Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone
Short-term effects on linear growth and bone turnover in children randomized to receive prednisolone or dexamethasone
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DOI：
10.1046/j.1365-2265.2002.01580.x
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发表时间：
2002-08-01
影响因子：
3.2
通讯作者：
Hughes, IA
中科院分区：
文献类型：
--
作者：
Ahmed, SF;Tucker, P;Hughes, IA
目的 比较泼尼松龙 (Pred) 和地塞米松 (Dex) 对短期生长和骨转换的相对效力。 方法 对儿童进行为期 16 周的前瞻性研究，随机接受前 5 周的 Pred (40 mg/m(2)) 或 Dex (6.5 mg/m(2))，作为急性淋巴细胞白血病 MRC-ALL97/99 诱导化疗的一部分(ALL). 测量小腿长度速度 (LLLV) 和体重、血清 IGF-I、血清骨碱性磷酸酶 (bALP) 水平以及肌酐调整后脱氧吡啶啉交联 (DPD) 的尿排泄量。 受试者 19 名儿童（8 名男孩，11 名女孩），中位年龄为 5.9 岁（范围 2.6-13），诊断为 ALL。 结果 周治疗第 2 周，Dex 组的中位 LLLV 为 -1.5 毫米/周（范围 0.7 至 -2.1），显着低于 Pred 组的 LLLV，即 -0.1 毫米/周（范围 0.20 至 -0.28；P < 0.05）。在 Dex 组中，第 8 周时的 LLLV 仍然较低（中位 LLLV，-0.3 毫米/周，范围 0 至 -1.3），而 Pred 组的 LLLV 为 0.3 毫米/周（范围 0.2-1.0；P < 0.05）。第 2 周后，两组儿童的体重均出现增加，并在第 6 周达到峰值。Dex 组的体重相对于基线的变化大于 Pred 组，到第 5 周时达到最大变化，分别为 17.5%（范围 5-25）和 8.7%（范围 -3 至 18）（P < 0.05）。目前，整个组的中位 IGF-I 水平为 83.5 μg/l（范围 31.8-293）。在 Dex 治疗期间 IGF-I 水平显着下降，并继续低于基线。在第 4、6 和 8 周，Dex 组的 IGF-I 相对于基线的中值变化低于 Pred 组。从第 1 周到第 3 周，Pred 组 bALP 的中位变化为 72%（范围 -8 至 304），而 Dex 组 bALP 的变化为 -1%（范围 23 至 -28；P < 0.005）。到第 3 周，Pred 组的中位 bALP 为 65 U/l（范围 36-187），高于 Dex 组的 39 U/l（范围 26-60；P < 0.05），但到第 6 周，Pred 组的中位 bALP 已降至与 Dex 组相似的水平。目前，Pred 和 Dex 组的中位 DPD 分别为 22 nmol/l（范围 17-38）和 20 nmol/l（范围 12-26）（ns），在第 3 周和第 6 周之间达到最低点。Pred 和 Dex 组从第 1 周到第 3 周的 DPD 中位百分比变化分别为 -34%（范围 -7 到 14）和 -53%（范围 -6 到 14）。 -69)，分别为(ns)。到第 8 周，Pred 组的 DPD 排泄量开始显着上升，Pred 组的中位 DPD 为 35 nmol/l（范围 10-53），Dex 组为 22 nmol/l（范围 9-30）（P < 0.05）。平均而言，在第 2 周至第 8 周期间，Dex 组的 LLLV 比 Pred 组低 3 倍，体重增加百分比高 3 倍，bALP 低 1.3 倍，DPD 低 1.5 倍。 结论 Pred 和 Dex 都会影响短期生长和骨转换。两种药物影响骨形成的机制可能不同。 Dex 在抑制短期线性生长和刺激体重增加方面比 Pred 强约 18 倍，在抑制骨转换方面强约 9 倍。糖皮质激素对生长和骨转换的不同参数具有不同的影响，其强度可能取决于所使用的类固醇。
AIM To compare the relative potency of prednisolone (Pred) and dexamethasone (Dex) on short-term growth and bone turnover.METHOD Prospective study over 16 weeks of children randomized to receive Pred (40 mg/m(2)) or Dex (6.5 mg/m(2)) for the first 5 weeks as part of the MRC-ALL97/99 induction chemotherapy for acute lymphoblastic leukaemia (ALL).MEASUREMENTS Lower leg length velocity (LLLV) and weight, serum IGF-I, serum bone alkaline phosphatase (bALP) levels and creatinine-adjusted, urinary excretion of deoxypyridinoline cross-links (DPD).SUBJECTS Nineteen children (eight boys, 11 girls) with a median age of 5.9 years (range 2.6-13) and with a diagnosis of ALL.RESULTS At week 2 of therapy, median LLLV in the Dex group was -1.5 mm/week (range 0.7 to -2.1) and significantly lower than the LLLV in the Pred group which was -0.1 mm/week (range 0.20 to -0.28; P < 0.05). In the Dex group, LLLV remained lower at week 8 (med LLLV, -0.3 mm/week, range 0 to -1.3) compared to LLLV in the Pred group at 0.3 mm/week (range 0.2-1.0; P < 0.05). Body weight showed an increase after week 2 and reached a peak in both groups of children at week 6. The change in weight from baseline was greater in the Dex group than the Pred group reaching a maximum change by week 5 of 17.5% (range 5-25) and 8.7% (range -3 to 18), respectively (P < 0.05). At presentation, median IGF-I level for the whole group was 83.5 μg/l (range 31.8-293). IGF-I levels fell markedly during Dex therapy and continued to remain lower than baseline. At weeks 4, 6 and 8, median change in IGF-I from baseline was lower in the Dex group than the Pred group. From week 1 to week 3, median change in bALP was 72% (range -8 to 304) in the Pred group, whereas in the Dex group change in bALP was -1% (range 23 to -28; P < 0.005). By week 3, median bALP was higher in the Pred group at 65 U/l (range 36-187) than in the Dex group at 39 U/l (range 26-60; P < 0.05) but by week 6 median bALP in the Pred group had fallen to a similar level to the Dex group. At presentation, median DPD was 22 nmol/l (range 17-38) and 20 nmol/l (range 12-26) in the Pred and Dex groups, respectively (ns), reaching a nadir between weeks 3 and 6. The median percentage change in DPD in the Pred and Dex group from week 1 to week 3 was -34% (range -7 to 14) and -53% (range -6 to -69), respectively (ns). By week 8, DPD excretion had started to rise more dramatically in the Pred group such that the median DPD was 35 nmol/l (range 10-53) in the Pred group and 22 (range 9-30) in the Dex group (P < 0.05). On average, between weeks 2 and 8, LLLV was three times lower, percentage gain in weight was three times higher, bALP was 1.3 times lower and DPD was 1.5 times lower in the Dex group than the Pred group.CONCLUSION Pred and Dex both affect short-term growth and bone turnover. The mechanism of the effect on bone formation may be different between the two drugs. Dex may be about 18 times more potent than Pred at suppressing short-term linear growth and stimulating weight gain, and about nine times more potent at suppressing bone turnover. Glucocorticoids have a variable effect on different parameters of growth and bone turnover and the intensity may depend on the steroid used.