THERIOGENOLOGY AND LAMENESS 5. Wingen F, Schma ¨hl D. Pharmacokinetics of the osteotro-
phic diphosphonate 3-amino-1-hydroxypropane-1,1- diphosphonic acid in mammals. Arzneim-Forsch/Drug Res 1987;37:1037–1042.
6. Rogers MJ, Crockett JC, Coxon FP, et al. Biochemical and molecular mechanisms of action of bisphosphonates. Bone 2011;49:34–41.
7. Zhang Q, Badell IR, Schwarz EM, et al. Tumor necrosis factor prevents alendronate-induced osteoclast apoptosis in vivo by stimulating Bcl-xL expression through Ets-2. Ar- thritis Rheum 2005;52:2708–2718.
8. Sutherland KA, Rogers HL, Tosh D, et al. RANKL increases the level of Mxl-1 in osteoclasts and reduces bisphosphonate- induced osteoclast apoptosis in vitro. Arthritis Res Ther 2009;11:R58.
9. Sahni M, Guenther HL, Fleisch H, et al. Bisphosphonates act on rat bone resorption through the mediation of osteo- blasts. J Clin Invest 1993;91:2004–2011.
10. Nishikawa M, Akatsu T, Katayama Y, et al. Bisphospho- nates act on osteoblastic cells and inhibit osteoclast formation in mouse marrow cultures. Bone 1996;18:9–14.
11. Vitte ´ C, Fleisch H, Guenther HL. Bisphosphonates induce
osteoblasts to secrete an inhibitor of osteoclast-mediated re- sorption. Endocrinology 1996;137:2324–2333.
12. Bellido T, Plotkin LI. Novel actions of bisphosphonates in bone: preservation of osteoblast and osteocyte viabil- ity. Bone 2011;49:50–55.
13. Plotkin LI. Apoptotic osteocytes and the control of targeted bone resorption. Curr Osteoporos Rep 2014;12:121–126.
14. Bonjour JP, Ammann P, Barbier A, et al. Tiludronate: bone pharmacology and safety. Bone 1995;17:473S–477S.
15. Varela A, Lepage OM, Doucet M, et al. Tiludronate chez le cheval: Tolerance et effets a court terme sur le metabolism osseux. Ann Med Vet 2002;146:123–130.
16. Delguste C, Amory H, Guyonnet J, et al. Comparative phar- macokinetics of two intravenous administration regimens of tiludronate in healthy adult horses and effects on the bone resorption marker CTX-1. J Vet Pharmacol Ther 2008;31: 108–116.
17. Lee SH, Chang SS, Lee M, et al. Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporo- sis: A systematic review and meta-analysis. Osteoporos Int 2014;25:1131–1139.
18. Liu J, Zhang HX, Lu XX, et al. Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: Sensitivity and trim and fill studies. Genet Test Mol Bio- markers 2014;18:117–122.
19. Saita Y, Ishijima M, Kaneko K. Atypical femoral fractures and bisphosphonate use: Current evidence and clinical im- plications. Ther Adv Chronic Dis 2015;6:185–193.
20. FDA Freedom of Information Summary Tildren. 2014;NADA 141–420. Accessed from:
http://www.fda.gov/downloads/ AnimalVeterinary/Products/ApprovedAnimalDrugProducts/ FOIADrugSummaries/UCM408781.pdf.
21. FDA Freedom of Information Summary Osphos. 2014;NADA 141–427. Accessed from:
http://www.fda.gov/downloads/ AnimalVeterinary/Products/ApprovedAnimalDrugProducts/ FOIADrugSummaries/UCM406997.pdf.
22. Denoix JM, Thibaud D, Riccio B. Tiludronate as a new thera- peutic agent in the treatment of navicular disease: A double- blind placebo-controlled clinical trial. Equine Vet J 2003;35: 407–413.
23. Whitfield CT, Schoonover MJ, Holbrook TC, et al. Quanti- tative assessment of two methods of tiludronate administra- tion for the treatment of lameness caused by navicular syndrome in horses. Am J Vet Res 2016;77:167–173.
24. Duesterdieck-Zellmer KF, Driscoll N, Ott J. Concentration- dependent effects of tiludronate on equine articular cartilage explants incubated with and without interleukin-1. Am J Vet Res 2012;73:1530–1539.
