Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa
Effects of short-term recombinant human insulin-like growth factor I administration on bone turnover in osteopenic women with anorexia nervosa
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DOI：
10.1210/jc.81.11.3864
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发表时间：
1996-11-01
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;Baum, H;Klibanski, A
严重骨质疏松影响超过一半的女性神经性厌食症（AN）。这种情况下骨质流失的机制尚不清楚，单独使用雌激素也未被证明能预防骨质流失。胰岛素样生长因子I （IGF-I）是一种营养依赖的骨营养激素，已知在体内和体外刺激成骨细胞功能和胶原合成。我们假设短期给药重组人IGF-I （rhIGF-I）会增加患有AN的年轻女性的骨转换。我们研究了23名年龄在18-29岁（平均+/- SD， 23 +/- 4岁）的AN患者。与年龄匹配的对照组相比，脊柱骨密度显著降低（双能x线骨密度测量结果为0.85 +/- 0.11比1.19 +/- 0.12 g/cm(2)）；P < 0.001)， 54%的女性低于正常平均值。患者随机接受rhigf - 1（100或30 μ g/kg）或安慰剂sc，每天两次，持续6天。在基线和治疗后3天和6天，使用两种骨形成标志物[骨钙素（OC）和I型前胶原羧基末端前肽（PICP）]和三种骨吸收特异性标志物[吡啶啉（PYRX），脱氧吡啶啉（DPYRX）和n -末端肽（NTX）]评估骨转换。与正常绝经前妇女相比，AN患者血清OC显著降低（P < 0.001） （5.4 +/- 3.8 vs. 8.6 +/- 4.5 ng/mL），并与脂肪含量百分比（r = 0.60; P < 0.01）和体重指数（r = 0.50; P < 0.05）相关。与正常水平相比，骨吸收指标显著升高[DPYRX， 18.2 +/- 7.0 vs. 11.4 +/- 5.2 nmol/mmol肌酐，（P < 0.001）；NTX, 53.5 +/- 22.5 vs. 36.5 +/- 14.6 nmol BCE/mmol肌酐[P < 0.01]。与年龄匹配的对照组相比，IGF-I水平在基线时相对较低（203 +/- 93 vs 262 +/- 84 ng/mL, P < 0.01），升高至673 +/- 268 ng/mL [P < 0.05；100 μ g/kg每日2次[BID]和545 +/- 255 ng/mL （P < 0.05; 30 μ g/kg BID）。在短期给予100 μ g/kg BID剂量的rhIGF-I期间，通过PICP（147 +/- 33至303 +/- 187 ng/mL）和OC（5.3 +/- 3.8至10.9 +/- 7.4 ng/mL）评估，骨形成标志物显著（P < 0.05）增加。PYRX （51.0 +/- 16.6 ~ 87.1 +/- 8.2 nmol/mmol肌酐）和DPYRX （17.3 +/- 4.5 ~ 26.3 +/- 3.7 nmol/mmol肌酐）测定的骨吸收指标也显著（P < 0.05）增加。随机分组短期给予30 μ g/kg BID剂量的rhIGF-I组PICP（110.9 +/- 47.0至134.8 +/- 43.2 ng/mL）显著升高（P < 0.05）， OC水平无显著升高（4.5 +/- 3.2至6.8 +/- 5.9 ng/mL）。然而，在该剂量的rhIGF-I给药期间，骨吸收标志物未发生变化。与安慰剂水平相比，两个治疗组的血清甲状旁腺激素、血清和尿钙没有变化。这些数据表明，患有神经性厌食症的年轻女性骨形成标志物减少，骨吸收增加。这是首次证明短期给予rhigf - 1可增加严重骨质减少的AN妇女的骨转换标志物。短期rhigf - 1对骨转换的影响是剂量依赖性的。在100 μ g BID剂量下，rhigf - 1显著刺激骨形成和骨吸收的标志物。在30 μ g BID的rhigf - 1剂量下，骨形成标志物PICP增加，骨吸收标志物没有变化。需要进一步的研究来确定慢性给药rhigf - 1是否会影响由神经性厌食症引起的深度骨质减少的年轻女性的骨量。
Significant osteoporosis affects over half of all women with anorexia nervosa (AN). The mechanisms of bone loss in this condition are not known, and estrogen administration alone has not been shown to prevent bone loss. Insulin-like growth factor I (IGF-I), a nutritionally dependent bone trophic hormone, is known to stimulate osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that short term administration of recombinant human IGF-I (rhIGF-I) would increase bone turnover in young women with AN. We studied 23 women, aged 18-29 yr (mean +/- SD, 23 +/- 4 yr) with AN. Spinal bone density was significantly reduced compared to that in age-matched controls (0.85 +/- 0.11 vs. 1.19 +/- 0.12 g/cm(2) by dual energy x-ray absorptiometry; P < 0.001) and was below the normal mean in 54% of the women. Patients were randomized to receive