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LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand
Helene Tietze1, Veronika Pott1, Nele Kanzelmeyer1
1Department of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Insights
This study establishes pediatric reference percentiles for soluble RANKL (sRANKL) and osteoprotegerin (OPG), crucial for assessing bone health in children. These new standards aid in calculating patient z-scores for better bone modeling evaluation.
Area of Science:
- Pediatric Endocrinology
- Bone Biology
- Biomarker Development
Background:
- Soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) are key regulators of osteoclast differentiation and bone turnover.
- Current pediatric reference values for sRANKL and OPG are insufficient for accurate clinical assessment.
- Lambda-Mu-Sigma (LMS) methodology provides continuous reference percentiles for laboratory parameters, enhancing data interpretation.
Purpose of the Study:
- To establish LMS-based continuous pediatric reference percentiles for serum/plasma concentrations of sRANKL, OPG, and their ratio.
- To enable the calculation of standardized z-scores for pediatric bone metabolic turnover assessment.
- To address the lack of adequate pediatric reference values for these critical bone regulators.
Main Methods:
- The HAnnover Reference values for Pediatrics (HARP) study enrolled 300 children aged 0.1-18 years.
- sRANKL and OPG concentrations were measured using ELISA.
- LMS-based continuous reference percentiles were generated using RefCurv software.
Main Results:
- Age-dependent LMS percentiles were established for sRANKL, OPG, and the sRANKL/OPG ratio.
- sRANKL and sRANKL/OPG percentiles showed associations with sex and distinct age-related patterns in boys and girls.
- OPG percentiles demonstrated a continuous decline from infancy to adulthood; sRANKL correlated with OPG and phosphate z-scores.
Conclusions:
- This study presents the first LMS-based continuous pediatric reference percentiles for sRANKL, OPG, and their ratio.
- These percentiles allow for the calculation of standardized z-scores, improving the assessment of bone metabolic turnover in children.
- The findings provide essential tools for evaluating pediatric bone health and related metabolic processes.
Abstract:
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.
