This study investigated the prevalence of the intravertebral vacuum phenomenon (IVP) and osteonecroses in vertebral compression fractures (VCFs). We therefore performed an histological analysis of biopsies obtained from VCFs prior to balloon kyphoplasty. Computed tomography (CT) scans were reviewed regarding the presence of an IVP (i.e. cleft sign, Kümmell disease). We reviewed the data of 266 consecutive patients treated by balloon kyphoplasty in 501 procedures from 2002 to 2004. From 180 patients (68%) we obtained adequate bone tissue for histological evaluation. Biopsy specimens were analysed regarding the presence of osteoporosis, infection, malignancy and osteonecrosis. CT scans of all 180 patients were reviewed for presence of an IVP. Histological examination revealed 135 (75%) osteoporoses, 20 (11%) neoplasms, 12 (7%) trauma cases and 13 (7%) osteonecroses. An IVP was present in 12 (7%) patients. There was a significant association of osteonecrosis and IVP (P < 0.0001). Eleven of 12 patients with a vacuum phenomenon showed an osteonecrosis on histology, whereas 11 of 13 patients with osteonecrosis showed an IVP on CT. The IVP is a specific sign of osteonecrosis in vertebral compression fractures (sensitivity 85%, specificity 99%, positive predictive value 91%). Our findings strongly support the thesis that an IVP indicates local bone ischemia associated with a non-healing vertebral collapse and pseudarthrosis.