The Risk of Knee Arthroplasty Following Cruciate Ligament Reconstruction

The Risk of Knee Arthroplasty Following CruciateLigament Reconstruction

A Population-Based Matched Cohort Study

Timothy Leroux, MD, MEd, Darrell Ogilvie-Harris, MBBS, FRCSC, Tim Dwyer, MD, FRCSC, FRACS,Jaskarndip Chahal, MD, MSc, FRCSC, Rajiv Gandhi, MD, MSc, FRCSC, Nizar Mahomed, MD, ScD, FRCSC,

and David Wasserstein, MD, MSc, FRCSC

Investigation performed at the Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada,and Toronto Western Hospital (University Health Network), Toronto, Ontario, Canada

Background: Evidence regarding the risk of end-stage osteoarthritis following cruciate ligament reconstruction is basedupon small sample sizes and radiographic, rather than clinical, criteria. The goals of this study were to determine the riskof knee arthroplasty, a surrogate for end-stage osteoarthritis, following cruciate ligament reconstruction, and to identifypatient, provider, and surgical factors that influence knee arthroplasty risk.

Methods: Using administrative databases, we identified all patients who were sixteen to sixty years of age and had undergonecruciate ligament reconstruction in Ontario from July 1993 to March 2008. Case patients were matched by demographic variablesto five individuals without knee injury from the general population of Ontario, Canada, who had not undergone previous kneesurgery, including cruciate ligament reconstruction. The main outcome was knee arthroplasty. Kaplan-Meier survival curves weregenerated for both cohorts. A Cox proportional hazards model determined those factors that influenced knee arthroplasty risk.

Results: We identified 30,301 eligible patients who had undergone cruciate ligament reconstruction; of these patients,30,277 were matched to 151,362 individuals from the general population; the median patient age was twenty-eight years and65% of the patients were male. Primary anterior cruciate ligament reconstruction accounted for >98% of index cases. Duringthe follow-up period, there was a significant difference (p < 0.001) between matched case and control cohorts with respect tothe number of patients who underwent knee arthroplasty during the study period; in the matched case cohort, 209 patientsunderwent knee arthroplasty (event rate, 0.68 of 1000 person-years), and in the control cohort, 125 patients underwent kneearthroplasty (event rate, 0.10 of 1000 person-years). Moreover, fifteen years after cruciate ligament reconstruction (casecohort) or study enrollment (control cohort), there was a significant difference (p < 0.001) in the cumulative incidence of kneearthroplasty between the case cohort (1.4%) and the control cohort (0.2%). Age of fifty years or more (hazard ratio, 37.28;p < 0.001), female sex (hazard ratio, 1.58; p = 0.001), comorbidity score of ‡5 points (hazard ratio, 5.91; p = 0.002), surgeon

continued

Disclosure: None of the authors received payments or services, eitherdirectly or indirectly (i.e., via his or her institution), from a third party insupport of any aspect of this work. One or more of the authors, or his orher institution, has had a financial relationship, in the thirty-six monthsprior to submission of this work, with an entity in the biomedical arenathat could be perceived to influence or have the potential to influencewhat is written in this work. No author has had any other relationships, orhas engaged in any other activities, that could be perceived to influenceor have the potential to influence what is written in this work. The com-plete Disclosures of Potential Conflicts of Interest submitted by authorsare always provided with the online version of the article.

Disclaimer: The Institute for Clinical Evaluative Sciences (ICES) sup-ported the following study. The ICES is funded by an annual grant fromthe Ontario Ministry of Health and Long-Term Care (MOHLTC). Theopinions, results and conclusions reported in this paper are those of theauthors and are independent from the funding sources. No endorsementby ICES or the Ontario MOHLTC is intended or should be inferred.

A commentary by Robert A. Magnussen,MD, is linked to the online version of thisarticle at jbjs.org.

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COPYRIGHT � 2014 BY THE JOURNAL OF BONE AND JOINT SURGERY, INCORPORATED

J Bone Joint Surg Am. 2014;96:2-10 d http://dx.doi.org/10.2106/JBJS.M.00393

annual volume of cruciate ligament reconstruction of twelve or fewer cases per year (hazard ratio, 2.53; p < 0.001), andcruciate ligament reconstruction undertaken in university-affiliated hospitals (hazard ratio, 1.51, p = 0.008) increased theodds of knee arthroplasty; however, male sex (hazard ratio, 0.63; p = 0.001) and patient age of less than twenty years (hazardratio, 0.07; p = 0.009) were protective. Concurrent meniscal repair or debridement did not increase arthroscopy risk.

