Effects of simvastatin on bone loss in vertebrae and intervertebral disc degeneration in ovariectomized rats / 医学研究生学报

ABSTRACT

Objective Simvastatin, as a widely used lipid-lowering drug, exhibits a potential effect of promoting bone forma-tion. The present study aimed to investigate the effect of oral simvastatin on lumbar vertebral bone mass and intervertebral disc ( IVD) degeneration in ovariectomized ( OVX ) rats. Methods Thirty female Sprague-Dawley rats were subjected to dual OVX ( n=20) or sham surgery ( n=10) and the OVX rats were treated orally with either saline vehicle (OVX+V, n=10) or simvastatin (OVX+SIM, n=10 ) at 5 mg per kg of the body weight per day. After 6 months of intervention, the microstructure of the L3 vertebra was ob-served by micro-CT, the bone mineral density ( BMD) in the L5-6 ver-tebrae determined by dual-energy X-ray absorptiometry, and histo-logical changes of the L5-6 vertebrae analyzed by van Gieson stainingand semi-quantitative evaluation. Results Compared with the sham-operation group, both the OVX+V and OVX+SIM groups showed significantly decreased BMD in L5([0.2933±0.0110] vs [0.2423±0.0081] and [0.2598±0.0249] g/cm2, P<0.05), L6 ([0.2907±0.0150] vs [0.2395±0.0061] and [0.2572±0.0121] g/cm2, P<0.05), and L5-6([0.2860±0.0115] vs [0.2380± 0.0059] and [0.2528±0.0126] g/cm2, P<0.05), but all the 3 parameters were remarkably higher in the OVX+SIM than in the OVX+V group (P<0.05). Micro-CT analysis manifested significantly lower BV/TV and Tb.N but higher Tb.Sp in the OVX+V than in the sham operation group ( P<0.05) . Abundant notochordal cells and extracellular matrix in the nucleus pulposus with well-arranged outer annulus fibrosus were observed in the rats of the sham operation group. The animals of the OVX+V and OVX+SIM groups displayed de-generation of the nucleus pulposus, annulus fibrosus, reduced notochordal cells and their replacement by chondrocyte-like cells in the nucleus pulposus, mucoid degeneration in the matrix, and disruption of the nuclear-annular border in the annulus fibrosus. The disc de-generation scores were significantly higher in the OVX+V and OVX+SIM than in the sham operation group (4.35±0.9 and 3.53±0.42 vs 2.48±0.92, P<0.05). Conclusion OVX induces not only bone loss in vertebrae but also IVD degeneration in rats, while simvasta-tin can partly prevent bone loss in lumbar vertebrae without aggravating IVD degeneration in OVX rats.