Bisphosphonate effects in rat unloaded hindlimb bone loss model: Three-dimensional microcomputed tomographic, histomorphometric, and densitometric analyses

The effects of antiresorptive drugs on bone loss remain unclear. Using thre e-dimensional microtomography, dual X-ray/densitometry, and histomorphometr y, we evaluated tiludronate effects in the bone loss model of immobilizatio n in tail-suspended rats after 7, 13, and 23 days. Seventy-eight 12-week-ol d Wistar male rats were assigned to 13 groups: 1 baseline group, and for ea ch time point, 1 control group treated with vehicle and three tail-suspende d groups treated with either tiludronate (0.5 or 5 mg/kg) or vehicle, admin istered s.c. every other day, during the last week before sacrifice. In pri mary spongiosa (ISP), immobilization-induced bone loss plateaued after day 7 and was prevented by tiludronate. In secondary spongiosa (IISP), bone los s appeared at day 13 with a decrease in trabecular thickness and trabecular number (Tb.N) as assessed by three-dimensional microtomography. Osteoclast ic parameters did not differ in tail-suspended rats versus control rats, wh ereas bone formation showed a biphasic pattern: after a marked decrease at day 7, osteoblastic activity and recruitment normalized at days 13 and 23, respectively. At day 23, the 80% decrease in bone mass was fully prevented by high-dose tiludronate with an increase in Tb.N without preventing trabec ular thinning. In summary, at day 7, tiludronate prevented bone loss in ISP . After day 13, tiludronate prevented bone loss in ISP and IISP despite a f urther decrease in bone formation. Thus, the preventive effects of tiludron ate in this model may be related to the alteration in bone modeling with an increase in Tb.N in ISP and subsequently in IISP.