Systematic Review of Surgical Treatments for Cranial Cruciate Ligament Disease in Dogs

Introduction

Cranial cruciate ligament (CCL) disease is the most common cause of pelvic limb lameness and stifle joint osteoarthritis in dogs.^1,2 Although its etiology is not completely understood, it is likely multifactorial, and considered to be a degenerative process, commonly affecting both pelvic limbs.^2–4 The socioeconomic impact of CCL disease is significant: in 2003, it was estimated that pet owners in the US annually spent an estimated $1 billion in CCL disease treatment.⁵ CCL disease may be treated either medically or surgically, but there are few data comparing the two treatment paradigms. Surgical treatment is frequently recommended for more rapid stifle joint stabilization, meniscal treatment, and an earlier return to clinical function.² Numerous surgical treatments have been described to stabilize the stifle joint either through the addition of bioscaffolds, stabilizing sutures, or with tibial osteotomies that change stifle joint kinematics. Currently, the most commonly performed surgical procedures include the lateral extracapsular suture (LS) stabilization, tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA).² Reportedly, each of those surgical procedures has a high success rate of improving limb function and decreasing lameness.^2,3,6–10 Direct comparisons between treatments are scarce; therefore, the recommended treatment is frequently determined by the clinician’s preference and experience level with a procedure or therapy.^2,11

A systematic review of the scientific literature describing surgical treatments for CCL disease was performed up to and including August 2004. At that time, most studies provided a low level of evidence.¹² Therefore, despite 28 publications that met the inclusion criteria of that study, there was not enough evidence to determine the superiority of one procedure over another. Since that time, there has been an increased awareness of evidence-based medicine, study design, and interpretation of study results in veterinary medicine. Additionally, several new surgical procedures have been introduced and dozens of new scientific articles have been published. It is possible that this additional information may allow for different conclusions to be made regarding the relative superiority of one surgical treatment.

The aim of this contemporary systematic review of the scientific peer-reviewed literature was to answer an a priori question whether one surgical procedure for CCL disease could consistently return a dog to normal clinical function. The study authors assumed the null hypothesis that the best available evidence does not support a surgical procedure’s ability to consistently achieve normal clinical function in dogs with CCL disease.

Materials and Methods

Prior to beginning the systematic review, the methodology was defined and a protocol was outlined. The a priori question defined for this systematic review was, “Is there a surgical procedure that will allow a consistent return to normal clinical function in dogs with CCL disease and is that procedure superior to others?” A “consistent return to normal clinical function” was defined as >90% of the treated population returning to the activity level of a dog unaffected by pelvic limb disease based on the reported outcome assessments in the study. Studies reporting kinetic data were compared with published values on normal dogs ambulating at similar speeds over similar surfaces (e.g., force plate or pressure mat).^13–15

Peer-reviewed scientific studies on dogs with naturally occurring CCL disease published in the English language were included. At least 6 mo postoperative follow-up was required. In addition, only single session surgical therapy was evaluated. If staged bilateral surgeries were performed, data from the first operated limb was evaluated, provided there was >6 mo time period between the first and second operated stifle. Abstracts, scientific proceedings, and book chapters were excluded. In addition, studies were excluded if either follow-up time or treatment outcome could not be determined, if the dogs underwent treatment of >1 ligament injury concomitantly or if treatment was described for traumatic CCL rupture.