Conclusions: After fifteen years, the cumulative incidence of knee arthroplasty following cruciate ligament reconstruc-tion was low (1.4%); however, it was seven times greater than the cumulative incidence of knee arthroplasty amongmatched control patients from the general population (0.2%). Older age, female sex, higher comorbidity, low surgeonannual volume of cruciate ligament reconstruction, and cruciate ligament reconstruction performed in a university-affiliated hospital were factors that increased knee arthroplasty risk.

Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Evidence pertaining to the risk of osteoarthritis followingcruciate ligament reconstruction is conflicted. A recentsystematic review showed the prevalence of osteoar-

thritis following anterior cruciate ligament reconstruction to be29% to 51% at a minimum ten-year follow-up1. However, theauthors of this systematic review noted that, among the highest-quality studies (as determined by a modified version of theColeman methodology score2), the prevalence of osteoarthritisat a minimum ten-year follow-up was only 0% to 13%1. Theauthors also criticized the existing literature for its heteroge-neity, small sample sizes, and the use of radiographic, ratherthan clinical, criteria to diagnose osteoarthritis1. There remainsa need to determine the risk of end-stage osteoarthritis followingcruciate ligament reconstruction and to evaluate long-termpatient symptoms and function using meaningful osteoarthritisoutcome measures.

A commonly performed and effective surgical interven-tion for end-stage osteoarthritis is prosthetic knee arthroplasty,including total knee arthroplasty and unicompartmental kneearthroplasty3. The indications for arthroplasty are largely clinicaland include patient symptoms, patient function, and failure ofalternative non-surgical and surgical interventions. For thesereasons, knee arthroplasty is a reasonable surrogate for clinicalend-stage osteoarthritis.

In the present study, two matched population cohortswere developed to compare the rate of knee arthroplasty followingcruciate ligament reconstruction with the rate of knee arthroplastyin the general population. Moreover, we identified and exploredthe patient, provider, and surgical factors that increased kneearthroplasty risk following cruciate ligament reconstruction.

Materials and MethodsCase Cohort Development

In this matched cohort study, all patients who underwent cruciate ligamentreconstruction (anterior cruciate ligament reconstruction and posterior

cruciate ligament reconstruction) from July 1993 to March 2008 were identifiedfrom Ontario Health Insurance Plan (OHIP) physician billings and were ac-cessed through the Institute for Clinical Evaluative Sciences (ICES; www.ices.on.ca). In Ontario, OHIP provides universal health coverage for medical ser-

vices to all Ontario residents, and OHIP fee codes are highly accurate (>96%)4.

For each patient, a unique and anonymous identification number was used toconfirm a relevant index hospital admission in the Canadian Institute for HealthInformation (CIHI) databases (Same Day Surgery Database [SDS] or DischargeAbstract Database [DAD]).

Exclusion criteria (see Appendix) included age less than sixteen years andage greater than sixty years, non-Ontario residents, nonelective cruciate ligamentreconstruction, billing anomalies, prior knee arthroplasty or cruciate ligament re-construction, and potential confounders of heightened osteoarthritis risk (chondralsurgery, lower-extremity osteotomy, or fracture fixation about the knee). Revisioncruciate ligament reconstruction cases were also excluded following the introduc-tion of a relevant OHIP billing code on July 1, 2003. Of note, database limitationsprecluded the exclusion of patients who had undergone posterior cruciate ligamentreconstruction prior to 2002. As such, all patients who had undergone cruciateligament reconstruction (anterior cruciate ligament reconstruction or posteriorcruciate ligament reconstruction) were included to lengthen the duration of follow-up and to capture the infrequent event of knee arthroplasty.

Control Cohort DevelopmentCase patients were randomly matched to five control patients from Ontario,Canada. Control subjects met the aforementioned exclusion criteria, had validOHIP coverage, and were matched to the corresponding case patient on the basisof patient demographic variables (age [within one year], sex, income quintile,urban or rural address, and comorbidity score). A case patient was ‘‘unmatched’’if five control patients sharing similar demographics could not be identified.

