Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms

Abstract Background Children with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene pol...

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Main Authors: Riham Eid, Maha Abdelsalam, Aya Ahmed Fathy, Hadil M. Abolenein, Eman Bakr Elmarghany, Aya Ahmed El-Hanafy, Nashwa Hamdy, Dina Salama Abd-Elmagid, Nermeen A. Niazy, Dina M. Abd-El Ghaffar
Format: Article
Language:English
Published: BMC 2023-06-01
Series:Pediatric Rheumatology Online Journal
Subjects:
Online Access:https://doi.org/10.1186/s12969-023-00843-6
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author Riham Eid
Maha Abdelsalam
Aya Ahmed Fathy
Hadil M. Abolenein
Eman Bakr Elmarghany
Aya Ahmed El-Hanafy
Nashwa Hamdy
Dina Salama Abd-Elmagid
Nermeen A. Niazy
Dina M. Abd-El Ghaffar
author_facet Riham Eid
Maha Abdelsalam
Aya Ahmed Fathy
Hadil M. Abolenein
Eman Bakr Elmarghany
Aya Ahmed El-Hanafy
Nashwa Hamdy
Dina Salama Abd-Elmagid
Nermeen A. Niazy
Dina M. Abd-El Ghaffar
author_sort Riham Eid
collection DOAJ
description Abstract Background Children with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA. Methods OPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI). Results Patients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children. Conclusions Egyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.
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spelling doaj.art-c4177ca62f4240cf9f0eed523b6494932023-07-02T11:10:12ZengBMCPediatric Rheumatology Online Journal1546-00962023-06-0121111210.1186/s12969-023-00843-6Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphismsRiham Eid0Maha Abdelsalam1Aya Ahmed Fathy2Hadil M. Abolenein3Eman Bakr Elmarghany4Aya Ahmed El-Hanafy5Nashwa Hamdy6Dina Salama Abd-Elmagid7Nermeen A. Niazy8Dina M. Abd-El Ghaffar9Paediatric Nephrology Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura UniversityImmunology Unit, Clinical Pathology Department, Faculty of Medicine, Mansoura UniversityPublic health and Community Department, Faculty of Medicine, Mansoura UniversityPaediatric Endocrinology and Diabetes Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura UniversityRheumatology, Rehabilitation and Physical Medicine Department, Faculty of Medicine, Mansoura UniversityMedical Biochemistry Department, Faculty of Medicine, Mansoura UniversityPaediatric Nephrology Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura UniversityPaediatric Neurology Unit, Faculty of Medicine, Mansoura University Children’s Hospital, Mansoura UniversityPublic health and Community Department, Faculty of Medicine, Mansoura UniversityRheumatology, Rehabilitation and Physical Medicine Department, Faculty of Medicine, Mansoura UniversityAbstract Background Children with juvenile idiopathic arthritis (JIA) are at higher risk of decreased bone mineral density (BMD) compared with healthy children due to genetic, disease and medication-related causes. This study aims to investigate the possible effects of osteoprotegerin (OPG) gene polymorphisms and serum levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB-ligand (RANKL) and RANKL/OPG ratio on BMD in children with JIA. Methods OPG gene rs2073617, rs3134069, serum RANKL, OPG and RANKL/OPG ratio were evaluated in 60 JIA children and 100 matched healthy controls. BMD was evaluated by lumbar dual energy X-ray absorptiometry (DEXA) according to which patients were classified in 2 groups (DEXA z-score above and below − 2). Composite disease activity was measured using the Juvenile Arthritis Disease Activity Score (JADAS) 27-joints. Articular damage was scored using the juvenile arthritis damage index (JADI). Results Patients aged 12.05 ± 3.2 years, included 38 females and 31% had BMD z-score below-2. Systemic-onset JIA was the most frequent phenotype (38%). Genotypes and alleles frequencies of the 2 studied polymorphisms did not differ between patients and controls (p > 0.05 for all) while serum RANKL and RANKL/OPG ratio were significantly higher in patients compared to controls (p = < 0.001 and 0.03 respectively). Patients with BMD < -2 had significantly greater frequencies of rs2073617 TT genotype and T allele (p < 0.001), higher serum RANKL, RANKL/OPG ratio (p = 0.01, 0.002), female predominance (p = 0.02), higher articular and extra-articular damage index (p = 0.008,0.009) and more frequent steroid usage (p = 0.02) compared to patients with BMD z-score >-2. Multivariate analysis showed rs2073617 TT genotype, RANKL/OPG ratio, long disease duration (above 36 months) and use of steroid to be associated with decreased BMD (p = 0.03,0.04,0.01,0.01 respectively) in JIA children. Conclusions Egyptian children with JIA have decreased BMD. rs2073617 TT genotype and T allele, RANKL/OPG ratio are possible determinants of reduced BMD in JIA. Our results underline the importance of frequent monitoring of BMD in JIA children and trying to control disease activity to preserve long term bone health.https://doi.org/10.1186/s12969-023-00843-6sRANKLOsteoprotegerinOPG geneJuvenile idiopathic arthritisBone mineral density
spellingShingle Riham Eid
Maha Abdelsalam
Aya Ahmed Fathy
Hadil M. Abolenein
Eman Bakr Elmarghany
Aya Ahmed El-Hanafy
Nashwa Hamdy
Dina Salama Abd-Elmagid
Nermeen A. Niazy
Dina M. Abd-El Ghaffar
Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
Pediatric Rheumatology Online Journal
sRANKL
Osteoprotegerin
OPG gene
Juvenile idiopathic arthritis
Bone mineral density
title Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
title_full Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
title_fullStr Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
title_full_unstemmed Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
title_short Bone mineral density in egyptian children with juvenile idiopathic arthritis: possible correlation to serum RANKL / osteoprotegerin (OPG) ratio and OPG gene polymorphisms
title_sort bone mineral density in egyptian children with juvenile idiopathic arthritis possible correlation to serum rankl osteoprotegerin opg ratio and opg gene polymorphisms
topic sRANKL
Osteoprotegerin
OPG gene
Juvenile idiopathic arthritis
Bone mineral density
url https://doi.org/10.1186/s12969-023-00843-6
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