The effects of femoral graft placement on cartilage thicknessafter anterior cruciate ligament reconstruction

Eziamaka C. Okafor a, Gangadhar M. Utturkar a, Margaret R. Widmyer a,c, Ermias S. Abebe d,Amber T. Collins a, Dean C. Taylor a,e, Charles E. Spritzer b, C.T. Moorman 3rda,William E. Garrett a,e, Louis E. DeFrate a,c,n

a Duke Sports Medicine Center, Department of Orthopaedic Surgery, Duke University Medical Center, 375 MSRB, Box 3093, Durham, NC 27710, United Statesb Department of Radiology, Duke University Medical Center, United Statesc Department of Biomedical Engineering, Duke University, United Statesd Department of Orthopaedics, University of Pittsburgh Medical Center, United Statese Durham VA Medical Center, Durham, NC, United States

a r t i c l e i n f o

Article history:Accepted 7 October 2013

Keywords:KinematicsMRIImagingOsteoarthritisMechanicsACL

a b s t r a c t

Altered joint motion has been thought to be a contributing factor in the long-term development ofosteoarthritis after ACL reconstruction. While many studies have quantified knee kinematics after ACLinjury and reconstruction, there is limited in vivo data characterizing the effects of altered knee motionon cartilage thickness distributions. Thus, the objective of this study was to compare cartilage thicknessdistributions in two groups of patients with ACL reconstruction: one group in which subjects received anon-anatomic reconstruction that resulted in abnormal joint motion and another group in whichsubjects received an anatomically placed graft that more closely restored normal knee motion. Tenpatients with anatomic graft placement (mean follow-up: 20 months) and 12 patients with non-anatomic graft placement (mean follow-up: 18 months) were scanned using high-resolution MRimaging. These images were used to generate 3D mesh models of both knees of each patient. Theoperative and contralateral knee models were registered to each other and a grid sampling system wasused to make site-specific comparisons of cartilage thickness. Patients in the non-anatomic graftplacement group demonstrated a significant decrease in cartilage thickness along the medial inter-condylar notch in the operative knee relative to the intact knee (8%). In the anatomic graft placementgroup, no significant changes were observed. These findings suggest that restoring normal knee motionafter ACL injury may help to slow the progression of degeneration. Therefore, graft placement may haveimportant implications on the development of osteoarthritis after ACL reconstruction.

& 2013 Elsevier Ltd. All rights reserved.

1. Introduction

ACL reconstruction is a commonly performed procedure thatimproves functional outcomes and allows many patients to return torecreational activities (Brophy et al., 2012; Feller and Webster, 2013;Koutras et al., 2013; Kvist, 2004). However, despite encouragingshort-term clinical results, the development of post-traumaticosteoarthritis is an important concern in the long-term after ACLreconstruction (Delince and Ghafil, 2012; Lohmander et al., 2007).Specifically, numerous studies with follow-up times beyond 10 yearshave reported radiographic evidence of degenerative changes inmore than half of patients (Holm et al., 2012; Janssen et al., 2013;

Salmon et al., 2006). While these changes are generally more severein subjects with a concurrent meniscal injury, cartilage degenerationremains a problem even in patients with intact menisci at the time ofsurgery (Kessler et al., 2008; Salmon et al., 2006). Since ACL injurygenerally afflicts a relatively young population, preventing thedevelopment of osteoarthritis in these patients is an importantclinical problem (Lohmander et al., 2007; Renstrom et al., 2008).

The precise mechanisms contributing to degenerative changesafter ACL reconstruction are not well understood. Although a numberof factors potentially contribute to the development of osteoarthritisafter ACL injury, altered joint motion is believed to be one importantfactor (Andriacchi et al., 2004; Chen et al., 2012; Papannagari et al.,2006; Tashman and Araki, 2013; Tochigi et al., 2011). In particular,recent studies have suggested that some ACL reconstruction techni-ques may not restore normal tibiofemoral joint motions underphysiological loading conditions (Abebe et al., 2011b; Gao andZheng, 2010; Papannagari et al., 2006; Tashman and Araki, 2013).

Contents lists available at ScienceDirect

journal homepage: www.elsevier.com/locate/jbiomechwww.JBiomech.com

Journal of Biomechanics

0021-9290/$ - see front matter & 2013 Elsevier Ltd. All rights reserved.http://dx.doi.org/10.1016/j.jbiomech.2013.10.003

n Corresponding author at: Duke Sports Medicine Center, Department of Ortho-paedic Surgery, Duke University Medical Center, 375 MSRB, Box 3093, Durham, NC27710, United States. Tel.: þ1 919 681 9959; fax: þ1 919 681 8490.

