RESUMO
The study was designed to investigate if pre-treating rats with a therapeutic equivalent dose of risedronate blunted the anabolic effects of PTH, and whether a withdrawal period prior to PTH treatment would alter any effect of risedronate on PTH treatment. Skeletally mature rats were treated for 18 weeks with vehicle, risedronate, or risedronate for 8 weeks followed by vehicle for 10 weeks (withdrawal period). At the end of this period, animals were treated for a further 12 weeks with PTH or PTH vehicle. Trabecular and cortical bone mass were monitored by serial pQCT, or by DXA and microCT. Bone histomorphometry was performed on the proximal tibiae and tibial shafts for bone turnover parameters at week 40. Risedronate alone moderately increased while PTH alone markedly increased trabecular bone mass at the proximal tibial (35% and 200%, respectively) and lumbar vertebral body (14% and 36%, respectively). The maximum bone gains were similar with and without pretreatment with risedronate as compared to the PTH alone. Continuous administration of risedronate for 18 weeks prior to PTH treatment had lower percentage increases in proximal tibial BMD during the first 8 weeks of PTH treatments, and had lower active bone forming surface and bone formation rates after being treated with PTH 12 weeks as compared to the PTH alone group. However, with the 10-week withdrawal period, risedronate did not blunt the stimulatory effect of PTH on osteoblast activity as shown by similar bone formation rates as with PTH alone. Our findings suggest that while risedronate pretreatment may slow the bone anabolic response to PTH, a withdrawal period prior to PTH treatment allows osteoblastic activity to respond normally to PTH stimulation.
