Long‐Term Treatment of Indomethacin Reduces Vertebral Bone Mass and Strength in Ovariectomized Rats

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Abstract
We investigated the effect of the long-term treatment of indomethacin, on lumbar spinal bone mineral density (LSBMD), cancellous bone mass, structure, and strength of vertebral body in old ovariectomized (OVX) rats. Ten-month-old female Wistar rats were divided into five groups: the sham operated + vehicle (sham + VEH) group, the OVX + vehicle (OVX + VEH) group, the OVX + indomethacin (IN) 1.5 mg/kg/week (OVX + IN1.5) group, the OVX + IN 6.0 mg/kg/week (OVX + IN6.0) group, and the OVX + IN 15.0 mg/kg/week (OVX + IN15.0) group. IN or vehicle were given by subcutaneous injection (s.c.) three times per week. The treatments were started at 1 week after operation and continued for 24 weeks. LSBMD (L2-L5) was measured at 0, 12, and 24 weeks after the beginning of treatment. At the end of the experimental period, the animals were sacrificed, and bone histomorphometrical and biomechanical analysis of lumbar vertebral body were done. LSBMD, trabecular bone volume (BV/TV), and trabecular thickness (Tb.Th) decreased significantly in a dose-related manner with IN. In the OVX + IN15.0 group, LSBMD decreased by 12.7%, BV/TV decreased by 65.5%, and Tb.Th decreased by 32.8%, compared with the OVX + VEH group. In addition, the maximum stress in a compressive mechanical test of L4 vertebral body in OVX groups was also decreased in a dose-related manner with IN, and this value in the OVX + IN15.0 group was 31.3% lower than in the OVX + VEH group. We conclude that long-term treatment with IN accentuated the OVX-related decrease in trabecular bone mass and the compressive strength of lumbar vertebrae.