Canine Cranial Cruciate Ligament Rupture Research Articles

Investigation of Variables Associated with Surgical Site Infection following the Management of Canine Cranial Cruciate Ligament Rupture with a Lateral Fabellotibial Suture.

This study investigated variables associated with surgical site infection (SSI) in dogs with cranial cruciate ligament rupture managed with stifle joint examination and lateral fabellotibial suture stabilization. A retrospective study of dogs that had stifle arthroscopy, stifle arthrotomy, or a combination of both, followed by lateral fabellotibial suture stabilization for cranial cruciate ligament rupture. All cases had a minimum follow-up of 90 days. Lameness grades were recorded preoperatively, and at 6-week and final follow-up. One hundred fifty procedures in 130 dogs met the inclusion criteria. Overall, SSI rate was 17.3% and removal of the lateral fabellotibial suture was performed in 53% of SSI. Multivariable analysis showed significant association between SSI and bodyweight (p = 0.013), and induction using propofol (p = 0.029). Multilevel ordinal logistic regression analysis showed a greater proportion of dogs had a higher lameness grade at 6-week (p = 0.021) and final follow-up (p = 0.002) assessments in the infected compared with non-infected dogs. Our study demonstrated a higher SSI incidence than previously reported in dogs undergoing a lateral fabellotibial suture for cranial cruciate ligament rupture. Bodyweight and induction with propofol were identified as significant risk factors for postoperative SSI. Owners could be advised of an increased SSI risk in larger dogs and consideration should be given to selection of induction agent. Dogs that develop an SSI have a worse lameness grade at 6-week and final follow-up.

In canine cranial cruciate ligament rupture is outcome following TPLO improved compared with lateral suture?

PICO question
 In dogs over 15 kg, with cranial cruciate ligament rupture is there evidence of improved outcome following tibial plateau levelling osteotomy or lateral fabellotibial suture?
 Clinical bottom line
 Although the evidence is not conclusive, the literature reviewed here suggests that tibial plateau levelling osteotomy (TPLO) results in superior limb function and owner satisfaction compared to placement of a lateral fabellotibial suture (LFS).
 There is currently insufficient evidence to determine if there is a difference in complication rates or osteoarthritis (OA) development following TPLO or LFS.

Synovial fluid lubricin increases in canine cruciate ligament rupture

Purpose: Loss of effective joint lubrication contributes to cartilage breakdown in post-traumatic osteoarthritis (PTOA). There are two major lubricants in synovial fluid: hyaluronic acid (HA), which confers viscous properties, and lubricin, which enables low friction boundary lubrication. The absence of functional lubricin results in severe, early onset of polyarthropathy in humans and lubricin knockout mice. Several studies have reported that lubricin decreases in experimental rodent models of PTOA; however, it is unclear whether similar losses are observed in naturally occurring, large animal models of joint injury and osteoarthritis (OA) progression. Naturally occurring cranial cruciate ligament rupture in the dog closely mimics anterior cruciate ligament injury in humans with respect to the development of joint instability and secondary osteoarthritic changes, making this a valuable translational model to study the role of lubricin in PTOA. Here, we investigated lubricin and pro-inflammatory cytokines in canine cranial cruciate ligament rupture (RCCL) and the relationship of these molecules to radiographic evidence of osteoarthritis. Methods: Stifle synovial fluid samples from 30 adult dogs (age 2.5-11 yrs; n=13 neutered males, 14 neutered females, 2 intact males and 1 intact female) sustaining rupture of the cranial cruciate ligament were obtained at the time of surgery and stored in liquid N2 for biobanking purposes. Medical histories, physical examination, and surgical data were obtained from patient medical records, including age, duration of injury prior to presentation, presence of concurrent meniscal injury and whether or not meniscectomy was performed. Stifle synovial fluid samples were also obtained from a cohort of 13 clinically healthy research Beagles (age 2.5 to 5 yrs; intact males). Synovial fluid lubricin levels were quantified using a lubricin sandwich ELISA, and pro-inflammatory cytokines (IL-2, IL-6, IL-8, TNF-α) were measured using a multiplex cytokine panel (Meso Scale Diagnostics, LLC). Pre-operative lateromedial and craniocaudal stifle radiographs were randomized, blinded and scored by two independent observers. A stifle OA scoring system was modified slightly from Innes et al, which evaluated: joint effusion, osteophytosis, intra-articular mineralization, and a global OA score. T-tests were used to analyze biochemical differences between healthy and RCCL joints (α=0.05), and Spearman’s rank-order correlations were performed to determine associations between lubricin and pro-inflammatory cytokines. Results: Lubricin concentrations were nearly six-fold greater in RCCL joints (mean ± SEM = 0.07 ± 0.02 mg/mL) as compared to healthy controls (mean ± SEM = 0.68 ± 0.06mg/mL) (Fig 1A), and this elevation persisted for more than one year after injury (Fig 1B). No significant differences in synovial fluid pro-inflammatory cytokines (IL-2, IL-6, IL8, and TNF-α) were detected between RCCL and healthy joints; however, pro-inflammatory cytokines were all correlated with one another. Duration of injury did not correlate with lubricin concentrations (Spearman’s test, ρ=-0.0205). Lubricin concentrations correlated with the presence of OA, but no associations between the severity of radiographic OA and lubricin levels were detected. Additionally, lubricin levels were not correlated with any of the pro-inflammatory cytokines measured (Table 1). Conclusions: Lubricin was significantly and persistently elevated in joints with RCCL. Interestingly, although pro-inflammatory cytokines in synovial fluid levels were correlated with one another, lubricin levels did not correlate with any pro-inflammatory cytokines. A limitation of this study is that dogs presented with varying degrees of OA and durations of injury prior to surgery, with many animals presenting with a history of lameness or injury of longer than one month. However, to our knowledge, this is the first study to demonstrate that synovial fluid lubricin is significantly increased in a translational, large animal model of knee joint instability. Lubricin may have value as a potential biomarker for knee instability (and perhaps osteoarthritis progression). Lubricin may also be elevated as a protective mechanism in joint instability; however, more mechanistic studies are required to determine the role of elevated synovial fluid lubricin in knee injuries.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Intraobserver and interobserver agreement on the radiographical diagnosis of canine cranial cruciate ligament rupture