Main OutcomeThe main outcome was knee arthroplasty (total knee arthroplasty or uni-compartmental knee arthroplasty) and was identified using OHIP fee codes (seeAppendix). Laterality was not available for the index event or the main outcome.

CovariatesAvailable patient, surgical, and provider factors were considered in the analysis.

Patient factors included age, sex, neighborhood income quintile, co-morbidity score, and residence. Neighborhood income quintile was calculatedthrough an established technique with use of Statistics Canada census data

5.

Patient comorbidity was estimated with use of the Collapsed Aggregated Di-agnosis Groups (CADG) method

6. Specifically, CIHI databases and Interna-

tional Classification of Diseases (ICD) codes were used to identify comorbidconditions associated with admissions to Canadian hospitals within two yearsof the index event. On the basis of the number of comorbid conditions, patientswere then assigned an overall CADG score and were assigned to one of twocategories: 0 to 4 points and ‡5 points

7. The postal code for each patient was used

Peer Review: This article was reviewed by the Editor-in-Chief and one Deputy Editor, and it underwent blinded review by two or more outside experts. It was also reviewedby an expert in methodology and statistics. The Deputy Editor reviewed each revision of the article, and it underwent a final review by the Editor-in-Chief prior to publication.Final corrections and clarifications occurred during one or more exchanges between the author(s) and copyeditors.

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TH E J O U R N A L O F B O N E & JO I N T SU R G E RY d J B J S . O R G

VO LU M E 96-A d NU M B E R 1 d JA N UA RY 1, 2014TH E RI S K O F K N E E AR T H R O P L A S T Y FO L LO W I N G C RU C I AT E

LI G A M E N T RE C O N S T R U C T I O N

TABLE I Cumulative Incidence of Knee Arthroplasty: Case Versus Control Cohorts

Time Since Cruciate LigamentReconstruction (yr)

Cumulative Incidence of Knee Arthroplasty*Cumulative Incidence Comparison

(Case:Control)Case Cohort Control Cohort

2 0.06 (0.04 to 0.09) 0.002 (0.0004 to 0.006) 30:1

5 0.15 (0.11 to 0.20) 0.02 (0.01 to 0.02) 8:1

10 0.40 (0.32 to 0.49) 0.06 (0.05 to 0.09) 7:1

15 1.44 (1.22 to 1.69) 0.21 (0.17 to 0.26) 7:1

*The values are given as the percentage, with the 95% CI in parentheses.

TABLE II Within-Group Comparison: Case Cohort (N = 30,301)

Variable With Knee Arthroplasty Without Knee Arthroplasty

Group size* 212 30,089

Age†‡ (yr) 42 (35 to 47) 28 (20 to 35)

Age distribution‡§Sixteen to nineteen years of age 0% 22%Twenty to twenty-four years of age 2% 18%Twenty-five to twenty-nine years of age 6% 17%Thirty to thirty-four years of age 14% 16%Thirty-five to thirty-nine years of age 17% 13%Forty to forty-nine years of age 42% 13%Fifty to sixty years of age 17% 2%

Male sex‡§ 54% 65%

CADG score of ‡5 points‡§ 1% 0%

Surgeon annual volume in the year preceding cruciate ligament reconstruction‡§None 4% 3%One to twelve 28% 19%Thirteen to fifty 36% 33%Fifty-one to 100 18% 24%More than 100 13% 21%

Year of index date distribution (non-fragmented)‡§1994 14% 5%1995 11% 5%1996 12% 6%1997 10% 6%1998 11% 6%1999 3% 6%2000 5% 6%2001 5% 6%2002 7% 7%2003 6% 7%2004 3% 8%2005 1% 9%2006 3% 9%2007 1% 9%

*The values are given as the number of patients. †The values are given as the median, with the interquartile range in parentheses. ‡Thedifferences were significant at p < 0.05. §The values are given as the percentage of patients.

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to determine urban or rural residence. Of note, age categories were determined apriori and were used for ease of interpretation (sixteen to nineteen years, twenty totwenty-four years, twenty-five to twenty-nine years, thirty to thirty-four years,thirty-five to thirty-nine years, forty to forty-nine years, and fifty to sixty years).

