RT Journal Article
SR Electronic
T1 Treatment with Tiludronic Acid Helps Reduce the Development of Experimental Osteoarthritis Lesions in Dogs with Anterior Cruciate Ligament Transection Followed by Reconstructive Surgery: A 1-Year Study with Quantitative Magnetic Resonance Imaging
JF The Journal of Rheumatology
JO J Rheumatol
FD The Journal of Rheumatology
SP 118
OP 128
DO 10.3899/jrheum.100642
VO 38
IS 1
A1 JEAN-PIERRE PELLETIER
A1 ÉRIC TRONCY
A1 THIERRY BERTAIM
A1 DOMINIQUE THIBAUD
A1 ANNE-CHRISTINE GOULET
A1 FRANÇOIS ABRAM
A1 JUDITH CARON
A1 CHRISTELLE BOILEAU
A1 MARC-ANDRÉ d’ANJOU
A1 MAXIM MOREAU
A1 BERTRAND LUSSIER
A1 JOHANNE MARTEL-PELLETIER
YR 2011
UL http://www.jrheum.org/content/38/1/118.abstract
AB Objective. To investigate over a 1-year period in dogs that underwent extracapsular stabilization surgery (ECS) following anterior cruciate ligament (ACL) transection: whether reconstructive surgery could prevent osteoarthritis (OA) progression and whether treatment with the bisphosphonate tiludronic acid (TA) could improve the chronic evolution of OA structural changes. Methods. ACL transection was performed on dogs on Day 0 and ECS on Day 28. Dogs were randomly divided into 2 groups: 15 received placebo and 16 were treated with TA (2 mg/kg subcutaneous injection) on Days 14, 28, 56, and 84. Magnetic resonance images were acquired on Days −10, 26, 91, 210, and 357, and cartilage volume was quantified. At sacrifice (Day 364), cartilage from femoral condyles and tibial plateaus was macroscopically and histologically evaluated. Expression levels of MMP-1, -3, -13, ADAMTS-4, -5, BMP-2, FGF-2, IGF-1, TGF-ß1, collagen type II, and aggrecan were determined using real-time RT-PCR. Results. The loss of cartilage volume observed after ACL transection stabilized following ECS. Thereafter, a gradual gain occurred, with the cartilage volume loss on the tibial plateaus reduced at Day 91 (p < 0.02) and Day 210 (p < 0.001) in the TA-treated dogs. At sacrifice, TA-treated dogs presented a reduction in the severity of macroscopic (p = 0.03 for plateaus) and histologic (p = 0.07 for plateaus) cartilage lesions, had a better preserved collagen network, and showed decreased MMP-13 (p = 0.04), MMP-1 and MMP-3 levels. Conclusion. Our findings indicate that in dogs with ACL transection, ECS greatly prevents development of cartilage volume loss. Treatment with TA provided an additional benefit of reducing the development of OA lesions.