糖皮质激素诱导胰岛素样生长因子1降低对原发性肾病综合征患者骨代谢的影响

Impact of the reduction of insulin-like growth factor 1 induced by glucocorticoid therapy on bone metabolism in primary nephrotic syndrome patients

目的观察糖皮质激素（GC）治疗的原发性肾病综合征（PNS）患者胰岛素样生长因子1（IGF-1）变化，探讨其水平改变对PNS患者骨代谢的影响及意义。方法以本院2008年1月至2009年8月临床资料完整的PNS患者39例为对象。口服泼尼松0．8～1．0mg·kg^-1·d，完全缓解2周后，以每2周减去原剂量的5％-10％的方式减量。最终每日或隔日5～10mg维持（总疗程〉24周）。测定应用激素前、治疗第4、8、12、24周末血白蛋白、24h尿蛋白量、血清钙、磷、甲状旁腺激素（PTH）、25羟基维生素D，（25-（OH）D，）、骨钙素（BGP）、I型胶原吡啶交联C终端肽（CTx）及尿钙／肌酐；双能x线骨密度仪检测患者骨密度（BMD）；酶联免疫法测定血清IGF—1水平。使用Pearson相关分析探讨IGF-1与骨代谢改变的关系。结果36例完成随访，并具备完整临床数据。治疗第4、8、12和24周与治疗前比较，患者血钙、25-（OH）I）3水平均早时间依赖性升高（P〈0．05），相关分析提示，与尿蛋白量呈负相关（r=-0．749，r=-0．831，P〈0．05）。骨形成指标血BGP、IGF-1水平呈时间依赖性降低（P〈0．05），骨吸收指标CTx逐渐升高，至第12周起差异有统计学意义（P〈0．05）。第4周各部位BMD与治疗前差异均无统计学意义；第8周起腰椎（L1～L4）BMD值较治疗前显著下降（P〈0．05）；第24周，股骨颈和股骨干的BMD与治疗前差异有统计学意义（P〈0．05）。PNS患者经糖皮质激素治疗后，IGF．1与BMD和BGP呈正相关（r=0．495和r=0．896，均P〈0．05），与血CTx呈负相关（r=-0．697，P〈0．05）。结论糖皮质激素呈时间依赖性导致PNS患者血清IGF—1水平降低。IGF-1下降与患者早期骨形成指标降低、骨吸收指标增高及后期骨密度下降相关。IGF-1途径可能参与GC引起的PNS患者骨代埘改变。IGF-1有望成为反映或预测糖皮质激素诱导的骨质疏松的新型生化指标。

Objective To observe the change of insulin-like growth factor 1 （IGF-1） before and after glucocorticoid （GC） therapy and to explore the effect of its change on bone metabolism in primary nephrotic syndrome （PNS） patients. Methods A total of 39 PNS patients with mean age of （36.73±12.15） years received GC therapy were selected from January 2008 to August 2009 in our hospital. Serum IGF-1, albumin, calcium, phosphorus, parathormone （PTH）, 25hydroxy vitamin D3, bone gla protein （BGP）, degradation products of C-terminal telopeptides of type I collagen （CTx）, 24-hour urinary protein excretion and the ratio of urinary calcium to creatinine were measured at five time points--before GC therapy, 4 weeks, 8 weeks, 12 weeks and 24 weeks after the use of GC. BMD was also detected at the same time points. Correlations among indexes were analyzed by Pearson. Results Thirty-six PNS patients fulfilled the follow-up and had complete clinical data, while other 3 patients lost. After GC treatment, serum calcium and 25 hydroxy vitamin D3 were significantly increased in a time-dependent manner and were negatively correlated with 24-hour urinary protein excretion （r=-0.749, r=-0.831, P〈0.05, respectively）. Serum BGP and IGF-1 were decreased after GC therapy in a time-dependent manner while CTx was significantly increased until week 12 after treatment （P〈0.05）. Compared with pre-treatment, BMD of various parts had no significant difference at week 4; BMD of lumbar spine （LI-IA） was significantly decreased until week 8 （P〈0.05）; BMD of femoral neck and femoral shaft was significantly decreased at week 24 （P〈0.05）. IGF-1 was positively correlated with BGP and BMD （r=0.896, r=0.495, P〈0.05） and negatively correlated with serum CTx （r=-0.697, P〈0.05 ）. Conclusions Serum IGF-1 level decreases in a time-dependent manner after GC treatment, which is correlated to BGP, CTx and BMD. Glucocorticoid treatment affects bone metabolism through IGF- 1 pathway possably in patients with PNS. IGF-1 may be used as a new bone biochemical marker of glucocoritcoid-indueed osteoporosis.