Twenty-seven fractured human vertebral bodies and 24 unfractured human vertebrae from adjacent levels were studied postmortem using histologic and high-resolution radiographic techniques. The findings were compared with those in the vertebral bodies of individuals without spinal fracture. Forty-six human thoracolumbar spines were obtained from individuals at autopsy. Standard radiographs were made of all specimens. Twelve of the 46 individuals had a total of 27 fractured vertebral bodies by plain radiographic criteria. Attention was focused on these fractured vertebrae as well as on 24 unfractured vertebral bodies that were harvested from a level immediately adjacent to the fractured vertebral bodies. Twelve vertebral bodies from four individuals with no evidence of fracture or inflammatory spondyloarthropathy were also studied for comparison. The vertebral bodies were graded by their mineral density as measured by dual-energy x-ray absorptiometry and sectioned into 3-mm sagittal cuts. High-resolution contact radiographs were prepared for each section prior to decalcification and tissue sectioning on a large format microtome. Mid-and parasagittal tissue sections of each vertebra were prepared for standard hematoxylin and eosin stains. A total of 126 sections were studied. The histologic characteristics of the fractured vertebrae (n = 27) were compared with those of adjacent unfractured levels (n = 24) and with vertebrae from individuals without fracture (n = 12). Vertebral bodies with fractures secondary to osteoporosis were consistently characterized histologically by focal areas of endochondral new bone formation adjacent to avascular necrotic bone and unreactive marrow. Such ongoing new bone and new vessel formation adjacent to nonhealing areas were also documented in radiographically unfractured vertebral bodies from individuals with osteoporotic fractures at adjacent levels. No areas of endochondral new bone formation or areas of focal necrosis were found in vertebral bodies from individuals without radiographic evidence of osteoporosis. A vascular necrosis of the vertebral body is a common histologic finding in individuals with osteoporosis. Indeed, our histologic observations suggest subclinical fractures and microfractures of the vertebral body may be the underlying pathologic process leading to avascular necrosis in individuals with osteoporosis. Microtrabecular fractures and endplate fractures were commonly seen in osteoporotic vertebral bodies, often in vertebrae that appeared to be uninvolved on specimen radiographs.