Objective: To investigate the early changes in serum osteoprotegerin/receptor activator of nuclear factor-κB ligand (RANKL) and related indexes of calcium and phosphorus in severe burn patients. Methods: Thirty severe burn patients who met the inclusion criteria and were admitted to Tongren Hospital of Wuhan University & Wuhan Third Hospital within 8 hours post injury from June 2017 to December 2018 were recruited into severe burn group (24 males and 6 females, aged (38±13) years). Ten healthy volunteers with normal physical examination results in the Physical Examination Center of the same hospital in the same period of time were recruited into healthy control group (7 males and 3 females, aged (37±8) years). A prospective controlled study was conducted. The fasting venous blood of 5 mL was taken from each patient in severe burn group on post injury day (PID) 1, 7, 14, 21, and 28, respectively, and the fasting venous blood of 5 mL was taken from each volunteer in healthy control group. The serum osteoprotegerin, RANKL, 25 hydroxyvitamin D, and parathyroid hormone (PTH) levels were determined by enzyme-linked immunosorbent assay, and the RANKL/osteoprotegerin ratio was calculated. Serum albumin, serum calcium, and serum phosphorus levels were determined by bromocresol green method, methylthymol blue method, and phosphomolybdic acid method, respectively. Data were statistically analyzed with Fisher's exact probability test, analysis of variance for repeated measurement, Mann-Whitney U test, independent sample t test, and Bonferroni correction. Results: (1) The serum osteoprotegerin levels of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 155.11 (102.91, 187.02), 170.07 (84.60, 196.86), 174.95 (59.09, 208.35), 190.01 (47.08, 214.52), and 188.85 (58.73, 223.13) pg/mL, respectively, which were significantly higher than 33.34 (28.59, 45.68) pg/mL of volunteers in healthy control group, Z=-3.436, -4.311, -3.248, -2.811, -4.217, P<0.01. The serum levels of RANKL of patients in severe burn group on PID 1, 7, 14, 21, and 28 were (1 869±791), (1 746±857), (1 781±713), (2 015±825), and (2 272±583) pg/mL, respectively, significantly higher than (49±16) pg/mL of volunteers in healthy control group, t=12.600, 10.844, 13.294, 13.041, 20.880, P<0.01. The ratios of RANKL/osteoprotegerin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were 12.23 (8.10, 24.73), 11.40 (8.25, 16.96), 11.15 (6.91, 38.32), 12.98 (9.22, 49.68), and 13.91 (10.29, 40.68), respectively, which were significantly higher than 1.17 (0.91, 1.74) of volunteers in healthy control group, Z=-4.560, -4.529, -4.529, -4.560, -4.623, P<0.01. (2) The serum level of 25 hydroxyvitamin D of patients in severe burn group on PID 1 was significantly lower than that of volunteers in healthy control group (Z=-2.749, P<0.01). Compared with those of volunteers in healthy control group, the serum levels of albumin of patients in severe burn group on PID 1, 7, 14, 21, and 28 were significantly lower (t=-4.374, -7.689, -8.257, -7.651, -6.259, P<0.01), the serum levels of PTH were significantly elevated (Z=-4.685, -4.685, -4.685, -4.654, -4.685, P<0.01), and the serum levels of phosphorus were not changed significantly. The serum levels of calcium of patients in severe burn group on PID 1, 7, 14, and 21 were significantly lower than the level of volunteers in healthy control group (Z=-2.375, -3.455, -2.442, -2.016, P<0.05 or P<0.01). Conclusions: The serum osteoprotegerin, RANKL, RANKL/osteoprotegerin ratio, and PTH are increased, and the serum 25 hydroxyvitamin D, albumin, and calcium are decreased in the early stage of severe burn patients, which may be the mechanism leading to bone loss in patients.
目的： 了解重度烧伤患者早期血清护骨因子/核因子κB受体激活蛋白配体(RANKL)和钙磷相关指标的变化。 方法： 将2017年6月—2018年12月武汉大学同仁医院暨武汉市第三医院收治的符合入选标准的30例伤后8 h内入院的重度烧伤患者纳入重度烧伤组[男24例、女6例，年龄(38±13)岁]，同期招募该单位体检中心体检结果正常的10名健康志愿者纳入健康对照组[男7名、女3名，年龄(37±8)岁]，进行前瞻性对照研究。重度烧伤组患者于伤后1、7、14、21、28 d各抽取5 mL空腹静脉血，健康对照组志愿者取5 mL空腹静脉血，采用酶联免疫吸附测定法检测血清中护骨因子、RANKL、25羟维生素D及甲状旁腺激素(PTH)水平并计算RANKL/护骨因子比值，分别采用溴甲酚绿法、甲基百里酚蓝比色法和磷钼酸法测定血清白蛋白、血钙和血磷水平。对数据行Fisher确切概率法检验、重复测量方差分析、独立样本t检验、Mann-Whitney U检验以及Bonferroni校正。 结果： (1)重度烧伤组患者伤后1、7、14、21、28 d血清护骨因子水平分别为155.11(102.91，187.02)、170.07(84.60，196.86)、174.95(59.09，208.35)、190.01(47.08，214.52)、188.85(58.73，223.13)pg/mL，均明显高于健康对照组志愿者的33.34(28.59，45.68)pg/mL，Z＝－3.436、－4.311、－3.248、－2.811、－4.217，P<0.01；血清RANKL水平分别为(1 869±791)、(1 746±857)、(1 781±713)、(2 015±825)、(2 272±583)pg/mL，均明显高于健康对照组志愿者的(49±16)pg/mL，t＝12.600、10.844、13.294、13.041、20.880，P<0.01；RANKL/护骨因子比值分别为12.23(8.10，24.73)、11.40(8.25，16.96)、11.15(6.91，38.32)、12.98(9.22，49.68)、13.91(10.29，40.68)，均明显高于健康对照组志愿者的1.17(0.91，1.74)，Z＝－4.560、－4.529、－4.529、－4.560、－4.623，P<0.01。(2)重度烧伤组患者伤后1 d血清25羟维生素D水平明显低于健康对照组志愿者(Z＝－2.749，P<0.01)。与健康对照组志愿者比较，重度烧伤组患者伤后1、7、14、21、28 d血清白蛋白水平明显降低(t＝－4.374、－7.689、－8.257、－7.651、－6.259，P<0.01)，血清PTH水平明显升高(Z＝－4.685、－4.685、－4.685、－4.654，－4.685，P<0.01)，血磷水平无明显变化。重度烧伤组患者伤后1、7、14、21 d血钙水平明显低于健康对照组志愿者(Z＝－2.375、－3.455、－2.442、－2.016，P<0.05或P<0.01)。 结论： 重度烧伤患者早期血清护骨因子、RANKL、RANKL/护骨因子比值、PTH升高，25羟维生素D、白蛋白及血钙下降，这可能是导致患者骨质流失的机制。.
Keywords: Bone loss; Burns; Calcium; Osteoprotegerin/receptor activator of nuclear factor-κB ligand; Parathyroid hormone; Phosphorus; Vitamin D.