E-mail address: lou.defrate@duke.edu (L.E. DeFrate).

Journal of Biomechanics 47 (2014) 96–101

These abnormal joint motions are believed to alter normal cartilagecontact mechanics (Andriacchi et al., 2004; Hosseini et al., 2012).Abnormal cartilage loading potentially disrupts normal cartilagehomeostasis (Griffin and Guilak, 2005; Halloran et al., 2012), whichcould ultimately influence the initiation and progression of jointdegeneration in these patients. Since a number of recent studies haveindicated that abnormal knee kinematics persist after ACL recon-struction (Deneweth et al., 2010; Gao and Zheng, 2010; Papannagariet al., 2006; Scanlan et al., 2010; Tashman et al., 2004), understandingthe relationship between altered joint motion and changes incartilage morphology could provide critical information for improv-ing long-term outcomes after ACL reconstruction.

Although many studies have quantified altered kinematics afterACL reconstruction, there is limited data relating these alteredknee kinematics to early degenerative changes in cartilage.In particular, there is a lack of in vivo data relating altered kneejoint motion to site-specific measurements of cartilage thicknessin patients with ACL reconstruction. Thus, the objective of thisstudy was to compare cartilage thickness distributions in twogroups of patients with ACL reconstruction (Abebe et al., 2011a,2009, 2011b): one group in which subjects received a non-anatomic reconstruction that resulted in abnormal joint motionand another group in which subjects received an anatomicallyplaced graft that more closely restored normal knee motion. Wehypothesized that the abnormal knee motions that were observedwith non-anatomic graft placement would result in an increasedloss of cartilage thickness compared to anatomically placed grafts.

2. Materials and methods

2.1. Patient recruitment and inclusion criteria

Twenty-two patients (16 men and 6 women, 19–49 years old) between 6 and36 months after unilateral ACL reconstruction and with healthy contralateral kneesparticipated in this IRB approved study. Patients were recruited from the clinics oftwo surgeons at the Duke University Sports Medicine Center and completed thesame post-surgery rehabilitation protocol. Study participants were excluded if theyexhibited any of the following features: varus–valgus deformity, osteoarthritis,tibiofemoral articular cartilage defects, removal of more than 10% of meniscus inthe operated knee, or any other history of trauma or surgery to either knee. Allparticipants had stable knees under Lachman and pivot-shift examinations. At thetime of testing, all study participants had returned to sports activity withoutrestriction. All patients meeting these recruitment criteria were sorted by operativedate, and invited to participate in a chronological order.

At the time of the study, 12 subjects (9 men, 3 women; mean age: 32 years;mean follow-up: 20 months) had received a procedure performed by one surgeonresulting in non-anatomic placement of the graft on the femur (Abebe et al., 2011a).Five patients had intact menisci, and the remaining seven had tears requiringremoval of less than 10% of the meniscus (five lateral tears and two medial tears).These subjects had a graft placed using a transtibial technique, where the femoraltunnel was placed through the tibial tunnel (Abebe et al., 2009; Kaseta et al., 2008).This technique resulted in anteroproximal graft placement on the femur, an averageof 9 mm from the center of the original ACL attachment (Abebe et al., 2011a). Thesesubjects had significantly increased anterior translation, medial translation, andinternal tibial rotation in their reconstructed knee relative to their normal kneeduring a quasi-static weight-bearing lunge (Abebe et al., 2011b).

The remaining 10 subjects (7 men, 3 women; mean age: 30 years; mean follow-up: 18 months) had received a procedure from another surgeon resulting inanatomic graft placement (Abebe et al., 2011a). Four patients had intact menisci,and the remaining six had tears requiring removal of less than 10% of the meniscus(three lateral tears and three medial tears). In these subjects, the femoral tunnelwas placed independently of the tibial tunnel (RetroDrill, Arthrex, Naples, FL;Abebe et al., 2009; Kaseta et al., 2008). Graft placement was within an average of3 mm from the center of the ACL (Abebe et al., 2011a). In these subjects, nodifferences in kinematics were detected between the intact and reconstructed kneeduring a quasi-static weight-bearing lunge (Abebe et al., 2011b).

