Effect of doxycycline on contra lateral canine cranial cruciate ligament rupture

D. J. F. von Pfeil; J. Sung; J. Barry; K. Hayashi; M. R. Edwards

doi:10.3415/VCOT-15-02-0034

Veterinary and Comparative Orthopaedics and Traumatology, Inhaltsverzeichnis

Vet Comp Orthop Traumatol 2015; 28(06): 371-378
DOI: 10.3415/VCOT-15-02-0034

Original Research

Schattauer GmbH

Effect of doxycycline on contra lateral canine cranial cruciate ligament rupture

A prospective randomized clinical trial in 69 dogs

Authors

D. J. F. von Pfeil

¹Friendship Surgical Services of the Friendship Hospital for Animals, Washington, DC, USA

²Department of Small Animal Clinical Sciences, Michigan State University, East Lansing, MI, USA
J. Sung

³Cornell University College of Veterinary Medicine, Ithaca, NY, USA
J. Barry

⁴Cornell Statistical Consulting Unit, Savage Hall, Cornell University, Ithaca, NY, USA
K. Hayashi

³Cornell University College of Veterinary Medicine, Ithaca, NY, USA
M. R. Edwards

⁵Veterinary Specialists of Alaska, P.C., Anchorage, Alaska, USA

Abstract

Summary

Objective: To evaluate whether doxycycline administered to dogs with unilateral cranial cruciate ligament rupture (Uni-CCLR) would decrease the risk of contralateral-CCLR (CoCCLR). To evaluate predictors for Co-CCLR survival. To evaluate if a predisposition of Labrador Retrievers to Co-CCLR exists when compared to other breeds.

Methods: In this prospective randomized controlled clinical trial, 69 client-owned dogs with Uni-CCLR were randomly assigned to a doxycycline (group-D: 7.5 mg/kg PO BID x 6 weeks) or non-doxycycline (group-ND: negative control). Medical and imaging data, time from Uni- to Co-CCLR and to follow-up were recorded. Statistics included chi-squared test, logistic regression, Kaplan-Meier survival analysis, log rank test, survival curves, and frailty model (p <0.05).

Results: This study included 32 dogs in group-D, and 37 dogs in group-ND. Median follow-up was 54.5 and 61 months, respectively. Contralateral CCLR occurred in 53.1% and 48.6% at medians of 20 and 11 months, respectively. Doxycycline did not significantly decrease the risk of Co-CCLR (p = 0.83). This risk was decreased by 14.2% with each year of age but increased with each increasing kilogram of body weight and each increasing degree of tibial plateau angle by 5.4% and 9.7%, respectively. Labrador Retrievers were not significantly predisposed (p = 0.37).

Clinical significance: At the dose regimen investigated doxycycline does not decrease the risk for Co-CCLR.

Keywords

Doxycycline - canine - cranial cruciate ligament rupture - tibial plateau levelling osteotomy - dog