Even though radiography is one of the most frequently used imaging techniques for orthopaedic disorders, it has been demonstrated that the interpretation can vary between assessors. As such, the purpose...

Combining a joint health supplement with tibial plateau leveling osteotomy in dogs with cranial cruciate ligament rupture. An exploratory controlled trial

Canine cranial cruciate ligament rupture (CrCLR) is a very common pathology. Surgical stabilization is the first choice treatment, although it does not fully eliminate the increased risk of osteoarthritis. This preliminary study was carried out to explore whether a newly formulated joint health supplement would benefit metabolic, clinical and radiographic changes in dogs with CrCLR surgically treated with tibial plateau leveling osteotomy (TPLO). Besides chondroitin sulfate and glucosamine hydrochloride, the studied supplement contained anti-inflammatory and antioxidant ingredients, the main ones being N-palmitoyl-D-glucosamine (Glupamid®) and quercetin. It was thus intended to target not only chondrodegenerative components of osteoarthritis, but also post-injury inflammatory response and oxidative stress of joint tissues. Thirteen dogs underwent TPLO and were randomly allocated to treatment (n=6) and control groups (n=7), the former receiving the joint supplement for 90 days. Lameness and radiographic osteoarthritis changes were scored before (i.e., baseline) and at 30 and 90 days post-surgery. Synovial fluid samples were collected from injured stifles at the same time points. Levels of representative metabolites were measured by proton nuclear magnetic resonance spectroscopy in a blinded fashion. In the metabolomic analysis, special attention was paid to lactate, due to its emerging recognition as a key marker of inflammation. In the last time period (from the 30th to the 90th day), lameness improved by a factor of 2.3 compared to control dogs. No significant difference was observed in the radiographic osteoarthritis score between groups. In the first postoperative month, lactate and creatine levels significantly dropped in treated compared to control dogs. Compared to surgery alone, combining the joint supplement with TPLO resulted in a trend to a better clinical outcome in the later time interval but did not influence osteoarthritis radiographic progression. A significantly better rebalance of joint microenvironment in the early time interval (baseline – 30 days) was shown by metabolomic analysis, thus suggesting that the study supplement could limit ongoing inflammatory responses.

Autologous Bone Marrow-Derived Mesenchymal Stem Cells Modulate Molecular Markers of Inflammation in Dogs with Cruciate Ligament Rupture.

