Paget's disease of bone (PDB) is a common disorder of the skeleton that affects up to 2% of individuals of European ancestry age 55 years and above. The disease is characterised by focal areas of increased and disorganised bone remodelling that leads to bone pain, bone deformity, pathological fracture, deafness and secondary osteoarthritis. Mutations of SQSTM1 have been identified in about 10% of individuals with “sporadic” PDB and in about 40% of individuals with familial PDB. Juvenile Paget's disease (JPD) is a rare disorder caused by inactivating mutations in the TNFRSF11B gene encoding osteoprotegerin. Mutations in this gene have never been found in patients with typical PDB, but previous studies have reported evidence of an association between common genetic variants of TNFRSF11B and PDB risk in subjects of Belgian and British descent, which was primarily driven by a gender-specific effect in females. Although the TNFRSF11B locus did not emerge as a significant determinant of PDB risk in our recent genome wide association study (Albagha et al., Nat Genet 2010), a gender-specific analysis was not performed. Here we looked for evidence of a gender-specific association between variants in the TNFRSF11B gene and PDB using data from this genome wide association study. We analysed 32 SNPs (12 genotyped and 20 imputed) in 750 PDB patients without SQSTM1 mutations and 2700 controls. The analysed SNPs included all those previously reported in the Belgian and the British cohorts. We performed a gender-specific analysis using PLINK software. Results showed an association between an intronic SNP (rs3134053) and PDB risk in men, but the association was not statistically significant after adjusting for multiple testing. There was no significant association between any of the analysed variants and PDB risk in women and no overall evidence of an association between variants at this locus and PDB. Our data suggest that common variants at the TNFRSF11B locus do not play a major role in regulating susceptibility to PDB.