Provider factors included surgeon annual volume of cruciate ligamentreconstruction and hospital academic status. The surgeon for each index eventwas identified anonymously, and the number of cruciate ligament reconstructionsperformed in the year preceding the index event (July 1 to June 30) wasdetermined. Volume categories were determined a priori on the basis of clinicalrelevance (none, one to twelve, thirteen to fifty, fifty-one to 100, and more than 100cruciate ligament reconstructions per year)

8. The index hospital was categorized as

either university-affiliated (active in research and/or health-care professionaltraining) or non-university-affiliated on the basis of membership in the Councilof Academic Hospitals of Ontario (www.caho-hospitals.com).

Surgical factors included concomitant meniscal surgery, specificallymeniscectomy or meniscal repair (see Appendix). Database limitations precludedthe identification of meniscal tears treated nonoperatively.

Statistical AnalysisAn overall knee arthroplasty event rate per 1000 person-years was calculated foreach cohort and was compared via t test. Within the case cohort only, a t test

(continuous variables) or chi-square test (categorical variables) was used tocompare demographics between the group of patients who underwent kneearthroplasty and the group of patients who did not.

A Kaplan-Meier survival analysis (index event to censorship) was gen-erated for each cohort and was compared with use of a log-rank test. Both thesurvival rate and the cumulative incidence (the inverse of the survival rate) at two,five, ten, and fifteen years from the index event (case cohort) or study inclusion(control cohort) were calculated. Censorship included knee arthroplasty, death,emigration, loss of OHIP coverage, and study end (March 31, 2012).

Two Cox proportional hazards models were calculated. The first Coxmodel (only matched case and control patients) quantified the magnitude ofeffect for cruciate ligament reconstruction as a risk factor for knee arthroplasty.The second Cox model (all case patients) identified factors that influenced kneearthroplasty risk following cruciate ligament reconstruction. Unmatched casepatients were included in the second Cox model to minimize bias from theirexclusion. Reference values for either Cox model were the median (referenceage, twenty-five to twenty-nine years; reference quintile, third) or most com-mon categories (reference sex, male; reference comorbidity score, CADG 0 to 4;reference hospital status, non-university affiliated). The reference surgeonvolume category (more than 100 cruciate ligament reconstructions per year)was selected on the basis of evidence in the orthopaedic literature that

TABLE III Cox Proportional Hazard Model: Knee Arthroplasty Risk Factors in Case Cohort

Variable Hazard Ratio* P Value†

AgeSixteen to nineteen years versus twenty-five to twenty-nine years 0.07 (0.01 to 0.50) 0.009Twenty to twenty-four years versus twenty-five to twenty-nine years 0.40 (0.14 to 1.13) 0.083Thirty to thirty-four years versus twenty-five to twenty-nine years 2.43 (1.26 to 4.68) 0.008Thirty-five to thirty-nine years versus twenty-five to twenty-nine years 4.35 (2.31 to 8.19) <0.001Forty to forty-nine years versus twenty-five to twenty-nine years 13.77 (7.64 to 24.79) <0.001Fifty to sixty years versus twenty-five to twenty-nine years 37.28 (19.59 to 70.93) <0.001

SexFemale versus male 1.58 (1.20 to 2.07) 0.001Male versus female 0.63 (0.48 to 0.83) 0.001

Income quintile1 versus 3 0.83 (0.50 to 1.38) 0.4672 versus 3 1.11 (0.72 to 1.72) 0.6234 versus 3 0.87 (0.58 to 1.32) 0.5225 versus 3 0.77 (0.52 to 1.14) 0.192

CADG‡5 points versus 0 to 4 points 5.91 (1.87 to 18.64) 0.002

Surgeon annual volume in the year preceding cruciate ligament reconstructionNone versus more than 100 1.88 (0.88 to 4.03) 0.103One to twelve versus more than 100 2.53 (1.56 to 4.11) <0.001Thirteen to fifty versus more than 100 2.15 (1.37 to 3.37) <0.001Fifty-one to 100 versus more than 100 1.17 (0.72 to 1.91) 0.534

Meniscal debridementYes versus no 0.72 (0.52 to 0.99) 0.046

Meniscal repairYes versus no 0.89 (0.48 to 1.65) 0.713

Academic health-care center (site of index cruciate ligament reconstruction)Yes versus no 1.51 (1.12 to 2.04) 0.008

*The values are given as the hazard ratio, with the 95% CI in parentheses. †Significance was set at p = 0.05.