Mid-substance rupture of the canine cranial cruciate ligament rupture (CR) and associated stifle osteoarthritis (OA) is an important veterinary health problem. CR causes stifle joint instability and contralateral CR often develops. The dog is an important model for human anterior cruciate ligament (ACL) rupture, where rupture of graft repair or the contralateral ACL is also common. This suggests that both genetic and environmental factors may increase ligament rupture risk. We investigated use of bone marrow-derived mesenchymal stem cells (BM-MSCs) to reduce systemic and stifle joint inflammatory responses in dogs with CR. Twelve dogs with unilateral CR and contralateral stable partial CR were enrolled prospectively. BM-MSCs were collected during surgical treatment of the unstable CR stifle and culture-expanded. BM-MSCs were subsequently injected at a dose of 2x106 BM-MSCs/kg intravenously and 5x106 BM-MSCs by intra-articular injection of the partial CR stifle. Blood (entry, 4 and 8 weeks) and stifle synovial fluid (entry and 8 weeks) were obtained after BM-MSC injection. No adverse events after BM-MSC treatment were detected. Circulating CD8+ T lymphocytes were lower after BM-MSC injection. Serum C-reactive protein (CRP) was decreased at 4 weeks and serum CXCL8 was increased at 8 weeks. Synovial CRP in the complete CR stifle was decreased at 8 weeks. Synovial IFNγ was also lower in both stifles after BM-MSC injection. Synovial/serum CRP ratio at diagnosis in the partial CR stifle was significantly correlated with development of a second CR. Systemic and intra-articular injection of autologous BM-MSCs in dogs with partial CR suppresses systemic and stifle joint inflammation, including CRP concentrations. Intra-articular injection of autologous BM-MSCs had profound effects on the correlation and conditional dependencies of cytokines using causal networks. Such treatment effects could ameliorate risk of a second CR by modifying the stifle joint inflammatory response associated with cranial cruciate ligament matrix degeneration or damage.

Efficacy of Intraarticular Administration of Hyaluronic Acid in Osteoarthritis After Surgical Correction of Canine Cranial Cruciate Ligament Rupture

Efficacy of Intraarticular Administration of Hyaluronic Acid in Osteoarthritis After Surgical Correction of Canine Cranial Cruciate Ligament Rupture

Development and Efficacy of a Canine Pelvic Limb Model Used to Teach the Cranial Drawer and Tibial Compression Tests in the Stifle Joint

Canine cranial cruciate ligament rupture (CCLR) is the most common cause of pelvic limb lameness in dogs. CCLR results in palpable stifle instability secondary to cranial translation of the tibial relative to the femur, and it can be diagnosed during the orthopedic exam using the cranial drawer test (CDT) and tibial compression test (TCT). Accurate diagnosis of CCLR depends on the efficacy in performing these tests. In this study, two three-dimensional canine pelvic limb models were developed: one simulating a normal stifle and one simulating CCLR. Thirty-eight veterinary student participants answered questionnaires and performed both the CDT and TCT on a randomly assigned model. Twenty-one participants also manipulated the models one week later to assess skill retention in the short term. Mean levels of reported confidence in diagnosing CCLR and finding anatomic landmarks for CDT/TCT were significantly higher following model manipulation. Nearly all participants reported that they desired a model for teaching the diagnosis of CCLR. Most participants (92.5%) felt that the tested model would be useful for teaching CCLR diagnosis. Accuracy in diagnosing CCLR with the TCT significantly improved over time. Participant response indicated that while the tested model was effective and desirable, an ideal model would be more durable and lifelike. Further studies are needed to evaluate the developed models' effectiveness for teaching CCLR diagnosis compared to traditional teaching methods.

Degenerative changes of the cranial cruciate ligament harvested from dogs with cranial cruciate ligament rupture.

Degenerative cranial cruciate ligament (CCL) rupture is characterized histologically by degenerating extracellular matrix (ECM) and chondroid metaplasia. Here, we describe the progression of chondroid metaplasia and the changes in the expression of ECM components in canine CCL rupture (CCLR). CCLs from 26 stifle joints with CCLR (CCLR group) and normal CCLs from 12 young beagles (control group) were examined histologically and immunohistochemically for expression of type I (COLI), type II (COLII), type III collagen (COLIII) and Sry-type HMG box 9 (SOX9). Cell density and morphology of CCLs were quantified using hematoxylin–eosin staining. The percentage of round cells was higher in the CCLR group than in controls. COLI-positive areas were seen extensively in the connecting fibers, but weakly represented in the cytoplasm of normal CCLs. In the CCLR group, there were fewer COLI-positive areas, but many COLI-positive cells. The percentages of COLII-, COLIII- and SOX9-positive cells were higher in the CCLR group than in controls. The number of spindle cells with perinuclear halo was high in the CCLR group, and most of these cells were SOX9-positive. Deposition of COLI, the main ECM component of ligaments, decreased with increased COLIII expression in degenerated CCL tissue, which shows that the deposition of the ECM is changed in CCLR. On the contrary, expression of SOX9 increased, which may contribute to the synthesis of cartilage matrix. The expression of COLII and SOX9 in ligamentocytes showed that these cells tend to differentiate into chondrocytes.

