(A–C) Hematoxylin and eosin stained sections of the distal femur of (A) wild-type, (B) OPG−/− mice, and (C) OPG−/− mice bearing OPG transgene. OPG−/− mice (B) show osteoporotic bone structure and lack of secondary spongiosa compared to wild-type (A). Osteopetrosis occurs in OPG−/− mice bearing OPG transgene (C). (D–F) Polarized light microscopy of the cortical bone in mid-femoral diaphysis in wild-type mice (D), OPG−/− mice (E), and OPG−/− mice bearing OPG transgene (F). Note the woven bone in OPG−/− mice (E), a characteristic of high bone turnover rate, compared to highly lamellar bone of OPG−/− mice bearing OPG transgene (F). (G–I) TRAP-stained sections of wild-type mice(G), OPG−/− mice (H), and OPG−/− mice bearing OPG transgene (I). Note the significant increase in osteoclasts (black arrows) in OPG−/− mice (H) compared with OPG−/− mice bearing OPG transgene (I). The visible increase in osteoblasts (yellow arrowheads) indicates a compensatory increase in bone formation in OPG−/− mice.