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correlates superior outcomes to higher surgeon volume9-11

. The Cox modelsgenerated hazard ratios (HRs) with 95% confidence intervals (95% CIs).

All statistical analyses were performed with use of SAS version 9.1 forUNIX (SAS Institute, Cary, North Carolina) and significance was set at p = 0.05.

Source of FundingThe entire study was funded by an internal source through the Arthritis Re-search Unit at the Toronto Western Hospital (University Health Network) inToronto, Ontario, Canada. Four authors of this study (D.O.-H., J.C., R.G., andN.M.) are employees at Toronto Western Hospital and affiliates of the ArthritisResearch Unit. Funds were used to pay for administration fees, analyst salaries,and data storage fees at the Institute for Clinical Evaluative Sciences.

Results

We identified 34,786 patients who underwent a cruciateligament reconstruction from July 1993 to March 2008.

Following application of the exclusion criteria, 30,301 patientswere eligible for study enrollment (see Appendix). The medianpatient age was twenty-eight years (interquartile range [IQR],twenty to thirty-six years), and the distribution of patient agewas significantly skewed to a younger age (p < 0.001) (see Ap-pendix). Moreover, 65% of case patients were male (p < 0.001),

89% lived at an urban address (p < 0.001), and the great majority(99.9%) had few medical comorbidities (CADG, 0 to 4) (p <0.001). Notably, the number of cruciate ligament reconstructionsperformed annually increased significantly from 1626 proceduresin 1994 to 2799 procedures in 2007 (p < 0.001) (see Appendix).

We matched 151,362 individuals from the general pop-ulation to 30,277 patients from the case cohort; there weretwenty-four unmatched case patients. The twenty-four un-matched case patients were compared with the 30,277 matchedcase patients. There was a significant difference in age (p =0.04) between unmatched case patients (median, thirty-threeyears [IQR, twenty-seven to forty years]) and matched casepatients (median, twenty-eight years [IQR, twenty to thirty-sixyears]). There was also a significant difference (p < 0.001) incomorbidity score (CADG, ‡5 points) between unmatchedcase patients (95.8%) and matched case patients (0%). In ad-dition, there was a significant difference (p < 0.001) in ruraladdress between unmatched case patients (33.3%) andmatched case patients (10.7%). There were no significantdifferences with respect to the distribution of sex or incomequintile.

Fig. 1

Kaplan-Meier (KM) survival curve of knee arthroplasty: case versus control cohorts. The y axis depicts survival, specifically the fraction of patients who

have yet to be censored from the study (knee arthroplasty, death, emigration, or study end), and the x axis depicts the number of years since the

index cruciate ligament reconstruction (case cohort) or study enrollment (control cohort). The difference in the event-free survival rate between case

and control patients was significant (p < 0.001).

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During the follow-up period, the matched case cohorthad 209 knee arthroplasty events, 181 (86.6%) of which weretotal knee arthroplasties, and the control cohort had 125 kneearthroplasty events, 111 (88.8%) of which were total knee ar-throplasties. The overall knee arthroplasty event rate per 1000person-years was 0.68 (95% CI, 0.59 to 0.78) for the matchedcase cohort and 0.10 (95% CI, 0.08 to 0.12) for the controlcohort (p < 0.001). According to the first Cox model, patientswho underwent cruciate ligament reconstruction had signifi-cantly increased odds (p < 0.001) of undergoing knee arthro-plasty at a later date (HR, 7.26 [95% CI, 5.79 to 9.11]). Moreover,the cumulative incidence of knee arthroplasty at two, five, ten,and fifteen years was greater among case patients as comparedwith control patients (Table I), and the log-rank test revealed asignificant difference in the case and control Kaplan-Meier sur-vival curves (p < 0.001) (Fig. 1). Among the case cohort, themedian time to knee arthroplasty following cruciate ligamentreconstruction was 11.0 years (IQR, six to fourteen years).

