Lucy A. Anthenill, DVM, PhD; Ian A. Gardner, BVSc, PhD; Roy R. Pool, DVM, PhD; Tanya C. Garcia, MS; Susan M. Stover, DVM, PhD American Journal of Veterinary Research July 2010 71 7 755-765 Objective—To compare macrostructural and microstructural features of proximal sesamoid bones (PSBs) from horses with and without PSB midbody fracture to gain insight into the pathogenesis of PSB fracture. Sample Population—PSBs from 16 Thoroughbred racehorses (8 with and 8 without a PSB midbody fracture). Procedures—Parasagittal sections of fractured and contralateral intact PSBs from horses with a PSB fracture and an intact PSB from age- and sex-matched control horses without a PSB fracture were evaluated for visual, radiographic, microradiographic, histologic, and his-tomorphometric differences in bone porosity, vascular channels, heme pigment, trabecular anisotropy, and pathological findings. Results—Fractured PSBs and their contralateral intact PSBs had more compacted trabecular bone than did control PSBs. Focal repair or remodeling was evident in the palmar aspect of many fractured and contralateral intact PSBs. Fracture coincided with microstructural features and propagated from the flexor to the articular surface. Conclusions and Clinical Relevance—Fractured PSBs had adapted to high loading but had focal evidence of excessive remodeling and porosity that likely predisposed the horses to complete fracture and catastrophic injury. Detection of focal injury before complete fracture provides an opportunity for prevention of catastrophic injury. Development of diagnostic imaging methods to assess porosity of PSBs may help to identify at-risk horses and allow for modifications of training and racing schedules to reduce the incidence of PSB fracture in Thoroughbred racehorses.