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Objectives This study aims to explore effects of osteoprotegerin (OPG) gene polymorphisms and other possible factors on bone mineral density (BMD) in children with systemic lupus erythematosus (SLE). Methods Osteoprotegerin gene rs2073617 and rs3134069 were evaluated in 74 SLE patients and 100 controls then genotypes, alleles and haplotypes’ frequencies were compared between cases and controls and between patients with BMD z-scores above and below −2 evaluated by dual energy X-ray absorptiometry (DEXA). Disease activity was evaluated by SLE disease activity index (SLEDAI). Results The patients aged 14.01 ± 2.6 years and included 57 (77%) females and 27 (36%) patients with BMD z-score below −2. Genotypes, alleles, and haplotypes frequencies did not differ between patients and controls (p>0.05 for all). Rs3134069 GG genotype and G allele (p=0.001, 0.002) and rs2073617 TT genotype and T allele (p=0.01, 0.006) were significantly higher in patients with BMD below −2. Cumulative glucocorticoids dose, disease duration, and SLEDAI scores were higher in patients with BMD below −2 (p=0.01, 0.01, p 0.02, 0.003, and 0.002, respectively). Conclusions This is the first study to demonstrate OPG gene influence on BMD in children with SLE. The studied SNPs are not risk for developing SLE but, rs2073617 T allele is a possible predictor for reduced BMD in SLE. Other predictors include long disease duration and high activity supporting that osteoporosis in SLE is multifactorial.