A　Summary　The　molecular　mechanism　of　osteoporosis　(OP)　in　Kashin-Beck　disease　(KBD)　patients　was　unclear.　Our　results　suggest　that　KBD　and　OP　shared　some　common　causal　genes,　functionally　involved　in　skeletal　growth　and　development　and　chronic　inflammation.　Our　results　provide　novel　clues　for　clarifying　the　molecular　mechanism　of　OP　in　KBD　patients.　Introduction　KBD　is　a　chronic　skeletal　disorder　with　osteopenia　and　OP.　The　pathogenesis　of　OP　in　KBD　patients　remains　elusive.　Methods　A　total　of　1717　subjects　participated　in　this　study.　KBD　was　diagnosed　according　to　the　clinical　diagnosis　criteria　of　China　(GB16395-1996).　The　bone　mineral　density　(BMD)　and　bone　areas　of　the　ulna　and　radius,　hip,　and　lumbar　(L1-L4)　were　measured　with　a　Hologic　4500　W　dual-energy　X-ray　absorptiometry　scanner.　Genotyping　was　conducted　using　Affymetrix　SNP　Array　6.0.　Gene　expression　profiling　of　peripheral　blood　mononuclear　cells　of　KBD　and　OP　patients　were　compared　using　Affymetrix　HG-U133　plus　2.0　arrays　and　Agilent　Human　1A　arrays,　respectively.　Genome-wide　association　studies　(GWAS)　were　conducted　by　PLINK.　SCEA　and　DAVID　were　applied　for　pleiotropy　and　functional　enrichment　analysis,　respectively.　Results　SCEA　analysis　observed　significant　pleiotropic　effects　between　KBD　and　the　ulna　and　radius　BMD　(P　value(-)　5.99　x　10(-3)).　GWAS　meta-analysis　identified　six　candidate　genes　with　pleiotropic　effects,　including　PDGFD,　SOX5,　DPYD,　CTR9,　SPP1,　and　COL4A1.　GO　analysis　identified　16　significant　GO　shared　by　KBD　and　the　ulna　and　radius　BMD,　involved　in　cell　morphogenesis　and　apoptosis.　Pathway　enrichment　analysis　detected　two　common　pathways　for　KBD　and　the　ulna　and　radius　BMD,　including　calcium　signaling　pathway　and　vascular　smooth　muscle　contraction　pathway.　Gene　expression　analysis　detected　three　up-regulated　inflammation-related　genes　for　KBD　and　OP,　including　IL1B,　IL8,　and　CCL1.　Conclusion　This　study　reported　several　candidate　genes　involved　in　the　development　of　OP　in　KBD　patients.