Quantifying RANKL and OPG levels in healthy children: A large cross-sectional analysis

Ali, S Akhtar; Kang, Harsimar; Olney, Robert C.; Ramos‐Platt, Leigh; Ryabets-Lienhard, Anna; Georgia, Senta; Pitukcheewanont, Pisit

doi:10.1016/j.bone.2019.06.012

Cited by 9 publications

(6 citation statements)

References 24 publications

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“…We identified an inverse correlation between OPG plasma concentrations and standardized values for body weight and BMI, which is in line with previous studies in healthy as well as obese children and adults [ 5 , 7 , 10 , 11 , 31 ]. Dimitri et al investigated OPG plasma levels in healthy lean and obese children and noted that OPG levels were lowest in obese children with a prior fracture, suggesting increased bone resorption in relation to formation in obese children [ 7 ].…”

Section: Discussionsupporting

confidence: 91%

“…Serum sRANKL concentrations were significantly associated with OPG values, irrespective of sex, which supports the concept of strong interrelations within the sRANKL/RANKL/OPG system, which was noted in smaller-sized previous studies [ 1 , 5 , 6 , 30 ]. In addition, sRANKL was positively associated with standardized serum phosphate and OPG was inversely associated with standardized urinary phosphate to creatinine ratio in both sexes, suggesting that both high sRANKL and low OPG levels stimulate bone resorption, thereby increasing serum phosphate levels and urinary phosphate excretion, respectively.…”

Section: Discussionsupporting

confidence: 86%

“…The previously largest pediatric cross-sectional study reporting on sRANKL, OPG and sRANKL/OPG ratio included 259 healthy children aged 1 to 20 years [ 5 ]. The authors noted significant associations between sRANKL and categorized values for age, Tanner stage, and BMI z-score.…”

Section: Discussionmentioning

confidence: 99%

“…RANKL exists in three forms: as a transmembrane protein expressed by osteoblasts and other cells of the mesenchymal lineage, as a soluble molecule released by enzymatic cleavage, and as a primary secreted form produced by activated T-lymphocytes [ 2 ]. OPG acts as a decoy receptor by blocking the binding between RANKL and RANK and is therefore the major inhibitor of osteoclast development and bone resorption [ 5 , 6 ]. OPG exists as monomer, dimer and RANKL/OPG complexes [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort

Tietze,

Pott,

Kanzelmeyer

et al. 2023

Osteoporos Int

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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. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-023-06959-5.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort

Tietze,

Pott,

Kanzelmeyer

et al. 2023

Osteoporos Int

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“…They concluded that OPG may be considered as a frailty marker in these patients [36]. Contrarily, Akhtar et al reported no correlation between OPG and age [37]. The crucial role of OPG in metabolic homeostasis has been extensively studied.…”

Section: Discussionmentioning

confidence: 99%

Selected Parameters of Bone Turnover in Neuroendocrine Tumors—A Potential Clinical Use?

Strzelczyk

Wójcik-Giertuga

Strzelczyk

et al. 2023

JCM

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Background: Currently, there are no effective markers to diagnose and monitor patients with neuroendocrine tumors (NETs). The aim of this study was to assess bone metabolism based on selected markers of bone turnover: OST, OPG, and IGFBP-3, in both the group of patients with NETs and the control group. Associations with selected sociodemographic, biochemical, and clinicopathological characteristics were examined. We also evaluated any potential associations between these markers and selected biochemical markers of NETs commonly used in clinical practice. Methods: The study group included 60 patients with GEP-NETs and BP-NETs, while the control group comprised 62 healthy individuals. The serum concentrations of OST, OPG and IGFBP-3 were assessed using ELISA. Results: OST and OPG levels were significantly higher in the study group compared to the control group. In the study group, we observed a significant correlation between OPG and the clinical stage and chromogranin A. Additionally, an association was found between OPG and histological grade, Ki-67, and metastasis in GEP-NET cases. Conclusions: Markers of bone turnover cannot be used in the routine diagnostics of neuroendocrine tumors. Nonetheless, these markers may help evaluate the skeletal system in patients with NETs. Further research is needed to determine the utility of osteocalcin (OST) and osteoprotegerin (OPG) as potential biomarkers for neuroendocrine tumors.

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Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF‐κB ligand in nonalcoholic fatty liver disease

Nikseresht

Azarmehr

Arya

et al. 2020

Biotechnology and Applied Biochemistry

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Pathogenesis of the beginning and progression of nonalcoholic fatty liver disease (NAFLD) has not been clarified exactly. The osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) axis seems to play an imperative function in the onset and progression of this disease. The goal of the present study was to investigate the peripheral blood mononuclear cell (PBMC) expression and plasma levels of RANKL and OPG cytokines in NAFLD patients and compare them with healthy group. Plasma levels of OPG and RANKL were determined with ELISA kits in 57 men with NAFLD and 25 healthy men as controls. Biochemical and anthropometric parameters tests were also evaluated in the study groups. RANKL and OPG mRNA contents were evaluated by quantitative RT-PCR. OPG contents were markedly decreased in NAFLD patients as compared with healthy patients [1.43 (1.05-5.45)] versus [2.94 (1.76-4.73)] ng/mL; P = 0.007). The levels of RANKL were significantly reduced in NAFLD patients [74.00 (56.26-203.52) ng/mL] than in healthy patients [119.37 (83.71-150.13) ng/mL]; (P = 0.03). Also, OPG and RANKL gene expression were significantly decreased in NAFLD patients in comparison with the control group (P < 0.05). Moreover, receiver operating characteristic curve indicated that OPG may have a good capability to discriminate between NAFLD patients and normal individuals. A positive correlation was observed between OPG and RANKL in plasma sample (r = 0.495) (P = 0.000). Decreased plasma levels and gene expression of RANKL and OPG cytokines in NAFLD patients indicate that there is a relationship between these cytokines and the pathology of NAFLD disease. Confirmation of this association as well as the mechanism and role of these cytokines in NAFLD require further studies.

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Quantifying RANKL and OPG levels in healthy children: A large cross-sectional analysis

Cited by 9 publications

References 24 publications

LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort

LMS-based continuous pediatric reference values for soluble receptor activator of nuclear factor kappa B ligand (sRANKL) and osteoprotegerin (OPG) in the HARP cohort

Selected Parameters of Bone Turnover in Neuroendocrine Tumors—A Potential Clinical Use?

Circulating mRNA and plasma levels of osteoprotegerin and receptor activator of NF‐κB ligand in nonalcoholic fatty liver disease

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