The very reasonable suggestion, that diarthrodial joint and juxta-discal (vertebral centra-marginal) bony overgrowths (referred to as osteophytes) have different etiologies, has eluded previous confirmation. The prevailing perspective is that diarthrodial osteophytes represent the product of compressive forces and that those on the margins of vertebral centra result from traction and therefore are enthesial in derivation. If diarthrodial joint osteophytes result from intrinsic pressures, any surface responses would require transcortical nutritional support, easily recognized by en face microscopic examination. This contrasts with enthesially derived growth, the surface of which is characterized by Sharpey's fiber insertions. These are recognized as inverted cones with a central protrusion on examination of related bone surfaces. We hypothesize that diarthrodial and disc-adjacent osteophytes have a different pathophysiology, distinguishable on the basis of microscopic surface appearance. We pursued microscopic examination of the surfaces of osteophytes present on diarthrodial joints (hip, knee, elbow, costovertebral) and vertebrae (cervical, thoracic, and lumbar) from the CAL Milano Cemetery Skeletal Collection for presence of transcortical channels and the inverted cones of Sharpey's fiber insertions. Examination of 22 diarthrodial joint osteophytes reveals the presence solely of transcortical channels, while examination of 35 vertebral centra marginal osteophytes reveals the presence only of inverted cones. Findings are independent of age, gender, joint affected, position in the spinal column and osteophyte "severity." It is now evidenced that all osteophytes are not created equal. Diarthrodial joint osteophytes are endochondrally derived; vertebral centra osteophytes, enthesial in derivation. Different pathophysiology at least partially explain the clinical character of these processes.