25. Duesterdieck-Zellmer KF, Moneta L, Ott JF, et al. Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses—A preliminary in- vestigation. Peer J 2014;2:e534.
26. Hunter BG, Duesterdieck-Zellmer KF, Larson MK. Tiludro- nate concentrations and cytologic findings in synovial fluid after intravenous regional limb perfusion with tiludronate in horses. Peer J 2015;3:e889.
27. Castan ˜eda S, Roman-Blas JA, Largo R, et al. Subchondral
bone as a key target for osteoarthritis treatment. Biochem Pharmacol 2012;83:315–323.
28. Burr DB, Gallant MA. Bone remodelling in osteoarthritis. Nat Rev Rheumatol 2012;8:665–673.
29. Bellido M, Lugo L, Roman-Blas JA, et al. Subchondral bone microstructural damage by increased remodelling aggravates experimental osteoarthritis preceded by osteoporosis. Ar- thritis Res Ther 2010;12:R152.
30. Coudry V, Thibaud D, Riccio B, et al. Efficacy of tiludronate in the treatment of horses with signs of pain associated with osteoarthritic lesions of the thoracolumbar vertebral column. Am J Vet Res 2007;68(3):329–337.
31. Gough MR, Thibaud D, Smith RK. Tiludronate infusion in the treatment of bone spavin: A double blind placebo- controlled trial. Equine Vet J 2010;42:381–387.
32. Delguste C, Armory H, Doucet M, et al. Pharmacological effects of tiludronate in horses after long-term immobiliza- tion. Bone 2007;41:414–421.
33. Kates SL, Ackert-Bicknell CL. How do bisphosphonates af- fect fracture healing? Injury 2016;47(S1):S65–S68.
34. Xue D, Li F, Chen G, et al. Do bisphosphonates affect bone healing? A meta-analysis of randomized controlled trials. J Orthop Surg Res 2014;9:45.
35. Li YT, Cai HF, Zhang ZL. Timing of the initiation of bis- phosphonates after surgery for fracture healing: A system- atic review and meta-analysis of randomized controlled trials. Osteoporos Int 2015;26:431–441.
36. Savaridas T, Wallace RJ, Salter DM, et al. Do bisphospho- nates inhibit direct fracture healing? A laboratory investi- gation using an animal model. Joint J 2013;95-B:1263– 1268.
37. Carpenter RS. How to treat dorsal metacarpal disease with regional tiludronate and extracorporeal shock wave therapies in Thoroughbred race horses, in Proceedings. Am Assoc Equine Pract 58:546–549, 2012.
38. Wilkinson JM, Little DG. Bisphosphonates in orthopedic applications. Bone 2011;49:95–102.
39. Baroncelli GI, Bertelloni S. The use of bisphosphonates in pediatrics. Horm Res Paediatr 2014;82:290–302.
40. Land C, Rauch F, Glorieux FH. Cyclical intravenous pamidronate treatment affects metaphyseal modeling in growing patients with osteogenesis imperfect. J Bone Min Res 2006;21:374–379.
41. Green SB, Pappas AL. Effects of maternal bisphosphonate use on fetal and neonatal outcomes. Am J Health Syst Pharm 2014;71:2029–2036.
42. Smith EJ, Little DG, Briody JN, et al. Transient distur- bance in physeal morphology is associated with long-term effects of nitrogen-containing bisphosphonates in growing rabbits. J Bone Min Res 2005;20:1731–1541.
43. Thibaud D, Guyonnet J, Toutain PL. Pharmacological ap- proaches of dose determination with tiludronate for use in the horse. J Vet Pharmacol Ther 26(Suppl 1):200–201, 2003 (Abstract).
aTildren, Ceva Animal Health LLC, Lenexa, KS 66215. bOsphos, Dechra Veterinary Products, Overland Park, KS
66211. c
VersaTron, PulseVet, Alpharetta, GA 30009.
