Association between RANK gene polymorphism and early femoral neck bone loss in kidney transplant recipients

Abstract Introduction Rapid bone mineral density (BMD) loss and fracture risk are major complications of kidney transplantation (KTx), partly attributed to glucocorticoid-impaired bone remodeling. We investigated associations between early postoperative femoral neck BMD (BMD-FN) decline and single nucleotide polymorphisms (SNPs) in genes related to glucocorticoid sensitivity and bone metabolism. Materials and methods Sixty-nine adult patients who underwent living-donor KTx in 2015–2024 were investigated. The primary endpoint was annualized BMD-FN change (%) between preoperative and 12 ± 6 months postoperative DXA. Patients with significant prior glucocorticoid exposure, postoperative pulse therapy, or anti-osteoporotic treatment were excluded. Four SNPs ( NR3C1 [rs41423247], TNFRSF11A [rs1805034, rs884205], and LRP5 [rs3736228]) were genotyped and analyzed using multiple linear regression adjusted for age and sex. Results The median annualized BMD-FN change was − 3.4% (IQR − 6.6 to − 0.7). Among the four SNPs, only TNFRSF11A rs884205 was significantly associated with greater BMD loss; A risk allele carriers showed greater decline than the CC genotype (β = − 2.75; 95% CI, − 4.82 to − 0.68; P = 0.010). No significant associations were observed for NR3C1 (rs41423247), TNFRSF11A (rs1805034), and LRP5 (rs3736228). However, after adjustment for baseline BMD-FN, which was higher in risk-allele carriers, the rs884205 association was attenuated and no longer significant (β = −1.92%; 95% CI, −3.94 to 0.09; P = 0.062). Conclusion In the early post-KTx period, the TNFRSF11A rs884205 risk allele may be associated with greater annualized BMD-FN decline, although this did not persist after baseline BMD-FN adjustment. These findings are preliminary and warrant confirmation in larger cohorts.