[Olpadronate prevents cortical and trabecular bone loss induced by supraphysiological dosis of thyroxine in...

The aim of the present report was to clarify the effect of excess T4 on axial and peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective effect of olpadronate (Olpa) on axial and peripheral bone mass in thyroxine-treated rats was also investigated. Female Sprague-Dawley rats were used: SHAM, OVX + Vh, OVX + Olpa (0.3 mg/kg/week), OVX + T4 (250 micrograms/kg/day) and OVX + T4 + Olpa rats. OVX + Vh group presented a BMD lower than SHAM in the tibia (p < 0.01) but not in femur or lumbar spine; the middle tibia BMD did not change but it was lower at the distal (pns.) and proximal levels (p < 0.003) in OVX + Vh. OVX + T4 rats presented a BMD significantly lower than OVX + Vh rats in total tibia (p < 0.02), femur (p < 0.006) and lumbar spine (p < 0.006). Moreover the BMD was lower in all studied areas of the tibia, but it was statistically significant only at the middle level (p < 0.004). OVX + Olpa rats had a BMD higher than OVX + Vh rats in femur (p < 0.002), lumbar spine (p < 0.0001), total (p < 0.001) and proximal tibia (p < 0.001). Surprisingly, total and proximal tibia BMD values in OVX + Olpa rats presented a BMD significantly higher than OVX + T4 rats in femur (p < 0.001), lumbar spine (p < 0.001), tibia (p < 0.001) and proximal tibia (p < 0.0001). It is important to point out that OVX + T4 + Olpa BMD was significantly higher than in SHAM rats at the lumbar spine, total and proximal tibia (p < 0.01). The present study suggests that although supraphysiological thyroid hormone affected both cortical and trabecular bone, under estrogen-depleted conditions, the cortical bone appears to be more sensitive than the trabecular bone to T4 treatment. We also found that Olpa could prevent the peripheral and axial bone loss induced by thyroid hormone excess.