Among all 30,301 patients who had undergone cruciateligament reconstruction, there were 212 knee arthroplasty events.Among those case patients who underwent knee arthroplasty, themedian age at the time of cruciate ligament reconstruction wasforty-two years (IQR, thirty-five to forty-seven years), and themedian age of case patients who did not undergo knee arthro-plasty was twenty-eight years (IQR, twenty to thirty-fiveyears) (p < 0.001). There were also significant differences insex, comorbidity score, surgeon volume, and year of the indexevent (Table II).

The second Cox model (all case patients) revealed thatolder patient age, female sex, higher comorbidity score, lowannual surgeon volume, and cruciate ligament reconstructionperformed at a university-affiliated hospital increased knee ar-throplasty risk (Table III). Neither meniscal repair or meniscaldebridement performed concurrently with the index event in-creased the risk of knee arthroplasty following cruciate ligamentreconstruction in this cohort (Table III).

Discussion

The cumulative incidence of knee arthroplasty at fifteenyears following cruciate ligament reconstruction was low

(1.4%); however, it was sevenfold greater than the cumulativeincidence of knee arthroplasty among a matched control cohortfrom the general population. This is an important finding that isnot only based upon the largest data set of its kind to date, but isalso reflective of general orthopaedic practice.

A notable limitation of past studies has been the use ofradiographic classification systems to diagnose osteoarthritis.In the available literature, seven different classification methodshave been used in either isolation or combination1,12-16. A majordownfall of this approach is that radiographic evidence of os-teoarthritis may not reflect patient symptomatology, nor does itdictate surgical treatment.

The main outcome in this study was knee arthroplasty, areasonable surrogate for both symptomatic and radiographicend-stage osteoarthritis. Certainly, our finding that patientswho have undergone cruciate ligament reconstruction are at

an increased risk of arthroplasty as compared with the generalpopulation is interesting; however, we found that the cumulativeincidence of knee arthroplasty among patients who had under-gone cruciate ligament reconstruction was in keeping with a re-cent systematic review suggesting that osteoarthritis prevalenceamong patients who had undergone cruciate ligament recon-struction was low1. Unfortunately, heterogeneity in past studies,particularly osteoarthritis diagnosis, precluded our attempts todraw any further reliable comparisons to the literature.

In this study, older age, female sex, higher comorbidityscore, low surgeon volume (cruciate ligament reconstruction),cruciate ligament reconstruction undertaken in university-affiliated hospitals, and an earlier cruciate ligament reconstruc-tion year increased the likelihood of knee arthroplasty followingcruciate ligament reconstruction. However, young age and malesex were associated with a decreased likelihood of arthroplasty.Several of these findings are consistent with previously identifiedrisk factors, including age17-22 and sex17,23. Not surprisingly,patients who underwent cruciate ligament reconstruction earlierin the study were at increased risk of undergoing arthroplasty.Unfortunately, cruciate ligament reconstruction technique couldnot be evaluated in this study.

The finding that provider factors such as surgeon volumeand hospital status influence osteoarthritis risk following cruciateligament reconstruction is novel. The relationship between lowsurgeon volume and poor outcomes has been well documentedin elective orthopaedic surgery practice9-11. With respect tocruciate ligament reconstruction, a 2009 population studyfailed to correlate reoperation following anterior cruciateligament reconstruction with low surgeon volume, and theauthors postulated that this may reflect the propensity forhigher-volume surgeons to take on more complex cases24. Incontrast, we demonstrated that cruciate ligament reconstructionperformed by high-volume surgeons translates into a lower riskof eventual knee arthroplasty, and we believe that this findingreflects an underlying relationship between experience andtechnical proficiency.

The observation that osteoarthritis risk is elevatedfollowing cruciate ligament reconstruction performed in auniversity-affiliated hospital is more difficult to interpret. Itmay be that this relationship reflects a difference in patientpractice and a tendency for university-affiliated orthopaedicsurgeons to take on more complex cases, but the potential neg-ative influence of the surgical trainee on cruciate ligament re-construction outcomes, specifically osteoarthritis, must also beconsidered. In fact, current evidence suggests that the learningcurve for arthroscopy is considerable25, and most trainees aremore comfortable with open rather than arthroscopic pro-cedures at graduation26.