2.2. MR imaging

The subjects were seated in a non-weight bearing position for 30 min (Bischofet al., 2010) before the start of the investigation in order to minimize compressionof the cartilage prior to imaging. Each subject's operative and intact contralateral

knees were imaged at the Center for Advanced Magnetic Resonance Developmentusing a 3 T MR scanner (Trio Trim, Siemens, Germany) while positioned in a supine,relaxed position. Sagittal MR images were acquired using a double-echo steady statesequence (DESS, field of view: 15�15 cm2, matrix: 512�512 pixels, slice thickness:1 mm, flip angle: 251, TR: 17 ms, TE: 6 ms) and an eight-channel knee coil (In Vivo,Orlando, FL; Abebe et al., 2009; Taylor et al., 2011). Total scan time was approxi-mately 9 min for each knee. All MR images were imported into solid modelingsoftware (Rhinoceros, Robert McNeel and Associates) for further processing.

2.3. MR imaging-based 3D modeling and cartilage thickness analysis

For each sagittal MR image slice, the outer margins of the femoral and tibialcortices as well as the surface contours of articular cartilage were outlined (Fig. 1).These traced curves were then used to generate anatomic 3D mesh models of thetibiofemoral joint using solid modeling software (Geomagic Studio, Geomagic Inc.,Raleigh, NC; Fig. 1). In order to measure the cartilage thickness on both the operativeand intact knee models using the same coordinate system, all operative knee modelswere mirrored to create two models with the same orientation. Next, the mirroredoperative knee models were aligned to the intact knee models using an iterativeclosest point technique (Caputo et al., 2009). This registration was performed toallow for site-specific comparisons of cartilage thickness. A grid sampling systemwasthen created on both the operative and intact knee models to quantify variations incartilage thickness by location (Fig. 2). Both the lateral and medial femoral condyleswere subdivided into 3�6 grids. Additionally, three points were sampled in themedial aspect of the intercondylar notch because this is a region where elevatedcartilage contact strains have been observed in patients with ACL injury (Sutter et al.,2013; Van de Velde et al., 2009). Furthermore, this is also a region where earlyevidence of degeneration has been observed clinically in patients with ACLdeficiency (Fairclough et al., 1990). A total of 18 evenly-spaced points were alsosampled on the lateral and medial tibial plateaus. Using mathematical analysissoftware (Mathematica, Wolfram, Champaign, IL), thickness measurements werecalculated by finding the smallest Euclidian distance between the vertex of thearticular surface to the cartilage–bone interface of the 3D surface mesh models(Coleman et al., 2013). This thickness information was color encoded on the cartilagesurface to generate a thickness map (Fig. 3). These calculations were then followedby averaging thickness at each vertex on the mesh model within a 2.5 mm radius ofthe grid sampling point for each joint (Coleman et al., 2013). Finally, at each point,the percent change in cartilage thickness was calculated relative to the intactcontralateral knee. This MR imaging technique for measuring cartilage thicknesshas been previously validated in the literature (Van de Velde et al., 2009).Additionally, a recent study from our laboratory indicated that this technique has acoefficient of repeatability of 0.03 mm for measuring tibial, femoral, and patellarcartilage thickness (Coleman et al., 2013), which corresponds to a difference incartilage thickness of 1% (Coleman et al., 2013; Widmyer et al., 2013).

2.4. Statistical methods

The Yates corrected chi-squared test was used to compare the proportion ofmales and females between groups and t-tests were used to compare differencesbetween follow-up time and age between groups. A two-way repeated measuresanalysis of variance (ANOVA) was performed to determine whether knee state(intact versus reconstructed) and location had significant effects on cartilagethickness. The Tukey post-hoc test was used to detect differences between means,as appropriate. Differences were considered statistically significant where po0.05.

3. Results

No statistically significant differences were observed betweengroups for proportion of males to females (p¼0.82), age (p¼0.19), orfollow-up time (p¼0.39).

In knees with an anatomic reconstruction, there was a statisticallysignificant effect of location on cartilage thickness (po0.001, Fig. 4).Cartilage in the lateral tibia was thicker than all other regions(po0.001). No differences in cartilage thickness were observedbetween the medial femur, lateral femur, medial tibia, and themedial aspect of the intercondylar notch. No statistically significanteffects of knee state (intact versus reconstructed, p¼0.30) or inter-actions between knee state and location were observed (p¼ 0.27). Inthe medial intercondylar notch, there was a mean difference of just1% in cartilage thickness between intact and reconstructed knees.

