Osteoporosis is a highly heritable trait. Among the genes associated with bone mineral density (BMD), the low-density lipoprotein receptor-related protein 5 gene (LRP5) has been consistently identified in Caucasians. However LRP5 contribution to osteoporosis in populations of other ethnicities remains poorly known.To determine whether LRP5 polymorphisms Ala1330Val and Val667Met are associated with BMD in North Africans, these genotypes were analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 ± 7 .7 years, of which 59.1% have low bone mass (T-score<-1 at spine or hip).In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC genotypes tended to be more frequent in women with osteopenia and osteoporosis than in women with normal BMD (p=0.066). Adjusting for body size and other potential confounders, LRP5 genotypes were no longer significantly associated with aBMD at any site.The less common Val667Met polymorphism showed no association with osteoporosis. The Ala1330Val polymorphism is weakly associated with lower lumbar spine bone density and osteopenia/osteoporosis in postmenopausal Tunisian women. These observations expand our knowledge about the contribution of LRP5 genetic variation to osteoporosis risk in populations of diverse ethnic origin.