Neuroendocrine Unit, Massachusetts General Hospital for Children and Harvard Medical School, Boston, MA 02114, USA.
Clin Endocrinol (Oxf). 2013 Sep;79(3):326-32. doi: 10.1111/cen.12144. Epub 2013 Jul 2.
Adolescents with anorexia nervosa (AN) are amenorrheic and have decreased bone mass accrual and low bone mineral density (BMD). The regulation of mesenchymal stem cell differentiation is an important factor governing bone formation. Preadipocyte factor 1 (Pref-1), an inhibitor of adipocyte and osteoblast differentiation, is elevated in states of oestrogen deficiency. In this study, we aim to (i) investigate effects of transdermal oestradiol on Pref-1 in adolescent girls with AN, and (ii) examine associations of changes in Pref-1 with changes in lumbar BMD and bone turnover markers.
Adolescent girls with AN and normal-weight controls were studied cross-sectionally. Girls with AN were examined longitudinally in a double-blind study and received transdermal oestradiol (plus cyclic medroxyprogesterone) or placebo for 12 months.
Sixty-nine girls (44 with AN, 25 normal-weight controls) 13-18 years were studied at baseline; 22 AN girls were followed prospectively.
Pref-1 levels, bone formation and resorption markers, and BMD.
Pref-1 levels decreased in girls with AN after treatment with transdermal oestradiol compared with placebo (-0·015 ± 0·016 vs 0·060±0·026 ng/ml, P = 0·01), although at baseline, levels did not differ in AN vs controls (0·246 ± 0·015 vs 0·267 ± 0·022 ng/ml). Changes in Pref-1 over 12 months correlated inversely with changes in lumbar BMD (r = -0·48, P = 0·02) and positively with changes in CTX (r = 0·73, P = 0·006).
For the first time, we show that Pref-1 is negatively regulated by oestradiol in adolescent girls with AN. Inhibition of Pref-1 may mediate the beneficial effects of transdermal oestradiol replacement on BMD in girls with AN.
神经性厌食症（AN）青少年处于闭经状态，骨量增加和骨密度（BMD）降低。间充质干细胞分化的调节是影响骨形成的重要因素。前脂肪细胞因子 1（Pref-1）是脂肪细胞和成骨细胞分化的抑制剂，在雌激素缺乏状态下升高。本研究旨在：（i）研究经皮雌激素对 AN 青少年 Pref-1 的影响，（ii）探讨 Pref-1 的变化与腰椎 BMD 和骨转换标志物的变化的相关性。
AN 少女和体重正常的对照组进行了横断面研究。AN 女孩进行了双盲研究的纵向检查，接受经皮雌激素（加环丙孕酮）或安慰剂治疗 12 个月。
69 名 13-18 岁的女孩（44 名 AN，25 名体重正常的对照组）在基线时进行了研究；22 名 AN 女孩进行了前瞻性随访。
Pref-1 水平、骨形成和骨吸收标志物以及 BMD。
与安慰剂相比，经皮雌激素治疗后 AN 女孩的 Pref-1 水平降低（-0.015 ± 0.016 对 0.060±0.026ng/ml，P = 0.01），尽管在基线时，AN 与对照组之间的水平无差异（0.246 ± 0.015 对 0.267 ± 0.022ng/ml）。12 个月期间 Pref-1 的变化与腰椎 BMD 的变化呈负相关（r = -0.48，P = 0.02），与 CTX 的变化呈正相关（r = 0.73，P = 0.006）。
我们首次证明 Pref-1 在 AN 青少年中受雌激素的负调节。Pref-1 的抑制可能介导经皮雌激素替代对 AN 女孩 BMD 的有益作用。