In knees with the non-anatomic graft placement, there was astatistically significant interaction between knee state (intact versusreconstructed) and location on cartilage thickness (p¼0.002, Fig. 5).

E.C. Okafor et al. / Journal of Biomechanics 47 (2014) 96–101 97

In particular, cartilage in the medial aspect of the intercondylarnotch in reconstructed knee was significantly thinner than intactcartilage by 8% (p¼0.02). No statistically significant differences incartilage thickness were observed between intact and reconstructedknees in any other region (p40.61). In both intact and recon-structed knees, cartilage in the lateral tibia was thicker than allother regions (po0.001).

4. Discussion

The long-term development of cartilage degeneration remainsa concern after ACL reconstruction (Janssen et al., 2013; Salmon

et al., 2006). This study used MR imaging and 3D modelingtechniques to make site-specific comparisons of femoral and tibialarticular cartilage thickness between reconstructed and intactcontralateral knees in two ACL reconstruction groups. Our datademonstrates that in the anatomic graft placement group, wherekinematics were restored (Abebe et al., 2011b), cartilage thicknesswas maintained. In the non-anatomic graft placement group,where altered joint kinematics were observed (Abebe et al.,2011b), cartilage thickness significantly decreased on the lateralaspect of the medial femoral condyle.

Abnormal knee motion is believed to be an important factorcontributing to the development of OA after ACL reconstruction(Gao et al., 2012; Papannagari et al., 2006; Tashman and Araki,

Fig. 2. A uniform grid of points was created to span the articular surfaces of the femur and tibia. In addition, three points were sampled along the medial intercondylar notch,a region where degeneration is observed clinically after ACL injury (Fairclough et al., 1990).

Fig. 1. Sagittal plane MR images were segmented to create 3D models of the femur, tibia, and articular cartilage.

E.C. Okafor et al. / Journal of Biomechanics 47 (2014) 96–10198

2013; Tashman et al., 2004). Specifically, recent studies havetheorized that abnormal knee motion alters cartilage stress andstrain distributions, thus initiating a cascade of degenerativechanges (Andriacchi et al., 2004; DeFrate et al., 2006; Li et al.,2006; Tashman et al., 2007; Tochigi et al., 2011). In particular,previous studies have indicated that the medial femoral condyle isa region where degeneration is commonly observed after ACLinjury and reconstruction. For example, quantitative MR imagingstudies have indicated that ACL reconstructed knees may demon-strate compositional evidence of cartilage degeneration in themedial femoral condyle (Haughom et al., 2012; Li et al., 2011). Inthis study, we examined a region on the lateral aspect of themedial femoral condyle because it may be at high risk for earlydegenerative changes (Fairclough et al., 1990; Feagin et al., 1982;Maffulli et al., 2003). One previous study noted the presence

of osteophytes on the medial side of the intercondylar notchadjacent to the medial tibial spine in ACL deficient knees(Fairclough et al., 1990). The appearance of osteophytes in thisarea was thought to be the earliest radiographic sign of ACLdeficiency and was hypothesized to be the result of impingementof the medial tibial spine on the medial femoral condyle(Fairclough et al., 1990). In support of this finding, recent studieshave identified this area to be a region where high cartilagecontact strains were observed in ACL deficient patients (Sutteret al., 2013; Van de Velde et al., 2009). In particular, cartilagecontact was shifted closer to the medial tibial spine. This shift wasattributed to the altered anterior tibial translation, medial tibialtranslation, and internal tibial rotations observed in ACL deficient

Non-anatomic Graft Placement

Anatomic Graft Placement

Intact Reconstructed

L M

P

A

Thickness (mm)

4

0

4

0

Fig. 3. Thickness maps of the femur for representative subjects in the anatomic graft placement group (top) and the non-anatomic graft placement group (bottom). In thenon-anatomic group, there is thinner cartilage along the medial intercondylar notch in the reconstructed knee compared to the intact knee. In the anatomic group, similarcartilage thickness is observed in this region. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Medial Femur

Lateral Femur

Medial Intercondylar

Notch

Medial Tibia

Lateral Tibia

Car

tilag

e Th

ickn

ess

(mm

) MF=LF=MIN=MT<LT

Anatomic graft placement

0

1

2

3

4 Intact Reconstructed

Fig. 4. In the anatomic graft placement group, cartilage thickness was the greatestin the lateral tibial plateau. No statistically significant differences in thickness wereobserved between intact and reconstructed knees. Bars represent mean7sem.

