Effect of simvastatin on osteogenesis of the lumbar vertebrae in ovariectomized rats

Abstract

The aim of the present study was to assess the role of simvastatin on osteoporosis of the vertebrae by examining the effect of simvastatin on the osteogenesis of the lumbar vertebra in ovariectomized (OVX) rats. A total of 60 6-month-old female Sprague Dawley rats were divided into one sham group and five ovariectomized groups, consisting of four simvastatin groups and one control group. Four dosages of simvastatin (5, 10, 20 and 40 mg/kg/d) were administered by gavage for three months. L4 vertebrae were examined by dual-energy X-ray absorptiometry (DEXA) and peripheral quantitative computed tomography (pQCT) to determine the mineral apposition rate (MAR). L5 vertebrae were examined using a compression biomechanical test. Although the measurements from DEXA, pQCT and MAR, and the biomechanical parameters in the OVX + simvastatin rats were higher than those for the OVX + vehicle group, no significant differences were detected. Therefore, simvastatin may not improve osteogenesis of the lumbar vertebra in OVX rats or prevent osteoporosis of the spinal vertebrae.

Keywords: osteogenesis; osteoporosis; ovariectomized; simvastatin.

Figure 1.

Schematic diagram of biomechanical experiments. LS, lumbar spine.

Figure 2.

Bone densitometry was assessed in OVX rats treated with 5, 10, 20 and 40 mg/kg/day simvastin, and the OVX model and sham groups. OVX, ovariectomized.

Figure 3.

Analysis of the L4 vertebral body by pQCT in OVX rats treated with 5, 10, 20 and 40 mg/kg/day simvastin, and the sham and OVX model groups. *P<0.05 vs. the OVX group. (A-F) Effect of simvastatin on (A) CNT (bone content), (B) DEN (bone mineral density), (C) A (bone area), (D) C (bone circumference), (E) THK (bone thickness) and (F) SSI (bone strength and mechanical properties). pQCT peripheral quantitative computed tomography; OVX, ovariectomized; CNT, bone content; TOT, total; TRAB, trabecular; CRT, cortical; DEN, bone mineral density; A, area; C, circumference; PERI, periosteal; ENDO, endocortical; THK, thickness; CRT_THK_C, cortical thickness of the circumference; SSI, bone strength and mechanical properties.

Figure 4.

Tetracycline labels in epifluorescence microscopy (magnification, ×400). (A) 5 mg/kg/day simvastin + ovariectomy; (B) 10 mg/kg/day simvastin + ovariectomy; (C) 20 mg/kg/day simvastin + ovariectomy; (D) 40 mg/kg/day simvastin + ovariectomy; (E) vehicle + ovariectomy; and (F) vehicle + sham. (G) Effect of simvastatin on MAR. MAR, mineral apposition rate; OVX, ovariectomized.

Figure 5.

Effects of simvastatin on the structural biomechanical property index in OVX rats treated with 5, 10, 20 and 40 mg/kg/day simvastin, and the sham and OVX model groups. (A-C) Effect of simvastatin on (A) F (ultimate load), (B) S (ultimate stiffness) and (C) W (work to failure). F, ultimate load; S, ultimate stiffness; W, work to failure; OVX, ovariectomized.

Figure 6.

Effects of simvastatin on the material biomechanical property index in OVX rats. *P<0.05 vs. the OVX group. (A-C) Effect of simvastatin on (A) σ (ultimate stress), (B) T (toughness) and (C) E (Young's modulus). OVX, ovariectomized; E, Young's modulus; T, toughness; σ, ultimate stress.