Summary

Soluble RANKL (sRANKL) and osteoprotegerin (OPG) are regulators of osteoclast differentiation and activation, but adequate pediatric reference values are lacking. Here we provide LMS (Lambda-Mu-Sigma)-based continuous pediatric reference percentiles for sRANKL, OPG and sRANKL/OPG ratio that will allow calculation of standardized patient z-scores to assess bone modeling in children.

Purpose

Soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) are regulators of osteoclast differentiation and activation and thus bone metabolic turnover in children. Adequate pediatric reference values for their serum/plasma concentrations are lacking. The development of Lambda-Mu-Sigma (LMS)-based continuous reference percentiles for laboratory parameters allow improved data interpretation in clinical practice.

Methods

A total of 300 children aged 0.1–18 years (166 boys) were enrolled in the HAnnover Reference values for Pediatrics (HARP) study. sRANKL and OPG were assessed by ELISA. LMS-based continuous reference percentiles were generated using RefCurv software.

Results

LMS-based percentiles were established for sRANKL, OPG and sRANKL/OPG ratio, which were all found to be age-dependent. sRANKL and sRANKL/OPG associated with sex. In boys, sRANKL percentiles were highest during infancy, followed by a continuous decline until the age of 7 years and a second peak around age 12–13 years. In girls, a continuous, slow decline of sRANKL percentiles was noticed from infancy onwards until the age of 13 years, followed by a rapid decline until adulthood. OPG percentiles continuously declined from infancy to adulthood. The percentiles for sRANKL/OPG ratio paralleled those of sRANKL. Serum concentrations of sRANKL correlated with OPG and serum phosphate z-scores, while OPG concentrations inversely associated with standardized body weight, BMI, and urinary phosphate to creatinine ratio (each p < 0.05).

Conclusion

This is the first report of LMS-based continuous pediatric reference percentiles for sRANKL, OPG and sRANKL/OPG ratio that allows calculation of standardized patient z-scores to assess bone metabolic turnover in children.

中文翻译：

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HARP 队列中基于 LMS 的可溶性核因子 kappa B 配体受体激活剂 (sRANKL) 和骨保护素 (OPG) 的连续儿科参考值

概括

可溶性 RANKL (sRANKL) 和骨保护素 (OPG) 是破骨细胞分化和活化的调节剂，但缺乏足够的儿科参考值。在这里，我们提供基于 LMS (Lambda-Mu-Sigma) 的 sRANKL、OPG 和 sRANKL/OPG 比率的连续儿科参考百分位数，这将允许计算标准化患者 z 分数以评估儿童骨建模。

目的

可溶性核因子 kappa B 配体受体激活剂 (sRANKL) 和骨保护素 (OPG) 是破骨细胞分化和活化以及儿童骨代谢更新的调节剂。其血清/血浆浓度缺乏足够的儿科参考值。基于 Lambda-Mu-Sigma (LMS) 的实验室参数连续参考百分位数的开发可以改进临床实践中的数据解释。

方法

共有 300 名 0.1-18 岁儿童（166 名男孩）参加了汉诺威儿科参考值 (HARP) 研究。通过 ELISA 评估 sRANKL 和 OPG。使用 RefCurv 软件生成基于 LMS 的连续参考百分位数。

结果

为 sRANKL、OPG 和 sRANKL/OPG 比率建立了基于 LMS 的百分位数，这些百分位数均被发现与年龄相关。sRANKL 和 sRANKL/OPG 与性别相关。在男孩中，sRANKL 百分位数在婴儿期最高，随后持续下降，直到 7 岁，并在 12-13 岁左右出现第二个峰值。在女孩中，从婴儿期到 13 岁，sRANKL 百分位数持续缓慢下降，随后快速下降，直到成年。OPG 百分位数从婴儿期到成年期持续下降。sRANKL/OPG 比率的百分位数与 sRANKL 的百分位数平行。sRANKL 的血清浓度与 OPG 和血清磷酸盐 z 评分相关，而 OPG 浓度与标准化体重、BMI 和尿磷酸盐与肌酐比值呈负相关（每个p  < 0.05）。

结论

这是第一份基于 LMS 的 sRANKL、OPG 和 sRANKL/OPG 比率连续儿科参考百分位数报告，可计算标准化患者 z 分数以评估儿童骨代谢更新。