Medial Femur

Lateral Femur

Medial Intercondylar

Notch

Medial Tibia

Lateral Tibia

Car

tilag

e Th

ickn

ess

(mm

)

*MF=LF=MIN=MT<LT

Non-anatomic graft placement

0

1

2

3

4 Intact Reconstructed

Fig. 5. In the non-anatomic graft placement group, cartilage thickness varied withlocation in the joint, with the lateral tibia (LT) significantly thicker than the medialtibia (MT), medial intercondylar notch (MIN), lateral femur (LF) and medial femur(MF). Significant differences in cartilage thickness were observed along the medialintercondylar notch between intact and reconstructed knees (a decrease of 8%).Bars represent mean7sem (npo0.05).

E.C. Okafor et al. / Journal of Biomechanics 47 (2014) 96–101 99

patients (DeFrate et al., 2006; Li et al., 2006; Van de Velde et al.,2009).

The results of the present study are in agreement with thesekinematic changes and regions of clinically observed cartilagedegeneration. Specifically, in subjects with non-anatomic graftplacement, where subjects had abnormal anterior tibial translation,medial tibial translation, and internal tibial rotation (Abebe et al.,2011b), we detected decreased cartilage thickness in the lateralaspect of the medial femoral condyle. In patients who had recon-structions that more closely mimicked normal ACL function (Abebeet al., 2011a) and restored normal knee motion (Abebe et al., 2011b),no changes in cartilage thickness were observed. These findingsprovide important evidence that abnormal joint motion maycontribute to the cartilage degeneration that is frequently observedafter ACL reconstruction. Furthermore, these findings suggest thatachieving anatomic graft placement may help to restore normalknee function and, ultimately, may help to slow long-term kneedegeneration compared to non-anatomic reconstructions. However,these subjects were evaluated at only one time point relatively closeto the time of surgery (averages of 18 and 20 months in the non-anatomic and anatomic placement groups, respectively). In thisregard, long-term follow-up studies measuring site specific changesin cartilage thickness, as well as MR-based measurements ofchanges in cartilage composition (Li et al., 2011), would provideimportant information regarding the development and progressionof post-traumatic osteoarthritis in these patients.

In this study, we used MR imaging to assess localized in vivocartilage morphology after ACL reconstruction. Conventionalradiographs of the tibiofemoral joint have been the principalmethod for quantifying joint space narrowing associated withknee osteoarthritis (Altman and Gold, 2007; Foucher et al., 2012;Kellgren and Lawrence, 1957; Wu et al., 2013). Although radio-graphic assessments provide important information regarding theprogression and severity of osteoarthritis in later stages of thedisease, they may be of limited use in detecting early stages ofosteoarthritis due to an inability to directly visualize cartilage(Eckstein et al., 2006). Therefore, directly assessing changes incartilage morphology using MRI might provide a more sensitivemeasure of osteoarthritis progression compared to radiographicmethods (Raynauld et al., 2006). Additionally, the present studysuggests that performing site-specific measurements of changes incartilage thickness might be more sensitive to detecting changes incartilage morphology than volumetric measurements. For exam-ple, we noted a significant decrease of 8% in cartilage thickness inthe medial aspect of the intercondylar notch in the reconstructedknees of patients with non-anatomic graft placement. If thethickness of the medial portion of the intercondylar notch wereaveraged together with that of the rest of the medial femoralcondyle, a decrease of only 2% would be detected.

More recently, several studies have used MRI to quantifychanges in cartilage volume after ACL injury or reconstruction(Andreisek et al., 2009; Li et al., 2012; Van Ginckel et al., 2013).For example, one recent study compared cartilage volumes andthicknesses in subjects 6 months after ACL reconstruction tomatched controls with no injury (Van Ginckel et al., 2013).Although differences in cartilage composition and function wereobserved between groups, no differences in volume or cartilagethickness were detected. Another study performed quantitativeanalysis of cartilage thickness using a regional cartilage surfacesegmentation approach and side-to-side comparisons of each knee(Andreisek et al., 2009). Average cartilage thickness was measuredon a number of different regions on both the femur and tibia(Andreisek et al., 2009). This study also found no differences incartilage thickness 7 years after ACL reconstruction. However,there are some methodological differences between these studiesand the present study that make a direct comparison of results

difficult. Specifically, these previous studies performed volumetricor regional cartilage thickness analyses (as opposed to site-specificthickness measurements) and did not report where the graft wasplaced relative to the ACL footprint.

