Little is known about the natural history of patients who have multiple compression fractures. During an eight-year period, eight patients who suffered relentless nonmechanical back pain after an initial compression fracture were evaluated. Radiographs and radionuclide bone scans were obtained in all eight patients and showed the temporal clustering of at least five spontaneous thoracic or lumbar vertebral compression fractures within a period of eight months. The patient database during this eight-year period included 21 patients with a similar number of fractures but without the phenomenon of temporal clustering. Age and gender distribution, premorbid activity levels, presence of secondary causes of osteopenia, dietary history, and vertebral bone density measurements were similar in both groups. Five of the eight patients with cluster fractures were on chronic glucocorticoid therapy for treatment of an underlying illness. All five patients experienced an exacerbation of their chronic illness that required an increase in the dose of their steroid medication within three months preceding the onset of the cluster fractures. No patient in the noncluster fracture control group experienced a similar exacerbation of an underlying illness or required a similar boost in their steroid medication. The temporal clustering of numerous fractures (cluster phenomenon) is a cause of transient severe disability in patients who have profound osteopenia, and may be precipitated by exacerbation of an intercurrent illness or by an associated obligate increase in glucocorticoid medication in a patient with preexisting severe osteopenia.