Bahamonde Marisol, Misra Madhusmita
Department of Pediatrics, Universidad San Francisco de Quito (USFQ), Cumbayá, Ecuador.
Division of Pediatric Endocrinology, Massachusetts General Hospital for Children, USA; Neuroendocrine Unit, Massachusetts General Hospital, Boston, MA, USA.
Growth Horm IGF Res. 2020 Jun;52:101317. doi: 10.1016/j.ghir.2020.101317. Epub 2020 Mar 23.
Growth hormone (GH) and insulin like growth factor-I (IGFI) are key bone trophic hormones, whose rising levels during puberty are critical for pubertal bone accrual. Conditions of GH deficiency and genetic resistance impact cortical and trabecular bone deleteriously with reduced estimates of bone strength. In humans, conditions of undernutrition (as in anorexia nervosa (AN), or subsequent to chronic illnesses) are associated with low IGF-I levels, which correlate with disease severity, and also with lower bone mineral density (BMD), impaired bone structure and lower strength estimates. In adolescents and adults with AN, studies have demonstrated a nutritionally acquired GH resistance with low IGF-I levels despite high concentrations of GH. IGF-I levels go up with increasing body weight, and are associated with rising levels of bone turnover markers. In short-term studies lasting 6-10 days, recombinant human IGF-I (rhIGF-I) administration in physiologic replacement doses normalized IGF-I levels and increased levels of bone formation markers in both adults and adolescents with AN. In a randomized controlled trial in adults with AN in which participants were randomized to one of four arms: (i) rhIGF-I with oral estrogen-progesterone (EP), (ii) rhIGF-I alone, (iii) EP alone, or (iv) neither for 9 months, a significant increase in bone formation markers was noted in the groups that received rhIGF-I, and a significant decrease in bone resorption markers in the groups that received EP. The group that received both rhIGF-I and EP had a significant increase in bone density at the spine and hip compared to the group that received neither. Side effects were minimal, with no documented fingerstick glucose of <50 mg/dl. These data thus suggest a potential role for rhIGF-I administration in optimizing bone accrual in states of undernutrition associated with low IGF-I.
生长激素（GH）和胰岛素样生长因子-I（IGF-I）是关键的骨营养激素，其在青春期水平的升高对于青春期骨量积累至关重要。生长激素缺乏和遗传抵抗状态会对皮质骨和小梁骨产生有害影响，导致骨强度估计值降低。在人类中，营养不良状况（如神经性厌食症（AN）或慢性疾病后）与低IGF-I水平相关，这与疾病严重程度相关，也与较低的骨矿物质密度（BMD）、受损的骨结构和较低的强度估计值相关。在患有AN的青少年和成年人中，研究表明尽管生长激素浓度很高，但存在营养性获得性生长激素抵抗，IGF-I水平较低。IGF-I水平随体重增加而升高，并与骨转换标志物水平升高相关。在持续6 - 10天的短期研究中，给予生理替代剂量的重组人IGF-I（rhIGF-I）可使患有AN的成年人和青少年的IGF-I水平正常化，并提高骨形成标志物水平。在一项针对患有AN的成年人的随机对照试验中，参与者被随机分为四组之一：（i）rhIGF-I联合口服雌激素 - 孕激素（EP），（ii）单独使用rhIGF-I，（iii）单独使用EP，或（iv）两者都不使用，为期9个月，接受rhIGF-I的组骨形成标志物显著增加，接受EP的组骨吸收标志物显著降低。与两者都不接受的组相比，接受rhIGF-I和EP的组脊柱和髋部的骨密度显著增加。副作用最小，没有记录到指尖血糖<50 mg/dl的情况。因此，这些数据表明rhIGF-I给药在优化与低IGF-I相关的营养不良状态下的骨量积累方面具有潜在作用。
