Alendronate Prevents Intervertebral Disc Degeneration Adjacent to a Lumbar Fusion in Ovariectomized Rats

Abstract

A model of disc degeneration adjacent to a lumbar fusion in osteoporotic rats. We determined the effect of alendronate (ALN) on the disc degeneration adjacent to a lumbar fusion in ovariectomized rats. Adjacent-segment disc degeneration (ASDD) is one of the negative sequelae of spinal fusion. Previous studies have shown that ALN can alleviate disc degeneration. However, no data have been documented regarding the effect of ALN on ASDD after posterolateral lumbar fusion (PLF) in osteoporosis. 50 female Sprague-Dawley rats underwent either a sham operation (sham) (n = 20) or bilateral ovariectomy (OVX) (n = 30). 4 weeks later, all but 10 rats from each group underwent PLF consisting of an intertransverse process spinal fusion using autologous-iliac-bone grafts with spinous-process wire fixation at the L4-L5 segment. Animals were subcutaneously administered vehicle (V) or ALN (70 μg/kg/wk) for 12 weeks post-PLF as follows: Sham+V, OVX+V, PLF+V, OVX+PLF+V, and OVX+PLF+ALN. Fusion status was analyzed by manual palpation and radiography. Adjacent-segment disc was assessed by histological, histomorphometric, immunohistochemical, and mRNA analysis. L6 vertebrae microstructures were evaluated by microcomputed tomography. The fused segments showed clear evidence of fusion based on manual palpation and radiographs. The OVX+PLF+V group showed more severe degenerative alterations and higher histological scores in the disc than the Sham+V, OVX+V, and PLF+V groups (P < 0.05). Compared with the OVX+PLF+V group, the OVX+PLF+ALN group exhibited significantly improved bone mass and vertebrae microstructures (P < 0.05), an increased disc height, and a decreased endplate calcification area (P < 0.05). ALN also significantly decreased Col-I, MMP-13, and ADAMTS-4 expression and increased Col-II and Aggrecan expression in the disc matrix (P < 0.05). ALN effectively alleviated ASDD post-PLF in ovariectomized rats. These data indicate that ALN can be used as a potential therapeutic agent to attenuate ASDD progression in osteoporosis.