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.
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.


CONCLUSIONS
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.
Pelletier
Jean-Pierre
JP
Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM) Notre-Dame Hospital, 1560 Sherbrooke Street East, Montreal, QC H2L 4M1, Canada. dr@jppelletier.ca
Troncy
Eric
E
Bertaim
Thierry
T
Thibaud
Dominique
D
Goulet
Anne-Christine
AC
Abram
François
F
Caron
Judith
J
Boileau
Christelle
C
d'Anjou
Marc-André
MA
Moreau
Maxim
M
Lussier
Bertrand
B
Martel-Pelletier
Johanne
J
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000473:pathology / Q000601:surgery*; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000473:pathology*; D004164:Diphosphonates / Q000627:therapeutic use*; D004285:Dogs; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D010003:Osteoarthritis / Q000188:drug therapy* / Q000473:pathology*
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; C058651:tiludronic acid