Volltext

Referenzen

References
1 Wilke VL, Robinson DA, Evans RB. et al. Estimate of the annual economic impact of treatment of cranial cruciate ligament injury in dogs in the United States. J Am Vet Med Assoc 2005; 15: 1604-1607.
2 Buote N, Fusco J, Radasch R. Age, tibial plateau angle, sex, and weight as risk factors for contralateral rupture of the cranial cruciate ligament in Labradors. Vet Surg 2005; 38: 481-489.
3 Fuller MC, Hayashi K, Bruecker A. et al. Evaluation of the radiographic infrapatellar fat pad sign of the contralateral stifle joint as a risk factor for subsequent contralateral cranial cruciate ligament rupture in dogs with unilateral rupture: 96 cases (2006-2007). J Am Vet Med Assoc 2014; 244: 328-338.
4 Bleedorn JA, Greuel EN, Manley PA. et al. Synovitis in dogs with stable stifle joints and incipient cranial cruciate ligament rupture: a cross-sectional study. Vet Surg 2011; 40: 531-543.
5 Grierson J, Asher L, Grainger K. An investigation into risk factors for bilateral canine cruciate ligament rupture. Vet Comp Orthop Traumatol 2011; 24: 192-196.
6 Cabrera SY, Owen TJ, Mueller MG. et al. Comparison of tibial plateau angles in dogs with unilateral versus bilateral cranial cruciate ligament rupture: 150 cases (2000-2006). J Am Vet Med Assoc 2008; 232: 889-892.
7 Hayashi K, Frank JD, Manley PA. et al. Doxycycline treatment for cruciate disease: A clinical trial in 12 dogs.. Proceedings of the European College of Veterinary Surgeons 14th Annual Scientific Meeting 2005. July 7-9 Lyon, France: 444-445.
8 Muir P, Schwartz Z, Malek S. et al. Contralateral cruciate survival in dogs with unilateral non-contact cranial cruciate ligament rupture. PLoS ONE 2011; 6: e25331
9 Hayashi K, Frank JD, Manley PA. et al. Effect of doxycycline on stifle lameness: a preliminary clinical observation in twelve dogs. Veterinary Science Development 2011; 1: e7
10 Doverspike M, Vasseur PB, Harb MF. et al. Contralateral cranial cruciate ligament rupture: incidence in 114 dogs. J Am Anim Hosp Assoc 1993; 29: 167-170.
11 Hayashi K, Manley PA, Muir P. Cranial cruciate ligament pathophysiology in dogs with cruciate disease: a review. J Am Anim Hosp Assoc 2004; 40: 385-390.
12 Muir P, Hayashi K, Manley PA. et al. Evaluation of tartrate-resistant acid phosphatase and cathepsin K in ruptured cranial cruciate ligament in dogs. Am J Vet Res 2002; 63: 1279-1284.
13 Muir P, Danova NA, Argyle DJ. et al. Collagenolytic protease expression in cranial cruciate ligament and stifle synovial fluid in dogs with cranial cruciate ligament rupture. Vet Surg 2005; 34: 482-490.
14 Breshears LA, Cook JL, Stoker AM. et al. Detection and evaluation of matrix metalloproteinases involved in cruciate ligament disease in dogs using multiplex bead technology. Vet Surg 2010; 39: 306-314.
15 Riitano MC, Pfister H, Engelhardt P. et al. Effects of stimulus with proinflammatory mediators on nitric oxide production and matrix metalloproteinase activity in explants of cranial cruciate ligaments obtained from dogs. Am J Vet Res 2002; 63: 1423-1428.
16 Boland L, Danger R, Cabon Q. et al. MMP-2 as an early synovial biomarker for cranial cruciate ligament disease in dogs. Vet Comp Orthop Traumatol 2014; 27: 210-215.
17 Muir P, Oldenhoff WE, Hudson AP. et al. Detection of DNA from a range of bacterial species in the knee joints of dogs with inflammatory knee arthritis and associated degenerative anterior cruciate ligament rupture. Microb Pathog 2007; 42: 47-55.
18 Bhandal J, Hayashi K, Kim SY. et al. Detection of bacterial DNA by PCR in dogs with stifle pathology. Vet Surg 2013; 42: 814-818.
19 Boothe DM. Antimicrobial drugs.. In: Boothe DM.. editor. Small animal clinical pharmacology and therapeutics. 1st edition Philadelphia, PA: Saunders; 2001: 152-154. and 169-170
