Abstract:

Objective　To investigate and analyze the iron overload and bone metabolism in children with transfusion-dependent thalassemia (TDT). Methods　A total of 93 children with TDT admitted to Dongguan Eighth People's Hospital from January 2021 to August 2023 were selected as the research subjects. The severity of iron overload was determined based on the serum ferritin (SF) level and the children were divided into three groups: children without iron overload (SF ≤1 000 μg/L, 14 cases), children with mild to moderate iron overload (1 000 μg/L < SF < 2 500 μg/L, 32 cases), and children with severe iron overload (SF ≥2 500 μg/L, 47 cases). There were 7 boys and 7 girls in the non-iron overload group, with an age of (7.14±1.29) years old. In the mild to moderate iron overload group, there were 17 boys and 15 girls, with an age of (7.10±1.12) years old. In the severe iron overload group, there were 19 boys and 28 girls, with an age of (7.44±1.45) years old. All children with iron overload received iron removal treatment. The levels of SF, bone metabolism indicators {parathyroid hormone (PTH) and serum 25-hydroxyvitamin D₃ [25(OH)D₃]}, and liver function indicators [alanine aminotransferase (ALT) and aspartate aminotransferase (AST)] in children with mild to moderate and severe iron overload were compared before and 3 months after medication. Pearson correlation analysis was used to investigate the correlations between the SF level and bone metabolism indicators in children with iron overload. Multivariate logistic regression analysis was conducted to identify the independent risk factors for severe iron overload in children with TDT. Statistical analysis was conducted using the χ² test, Fisher's exact probability method, independent sample t test, and one-way analysis of variance. Results　The levels of SF, PTH, ALT, and AST before medication and SF after medication in the severe iron overload group were (5 410.74±930.15) μg/L, (9.57±1.79) pmol/L, (45.50±8.47) U/L, (65.88±8.19) U/L, and (3 197.13±629.49) μg/L, which were all higher than those in the mild to moderate iron overload group [(1 801.53±388.21) μg/L, (6.17±1.23) pmol/L, (37.45±8.80) U/L, (54.74±6.75) U/L, and (1 225.62±199.48) μg/L] (all P<0.05); the level of 25(OH)D₃ before medication in the severe iron overload group was (18.22±4.48) μg/L, which was lower than that in the mild to moderate iron overload group [(24.86±5.48) μg/L] (P<0.05). The Pearson correlation analysis results showed that before treatment, the SF level was negatively correlated with the 25(OH)D₃ level (r = -0.561, P<0.05), and positively correlated with the PTH, ALT, and AST levels (r = 0.646, 0.392, and 0.544, all P<0.05); after treatment, the SF level was negatively correlated with the 25(OH)D₃ level (r = -0.484, P<0.05), and positively correlated with the PTH, ALT, and AST levels (r = 0.623, 0.342, and 0.448, all P<0.05). The logistic regression analysis results showed that pre-medication high PTH (OR = 3.914, 95%CI = 2.168 - 7.065), low 25(OH)D₃ (OR = 0.755, 95%CI = 0.659 - 0.864), high ALT (OR = 1.114, 95%CI = 1.048 - 1.184), and high AST (OR = 1.203, 95%CI = 1.108 - 1.307) were all independent risk factors for severe iron overload in children with TDT (all P<0.05). Conclusions　Iron overload is common in children with TDT in Dongguan, and the severity of iron overload is correlated with bone metabolism disorders. It is recommended to include bone metabolism markers in routine monitoring of TDT children and initiate early combined iron removal therapy for those with SF >2 500 μg/L.

Key words:

Transfusion-dependent thalassemia, Iron overload, Serum ferritin, Bone metabolism, Children

摘要：

目的　调查分析输血依赖型地中海贫血（TDT）患儿铁过载与骨代谢情况。方法　选取2021年1月至2023年8月东莞市第八人民医院收治的93例TDT患儿作为研究对象，依据血清铁蛋白（SF）水平判定铁过载严重程度，分为无铁过载患儿（SF≤1 000 μg/L，14例）、轻中度铁过载患儿（1 000 μg/L < SF < 2 500 μg/L，32例）和重度铁过载患儿（SF ≥2 500 μg/L，47例）。无铁过载组男7例，女7例，年龄（7.14±1.29）岁；轻中度铁过载组男17例，女15例，年龄（7.10±1.12）岁；重度铁过载组男19例，女28例，年龄（7.44±1.45）岁。铁过载患儿均接受祛铁治疗。比较轻中度、重度铁过载患儿用药前、用药3个月后SF、骨代谢指标｛甲状旁腺激素（PTH）、血清25-羟基维生素D₃［25（OH）D₃］｝、肝功能指标［丙氨酸氨基转移酶（ALT）、天门冬氨酸氨基转移酶（AST）］，采用Pearson相关性分析铁过载患儿SF水平与骨代谢指标的相关性，行多因素logistic回归分析识别TDT患儿重度铁过载的独立危险因素。采用χ²检验、Fisher确切概率法、独立样本t检验、单因素方差分析进行统计学分析。结果　重度铁过载组用药前SF、PTH、ALT、AST及用药后SF水平分别为（5 410.74±930.15）μg/L、（9.57±1.79）pmol/L、（45.50±8.47）U/L、（65.88±8.19）U/L、（3 197.13±629.49）μg/L，均高于轻中度铁过载组的（1 801.53±388.21）μg/L、（6.17±1.23）pmol/L、（37.45±8.80）U/L、（54.74±6.75）U/L、（1 225.62±199.48）μg/L（均P<0.05）；重度铁过载组用药前25（OH）D₃水平为（18.22±4.48）μg/L，低于轻中度铁过载组（24.86±5.48）μg/L（P<0.05）。Pearson相关性分析结果显示，治疗前SF水平与25（OH）D₃水平呈负相关（r=-0.561，P<0.05），与PTH、ALT、AST水平呈正相关（r=0.646、0.392、0.544，均P<0.05）；治疗后，SF水平与25（OH）D₃呈负相关（r=-0.484，P<0.05），与PTH、ALT、AST水平呈正相关（r=0.623、0.342、0.448，均P<0.05）。logistic回归分析结果显示，用药前高PTH（OR=3.914，95%CI=2.168～7.065）、低25（OH）D₃（OR=0.755，95%CI=0.659～0.864）、高ALT（OR=1.114，95%CI=1.048～1.184）、高AST（OR=1.203，95%CI=1.108～1.307）均是TDT患儿发生重度铁过载的独立危险因素（均P<0.05）。结论　东莞地区TDT患儿常见铁过载，且铁过载严重程度与骨代谢紊乱相关，建议将骨代谢标志物纳入TDT患儿常规监测，并对SF >2 500 μg/L者启动早期联合祛铁治疗。

关键词:

输血依赖型地中海贫血, 铁过载, 血清铁蛋白, 骨代谢, 儿童