This study used the contralateral limb as a control rather thanhealthy limbs from matched subjects. The use of the contralaterallimb as a control is supported by a previous study that advocatedthe use of cartilage parameters from the contralateral limb forretrospectively estimating cartilage loss in patients with unilateralosteoarthritis (Eckstein et al., 2002). Inter-subject variability hasbeen noted to be substantially larger than side-to-side differencesin a number of parameters, including volume, mean thickness,maximum thickness, and joint surface area (Eckstein et al., 2002).However, to further address this issue, we compared left to rightdifferences in cartilage thickness along the medial intercondylarnotch in a group of four male control subjects with no history ofknee injury (age range: 20–40 years old). Using an identicalmethodology as described above, 3D models of both knees werecreated and registered to each other. Side to side differences incartilage thickness averaged less than 2% between sides (p¼0.45,paired t-test). Based on these findings, we believe the contralateralknee to be an appropriate control for site-specific measurementsof cartilage thickness in this population.

In conclusion, this study performed site-specific comparisonsof femoral and tibial articular cartilage thickness distributionsin two groups of patients with ACL reconstructions. Our datademonstrates that in the anatomic graft placement group, wherekinematics were restored (Abebe et al., 2011b), no changes incartilage thickness were detected. In the non-anatomic graftplacement group, where altered joint kinematics were observed(Abebe et al., 2011b), cartilage thickness was significantlydecreased in the medial aspect of the intercondylar notch. Thesefindings suggest that restoring normal knee motion after ACLinjury may help to slow the progression of degeneration. Thus,graft placement may have important implications on the devel-opment of osteoarthritis after ACL reconstruction. In the future,long-term follow-up studies are needed to evaluate site-specificchanges in cartilage thickness at multiple time points in thispatient population.

Conflict of interest statement

The authors have no other disclosures related to this work.

Acknowledgments

The authors gratefully acknowledge the support of researchgrants from Arthrex, the National Football Charities, and the NIH(AR063325 and AR055659).

References

Abebe, E.S., Kim, J.P., Utturkar, G.M., Taylor, D.C., Spritzer, C.E., Moorman 3rd, C.T.,Garrett, W.E., DeFrate, L.E., 2011a. The effect of femoral tunnel placement onACL graft orientation and length during in vivo knee flexion. J. Biomech. 44,1914–1920.

Abebe, E.S., Moorman 3rd, C.T., Dziedzic, T.S., Spritzer, C.E., Cothran, R.L., Taylor, D.C., Garrett Jr., W.E., DeFrate, L.E., 2009. Femoral tunnel placement duringanterior cruciate ligament reconstruction: an in vivo imaging analysis compar-ing transtibial and 2-incision tibial tunnel-independent techniques. Am. J.Sports Med. 37, 1904–1911.

Abebe, E.S., Utturkar, G.M., Taylor, D.C., Spritzer, C.E., Kim, J.P., Moorman 3rd, C.T.,Garrett, W.E., DeFrate, L.E., 2011b. The effects of femoral graft placement onin vivo knee kinematics after anterior cruciate ligament reconstruction. J.Biomech. 44, 924–929.

Altman, R.D., Gold, G.E., 2007. Atlas of individual radiographic features in osteoar-thritis, revised. Osteoarthritis Cartilage 15 (Suppl. A), A1–56.

E.C. Okafor et al. / Journal of Biomechanics 47 (2014) 96–101100

Andreisek, G., White, L.M., Sussman, M.S., Kunz, M., Hurtig, M., Weller, I., Essue, J.,Marks, P., Eckstein, F., 2009. Quantitative MR imaging evaluation of the cartilagethickness and subchondral bone area in patients with ACL-reconstructions7 years after surgery. Osteoarthritis Cartilage 17, 871–878.

Andriacchi, T.P., Mundermann, A., Smith, R.L., Alexander, E.J., Dyrby, C.O., Koo, S.,2004. A framework for the in vivo pathomechanics of osteoarthritis at the knee.Ann. Biomed. Eng. 32, 447–457.

