Osteoporosis　is　a　systemic　skeletal　disorder　characterized　by　reduced　bone　mineral　density　(BMD)　and　disrupted　bone　architecture,　predisposing　the　patient　to　increased　fracture　risk.　Evidence　from　early　genetic　epidemiological　studies　has　indicated　a　major　role　for　genetics　in　the　development　of　osteoporosis　and　the　variation　in　BMD.　In　this　study,　we　focused　on　two　key　genes　in　the　endochondral　ossification　pathway,　IBSP　and　PTHLH.　Over　9,000　postmenopausal　Han　Chinese　women　were　recruited,　and　54　SNPs　were　genotyped.　Two　significant　SNPs　within　IBSP,　rs1054627　and　rs17013181,　were　associated　with　BMD　and　postmenopausal　osteoporosis　by　the　two-stage　strategy,　and　rs17013181　was　also　significantly　associated　with　serum　IBSP　levels.　Moreover,　one　haplotype　(rs12425376-rs10843047-rs42294)　covering　the　5＇　end　of　PTHLH　was　associated　with　postmenopausal　osteoporosis.　Our　results　provide　evidence　for　the　association　of　these　two　key　endochondral　ossification　pathway　genes　with　BMD　and　osteoporosis　in　postmenopausal　Han　Chinese　women.　Combined　with　previous　findings,　we　provide　evidence　that　a　particular　SNP　in　IBSP　has　an　allele-specific　effect　on　mRNA　levels,　which　would,　in　turn,　reflect　serum　IBSP　levels.