Bone Abstracts

Osteoporosis is a common disorder with a partly genetic pathogenesis. Interaction between RANKL and its receptor RANK is essential in bone remodeling.

We therefore investigated the effect of polymorphisms in the RANK and RANKL genes and interaction between the effects on bone mineral density (BMD) and vertebral fractures.

The study was a case-control study with 462 osteoporotic patients and 336 controls. Ten polymorphisms in RANK and seven in RANKL were selected for genotyping. We genotyped using Taqman or sequencing and examined BMD by DXA. We examined interaction of polymorphisms on BMD or vertebral fractures using the software FAMHAP and performed other statistical analyses using SPSS.

None of the polymorphisms affected BMD or fracture risk. Interaction analyses revealed interaction between the effects of RANK polymorphism rs9653064 and RANKL polymorphisms rs2277439, rs2875459, rs922996, and rs1054016 on lumbar spine BMD (global P<0.1 for all). Interaction was also found between the effects of RANK polymorphism rs56231704 and RANKL polymorphisms rs2277439 on lumbar spine-, femoral neck, and total hip BMD, rs922996 and rs1054016 on lumbar spine BMD, and rs56231704 on total hip BMD (global P<0.1 for all). Subsequent analyses of the effect of RANKL polymorphisms on BMD were stratified for RANK genotypes and revealed several interactions between polymorphisms in the two genes, for example that BMD was higher at all sites in individuals homozygous for the normal allele at RANK rs9653064 and carrying the variant allele at RANKL rs2277439 compared with individuals homozygous for the normal allele at both polymorphisms, whereas BMD was lower at all sites in individuals carrying the variant allele at both polymorphisms compared with individuals carrying the variant allele at RANK rs9653064 and homozygous for the normal allele at RANKL rs2277439 (P<0.05).

This study shows that RANK and RANKL interact at the DNA level as at the protein level.