Tbe effects of anorexia nervosa on bone metabolism in female adolescents
Tbe effects of anorexia nervosa on bone metabolism in female adolescents
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DOI：
10.1210/jc.84.12.4489
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发表时间：
1999-12-01
影响因子：
5.8
通讯作者：
Klibanski, A
中科院分区：
文献类型：
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作者：
Soyka, LA;Grinspoon, S;Klibanski, A
骨质减少是青春期女孩神经性厌食症（AN）的一种常见且持续的并发症，发生在骨骼发育的关键时期。对该患者人群的骨代谢知之甚少。因此，我们测量骨密度（BMD）和身体组成的双能X线吸收法，营养状况，骨代谢，钙;和激素状态在19个青春期女孩与AN（平均值+/- SEM，16.0 +/- 0.4岁）和19骨龄匹配的对照。AN的平均持续时间为19 +/- 5个月。脊椎（L1-L4）骨量减少在AN中常见。与对照组相比，42%的患者腰椎前后位BMD低于平均值1个标准差以上，63%的患者腰椎侧位BMD低于平均值1个标准差以上。仅在对照组中，瘦体重显著预测腰椎骨矿物质含量（r = 0.75; P < 0.0001）。在AN中，病程是脊柱BMD最重要的预测因素（腰椎：r = -0.44; P = 0.06;侧位：r = -0.59; P = 0.008）。患有成熟BA的AN青少年（15岁及以上）性腺功能减退[雌二醇，16.2 +/- 1.9 vs 23.3 +/- 1.6 pg/mL（P = 0.01）;游离睾酮，0.70 +/- 0.17 us。1.36+/- 0.14 pg/mL（P = 0.01）1，但硫酸脱氢表雄酮和尿游离皮质醇水平无差异。AN患者的瘦素水平降低（2.9 +/- 2.1 vs. 16.5 +/- 1.8 ng/mL; P < 0.0001）。AN患者的胰岛素样生长因子I（IGF-I）水平降低至对照组水平的50%（219 +/- 41 vs. 511 +/- 35 ng/mL; P < 0.0001），并与所有营养状况指标相关，尤其是瘦素（r = 0.80; P < 0.0001）。骨形成的替代标志物，血清骨钙素（OC）和骨特异性碱性磷酸酶（BSAP），在AN中与对照组相比显著降低（P = 0.02）（OC，39.1 r 6.4 vs. 59.2 +/- 5.2 ng/mL; BSAP，27.9 +/- 4.0 vs. 40.6 +/- 3.4 U/L）。在逐步回归分析中，AN中骨形成的大部分变化是由于IGF-I水平（OC：r（2）= 0.72：P = 0.002; BSAP：r（2）= 0.53; P = 0.01）。患者和对照组的骨吸收相当。这些数据表明，骨形成减少，并与骨吸收脱钩，在成熟的青少年与AN与低骨密度。瘦体重是对照组BMD的一个重要预测因子，但对AN患者不是。AN中骨形成的主要相关因素是营养依赖性骨营养因子IGF-I。在骨矿物质积累的关键时期，IGF-I的减少可能是青少年AN发生骨质减少的重要因素。
Osteopenia is a frequent, often persistent, complication of anorexia nervosa (AN) in adolescent girls and occurs during a critical time in bone development. Little is known about bone metabolism in this patient population. Therefore, we measured bone density (BMD) and body composition by dual energy x-ray absorptiometry, nutritional status, bane turnover, calcium; and hormonal status in 19 adolescent girls with AN (mean +/- SEM, 16.0 +/- 0.4 yr) and 19 bone age-matched controls. The mean duration of AN was 19 +/- 5 months. Spinal (L1-L4) osteopenia was common in AN. Lumbar anterioposterior BMD was more than 1 sn below the mean in 42% of patients, and lateral spine BMD was more than 1 SD below in 63% of patients compared with controls. Lean body mass significantly predicted lumbar bone mineral content (r = 0.75; P < 0.0001) in controls only. In AN, duration of illness was the most significant predictor of spinal BMD (lumbar: r = -0.44; P = 0.06; lateral: r = -0.59; P = 0.008). AN adolescents with mature BA (15 yr and greater) were hypogonadal [estradiol, 16.2 +/- 1.9 vs. 23.3 +/- 1.6 pg/mL (P = 0.01); free testosterone, 0.70 +/- 0.17 us. 1.36 +/- 0.14 pg/mL (P = 0.01)1 although dehydroepiandrosterone sulfate and urinary free cortisol levels did not differ. Leptin levels were reduced in AN (2.9 +/- 2.1 vs. 16.5 +/- 1.8 ng/mL; P < 0.0001). Insulin like growth factor I (IGF-I) was reduced in AN to 50% of control levels (219 +/- 41 vs. 511 +/- 35 ng/mL; P < 0.0001) and correlated with all measures of nutritional status, particularly leptin (r = 0.80; P < 0.0001). Surrogate markers of bone formation, serum osteocalcin (OC) and bone-specific alkaline phosphatase (BSAP), were significantly (P = 0.02) reduced in AN vs. controls (OC, 39.1 r 6.4 vs. 59.2 +/- 5.2 ng/mL; BSAP, 27.9 +/- 4.0 vs. 40.6 +/- 3.4 U/L). The majority of the variation in bone formation in AN was due to IGF-I levels (OC: r(2) = 0.72: P = 0.002; BSAP: r(2) = 0.53; P = 0.01) in stepwise regression analyses. Bone resorption was comparable in patients and controls. These data demonstrate that bone formation is reduced and uncoupled to bone resorption in mature adolescents with AN in association with low bone density. Lean body mass was a significant predictor of BMD in controls, but not AN patients. The major correlate of bone formation in AN was the nutritionally dependent bone trophic factor, IGF-I. Reduced IGF-I during the critical period of bone mineral accumulation may be an important factor in the development of osteopenia in adolescents with AN.