Abstract/Details

Bisphosphonate antiresorptive drug use in a rabbit model of osteoarthritis

Doschak, Michael Roman.   University of Calgary (Canada) ProQuest Dissertations & Theses,  2004. NQ97740.

Abstract (summary)

Following anterior cruciate ligament rupture (ACLX) in the knee, rapid periarticular bone loss often occurs prior to the subchondral sclerosis of end-stage osteoarthritis (OA). In a model of knee osteoarthritis, changes were examined in subchondral periarticular bone mineral and microarchitecture (μCT) and in the femoral insertion of the medial collateral ligament (MCL). Also assessed were whether antiresorptive therapy with a bisphosphonate (BP [risedronate]) altered those bone adaptations in the subchondral plate, at the MCL-insertion, and after ACL-reconstruction, and if BP intervention influenced ligament-complex biomechanics and OA progression. Finally, molecular expression of a bone cytokine (osteoprotegerin [OPG]) in periarticular tissues undergoing remodeling and the influence of BP therapy upon the regulation of that gene were investigated.

Early alterations of periarticular bone mineral after ACLX included significant loss in subchondral trabecular bone and in bone at the MCL-insertion. Compared to normal controls, MCL-complex laxity and bone loss at the MCL-insertion were significantly greater in the ACLX cohort at 6 wk and had increased further by 14 wk after ACLX. If ACLX animals were dosed daily with risedronate bisphosphonate for 6 wk, however, MCL-complex laxity was significantly improved, and the loss of MCL insertional bone was significantly less and not significantly different from normal control animals. When animals were dosed up to 24 wk after ACLX with BP, however, the progression of OA was not altered. The transient restabilization of the joint by ACL-reconstruction, in conjunction with BP-dosing, did little to block the progression of OA. The expression of OPG was altered following loss of the ACL, and the BP risedronate countered that effect—resulting in the return of OPG expression in bone and fibrocartilaginous tissues. Such adaptive responses in connective tissues after ACLX may have been necessary for the maintenance and repair of the injured structures.

The results suggested a potential therapeutic role for antiresorptive bisphosphonate therapy to inhibit adaptive remodeling early following non-fracture joint trauma. Long-term administration of the BP, however, did not appear to be beneficial, and the ultimate effect of the short-term use of the BP on osteoarthritis progression remains to be determined.

Indexing (details)


Subject
Surgery;
Pharmacology;
Medicine
Classification
0564: Medicine
0419: Pharmacology
0576: Surgery
Identifier / keyword
Health and environmental sciences; Anterior cruciate ligament; Antiresorptive; Bisphosphonate; Osteoarthritis
Title
Bisphosphonate antiresorptive drug use in a rabbit model of osteoarthritis
Author
Doschak, Michael Roman
Number of pages
162
Degree date
2004
School code
0026
Source
DAI-B 65/12, Dissertation Abstracts International
ISBN
978-0-612-97740-2
Advisor
Zernicke, Ronald
University/institution
University of Calgary (Canada)
University location
Canada -- Alberta, CA
Degree
Ph.D.
Source type
Dissertation or Thesis
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
NQ97740
ProQuest document ID
305223998
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
https://www.proquest.com/docview/305223998