Bischof, J.E., Spritzer, C.E., Caputo, A.M., Easley, M.E., DeOrio, J.K., Nunley 2nd, J.A.,DeFrate, L.E., 2010. In vivo cartilage contact strains in patients with lateral ankleinstability. J. Biomech. 43, 2561–2566.

Brophy, R.H., Schmitz, L., Wright, R.W., Dunn, W.R., Parker, R.D., Andrish, J.T.,McCarty, E.C., Spindler, K.P., 2012. Return to play and future ACL injury risk afterACL reconstruction in soccer athletes from the Multicenter Orthopaedic Out-comes Network (MOON) Group. Am. J. Sports Med. 40, 2517–2522.

Caputo, A.M., Lee, J.Y., Spritzer, C.E., Easley, M.E., DeOrio, J.K., Nunley 2nd, J.A.,DeFrate, L.E., 2009. In vivo kinematics of the tibiotalar joint after lateral ankleinstability. Am. J. Sports Med. 37, 2241–2248.

Chen, C.H., Li, J.S., Hosseini, A., Gadikota, H.R., Gill, T.J., Li, G., 2012. Anteroposteriorstability of the knee during the stance phase of gait after anterior cruciateligament deficiency. Gait Posture 35, 467–471.

Coleman, J.L., Widmyer, M.R., Leddy, H.A., Utturkar, G.M., Spritzer, C.E., Moorman3rd, C.T., Guilak, F., DeFrate, L.E., 2013. Diurnal variations in articular cartilagethickness and strain in the human knee. J. Biomech. 46, 541–547.

DeFrate, L.E., Papannagari, R., Gill, T.J., Moses, J.M., Pathare, N.P., Li, G., 2006. The6 degrees of freedom kinematics of the knee after anterior cruciate ligamentdeficiency: an in vivo imaging analysis. Am. J. Sports Med. 34, 1240–1246.

Delince, P., Ghafil, D., 2012. Anterior cruciate ligament tears: conservative orsurgical treatment? A critical review of the literature. Knee Surg. SportsTraumatol. Arthrosc. 20, 48–61.

Deneweth, J.M., Bey, M.J., McLean, S.G., Lock, T.R., Kolowich, P.A., Tashman, S., 2010.Tibiofemoral joint kinematics of the anterior cruciate ligament-reconstructedknee during a single-legged hop landing. Am. J. Sports Med. 38, 1820–1828.

Eckstein, F., Cicuttini, F., Raynauld, J.P., Waterton, J.C., Peterfy, C., 2006. Magneticresonance imaging (MRI) of articular cartilage in knee osteoarthritis (OA):morphological assessment. Osteoarthritis Cartilage 14 (Suppl. A), A46–75.

Eckstein, F., Muller, S., Faber, S.C., Englmeier, K.H., Reiser, M., Putz, R., 2002. Sidedifferences of knee joint cartilage volume, thickness, and surface area, andcorrelation with lower limb dominance—an MRI-based study. OsteoarthritisCartilage 10, 914–921.

Fairclough, J.A., Graham, G.P., Dent, C.M., 1990. Radiological sign of chronic anteriorcruciate ligament deficiency. Injury 21, 401–402.

Feagin Jr., J.A., Cabaud, H.E., Curl, W.W., 1982. The anterior cruciate ligament:radiographic and clinical signs of successful and unsuccessful repairs. Clin.Orthop. Relat. Res., 54–58.

Feller, J., Webster, K.E., 2013. Return to sport following anterior cruciate ligamentreconstruction. Int. Orthop. 37, 285–290.

Foucher, K.C., Schlink, B.R., Shakoor, N., Wimmer, M.A., 2012. Sagittal plane hipmotion reversals during walking are associated with disease severity andpoorer function in subjects with hip osteoarthritis. J. Biomech. 45, 1360–1365.

Gao, B., Cordova, M.L., Zheng, N.N., 2012. Three-dimensional joint kinematics ofACL-deficient and ACL-reconstructed knees during stair ascent and descent.Hum. Mov. Sci. 31, 222–235.

Gao, B., Zheng, N.N., 2010. Alterations in three-dimensional joint kinematics ofanterior cruciate ligament-deficient and -reconstructed knees during walking.Clin. Biomech. (Bristol, Avon) 25, 222–229.

