Objective To investigate the effect of neridronate on osteoporosis-associated degeneration of lumbar disc in ovariectomized rats. Methods Totally 30 female SD rats, aged 3 months old, were divided into three groups randomly: Sham group, OVx (ovariectomy) +N (neridronate) group (receiving a subcutaneous injection of 15 μg/kg neridronate twice a week for 6 months), and OVx + PBO (placebo) group (receiving the same dosage of placebo). The rats were sacrificed and the bone mineral density (BMD), bone histomorphometry and biomechanical properties were measured 6 months later. The histological analysis and score were used to determine the process of lumbar disc degeneration, and the disc height index (DHI) and thickness of cartilage endplate (TCE) were also measured. The protein and mRNA expression levels of collagen type Ⅰ (COL-Ⅰ), collagen type Ⅱ (COL-Ⅱ), matrix metalloproteinase-1(MMP-1), matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-13 (MMP-13) in the lumbar disc of ovariectomized rats were detected by Western blotting analysis and real-time RT-PCR, respectively. Results The BMD, bone histomorphometry and biomechanical properties were better in the OVx+N group compared with OVx+PBO group. Histological evaluation showed that the DHI of rats in the OVx+N group was shorter than that in the Sham group, and the TCE of rats in the OVx+N group was higher than that in the Sham group, but showing no significant difference, which indicated that neridronate could effectively maintain the DHI and delay the calcification of the cartilage endplate. The histological score of the OVx+N group was significantly lower than that of the OVx+PBO group (P<0.05), suggesting neridronate could delay the degeneration of lumbar disc. We also found that, compared with the OVx+PBO, the protein and mRNA expression levels of COL-Ⅰ and COL-Ⅱ in the OVx+N group were significantly higher and those of MMP-1, MMP-3 and MMP-13 were significantly reduced (P<0.05). Conclusion Neridronate can delay the process of lumbar disc degeneration in ovariectomized rats, which may be related to maintaining the integrity of lumbar, promoting COL-Ⅰ and COL-Ⅱ expression and suppressing MMP-1, MMP-3 and MMP-13 expression.