OLPADRONATE PREVENTS THYROID HORMONE-INDUCED CORTICAL AND TRABECULAR BONE LOSS IN OVARIECTOMIZED RATS

The aim of the present report was to clarify the effect of excess T4 o n axial and peripheral bone mineral density (BMD) in estrogen-depleted rats. The protective effect of olpadronate (Olpa) on axial and periph eral 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 mu g/kg/day) and OVX+T4+Olpa rats. OVX+Vh group present ed a BMD tower than SHAM in the tibia (p < 0.01) but not in femur or l umbar spine; the middle tibia BMD did not change but it Was lower at t he distal (pns.) and proximal levels (p < 0.003) in OVX+Vh. OVX+T4 rat s 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 t he BMD was lower in all studied areas of the tibia, but it was statist ically 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). Surpris ingly, total and proximal tibia BMD Values in OVX+Olpa rats presented a BMD significantly higher than OVX+T4 rats in femur (p < 0.001), lumb ar 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 tibi a (p < 0.01). The present study suggests that although supraphysiologi cal thyroid hormone affected both cortical and trabecular bone, under estrogen-depleted conditions, the cortical bone appears to be more sen sitive than the trabecular bone to T4 treatment. We also found that Ol pa could prevent the peripheral and axial bone loss induced by thyroid hormone excess.