Effect of doxycycline on contralateral canine cranial cruciate ligament rupture. A prospective randomized clinical trial in 69 dogs.

To evaluate whether doxycycline administered to dogs with unilateral cranial cruciate ligament rupture (Uni-CCLR) would decrease the risk of contralateral-CCLR (Co-CCLR). To evaluate predictors for Co-CCLR survival. To evaluate if a predisposition of Labrador Retrievers to Co-CCLR exists when compared to other breeds. 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). 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). At the dose regimen investigated doxycycline does not decrease the risk for Co-CCLR.

Two-hole extracapsular technique for the repair of canine cranial cruciate ligament rupture in thirty-eight dogs

Extracapsular technique with lateral fabellar suture (LFS) is one of the commonest surgical techniques for canine cranial cruciate ligament (CRCL) rupture. Among LFS methods, parallel double holes in the tibia are the most effective for the repair of canine stifle joint. The aim of this study was to evaluate the effectiveness of two-hole LFS for canine CRCL rupture. We retrospectively evaluated the outcome of canine CRCL rupture treated with two-hole LFS technique performed by two surgeons from October 2011 to September 2013. Breeds included Beagle (n=5), Yorkshire terrier (n=5), German shepherd (n=4), and so on. Mean body weight was 14.0±11.6 kg (&amp;gt;10 kg: n=16, &amp;lt;10 kg: n=22). Body condition score (5 scales) was as follows: 1 (n=0), 2 (n=1), 3 (n=18), 4 (n=18), and 5 (n=1). There were 18 males [neutered (n=11)] and 20 females [spayed (n=12)]. Mean age was 83.4±44.8 months (&amp;gt;12 months: n=35, &amp;lt;12 months: n=3). The type of rupture was partial (n=17) and complete (n=21). The affected site was right (n=20), left (n=18), and bilateral (n=4). Rehabilitation after operation was needed in 8 cases. There were 12 cases of previous medial patellar luxation operation, and 6 cases of opposite site CRCL surgery. Start of weight bearing and resolution of extension function was on day 1 (n=30), day 2 (n=0), and after day 2 (n=8). There was no evidence of surgical site infection/inflammation in any cases. The results of this study showed that two-hole LFS is an easy and effective technique for the repair of canine CRCL.

Genetic basis of cranial cruciate ligament rupture (CCLR) in dogs

Cranial Cruciate Ligament rupture (CCLR) is one of the most common forms of lameness in dogs and is analogous to rupture of the anterior cruciate ligament in humans, for which it can serve as a model. As there is a strong breed-related predisposition to CCLR in dogs, a study was undertaken to consider putative genetic components in susceptible dog breeds. A candidate gene, single nucleotide polymorphism (SNP) genotyping approach using MALDI-TOF mass spectrometry (Sequenom Ltd) was designed to investigate several CCLR-susceptible dog breeds and identify CCLR-associated genes/gene regions that may confer susceptibility or resistance. A meta-analysis was performed using the breed case/control candidate gene data to identify SNP associations that were common to the whole cohort of susceptible dogs. We identified SNPs in key genes involved in ligament strength, stability and extracellular matrix formation (COL5A1, COL5A2, COL1A1, COL3A1, COL11A1, COL24A1, FBN1, LOX, LTBP2) which were significantly associated with CCLR susceptibility across the dog breeds used in this study. These SNPs could have an involvement in CCLR due to a detrimental effect on ligament structure and strength. This is the first published candidate gene study that has revealed significant genetic associations with canine CCLR.

Risk of canine cranial cruciate ligament rupture is not associated with the major histocompatibility complex

To investigate the association of the major histocompatability (MHC) class II allele haplotype frequencies with the diagnosis of cranial cruciate ligament (CCL) rupture in two breeds of dog. DNA samples from populations of Labrador Retrievers and Golden Retrievers with CCL rupture and general populations of the same breeds were characterised for three DLA class II loci (DRB1*, DQA1* and DQB1*) alleles using sequence-based typing or reference strand-mediated conformation analysis. Although distinct differences in haplotype types, frequencies and homozygozity were observed between the two breeds, no disease specific association could be identified for the development of the CCL rupture within either population. The risk for developing CCL rupture was not associated with DLA haplotype group(s) in Labrador Retrievers or Golden Retrievers, thus the hypothesis that there is an autoimmune basis to CCL rupture was not supported.