A systematic review of the scientific literature was performed up to and including September 2013. Online databases including PubMed, Medline, Google, Google Scholar, CAB Abstracts, and the Veterinary Information Network were searched in addition to specific veterinary journals including the Journal of the American Animal Hospital Association, the Journal of the American Veterinary Medical Association, Veterinary Surgery, the Veterinary Journal, Vet Record, the Journal of Small Animal Practice, and Veterinary Comparative Orthopedics and Traumatology. Search terms included the following with both “canine” and “dog” descriptors: cranial cruciate ligament, CCL, tibial plateau leveling, TPLO, lateral suture, extracapsular suture, tibial tuberosity advancement, TTA, intra-articular, stifle surgery, tight rope, cruciate ligament over the top, cruciate ligament fascia lata, cruciate ligament fibular, cruciate ligament fracture, cruciate ligament carbon fiber, cruciate ligament fabella, cruciate ligament autograft, cruciate ligament allograft, ligament meniscal, cruciate ligament force plate, cruciate ligament kinematic, cranial cruciate ligament treatment, and cranial cruciate ligament therapy. The sources were searched using the aforementioned keywords and titles of manuscripts that met the inclusion criteria were identified and recorded. The abstract was then read and exclusions were noted. If the abstract description met the inclusion criteria then the full manuscript was obtained and evaluated. If information reported in the full manuscript met the inclusion criteria then the study was included in the final analysis.

Those studies were evaluated by the primary authors (M.B. and S.B.) and compared in regard to surgical treatment, study design, and evidence classification on a scale of 1–4, from the strongest to the weakest evidence, relative to the primary research question as described in Table 1.¹⁶ In addition, the number of treated dogs, dog size (small, <13 kg; large, >27 kg), follow-up time, type of outcome measurements (force plate data, goniometry, orthopedic examination, visual gait observation, and owner questionnaire) were determined, and whether >90% of treated animals were either reported or described to return to normal function after the surgical treatment. The quality of evidence was weighted based on the type of outcome data (A–C, from strongest to weakest) as described in Table 2.

TABLE 1 Schematic Used to Grade the Quality of Evidence in This Systematic Review*

*This scale is for evaluating therapeutic outcomes. Adapted from Wright (2003).¹⁶

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TABLE 2 Schematic Used to Grade the Type of Outcome Assessments in This Systematic Review

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The relative importance of the findings for each procedure was weighted based on the type of studies and the outcome measurements they used. Prospective, blinded, and randomized studies (level 1 evidence) and studies with objective outcome data (level A data) were given the highest evidentiary value and retrospective case series (level 4 evidence) and studies with subjective or unvalidated outcomes (level C data) were given lower evidentiary value.

Results

The initial search revealed 444 manuscripts, and 410 were excluded. The most common indications for exclusion were for articles not describing naturally occurring CCL disease (n = 162), studies with <6 mo postoperative follow-up (n = 96), articles not related to CCL (n = 66), follow-up unable to be determined (n = 31), and studies in which the outcomes were not able to be determined for the population of dogs that might be included in the analysis (n = 30).

After reviewing potential abstracts and full manuscripts, 34 met the inclusion criteria and were included in the analysis. A summary of the included studies and surgical procedures is presented in Table 3. Of the included studies, 2 provided level 1 evidence, 6 provided level 2 evidence, 6 provided level 3 evidence, and 20 provided level 4 evidence relative to the study question.^17–50 Eleven surgical procedures were evaluated, including TPLO (n = 14), LS (n = 13), TTA (n = 6), intracapsular repair (n = 4), cranial tibial closing wedge ostectomy (CTWO; n = 2), tightrope (n = 2), and one study evaluating each of the following: total knee replacement, proximal intra-articular osteotomy, fibular head transposition, biceps femoris transposition, proximal tibial epiphysiodesis, and a combination of TPLO and CTWO. One study combined the assessment of all osteotomies into one outcome group, and data from that group was not considered in the analysis.²⁷ Ten studies evaluated >1 surgical procedure.^{18–21,23,25–29} Follow-up time reported ranged from 6 to 60 mo and evaluated the outcome in groups of dogs ranging from 5 to 253 animals. Seven studies reported the outcome of dogs weighing <13 kg.^{22,27,28,30,44,45,47}

TABLE 3 Distribution of Evaluated Studies in Regard to the Evaluated Procedure, the Level of Evidence It Provided, and the Assessment of Outcome from the Procedure

