LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort.
Children
LMS method
OPG
percentile curves
sRANKL
sRANKL/OPG ratio
Journal
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
ISSN: 1433-2965
Titre abrégé: Osteoporos Int
Pays: England
ID NLM: 9100105
Informations de publication
Date de publication:
Mar 2024
Mar 2024
Historique:
received:
01
08
2023
accepted:
23
10
2023
medline:
15
2
2024
pubmed:
9
11
2023
entrez:
8
11
2023
Statut:
ppublish
Résumé
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. 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. 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. 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). 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.
Identifiants
pubmed: 37940696
doi: 10.1007/s00198-023-06959-5
pii: 10.1007/s00198-023-06959-5
pmc: PMC10866762
doi:
Substances chimiques
Carrier Proteins
0
Cytokines
0
Osteoprotegerin
0
Phosphates
0
pleiotrophin
134034-50-7
RANK Ligand
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
533-542Informations de copyright
© 2023. The Author(s).
Références
Wasilewska A, Rybi-Szuminska A, Zoch-Zwierz W (2010) Serum RANKL, osteoprotegerin (OPG), and RANKL/OPG ratio in nephrotic children. Pediatr Nephrol 25:2067. https://doi.org/10.1007/s00467-010-1583-1
doi: 10.1007/s00467-010-1583-1
pubmed: 20602239
pmcid: 2923718
Findlay DM, Atkins GJ (2011) Relationship between serum RANKL and RANKL in bone. Osteoporos Int 22:2597–2602. https://doi.org/10.1007/s00198-011-1740-9
doi: 10.1007/s00198-011-1740-9
pubmed: 21850548
Maggioli C, Stagi S (2017) Bone modeling, remodeling, and skeletal health in children and adolescents: mineral accrual, assessment and treatment. Ann Pediatr Endocrinol Metab 22:1–5. https://doi.org/10.6065/apem.2017.22.1.1
doi: 10.6065/apem.2017.22.1.1
pubmed: 28443253
pmcid: 5401817
Boyce BF, Xing L (2008) Functions of RANKL/RANK/OPG in bone modeling and remodeling. Arch Biochem Biophys 473:139–146. https://doi.org/10.1016/j.abb.2008.03.018
doi: 10.1016/j.abb.2008.03.018
pubmed: 18395508
pmcid: 2413418
Akhtar Ali S, Kang H, Olney R, Ramos-Platt L, Ryabets-Lienhard A, Georgia S, Pitukcheewanont P (2019) Quantifying RANKL and OPG levels in healthy children: A large cross-sectional analysis. Bone 127:215–219. https://doi.org/10.1016/j.bone.2019.06.012
doi: 10.1016/j.bone.2019.06.012
pubmed: 31212033
Buzi F, Maccarinelli G, Guaragni B, Ruggeri F, Radetti G, Meini A, Mazzolari E, Cocchi D (2004) Serum osteoprotegerin and receptor activator of nuclear factors kB (RANKL) concentrations in normal children and in children with pubertal precocity, Turner’s syndrome and rheumatoid arthritis. Clin Endocrinol 60:87–91. https://doi.org/10.1046/j.1365-2265.2003.01951.x
doi: 10.1046/j.1365-2265.2003.01951.x
Dimitri P, Wales JK, Bishop N (2010) Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass. Bone 48:189–196. https://doi.org/10.1016/j.bone.2010.09.034
doi: 10.1016/j.bone.2010.09.034
pubmed: 20932948
Lien G, Ueland T, Godang K, Selvaag AM, Førre ØT, Flatø B (2010) Serum levels of osteoprotegerin and receptor activator of nuclear factor -κB ligand in children with early juvenile idiopathic arthritis: a 2-year prospective controlled study. Pediatr Rheumatol Online J 8:30. https://doi.org/10.1186/1546-0096-8-30
doi: 10.1186/1546-0096-8-30
pubmed: 21134287
pmcid: 3014923
Ali R, Hammad A, El-Nahrery E, Hamdy N, Elhawary AK, Eid R (2019) Serum RANKL, osteoprotegerin (OPG) and RANKL/OPG ratio in children with systemic lupus erythematosus. Lupus 28:1233–1242. https://doi.org/10.1177/0961203319867129