Stromelysin Activity in Canine Cranial Cruciate Ligament Rupture

SummaryThe goal of our study was to compare values of stromelysin activity in stifle joint tissues, from dogs with osteoarthritis, secondary to naturally acquired cranial cruciate ligament (CCL) rupture and from a control population.Twenty four dogs (CCL group) with osteoarthritis (OA), secondary to CCL rupture, were evaluated. The control groups consisted of 22 beagles (control #1) and 14 dogs (control #2) without CCL rupture. Articular cartilage, synovial membrane and CCL tissue specimens were harvested during operations in the CCL group and immediately following euthanasia in the control groups. The specimens were submitted for routine histology and for explant tissue cultures.Stromelysin activity was measured in the supernatant of explanted cultures. The results of stromelysin concentrations were reported as mean ± STD and compared to histological cartilage degeneration, synovial membrane inflammation and ligament changes. Stromelysin activity in cartilage explants of the CCL group (70 ± 82.5 U/g) was significantly higher when compared to the control #1 (4.2 ± 6.3 U/g) and control #2 (15 ±10 U/g) groups. The synovial membrane explant cultures of the CCL group produced less stromelysin compared to the control group. Whereas ligament cultures showed a tendency toward higher activity of stromelysin when compared to the control groups. An association between the severity of histological OA changes in the cartilage and stromelysin activity in cartilage explants was demonstrated. We conclude that dogs with OA, secondary to naturally acquired CCL rupture, release higher stromelysin levels in articular cartilage and cranial cruciate ligament explant cultures when compared to the controls. Our results indicate that stromelysin production in articular cartilage is related to the severity of OA.Stromelysin, one of the major metalloproteinases degrades articular cartilage mainly by cleavage of proteoglycans. Increased levels of stromelysin could be demonstrated in cartilage of stifle joints from dogs with naturally acquired cranial cruciate ligament rupture using a radioimmunoassay. There was an indication in this study that the activity of stromelysin is associated with the severity of osteoarthritic changes.Presented in part at the European College of Veterinary Surgeons Annual Scientific Meeting, Pörtschach-Austria, June 1998.

A New Technique of Extracapsular Restoration with a Tie Made of Ethylene Tetrafluoroethylene (ETFE) for Rupture of the Cranial Cruciate Ligament in Dogs.

A new extracapsular technique for repair of canine cranial cruciate ligament rupture using an ethylene tetrafluoroethylene (ETFE) tie was presented. Eighteen dogs (body weight: 6.0-46 kg) with this problem were used for this study. The advantages of this method were 1) the operation was easily performed. 2) Joint could be stabilized by proper fixation with microadjustment during operation. 3) This method presented less surgical invasion than the intracapsular one, since wide incision was not conducted over peripheral tissue of the stifle joint.

An Evaluation of Three Different Cranial Cruciate Ligament Surgical Stabilization Procedures As They Relate to Postoperative Meniscal Injuries

SummaryCranial cruciate ligament (CrCL) rupture is the most commonly diagnosed stifle condition in the dog. Meniscal injury, in conjunction with CrCL rupture is also common in both man and dogs. There is a growing concern regarding meniscal injuries, whether unrecognized at the time of CrCL surgical stabilization or subsequent to stabilization, and the relationship to poor postoperative functional outcome. However, current literature is not specific as to an actual number of dogs subsequently requiring a second arthrotomy/meniscectomy.Three different CrCL stabilization operations in dogs were compared, retrospectively, for the occurrence of post-operative meniscal damage requiring a second arthrotomy and meniscectomy. Additional information concerning: signalment, weight, history of injury, CrCL ruptured, surgeon, type of CrCL rupture and amount of arthritis present was recorded in 665 cases. It was found that 13.8% of the stifles at risk (i. e. those stifles that did not have the meniscus removed at the time of initial surgical stabilization) returned for a second arthrotomy/meniscectomy. A significant difference in outcome was not found between the results when initially performed by different surgeons. The number of dogs which returned for a second arthrotomy/ meniscectomy whose weight were ≤ 15 kg was significant, when compared to the total number of dogs considered at risk for this weight range. There was a significantly lower rate of return, in those dogs at risk, which had received fibular head transposition stabilization.A retrospective study of 665 canine cranial cruciate ligament rupture cases documents the incidence (13.8%) of those dogs requiring a second arthrotomy, and subsequent meniscectomy, after one of three initial surgical stabilization procedures. Of the three procedures, the fibular head transposition technique had a significantly lower return rate requiring subsequent meniscectomy.