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Eleven of the included studies used level A data.^{17–20,23,24,35,39,41,43,50} Two reported level B data.^21,30 Twenty-one reported level C data.^{22,25–29,31–34,36–38,40,42,44–49} The distribution of data and evidence levels is summarized in Figure 1. The most common outcome measurements were interview/questionnaire (n = 21; 61.8%), visual gait observation (n = 14; 41.2%), force plate gait evaluation (n = 12; 34.3%), and thigh circumference (n = 10; 29.4%). Twenty studies (58.8%) were prospective in nature.^{17–24,32,35–39,41–43,47,49,50} One study was blinded.¹⁸ Three studies were randomized.^17,18,24

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Of the 14 studies reporting on the outcome of TPLO, 7 reported a return to normal clinical function, and 4 of those used level A data.^18,19,23,39 Four of the 13 studies reporting the outcome of LS and 1 of the 6 studies reporting the outcome of TTA reported >90% of animals returned to normal clinical function. Total knee replacement, the proximal tibial intra-articular osteotomy, and the biceps femoris transposition were reported to have >90% of animals return to normal clinical function. A return to normal clinical function was not reported for >90% of the dogs in the studies describing the outcome of the tightrope, CTWO, intracapsular repair, fibular head transposition, proximal tibial epiphysiodesis, and the TPLO/CTWO combination.

Ten studies evaluated more than one surgical procedure, and four studies compared three surgical procedures.^20,25,27,28 Four studies compared TPLO and LS.^18–20,23 Two studies compared TPLO and the tightrope procedure.^21,25 Two studies compared TPLO and CTWO.^26,29 Of the studies that compared TPLO and LS, two studies (level 1 and 2 evidence, level A data) found that the TPLO, but not the LS, allowed a return to normal clinical function.^18,19 One study (level 2 evidence, level A data) found that both the TPLO and LS allowed a return to normal clinical function.²³ Another study (level 2 evidence, level A data) found that neither procedure allowed a normal return to function.²⁰

Taken together, the evidence most strongly supports the TPLO as a procedure that allows a dog with naturally occurring unilateral CCL disease to return to normal clinical function. In addition, it provides evidence that functional recovery in the intermediate postoperative time period is superior following TPLO compared with LS. There was insufficient data to adequately evaluate other surgical procedures.

Discussion

CCL disease results in pain, lameness, osteoarthritis, stifle instability, and subsequent meniscal injury in dogs. Although surgical therapy has been the primary treatment of this condition, numerous procedures are currently performed in clinical practice, and it is unclear if one surgical procedure results in a better clinical outcome. This systematic review allowed a rigorous and explicit means of identifying, appraising, and synthesizing historical and contemporary peer-reviewed data on all treatments and clinical outcomes of dogs with CCL disease. Despite a large number of published scientific reports, relatively few met the inclusion criteria. Many of those studies offered high-quality evidence and, therefore, allowed assessments of some procedures to be made. Although the data were not homogenous, the strength of the evidence evaluated in this study most strongly supports the ability of the TPLO in the ability to dogs to return to normal function postoperatively. The study authors’ hypothesis was, therefore, rejected. The evidence also provided strong evidentiary support that functional recovery in the intermediate postoperative time period was superior following TPLO compared with LS. There was insufficient data to adequately evaluate other surgical procedures.

The controversy over what surgical procedure is the best for an individual dog with CCL disease is not new. Since the first surgical procedure was described, there have been >60 variations of procedures used to stabilize the stifle joint. Despite the high number of procedures, there are few studies reporting intermediate- to long-term outcome and even fewer studies comparing one procedure to another. The culture of surgeons strongly values personal experience, and the identified evidence supports that theory because the predominant form of research was observational case series, resulting in the preponderance of studies with level 4 evidence and level C data. Unfortunately, although the evidence is useful, this type of study cannot resolve clinical controversies because it is limited by confounding variables that decreases the evidentiary value.^51–58 The only study design that can determine a causal interference is a randomized, controlled clinical trial, and there was only one such study included in this systematic review.¹⁸