378 2016 Vol. 62 AAEP PROCEEDINGS
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132 |
Page 133 |
Page 134 |
Page 135 |
Page 136 |
Page 137 |
Page 138 |
Page 139 |
Page 140 |
Page 141 |
Page 142 |
Page 143 |
Page 144 |
Page 145 |
Page 146 |
Page 147 |
Page 148 |
Page 149 |
Page 150 |
Page 151 |
Page 152 |
Page 153 |
Page 154 |
Page 155 |
Page 156 |
Page 157 |
Page 158 |
Page 159 |
Page 160 |
Page 161 |
Page 162 |
Page 163 |
Page 164 |
Page 165 |
Page 166 |
Page 167 |
Page 168 |
Page 169 |
Page 170 |
Page 171 |
Page 172 |
Page 173 |
Page 174 |
Page 175 |
Page 176 |
Page 177 |
Page 178 |
Page 179 |
Page 180 |
Page 181 |
Page 182 |
Page 183 |
Page 184 |
Page 185 |
Page 186 |
Page 187 |
Page 188 |
Page 189 |
Page 190 |
Page 191 |
Page 192 |
Page 193 |
Page 194 |
Page 195 |
Page 196 |
Page 197 |
Page 198 |
Page 199 |
Page 200 |
Page 201 |
Page 202 |
Page 203 |
Page 204 |
Page 205 |
Page 206 |
Page 207 |
Page 208 |
Page 209 |
Page 210 |
Page 211 |
Page 212 |
Page 213 |
Page 214 |
Page 215 |
Page 216 |
Page 217 |
Page 218 |
Page 219 |
Page 220 |
Page 221 |
Page 222 |
Page 223 |
Page 224 |
Page 225 |
Page 226 |
Page 227 |
Page 228 |
Page 229 |
Page 230 |
Page 231 |
Page 232 |
Page 233 |
Page 234 |
Page 235 |
Page 236 |
Page 237 |
Page 238 |
Page 239 |
Page 240 |
Page 241 |
Page 242 |
Page 243 |
Page 244 |
Page 245 |
Page 246 |
Page 247 |
Page 248 |
Page 249 |
Page 250 |
Page 251 |
Page 252 |
Page 253 |
Page 254 |
Page 255 |
Page 256 |
Page 257 |
Page 258 |
Page 259 |
Page 260 |
Page 261 |
Page 262 |
Page 263 |
Page 264 |
Page 265 |
Page 266 |
Page 267 |
Page 268 |
Page 269 |
Page 270 |
Page 271 |
Page 272 |
Page 273 |
Page 274 |
Page 275 |
Page 276 |
Page 277 |
Page 278 |
Page 279 |
Page 280 |
Page 281 |
Page 282 |
Page 283 |
Page 284 |
Page 285 |
Page 286 |
Page 287 |
Page 288 |
Page 289 |
Page 290 |
Page 291 |
Page 292 |
Page 293 |
Page 294 |
Page 295 |
Page 296 |
Page 297 |
Page 298 |
Page 299 |
Page 300 |
Page 301 |
Page 302 |
Page 303 |
Page 304 |
Page 305 |
Page 306 |
Page 307 |
Page 308 |
Page 309 |
Page 310 |
Page 311 |
Page 312 |
Page 313 |
Page 314 |
Page 315 |
Page 316 |
Page 317 |
Page 318 |
Page 319 |
Page 320 |
Page 321 |
Page 322 |
Page 323 |
Page 324 |
Page 325 |
Page 326 |
Page 327 |
Page 328 |
Page 329 |
Page 330 |
Page 331 |
Page 332 |
Page 333 |
Page 334 |
Page 335 |
Page 336 |
Page 337 |
Page 338 |
Page 339 |
Page 340 |
Page 341 |
Page 342 |
Page 343 |
Page 344 |
Page 345 |
Page 346 |
Page 347 |
Page 348 |
Page 349 |
Page 350 |
Page 351 |
Page 352 |
Page 353 |
Page 354 |
Page 355 |
Page 356 |
Page 357 |
Page 358 |
Page 359 |
Page 360 |
Page 361 |
Page 362 |
Page 363 |
Page 364 |
Page 365 |
Page 366 |
Page 367 |
Page 368 |
Page 369 |
Page 370 |
Page 371 |
Page 372 |
Page 373 |
Page 374 |
Page 375 |
Page 376 |
