School of Medicine, Southern University of Science and Technology, Shenzhen, 518055, Guangdong, People's Republic of China.
Department of Endocrinology, Shenzhen Children's Hospital, Shenzhen, 518038, Guangdong, People's Republic of China.
Sci Rep. 2022 Sep 7;12(1):15166. doi: 10.1038/s41598-022-19470-4.
Estrogen can promote the acceleration of bone maturation and phthalate esters (PAEs) have estrogen-mimicking effects. We investigated whether PAEs are associated with the acceleration of bone age (BA) in girls with early onset of puberty (EOP). This case-control study enrolled 254 girls with EOP from the Endocrinology Department at Shenzhen Children's Hospital between December 2018 and August 2019. Ultra-performance liquid chromatography and tandem mass spectrometry were used to analyze the 10 metabolites of PAEs (mPAEs) in urine samples. BA was measured using an artificial intelligence system. BA exceeding the chronological age (CA) by > 2 years (BA-CA ≥ 2 years) was referred to as significant BA advancement. Participants were divided into groups A (BA-CA ≥ 2 years; case group) and B (BA-CA < 2 years; control group). Propensity score matching (PSM) was performed for both groups in a 1:2 ratio with a caliper of 0.25. To identify potential dose-response relationships between PAEs exposure and BA advancement, we grouped the participants after PSM according to the tertiles of the mPAE concentrations. After PSM, 31 and 62 girls in groups A and B were selected. The concentration of Mono-ethyl phthalate (MEP) in group A was significantly higher than in group B (11.83 μg/g vs. 7.11 μg/g, P < 0.05); there was no significant difference in the levels of other mPAEs between the groups. The degree of BA advancement and proportion of significantly advanced BA in the lowest, middle, and highest tertiles of the MEP sequentially increased, as well as in the lowest, middle, and highest tertiles of Mono-(2-ethyl-5-carboxypentyl) phthalate; however, these were only statistically different between the highest and lowest MEP tertiles (both P < 0.05). For the remaining mPAEs, differences in the degree of BA advancement among the lowest, middle, and highest tertiles, as well as differences in the proportion of significantly advanced BA among the lowest, middle, and highest tertiles, were not significant (all P > 0.05). Our findings suggested that MEP was positively associated with BA advancement in girls with EOP. Exposure to PAEs may promote accelerated bone maturation.
雌激素可促进骨成熟加速，邻苯二甲酸酯（PAEs）具有类雌激素作用。我们研究了 PAEs 是否与性早熟（EOP）女孩的骨龄（BA）加速有关。这项病例对照研究纳入了 2018 年 12 月至 2019 年 8 月期间在深圳市儿童医院内分泌科就诊的 254 例 EOP 女孩。采用超高效液相色谱串联质谱法分析尿液样本中 10 种邻苯二甲酸单酯（mPAEs）代谢物。使用人工智能系统测量 BA。BA 超过年龄（CA）>2 年（BA-CA≥2 年）被认为是显著的 BA 提前。参与者分为 A 组（BA-CA≥2 年；病例组）和 B 组（BA-CA＜2 年；对照组）。两组均采用卡尺为 0.25 的 1:2 比例进行倾向评分匹配（PSM）。为了确定 PAEs 暴露与 BA 进展之间的潜在剂量-反应关系，我们在 PSM 后根据 mPAE 浓度的三分位将参与者分组。PSM 后，A 组和 B 组分别选择了 31 名和 62 名女孩。A 组的单乙基邻苯二甲酸酯（MEP）浓度明显高于 B 组（11.83μg/g vs. 7.11μg/g，P＜0.05）；两组间其他 mPAEs 水平无显著差异。MEP 最低、中、高三分位组的 BA 进展程度和显著提前 BA 的比例依次升高，单-（2-乙基-5-羧基戊基）邻苯二甲酸酯的最低、中、高三分位组也是如此；然而，只有 MEP 最高和最低三分位组之间的这些差异有统计学意义（均 P＜0.05）。对于其余的 mPAEs，最低、中、高三分位组的 BA 进展程度差异以及最低、中、高三分位组显著提前 BA 的比例差异均无统计学意义（均 P＞0.05）。我们的研究结果表明，MEP 与 EOP 女孩的 BA 进展呈正相关。PAEs 暴露可能促进骨成熟加速。
