计学意义,P>0.05),大转子区增加了8.2%(P<0.001)。在生长激素治疗的前6个月,血清PICP浓度(202.6±11.5 vs 116.3±5.4 μg/l;均值±标准误)和ICTP浓度(10.5±0.6 vs 4.4±0.3 μg/l)翻倍(P<0.001),但在研究结束时恢复到基线水平(分别为130.0±10.4和5.6±0.7 μg/l),尽管血清IGF-I水平持续升高(42个月时为39.6±4.1 nmol/l,基线时为11.9±0.9 nmol/l;P<0.001)。生长激素治疗对血清IGF-I、PICP、ICTP的反应(均P<0.001;方差分析)以及对腰椎、股骨颈和大转子骨密度的反应(腰椎P<0.05,股骨颈和大转子均P<0.001),男性比女性更明显。研究结束时,基线时至少存在骨质减少的患者在四个测量部位的骨密度增加了5.7 - 10.6%(P<0.01 - 0.001),而骨状态正常的患者骨密度增加了0.1 - 5.3%(无统计学意义,P>0.05)(组间差异P<0.001;方差分析)。在完成36 - 42个月治疗的患者中,至少存在骨质减少的患者数量减少至一半以上。在三个测量部位,年轻患者的骨密度对生长激素治疗的反应比老年患者更明显(P<0.05 - <0.001;方差分析)。在多元回归分析中,性别和治疗前骨量似乎是三个测量部位骨密度的独立预测因素,而年龄仅独立决定腰椎骨密度。
生长激素缺乏的成年人接受生长激素治疗后,骨密度在30 - 36个月内增加,之后趋于平稳。随着骨密度趋于平稳骨转换率恢复正常。从骨骼角度来看,患有骨质减少或骨质疏松的生长激素缺乏患者应被视为至少补充3 - 4年生长激素的候选者。