Association of Osteoprotegerin Gene Polymorphisms (rs2073618 and rs3102735) with Bone Mineral Density in Childhood Acute Lymphoblastic Leukemia Survivors

Background: Reduced bone mineral density (BMD) is a frequent late complication among survivors of childhood acute lymphoblastic leukemia (ALL). Osteoprotegerin is an important regulator of bone remodeling, and genetic variations within TNFRSF11B, which encodes osteoprotegerin, may contribute to individual susceptibility to impaired bone health. This study investigated the association between two polymorphisms (rs2073618 and rs3102735) and BMD in survivors of childhood ALL. Methods: This single-center cohort study included 60 survivors of childhood ALL. Lumbar spine BMD was assessed by dual-energy X-ray absorptiometry, and age-, sex-, and height-adjusted Z-scores were calculated. Low BMD was defined as a Z-score ≤ −1. Genotyping of rs2073618 and rs3102735 polymorphisms was performed using TaqMan real-time polymerase chain reaction assays. Results: Low BMD was observed in 22 patients (36.7%). We found no significant associations between BMD and demographic or treatment-related factors. Mean BMD Z-scores differed significantly among rs2073618 genotypes (ANOVA, p = 0.030). Carriers of the GG genotype had significantly higher BMD Z-scores than carriers of the CC or CG genotype (−0.05 ± 1.29 vs. −0.78 ± 0.88; p = 0.026). After adjustment for sex, treatment risk group, dexamethasone exposure, and age at diagnosis, rs2073618 remained independently associated with BMD Z-score (β = 0.337, p = 0.019). No significant association was found between rs3102735 and BMD. Conclusions: The rs2073618 polymorphism of the TNFRSF11B gene was associated with BMD Z-scores in survivors of childhood ALL, whereas rs3102735 showed no significant relationship. These findings suggest that genetic variations within the OPG gene may contribute to long-term skeletal health after childhood ALL treatment, but warrant confirmation in larger multicenter studies.