Effects of recombinant human IGF-1 and oral contraceptive administration on bone density in anorexia nervosa
Effects of recombinant human IGF-1 and oral contraceptive administration on bone density in anorexia nervosa
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DOI：
10.1210/jc.87.6.2883
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发表时间：
2002-06-01
影响因子：
5.8
通讯作者：
Klibanski, A
中科院分区：
文献类型：
--
作者：
Grinspoon, S;Thomas, L;Klibanski, A
超过90%的患有神经性厌食症的女性表现出骨量减少，几乎40%的女性在一个或多个骨骼部位表现出骨质疏松。除了雌激素缺乏导致骨吸收增加外，GH-IGI-I轴上的营养效应可能通过减少骨形成而导致该人群的严重骨丢失。我们测试了重组人IGF-I(重组人IGF-I)会增加神经性厌食症女性的骨密度的假设，并进一步评估了联合使用rhIGF-I和口服避孕药(OCP)在这一人群中的效果。60名符合第四版《精神疾病诊断和统计手册》修订的骨质疏松症妇女[年龄(25.2+/-0.7岁，范围18-38岁)]，体重指数(17.8+/-0.3 kg/m(2))，脊柱骨密度T评分(-2.1+/-0.1SD)，随机分为四个治疗组[重组人IGF-I(30µg/kg sc，每日两次)和每日口服避孕药(Ovcon35，35µg雌二醇和0.4 mg去甲肾上腺素)]，单用重组人胰岛素样生长因子-I(30 mg/kg皮下注射，每日两次)，单独口服避孕药，或不治疗9个月。所有受试者每天服用1500毫克钙和含有400IU维生素D的标准复合维生素，重组人胰岛素样生长因子-I的服药是安慰剂对照，受试者是盲人。对每个患者进行了重组人胰岛素样生长因子-I的滴定，使其IGF-I水平保持在年龄调整后的正常范围内，且耐受性良好。在所有受试者中，用析因分析和四个单独治疗组的分析同时分析了重组人胰岛素样生长因子-I和口服环磷酰胺的效果。经协方差分析，接受rhIGF-I治疗的患者脊柱前后位骨密度显著增加(分别为1.1%+/-0.5%vs.-0.6%+/-0.8%，P=0.05，均为rh-IGF-I组与所有安慰剂组)。相比之下，OCP组并未导致骨密度增加(协方差分析分别为0.8%+/-0.6%vs.-0.4%+/-0.8%，P=0.21，均为OCP组与非OCP组)。然而，联合治疗组(rhIGF-I和OCP)的骨密度增加幅度最大，与不接受主动治疗的对照组患者相比(1.8%，+/-0.8%vs.0.3%+/-0.6%vs.-0.2%+/-0.8%vs.-1.0%+/-1.3%，rh IGF-I和OCP组与单独使用rhIGF-I组与不主动治疗组相比，P<；0.05)。这些数据表明，与没有接受rhIGF-I治疗的患者相比，接受rhIGF-I治疗的骨量减少的神经性厌食症患者显示出更有益的骨密度变化。OCP的抗吸收治疗不足以改善营养不良患者的骨密度，但这种治疗可能会在联合治疗策略中增强重组人IGF-I的效果。需要进一步的长期研究来研究重组人胰岛素样生长因子-I和合成代谢/抗吸收联合治疗对神经性厌食症妇女骨骼的影响。
Over 90% of women with anorexia nervosa demonstrate osteopenia, and almost 40% demonstrate osteoporosis at one or more skeletal sites. In addition to estrogen deficiency causing an increase in bone resorption, nutritional effects on the GH-IGI-I axis may contribute to the severe bone loss in this population by decreasing bone formation. We tested the hypothesis that recombinant human IGF-I (rhIGF-I) would increase bone density in women with anorexia nervosa and furthermore assessed the effects of combined rhIGF-I and oral contraceptive administration (OCP) in this population. Sixty osteopenic women with Diagnosis and Statistical Manual of Mental Disorders IV Revised confirmed anorexia nervosa [age (25.2 +/- 0.7 yr, range 18-38 yr), body mass index (17.8 +/- 0.3 kg/m(2)), spinal bone mineral density T score (-2.1 +/- 0.1 SD) were randomized to one of four treatment groups [rhIGF-I (30 mug/kg sc twice daily) and a daily oral contraceptive (Ovcon 35, 35 mug ethinyl estradiol and 0.4 mg norethindrone], rhIGF-I alone (30 mug/kg sc twice daily), oral contraceptive alone, or neither treatment for 9 months. All subjects received calcium 1500 mg/d and a standard multivitamin containing 400 IU of vitamin D. Administration of rhIGF-I was placebo controlled and blinded to subjects. The rhIGF-I was titrated to maintain IGF-I levels within the age-adjusted normal range for each patient and was well tolerated. The effects of rhIGF-I and OCP were analyzed simultaneously among all subjects in a factorial analysis and in an analysis of the four individual treatment groups. Anteroposterior spinal bone density increased significantly in response to rhIGF-I (1.1% +/- 0.5% vs. -0.6% +/- 0.8%, P = 0.05, all rhIGF-I vs. all placebo treated, respectively, by analysis of covariance). In contrast, OCP did not result in increased bone density (0.8% +/- 0.6% vs. -0.4% +/- 0.8%, P = 0.21, all OCP vs. all non-OCP treated, respectively, by analysis of covariance). However, bone density increased to the greatest extent in the combined treatment group (rhIGF-I and OCP), compared with control patients receiving no active therapy (1.8%, +/- 0.8% vs. 0.3% +/- 0.6% vs. - 0.2% +/- 0.8% vs. - 1.0% +/- 1.3%, rhIGF-I and OCP vs. rhIGF-I alone vs. OCP alone vs. no active therapy, P < 0.05 for rhIGF-I and OCP vs. no active therapy). These data demonstrate that osteopenic women with anorexia nervosa treated with rhIGF-I showed more beneficial changes in bone density, compared with patients not treated with rhIGF-I. Antiresorptive therapy with OCP is not sufficient to improve bone density in undernourished patients, but such therapy may augment the effects of rhIGF-I in a combined treatment strategy. Further long-term studies are needed to investigate the effects of rhIGF-I and combined anabolic/antiresorptive strategies on bone in women with anorexia nervosa.