There was mixed evidence on the clinical outcome for several of the procedures. This is not surprising because there were variable methodologies and outcome measurements used in the included studies, including visual gait evaluation at a walk or trot, owner impression, objective force plate analysis. Even within a singular outcome assessment, the interpretation and clinical implications may be variable. For example, while 21 studies used either an owner questionnaire or interview as an outcome assessment, the type of information gained from the questionnaire, the timing relative to surgery, and the method of obtaining that information may greatly influence both the outcome and the assessment.⁵⁹ Unless validated questionnaires are used, comparisons between studies are not reliable. Similarly, there may be difficulties directly comparing the outcomes with objective outcome data such as kinetics. As such, data may vary based on dog conformation, speed, and the gaiting conditions of the animal. Mild lameness is more easily detected at a trotting gait compared with a walking gait; therefore, studies that evaluated dogs while trotting may be more sensitive at identifying abnormalities.⁶⁰

All evidence is valuable, but the studies with the highest evidentiary value are prospective, blinded, randomized clinical trials. The awareness of that concept and the principle of evidence-based medicine have infiltrated veterinary medicine over the past decade, and that is reflected in the study design and evidence level of the more recent studies. The first prospective, randomized, controlled clinical trial comparing two CCL surgical treatments was published in the veterinary literature in September 2013.¹⁸ As more of those studies are performed, a Cochrane review of multiple, randomized, controlled trials could be performed to summarize and evaluate the best available data. At this time, such a study is not possible.

Although prospective, controlled, blinded, randomized clinical studies are difficult to perform, they provide the highest quality evidence from which conclusions can be made that affect future treatment paradigms. There are numerous ways that the veterinary community can continue to improve the quality of evidence available and allow better comparisons between clinical studies and, therefore, help improve clinical decision making for patients. At a minimum, the utilization of a uniform outcomes reporting system including terminology and outcome measurements may allow better comparisons between case series.⁶¹ This systematic review defined a minimum follow-up time of 6 mo. Longer-term postoperative follow-up is important because many of the described surgical procedures alter the biomechanics within the stifle joint and may have either positive or negative long-term effects on joint biology and biomechanics, and the clinical outcomes may be significantly different.

Interpretation of this systematic review should be made with the consideration of several potential limitations. Many outcome measurements were subjective in nature, and study designs were neither blinded nor randomized. In addition, the inclusion criteria for each study were well-defined and were, therefore, subject to many biases. Publication bias may have resulted in an underrepresentation of studies with negative findings, and some studies may have been excluded from analysis if the abstract did not contain a relevant search term. The postoperative follow-up time was variable and that may have had an influence on the assessed outcome following surgery. In addition, the current study did not evaluate the effect of either meniscal disease or meniscal treatment on the outcome of the surgical procedures. In many studies, it was unclear whether postoperative meniscal tear in the operated limb, contralateral CCL disease, or other pelvic limb disease was present, which may have been a contributing factor in the assessment of functional recovery, especially in regards to owner assessments. The current study did not account for technical variations within each surgical procedure, implants, or postoperative care, which may have affected the outcome of a surgical procedure. That may be an especially important issue, particularly regarding postoperative rehabilitation protocols because rehabilitation may make the difference between an incomplete and complete recovery from a surgical procedure.^43,44 Despite those limitations, this systematic review provides a global view of the peer-reviewed literature to date.

Conclusion

This systematic review found that the best available evidence most strongly supports a normal return to clinical function following TPLO surgery in dogs with naturally occurring CCL disease. The evidence also provided strong support that functional recovery in the intermediate postoperative time period was superior following TPLO compared with LS. There was insufficient data to adequately evaluate other surgical procedures, and additional investigation into the clinical outcome of those procedures is warranted. This systematic review highlights the current best knowledge of surgical treatment of CCL disease and thus allows clinicians to make decisions based on the best available evidence. It allows researchers to better identify the current information gaps and plan future investigations in the treatment of CCL disease in dogs and may result in improved care and quality of life for dogs affected with CCL disease.