Page 377 |
Page 378 |
Page 379 |
Page 380 |
Page 381 |
Page 382 |
Page 383 |
Page 384 |
Page 385 |
Page 386 |
Page 387 |
Page 388 |
Page 389 |
Page 390 |
Page 391 |
Page 392 |
Page 393 |
Page 394 |
Page 395 |
Page 396 |
Page 397 |
Page 398 |
Page 399 |
Page 400 |
Page 401 |
Page 402 |
Page 403 |
Page 404 |
Page 405 |
Page 406 |
Page 407 |
Page 408 |
Page 409 |
Page 410 |
Page 411 |
Page 412 |
Page 413 |
Page 414 |
Page 415 |
Page 416 |
Page 417 |
Page 418 |
Page 419 |
Page 420 |
Page 421 |
Page 422 |
Page 423 |
Page 424 |
Page 425 |
Page 426 |
Page 427 |
Page 428 |
Page 429 |
Page 430 |
Page 431 |
Page 432 |
Page 433 |
Page 434 |
Page 435 |
Page 436 |
Page 437 |
Page 438 |
Page 439 |
Page 440 |
Page 441 |
Page 442 |
Page 443 |
Page 444 |
Page 445 |
Page 446 |
Page 447 |
Page 448 |
Page 449 |
Page 450 |
Page 451 |
Page 452 |
Page 453 |
Page 454 |
Page 455 |
Page 456 |
Page 457 |
Page 458 |
Page 459 |
Page 460 |
Page 461 |
Page 462 |
Page 463 |
Page 464 |
Page 465 |
Page 466 |
Page 467 |
Page 468 |
Page 469 |
Page 470 |
Page 471 |
Page 472 |
Page 473 |
Page 474 |
Page 475 |
Page 476 |
Page 477 |
Page 478 |
Page 479 |
Page 480 |
Page 481 |
Page 482 |
Page 483 |
Page 484 |
Page 485 |
Page 486 |
Page 487 |
Page 488 |
Page 489 |
Page 490 |
Page 491 |
Page 492 |
Page 493 |
Page 494 |
Page 495 |
Page 496 |
Page 497 |
Page 498 |
Page 499 |
Page 500 |
Page 501 |
Page 502 |
Page 503 |
Page 504 |
Page 505 |
Page 506 |
Page 507 |
Page 508 |
Page 509 |
Page 510 |
Page 511 |
Page 512 |
Page 513 |
Page 514 |
Page 515 |
Page 516 |
Page 517 |
Page 518 |
Page 519 |
Page 520 |
Page 521 |
Page 522 |
Page 523 |
Page 524 |
Page 525 |
Page 526 |
Page 527 |
Page 528 |
Page 529 |
Page 530 |
Page 531 |
Page 532 |
Page 533 |
Page 534 |
Page 535 |
Page 536 |
Page 537 |
Page 538 |
Page 539 |
Page 540 |
Page 541 |
Page 542 |
Page 543 |
Page 544 |
Page 545 |
Page 546 |
Page 547 |
Page 548 |
Page 549 |
Page 550 |
Page 551 |
Page 552 |
Page 553 |
Page 554 |
Page 555 |
Page 556 |
Page 557 |
Page 558 |
Page 559 |
Page 560 |
Page 561 |
Page 562 |
Page 563 |
Page 564 |
Page 565 |
Page 566 |
Page 567 |
Page 568 |
Page 569 |
Page 570 |
Page 571 |
Page 572 |
Page 573 |
Page 574 |
Page 575 |
Page 576 |
Page 577 |
Page 578 |
Page 579 |
Page 580 |
Page 581 |
Page 582 |
Page 583 |
Page 584 |
Page 585 |
Page 586 |
Page 587 |
Page 588 |
Page 589 |
Page 590 |
Page 591 |
Page 592 |
Page 593 |
Page 594 |
Page 595 |
Page 596 |
Page 597 |
Page 598 |
Page 599 |
Page 600 |
Page 601 |
Page 602 |
Page 603 |
Page 604 |
Page 605 |
Page 606 |
Page 607 |
Page 608 |
Page 609 |
Page 610 |
Page 611 |
Page 612 |
Page 613 |
Page 614 |
Page 615 |
Page 616 |
Page 617 |
Page 618 |
Page 619 |
Page 620 |
Page 621 |
Page 622 |
Page 623 |
Page 624 |
Page 625 |
Page 626 |
Page 627 |
Page 628