doi: 10.1177/0961203319867129
pubmed: 31403902
Stanik J, Kratzsch J, Landgraf K, Vogel M, Thiery J, Kiess W, Körner A (2019) The bone markers sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase are related to insulin resistance in children and adolescents, independent of their association with growth and obesity. Horm Res Paediatr 91:1–8. https://doi.org/10.1159/000497113
doi: 10.1159/000497113
pubmed: 30904905
Erol M, BostanGayret O, TekinNacaroglu H, Yigit O, Zengi O, SalihAkkurt M, Tasdemir M (2016) Association of osteoprotegerin with obesity, insulin resistance and non-alcoholic fatty liver disease in children. Iran Red Crescent Med J 18:e41873. https://doi.org/10.5812/ircmj.41873
doi: 10.5812/ircmj.41873
pubmed: 28203453
pmcid: 5294423
Lun MX, Gui C, Zhang L, Shang N, Xiao YW, Lv LJ, Huang HL (2021) Application of the LMS method of constructing fetal reference charts: comparison with the original method. J Matern Fetal Neonatal Med 34:395–402. https://doi.org/10.1080/14767058.2019.1608942
doi: 10.1080/14767058.2019.1608942
pubmed: 31039657
Jo BS, Myong JP, Rhee CK, Yoon HK, Koo JW, Kim HR (2018) Reference values for spirometry derived using Lambda, Mu, Sigma (LMS) method in Korean adults: in comparison with previous references. J Korean Med Sci 33:e16. https://doi.org/10.3346/jkms.2018.33.e16
doi: 10.3346/jkms.2018.33.e16
pubmed: 29215803
Liu S, Su Z, Pan L, Chen J, Zhao X, Wang L, Zhang L, Su Q, Su H (2023) Pattern of linear growth and progression of bone maturation for girls with early-onset puberty: A mixed longitudinal study. Front Pediatr 11:1056035. https://doi.org/10.3389/fped.2023.1056035
doi: 10.3389/fped.2023.1056035
pubmed: 36969285
pmcid: 10034074
Linden K, Otte F, Winkler C, Laser KT, Goldschmidt F, Breuer J, Herberg U (2022) Atrioventricular coupling in infants and children assessed by three-dimensional echocardiography. J Am Soc Echocardiogr 35:976–984. https://doi.org/10.1016/j.echo.2022.04.014
doi: 10.1016/j.echo.2022.04.014
pubmed: 35537616
Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, Murad MH, Weaver CM, Endocrine Society (2011) Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 96:1911–1930. https://doi.org/10.1210/jc.2011-0385
doi: 10.1210/jc.2011-0385
pubmed: 21646368
Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, Furth SL (2009) New equations to estimate GFR in children with CKD. J Am Soc Nephrol 20:629–637. https://doi.org/10.1681/asn.2008030287
doi: 10.1681/asn.2008030287
pubmed: 19158356
pmcid: 2653687
Schwartz GJ, Work DF (2009) Measurement and estimation of GFR in children and adolescents. Clin J Am Soc Nephrol 4:1832–1843. https://doi.org/10.2215/CJN.01640309
doi: 10.2215/CJN.01640309
pubmed: 19820136
Neuhauser H, Schienkiewitz A, Schaffrath Rosario A, Dortschy R, Kurth BM (2013) Referenzperzentile für anthropometrische Maßzahlen und Blutdruck aus der Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS). (Reference percentiles for anthropometric measures and blood pressure from the Study on the Health of Children and Adolescents in Germany (KiGGS)). Robert Koch Institut 2:1–129
Matos V, van Melle G, Boulat O, Markert M, Bachmann C, Guignard JP (1997) Urinary phosphate/creatinine, calcium/creatinine, and magnesium/creatinine ratios in a healthy pediatric population. J Pediatr 131:252–257. https://doi.org/10.1016/s0022-3476(97)70162-8
doi: 10.1016/s0022-3476(97)70162-8