rhIGF-I (100 or 30 mu g/kg) or placebo sc twice a day for 6 days. Bone turnover was assessed at baseline and after 3 and 6 days of treatment using two markers of bone formation [osteocalcin (OC) and type I procollagen carboxyl-terminal propeptide (PICP)] and three specific markers of bone resorption [pyridinoline (PYRX), deoxypyridinoline (DPYRX), and N-telopeptide (NTX)]. Serum OC was reduced significantly (P < 0.001) in women with AN compared to normal premenopausal women (5.4 +/- 3.8 vs. 8.6 +/- 4.5 ng/mL) and correlated with percent fat mass (r = 0.60; P < 0.01) and body mass index (r = 0.50; P < 0.05). Markers of bone resorption were elevated significantly compared to normal levels [DPYRX, 18.2 +/- 7.0 vs. 11.4 +/- 5.2 nmol/mmol creatinine, (P < 0.001); NTX, 53.5 +/- 22.5 vs. 36.5 +/- 14.6 nmol BCE/mmol creatinine (P < 0.01)]. IGF-I levels were relatively low at baseline compared to those in age-matched controls (203 +/- 93 vs. 262 +/- 84 ng/mL; P < 0.01) and increased to 673 +/- 268 ng/mL [P < 0.05; 100 mu g/kg twice daily (BID)] and 545 +/- 255 ng/mL (P < 0.05; 30 mu g/kg BID). During short term administration of rhIGF-I at a dose of 100 mu g/kg BID, there was a significant (P < 0.05) increase in markers of bone formation, as assessed by both PICP (147 +/- 33 to 303 +/- 187 ng/mL) and OC (5.3 +/- 3.8 to 10.9 +/- 7.4 ng/mL). There was also a significant (P < 0.05) increase in markers of bone resorption as assessed by PYRX (51.0 +/- 16.6 to 87.1 +/- 8.2 nmol/mmol creatinine) and DPYRX (17.3 +/- 4.5 to 26.3 +/- 3.7 nmol/mmol creatinine). The group randomized to receive short term administration of rhIGF-I at a dose of 30 mu g/kg BID demonstrated a significant (P < 0.05) increase in PICP (110.9 +/- 47.0 to 134.8 +/- 43.2 ng/mL) and an insignificant increase in OC levels (4.5 +/- 3.2 to 6.8 +/- 5.9 ng/mL). However, markers of bone resorption were unchanged during rhIGF-I administration at this dose. Serum PTH and serum and urinary calcium were unchanged in both treatment groups compared to placebo levels. These data demonstrate that young women with anorexia nervosa have decreased markers of bone formation and increased bone resorption. This is the first demonstration that short term rhIGF-I administration increases markers of bone turnover in severely osteopenic women with AN. The effects of short term rhIGF-I on bone turnover are dose dependent. At a dose of 100 mu g BID, rhIGF-I administration significantly stimulated both markers of bone formation and bone resorption.At a dose of rhIGF-I of 30 mu g BID, there was an increase in one marker of bone formation, PICP, without a change in markers of bone resorption. Further studies are required to determine whether chronic administration of rhIGF-I can affect bone mass in young women with profound osteopenia due to anorexia nervosa.