Neuroendocrine Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Division of Pediatric Endocrinology, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA, USA.
J Clin Endocrinol Metab. 2021 Jun 16;106(7):2021-2035. doi: 10.1210/clinem/dgab145.
Anorexia nervosa (AN) is prevalent in adolescent girls and is associated with bone impairment driven by hormonal alterations in nutritional deficiency.
To assess the impact of estrogen replacement with and without recombinant human insulin-like growth factor-1 (rhIGF-1) administration on bone outcomes.
Double-blind, randomized, placebo-controlled 12-month longitudinal study.
Seventy-five adolescent and young adult women with AN age 14 to 22 years. Thirty-three participants completed the study.
Transdermal 17-beta estradiol 0.1 mg/day with (i) 30 mcg/kg/dose of rhIGF-1 administered subcutaneously twice daily (AN-IGF-1+) or (ii) placebo (AN-IGF-1-). The dose of rhIGF-1 was adjusted to maintain levels in the upper half of the normal pubertal range.
Bone turnover markers and bone density, geometry, microarchitecture, and strength estimates.
Over 12 months, lumbar areal bone mineral density increased in AN-IGF-1- compared to AN-IGF-1+ (P = 0.004). AN-IGF-1+ demonstrated no improvement in areal BMD in the setting of variable compliance to estrogen treatment. Groups did not differ for 12-month changes in bone geometry, microarchitecture, volumetric bone mineral density (vBMD), or strength (and results did not change after controlling for weight changes over 12 months). Both groups had increases in radial cortical area and vBMD, and tibia cortical vBMD over 12 months. Levels of a bone resorption marker decreased in AN-IGF-1- (P = 0.042), while parathyroid hormone increased in AN-IGF-1+ (P = 0.019). AN-IGF-1- experienced irregular menses more frequently than did AN-IGF-1+, but incidence of all other adverse events did not differ between groups.
We found no additive benefit of rhIGF-1 administration for 12 months over transdermal estrogen replacement alone in this cohort of young women with AN.
神经性厌食症（AN）在青春期少女中较为普遍，与营养缺乏导致的激素改变引起的骨骼损伤有关。
评估雌激素替代治疗联合和不联合重组人生长因子-1（rhIGF-1）治疗对骨骼结局的影响。
双盲、随机、安慰剂对照的 12 个月纵向研究。
75 名年龄在 14 至 22 岁的患有 AN 的青少年和年轻女性。33 名参与者完成了研究。
经皮 17-β雌二醇 0.1mg/天，联合（i）皮下每日两次给予 30mcg/kg/剂量的 rhIGF-1（AN-IGF-1+）或（ii）安慰剂（AN-IGF-1-）。rhIGF-1 的剂量调整为维持在正常青春期范围的上半部分。
骨转换标志物和骨密度、几何形状、微结构和强度估计。
在 12 个月期间，与 AN-IGF-1+相比，AN-IGF-1-的腰椎面积骨密度增加（P=0.004）。在雌激素治疗依从性可变的情况下，AN-IGF-1+组的面积 BMD 没有改善。两组在 12 个月时的骨几何形状、微结构、体积骨密度（vBMD）或强度方面没有差异（并且在控制 12 个月期间体重变化后结果没有改变）。两组的桡骨皮质面积和 vBMD以及胫骨皮质 vBMD 在 12 个月内均增加。AN-IGF-1-组的骨吸收标志物水平下降（P=0.042），而 AN-IGF-1+组的甲状旁腺激素增加（P=0.019）。与 AN-IGF-1+相比，AN-IGF-1-的不规则月经更为常见，但两组之间的其他不良事件发生率没有差异。
在该队列中，我们未发现 rhIGF-1 治疗联合经皮雌激素替代治疗在年轻女性 AN 患者中对骨骼结局的 12 个月的额外获益。