pubmed: 9290612
Asgari S, Higgins V, McCudden C, Adeli K (2019) Continuous reference intervals for 38 biochemical markers in healthy children and adolescents: Comparisons to traditionally partitioned reference intervals. Clin Biochem 73:82–89. https://doi.org/10.1016/j.clinbiochem.2019.08.010
doi: 10.1016/j.clinbiochem.2019.08.010
pubmed: 31445880
Uday S, Shaw NJ, Mughal MZ, Randell T, Högler W, Santos R, Padidela R (2021) Monitoring response to conventional treatment in children with XLH: Value of ALP and Rickets Severity Score (RSS) in a real-world setting. Bone 151:116025. https://doi.org/10.1016/j.bone.2021.116025
doi: 10.1016/j.bone.2021.116025
pubmed: 34052463
Winkler C, Linden K, Mayr A, Schultz T, Welchowski T, Breuer J, Herberg U (2019) RefCurv: A software for the construction of pediatric reference curves. Softw Impacts 6. https://doi.org/10.1016/j.simpa.2020.100040
Cole TJ (1990) LMS method for constructing normalized growth standards. Eur J Clin Nutr 44:45–60
pubmed: 2354692
Cole TJ, Green PJ (1992) Smoothing reference centile curves: The lms method and penalized likelihood. Stat Med 11:1305–1319. https://doi.org/10.1002/sim.4780111005
doi: 10.1002/sim.4780111005
pubmed: 1518992
Cole TJ, Freeman JV, Preece MA (1998) British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood. Stat Med 17:407–429
doi: 10.1002/(SICI)1097-0258(19980228)17:4<407::AID-SIM742>3.0.CO;2-L
pubmed: 9496720
Goulding A (2007) Risk factors for fractures in normally active children and adolescents. Med Sport Sci 51:102–120. https://doi.org/10.1159/000103007
doi: 10.1159/000103007
pubmed: 17505122
Pan R, Liu Y, Deng H, Dvornyk V (2012) Association analyses suggest the effects of RANK and RANKL on age at menarche in Chinese women. Climacteric 15:75–81. https://doi.org/10.3109/13697137.2011.587556
doi: 10.3109/13697137.2011.587556
pubmed: 22023082
Stagi S, Cavalli L, Iurato C, Seminara S, Brandi ML, de Martino M (2013) Bone metabolism in children and adolescents: main characteristics of the determinants of peak bone mass. Clin Cases Miner Bone Metab 10:172–179
pubmed: 24554926
Wasilewska A, Rybi-Szuminska AA, Zoch-Zwierz W (2009) Serum osteoprotegrin (OPG) and receptor activator of nuclear factor κΒ (RANKL) in healthy children and adolescents. J Pediatr Endocrinol Metab 22:1099–1104. https://doi.org/10.1515/JPEM.2009.22.12.1099
doi: 10.1515/JPEM.2009.22.12.1099
pubmed: 20333868
Holecki M, Zahorska-Markiewicz B, Janowska J, Nieszporek T, Wojaczyńska-Stanek K, Żak-Gołąb A, Więcek A (2007) The influence of weight loss on serum osteoprotegerin concentration in obese perimenopausal women. Obesity (Silver Spring) 15:1925–1929. https://doi.org/10.1038/oby.2007.229
doi: 10.1038/oby.2007.229
pubmed: 17712108
Serrano-Piña R, Trujillo-Güiza ML, ScougallVilchis RJ, Layton-Tovar CF, Mendieta-Zerón H (2017) sRANKL and its correlation with metabolic syndrome parameters in children. Int J Paediatr Dent 28:633–640. https://doi.org/10.1111/ipd.12422
doi: 10.1111/ipd.12422
Russell M, Breggia A, Mendes N, Klibanski A, Misra M (2011) Growth hormone is positively associated with surrogate markers of bone turnover during puberty. Clin Endocrinol (Oxf) 75:482–488. https://doi.org/10.1111/j.1365-2265.2011.04088.x
doi: 10.1111/j.1365-2265.2011.04088.x
pubmed: 21535073
Bachrach LK (2020) Hormonal contraception and bone health in adolescents. Front Endocrinol (Lausanne) 11:603. https://doi.org/10.3389/fendo.2020.00603
doi: 10.3389/fendo.2020.00603
pubmed: 32973688