A relationship between disc lesion and microdamage accumulation in adjacent vertebrae during fatigue loading was investigated in a canine model. Eighteen functional spinal units obtained from 6 skeletally mature mongrel dogs were divided into 3 groups: I, control (without loading) (n = 6); II, loading with normal disc (n = 6); and III, loading with disc lesion created by nucleotomy (n = 6). Physiologic cyclic compression was performed for 10(5) cycles, and fractional trabecular bone area and microcrack density in the vertebrae were measured. There was a significant difference in microcrack density among groups and regions (p < 0.0001) with significantly more microdamage in functional spinal units with disc lesions than in the other 2 groups (p < 0.0001). The microcracks were distributed predominantly in the vertebral region adjacent to the nucleotomized disc (p < 0.005). There was a negative association of microcrack density with fractional trabecular bone area (R2 = 0.236, p < 0.02). These results support the hypothesis that disc degeneration contributes to vertebral fragility by causing microdamage accumulation, especially in vertebrae with low bone mass.