rs9594738

A cross-sectional study of 881 postmenopausal Chinese women examined associations between 22 SNPs in the RANKL/RANK/OPG pathway genes (TNFSF11, TNFRSF11A, TNFRSF11B) and bone mineral density (BMD). Two TNFSF11 SNPs (rs2277439 and rs2324851; p=0.014, 0.013) and one TNFRSF11A SNP (rs7239261; p=0.047) were significantly associated with femoral neck BMD. A haplotype in TNFSF11 was a genetic risk factor for lower femoral neck BMD (beta=-0.1473; p=0.011), while another was protective for lumbar spine BMD (beta=0.3923; p=0.049).

This genetic association study examined four SNPs in the RANK/RANKL/OPG signaling pathway in 518 elite athletes (125 with stress fractures, 376 controls). rs3018362 (RANK) and rs1021188 (RANKL) were significantly associated with stress fracture injury (p=0.008 and p=0.024, respectively). rs1021188 homozygotes were 2.93-fold more likely to have stress fractures (OR 2.93, 95% CI 1.18-7.28). In multiple stress fracture analysis, rs4355801 (OPG) carriers showed increased risk (OR 2.05). The RANK/RANKL/OPG pathway appears to contribute to stress fracture susceptibility in elite athletes.

This association study examined 589 European men to determine whether SNPs in RANKL, RANK, and OPG genes influence volumetric bone mineral density (vBMD) and bone geometry at the radius. The authors identified 12 OPG SNPs associated with vBMD and geometric parameters (e.g., rs10505348 associated with total vBMD β=9.35, P=0.011; rs2073618 associated with cortical vBMD β=-4.30, P=0.015), three RANK SNPs associated with vBMD including rs12956925 associated with trabecular vBMD β=-7.58, P=0.021, and five RANK SNPs associated with geometric parameters including rs8083511 associated with cross-sectional area β=8.90, P=0.029. No significant associations were found with RANKL SNPs, suggesting genetic variation in OPG and RANK influences radius bone density and geometry in men.

This case-control study of 159 Ukrainian individuals (144 born macrosomic, 27 normosomic) investigates genetic associations with deciduous tooth eruption timing. The study identified associations between RANKL rs9594759 (multiplicative model, increased risk of delayed eruption) and IL10 rs1800896 (overdominant model, increased risk of delayed eruption). CYP19A1 rs2414096 G allele and ESR1 rs9340799 -351 A allele were found as risk factors for fetal macrosomia formation. RANKL and IL10 variants showed multidirectional modifying effects on tooth eruption timing in macrosomic individuals.