Supplementary Material for: Evaluating Weight Status and Sex as Moderators of the Association of Serum Leptin with Bone Mineral Density in Children and Adolescents

<i>Background/Aims:</i> Animal studies suggest that leptin may adversely affect bone mineral density (BMD). Clinical studies have yielded conflicting results. We therefore investigated associations between leptin and bone parameters in children. <i>Methods:</i> 830 healthy children (age = 11.4 ± 3.1 years; 75% female; BMI standard deviation score [BMIz] = 1.5 ± 1.1) had fasting serum leptin measured with ELISA and body composition by dual-energy X-ray absorptiometry. The main effects for leptin and BMIz plus leptin’s interactions with sex and BMIz were examined using hierarchical linear regressions for appendicular, pelvis, and lumbar spine BMD as well as bone mineral content (BMC), and bone area (BA). <i>Results:</i> Accounting for demographic, pubertal development, and anthropometric variables, leptin was negatively and independently associated with lumbar spine BMC and BA, pelvis BA, and leg BA (<i>p</i> &lt; 0.05 for all). Sex, but not BMIz, moderated the associations of leptin with bone parameters. In boys, leptin was negatively correlated with leg and arm BMD, BMC at all bone sites, and BA at the subtotal and lumbar spine (<i>p</i> &lt; 0.01 for all). In girls, leptin was positively correlated with leg and arm BMD (<i>p</i> &lt; 0.05 for both). <i>Conclusion:</i>Independent of body size, leptin is negatively associated with bone measures; however, these associations are moderated by sex: boys, but not girls, have a negative independent association between leptin and BMD.

背景与目的：已有动物实验研究表明，瘦素（leptin）可能对骨密度（BMD, bone mineral density）产生不良影响，但临床研究结果却存在不一致性。为此，本研究旨在探讨儿童体内瘦素水平与骨骼参数之间的关联。
方法：本研究纳入830名健康儿童，年龄为11.4±3.1岁，女性占比75%，BMI标准偏差评分（BMIz）为1.5±1.1。所有受试者均接受空腹血清瘦素水平的酶联免疫吸附测定（ELISA），并通过双能X线吸收法（dual-energy X-ray absorptiometry）检测身体成分。以四肢、骨盆及腰椎的骨密度，骨矿物质含量（BMC, bone mineral content）和骨面积（BA, bone area）为研究结局，采用分层线性回归分析瘦素、BMIz的主效应，以及瘦素与性别、BMIz的交互作用。
结果：在校正人口学特征、青春期发育状态及人体测量学变量后，瘦素与腰椎骨矿物质含量、骨面积，骨盆骨面积及下肢骨面积均呈显著负相关（所有指标p<0.05）。性别而非BMIz可调节瘦素与骨骼参数之间的关联。在男性儿童中，瘦素与四肢及上肢骨密度、所有骨骼部位的骨矿物质含量，以及整体和腰椎骨面积均呈显著负相关（所有指标p<0.01）；在女性儿童中，瘦素与下肢及上肢骨密度呈显著正相关（两者p<0.05）。
结论：独立于体质量水平，瘦素与骨骼测量指标呈负相关，但此类关联受性别调节：仅男性儿童存在瘦素与骨密度之间的负向独立关联，女性儿童则无此现象。