20 Yu Jr LP ., Smith Jr GN ., Brandt KD. et al. Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline. Arthritis Rheum 1992; 35: 1150-1159.
21 Jauernig S, Schweighauser A, Reist M. et al. The effects of doxycycline on nitric oxide and stromelysin production in dogs with cranial cruciate ligament rupture. Vet Surg 2001; 30: 132-139.
22 Rabillard M, Danger R, Doran IP. et al. Matrix metalloproteinase activity in stifle synovial fluid of cranial cruciate ligament deficient dogs and effect of postoperative doxycycline treatment. Vet J 2012; 193: 271-273.
23 Wienke A. Frailty Models in Survival Analysis.. Boca Raton: CRC Press, Taylor & Francis Group ISBN: 13: 978-1-4200-7391-1 (eBook - PDF) 2011; 1-299.
24 Adams VJ, Campbell JR, Waldner CL. et al. Evaluation of client compliance with short-term administration of antimicrobials to dogs. J Am Vet Med Assoc 2005; 226: 567-574.
25 Duval JM, Budsberg SC, Flo GL. et al. Breed, sex, and body weight as risk factors for rupture of the cranial cruciate ligament in young dogs. J Am Vet Med Assoc 1999; 215: 811-814.
26 Whitehair JG, Vasseur PB, Willits NH. Epidemiology of cranial cruciate ligament rupture in dogs. J Am Vet Med Assoc 1993; 203: 1016-1019.
27 Krotscheck U, Nelson S, Mohammed HO. Long Term functional outcome of tibial tuberosity advancement versus tibial plateau leveling osteotomy and extracapsular repair in a heterogeneous population of dogs. American College of Veterinary Surgeons Symposium: The Surgical Summit; 2014 October 16-18; San Diego, CA, USA. Vet Surg 2014; 43: E167-177.
28 Vasseur PB, Pool RR, Arnoczky SP. et al. Correlative biomechanical and histologic study of the cranial cruciate ligament in dogs. Am J Vet Res 1985; 46: 1842-1854.
29 Comerford EJ, Tarlton JF, Wales A. et al. Ultrastructural differences in cranial cruciate ligaments from dogs of two breeds with a differing predisposition to ligament degeneration and rupture. J Comp Pathol 2006; 134: 8-16.
30 Inauen R, Koch D, Bass M. et al. Tibial tuberosity conformation as a risk factor for cranial cruciate ligament rupture in the dog. Vet Comp Orthop Traumatol 2009; 22: 16-20.
31 Duerr FM, Duncan CG, Savicky RS. et al. Risk factors for excessive tibial plateau angle in large-breed dogs with cranial cruciate ligament disease. J Am Vet Med Assoc 2007; 231: 1688-1691.
32 Morris E, Lipowitz AJ. Comparison of tibial plateau angles in dogs with and without cranial cruciate ligament injuries. J Am Vet Med Assoc 2001; 218: 363-366.
33 Colborne GR, Innes JF, Comerford EJ. et al. Distribution of power across the hind limb joints in Labrador Retrievers and Greyhounds. Am J Vet Res 2005; 66: 1563-1571.
34 Wikipedia contributors. List of most popular dog breeds [Internet]. Wikipedia, The Free Encyclopedia; 2015 August 8, 08:14 UTC [cited 2015 February 1] Available from: http://en.wikipedia.org/wiki/List_of_most_popular_dog_breeds
35 Chuang C, Ramaker MA, Kaur S. et al. Radiographic risk factors for contralateral rupture in dogs with unilateral cranial cruciate ligament rupture. PLoS One. 2014; 25: e 106389
36 Von Pfeil DJ, Edwards MR, Nelson NC. Handling of the tibial muscle envelope in tibial plateau leveling osteotomy - to elevate or not? A clinical study of 40 dogs. Vet Comp Orthop Traumatol 2013; 26: 392-398.
37 Stang A, Hense HW, Jöckel KH. et al. Is it always unethical to use a placebo in a clinical trial?. PLoS Med 2005; 2: e72
38 Nazarali A, Singh A, Weese JS. Perioperative administration of antimicrobials during tibial plateau leveling osteotomy. Vet Surg 2014; 43: 966-971.
39 Fitzpatrick N, Solano MA. Predictive variables for complications after TPLO with stifle inspection by arthrotomy in 1000 consecutive dogs. Vet Surg 2010; 39: 460-474.
40 Solano MA, Danielski A, Kovach K. et al. Locking plate and screw fixation after tibial plateau leveling osteotomy reduces postoperative infection rate in dogs over 50 kg. Vet Surg 2015; 44: 59-64.