The relationship between meniscal pathology and oste-oarthritis development has been extensively studied27. In thepresent study, meniscal repair did not influence knee arthro-plasty risk, a finding consistent with the current literature18,28,29.However, many studies have demonstrated that meniscectomyperformed with cruciate ligament reconstruction is a risk factorfor the development of osteoarthritis18-20,22,23,28-40, including a

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systematic review that found the prevalence of osteoarthritisfollowing meniscectomy and cruciate ligament reconstructionto be 21% to 48%1. Our data do not support a relationshipbetween cruciate ligament reconstruction with meniscectomyand an increased long-term arthroplasty risk. The discrepancybetween past and present data could be explained by a differ-ence in osteoarthritis diagnosis, small sample sizes in previousstudies, or a variation in the amount of meniscus resected. Infact, osteoarthritis risk following total meniscectomy is increasedas compared with partial meniscectomy41, and a notable limita-tion of past studies (including our own) is the failure or inabilityto report meniscectomy details.

There were several limitations to this study. First, cruciateligament reconstruction as we have defined it includes primaryanterior cruciate ligament reconstruction, primary posteriorcruciate ligament reconstruction, and some revision procedures.Prior to 2002, hospital admission databases did not allow us todistinguish between anterior cruciate ligament reconstructionand posterior cruciate ligament reconstruction. However, we doknow that posterior cruciate ligament reconstruction representedonly ;0.7% of all cruciate ligament reconstructions in Ontariosince 200242, a figure consistent with other population studies24.Similarly, a revision cruciate ligament reconstruction OHIPfee code was not available prior to July 1, 2003. In our cohortof patients, we identified 312 revision cruciate ligament recon-struction cases (2.8% of all cases since 2003) (see Appendix). Thisfinding is similar to another large population study with similarinclusion parameters43. Despite the fact that primary posteriorcruciate ligament reconstruction and revision cruciate ligamentreconstruction represent <2% of all cruciate ligament recon-struction cases included in this study, their potential influence onthe study findings is unknown. A potential resolution to thislimitation would be the inclusion of only anterior cruciate liga-ment reconstruction cases after 2003; however, this would havelessened the follow-up period, the sample size, and our abilityto detect what we have shown to be a significant, yet uncommon,event.

Another limitation of this study was the unknown in-fluence of the cruciate ligament reconstruction technique. Wedemonstrated that patients managed early in the study had ahigher incidence of subsequent arthroplasty, and the potentialinfluence of previously used techniques cannot be ignored. Thecruciate ligament reconstruction technique has evolved since1993, and it is possible that modern techniques could diminishosteoarthritis risk. Unfortunately, a comparison between out-dated and modern cruciate ligament reconstruction techniqueswas beyond the scope of this study.

The influence of chondral injury on the development ofosteoarthritis following cruciate ligament reconstruction is animportant consideration. Although we could not directly studythis relationship, given the limitations of our databases, we didattempt to exclude patients with a history of surgery that wouldpotentially increase osteoarthritis risk, such as chondral ormeniscal surgery. Despite this, it remains possible that bothcase and control patients who underwent knee arthroplasty hadincreased chondral pathology and/or preexisting osteoarthritis

at the time of study inclusion, and that the difference in nativeknee survivorship between the case and control cohorts canbe accounted for by a difference in the rate of chondral pa-thology and/or preexisting osteoarthritis at the time of studyinclusion.

The utilization of knee arthroplasty in the treatment ofend-stage osteoarthritis can be influenced by social, demographic,medical, and geographic factors. Despite similar disease se-verity, studies have shown that older44, male45 patients from ahigher socioeconomic status46,47 are more likely to undergo totalknee arthroplasty. In Canada, health-care resources can also in-fluence total knee arthroplasty utilization rates, as exemplified bythe dramatic increase in total knee arthroplasty volumes thatfollowed the Ontario Wait Times Strategy initiative in 200448. Inthis study, we controlled for utilization factors by developing acomparison matched cohort; however, patient age remains animportant influence on our study findings. Specifically, surgeonsare less inclined to perform knee arthroplasty in younger patients,and given that patients in our study were younger than the typicalpatient undergoing arthroplasty, we may have underestimatedthe burden of disease. Furthermore, our follow-up period waslimited to fifteen years, and although we found older patients tobe at increased knee arthroplasty risk within this time period, aconsiderably longer follow-up is needed to determine the overallknee arthroplasty risk among younger patients undergoing cru-ciate ligament reconstruction. Nevertheless, the use of a matchedcohort diminishes intra-cohort utilization factor influenceon eventual knee arthroplasty, and the best interpretation ofour findings is in the comparison between the case andcontrol cohorts.

