PT  - JOURNAL ARTICLE
AU  - JEAN-PIERRE PELLETIER
AU  - ÉRIC TRONCY
AU  - THIERRY BERTAIM
AU  - DOMINIQUE THIBAUD
AU  - ANNE-CHRISTINE GOULET
AU  - FRANÇOIS ABRAM
AU  - JUDITH CARON
AU  - CHRISTELLE BOILEAU
AU  - MARC-ANDRÉ d’ANJOU
AU  - MAXIM MOREAU
AU  - BERTRAND LUSSIER
AU  - JOHANNE MARTEL-PELLETIER
TI  - 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
AID  - 10.3899/jrheum.100642
DP  - 2011 Jan 01
TA  - The Journal of Rheumatology
PG  - 118--128
VI  - 38
IP  - 1
4099  - http://www.jrheum.org/content/38/1/118.short
4100  - http://www.jrheum.org/content/38/1/118.full
SO  - J Rheumatol2011 Jan 01; 38
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.