To describe clinical and scintigraphic abnormalities in horses with a bone fragility disorder. Retrospective case series. 16 horses with scintigraphic evidence of multiple sites of increased radiopharmaceutical uptake (IRU). Procedures-Medical records were reviewed for information on signalment; history; clinical, clinicopathologic, and diagnostic imaging findings; and treatment. Follow-up information was obtained through telephone interviews with owners. Horses ranged from 4 to 22 years old; there were 8 castrated males and 8 females. Foci of IRU most commonly involved the scapulae, ribs, sternebrae, sacral tubers, ilia, and cervical vertebrae. Most horses were examined because of chronic intermittent (n = 10) or acute (6) lameness involving a single (10) or multiple (6) limbs that could not be localized by means of regional anesthesia. Cervical stiffness (n = 3), scapular bowing (3), swayback (3), and ataxia (1) were also seen in more advanced cases. Signs of respiratory tract disease and exercise intolerance were evident in 4 horses. Ultrasonographic or radiographic evidence of bone remodeling or degeneration was seen in 19 of 33 affected bones. Histologic examination of bone biopsy specimens revealed reactive bone. Improvement was initially seen with conservative treatment in some horses, but the condition worsened in all horses, and 11 horses were euthanized within 7 years. Results suggested that horses may develop a bone fragility disorder characterized clinically by an unlocalizable lameness and scintigraphically by multiple sites of IRU involving the axial skeleton and proximal portion of the appendicular skeleton.