The development of osteoarthritis following cruciateligament injury is asymmetric49. In this study, unicompartmentalknee arthroplasty was included in the main outcome to accountfor this possibility, although we have demonstrated that it is arelatively uncommon procedure as compared with total kneearthroplasty. In fact, >85% of all knee arthroplasty proceduresidentified in this study were total knee arthroplasty, and there wasno difference in the distribution of total knee arthroplasty andunicompartmental knee arthroplasty events in both the case andcontrol cohorts.

Two additional limitations were inherent to this type ofstudy. First, it was possible that some surgical cohort or controlcohort patients elected to undergo arthroplasty in a jurisdictionoutside of Ontario. However, patients would have paid for thissurgery out-of-pocket, and we presume that this is an infre-quent occurrence. Second, determination of the involved sidewas not possible in this study, and the study findings reflectcontributions from the ipsilateral involved knee and the con-tralateral knee. A careful matched cohort study design and theexclusion of patients with prior cruciate ligament reconstruc-tion or knee arthroplasty minimized this influence; however,the baseline rate of knee arthroplasty in the cruciate ligamentreconstruction cohort may be inflated secondary to contribu-tions from the contralateral side. The comparative risk betweencase patients and control patients is the most accurate inter-pretation of our findings, in which the patients who have

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undergone cruciate ligament reconstruction are seven timesmore likely to undergo a knee arthroplasty after fifteen years.

Lastly, the intent of this study was not to uncover theetiology of osteoarthritis following cruciate ligament recon-struction. Rather, the sole intent was to determine knee ar-throplasty risk following cruciate ligament reconstruction.Certainly, the initial cruciate ligament injury cannot be over-looked as a causative agent in the development of osteoarthritisfollowing cruciate ligament reconstruction, including chondralinjury, and we recognize the importance of drawing compari-sons to patients who are cruciate ligament-deficient, but do notundergo reconstruction to make such claims. Unfortunately,this was beyond the scope of our study.

In conclusion, after fifteen years, the cumulative in-cidence of knee arthroplasty following cruciate ligamentreconstruction was low (1.4%); however, it was seven timesgreater than the cumulative incidence of knee arthroplastyamong a cohort of matched control patients from the generalpopulation. Factors that increase risk include older age,female sex, higher comorbidity, low surgeon volumes, andtreatment at university-affiliated hospitals. Meniscal surgery,including debridement and repair, did not increase arthro-plasty risk.

AppendixFigures showing a bar graph of the age distribution of casecohort patients and a line graph showing the annual vol-

ume of cruciate ligament reconstruction procedures performedin Ontario, Canada, during each non-fragmented study yearand tables showing cohort development and administrativecodes are available with the online version of this article as adata supplement at jbjs.org. n

Timothy Leroux, MD, MEdDarrell Ogilvie-Harris, MBBS, FRCSCTim Dwyer, MD, FRCSC, FRACSJaskarndip Chahal, MD, MSc, FRCSCUniversity of Toronto Orthopaedic Sports Medicine,149 College Street, Room 508-A, Toronto,ON M5T 1P5, Canada.E-mail address for T. Leroux: [email protected]

Rajiv Gandhi, MD, MSc, FRCSCNizar Mahomed, MD, ScD, FRCSCArthritis Research Unit,Toronto Western Hospital (University Health Network),399 Bathurst Street, Suite 1E-435, Toronto,ON M5T 2S8, Canada

David Wasserstein, MD, MSc, FRCSCSunnybrook Health Sciences Center,2075 Bayview Avenue, Room MG 301, Toronto,ON M4Y 1H1, Canada.E-mail address: [email protected]

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The Risk of Knee Arthroplasty Following Cruciate Ligament Reconstruction