Greater magnitude of turnover suppression occurs earlier after treatment initiation with risedronate than alendronate.
Clinical data suggest that reductions in fractures associated with osteoporosis may occur sooner in patients treated with risedronate (RIS) compared to those treated with alendronate (ALN). This could be explained by differences in the time course of turnover suppression between these two bisphosphonates. To determine if differences in the onset of turnover suppression exist between RIS and ALN, female New Zealand white rabbits (total n=32) were treated with clinically relevant doses of RIS or ALN and then administered different fluorochrome labels weekly for four weeks in order to allow histological assessment of the time-course of turnover suppression. By the third week of treatment vertebral trabecular bone formation rate (BFR/BS) was significantly suppressed with RIS-treatment compared to both VEH and ALN. By the 4th week of treatment, turnover rates in RIS-treated animals remained significantly lower than in VEH-treated animals and were also lower than ALN; at this time-point ALN was significantly lower than VEH. There was no significant reduction in intra-cortical remodeling in the tibial mid-diaphysis at any time point for either RIS or ALN. This greater effect on turnover suppression with RIS early in treatment compared to ALN is likely the result of both risedronate's greater potency on osteoclast inhibition and its lower binding affinity. Together with studies showing more rapid return toward baseline turnover following withdrawal of RIS compared to ALN, this pre-clinical study provides evidence of the differences between bisphosphonates with respect to onset and recovery of bone turnover suppression.
Allen
Matthew R
MR
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, 46202, USA. matallen@iupui.edu
Turek
John J
JJ
Phipps
Roger J
RJ
Burr
David B
DB
D019386:Alendronate / Q000494:pharmacology*; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D016723:Bone Remodeling / Q000187:drug effects*; D018483:Diaphyses / Q000187:drug effects / Q000473:pathology; D012968:Etidronic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D011817:Rabbits; D000068296:Risedronic Acid; D013131:Spine / Q000187:drug effects / Q000473:pathology; D013977:Tibia / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
D050071:Bone Density Conservation Agents; D005456:Fluorescent Dyes; D000068296:Risedronic Acid; D012968:Etidronic Acid; D019386:Alendronate