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

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.