Griffin, T.M., Guilak, F., 2005. The role of mechanical loading in the onset andprogression of osteoarthritis. Exercise Sport Sci. Rev. 33, 195–200.

Halloran, J.P., Sibole, S., van Donkelaar, C.C., van Turnhout, M.C., Oomens, C.W.,Weiss, J.A., Guilak, F., Erdemir, A., 2012. Multiscale mechanics of articularcartilage: potentials and challenges of coupling musculoskeletal, joint, andmicroscale computational models. Ann. Biomed. Eng. 40, 2456–2474.

Haughom, B., Schairer, W., Souza, R.B., Carpenter, D., Ma, C.B., Li, X., 2012. Abnormaltibiofemoral kinematics following ACL reconstruction are associated with earlycartilage matrix degeneration measured by MRI T1rho. Knee 19, 482–487.

Holm, I., Oiestad, B.E., Risberg, M.A., Gunderson, R., Aune, A.K., 2012. No differencesin prevalence of osteoarthritis or function after open versus endoscopictechnique for anterior cruciate ligament reconstruction: 12-year follow-upreport of a randomized controlled trial. Am. J. Sports Med. 40, 2492–2498.

Hosseini, A., Van de Velde, S., Gill, T.J., Li, G., 2012. Tibiofemoral cartilage contactbiomechanics in patients after reconstruction of a ruptured anterior cruciateligament. J. Orthop. Res. 30, 1781–1788.

Janssen, R.P., du Mee, A.W., van Valkenburg, J., Sala, H.A., Tseng, C.M., 2013. Anteriorcruciate ligament reconstruction with 4-strand hamstring autograft and accel-erated rehabilitation: a 10-year prospective study on clinical results, kneeosteoarthritis and its predictors. Knee Surg. Sports Traumatol. Arthrosc. 21,1977–1988.

Kaseta, M.K., DeFrate, L.E., Charnock, B.L., Sullivan, R.T., Garrett Jr., W.E., 2008.Reconstruction technique affects femoral tunnel placement in ACL reconstruc-tion. Clin. Orthop. Relat. Res. 466, 1467–1474.

Kellgren, J.H., Lawrence, J.S., 1957. Radiological assessment of osteo-arthrosis. Ann.Rheum. Dis. 16, 494–502.

Kessler, M.A., Behrend, H., Henz, S., Stutz, G., Rukavina, A., Kuster, M.S., 2008.Function, osteoarthritis and activity after ACL-rupture: 11 years follow-upresults of conservative versus reconstructive treatment. Knee Surg. SportsTraumatol. Arthrosc. 16, 442–448.

Koutras, G., Papadopoulos, P., Terzidis, I.P., Gigis, I., Pappas, E., 2013. Short-termfunctional and clinical outcomes after ACL reconstruction with hamstringsautograft: transtibial versus anteromedial portal technique. Knee Surg. SportsTraumatol. Arthrosc. 21, 1904–1909.

Kvist, J., 2004. Rehabilitation following anterior cruciate ligament injury: currentrecommendations for sports participation. Sports Med. 34, 269–280.

Li, G., Moses, J.M., Papannagari, R., Pathare, N.P., DeFrate, L.E., Gill, T.J., 2006.Anterior cruciate ligament deficiency alters the in vivo motion of the tibiofe-moral cartilage contact points in both the anteroposterior and mediolateraldirections. J. Bone Joint Surg. Am. 88, 1826–1834.

Li, H., Hosseini, A., Li, J.S., Gill, T.J.t., Li, G., 2012. Quantitative magnetic resonanceimaging (MRI) morphological analysis of knee cartilage in healthy and anteriorcruciate ligament-injured knees. Knee Surg. Sports Traumatol. Arthrosc. 20,1496–1502.

Li, X., Kuo, D., Theologis, A., Carballido-Gamio, J., Stehling, C., Link, T.M., Ma, C.B.,Majumdar, S., 2011. Cartilage in anterior cruciate ligament-reconstructedknees: MR imaging T1{rho} and T2—initial experience with 1-year follow-up.Radiology 258, 505–514.

Lohmander, L.S., Englund, P.M., Dahl, L.L., Roos, E.M., 2007. The long-termconsequence of anterior cruciate ligament and meniscus injuries: osteoarthri-tis. Am. J. Sports Med. 35, 1756–1769.

Maffulli, N., Binfield, P.M., King, J.B., 2003. Articular cartilage lesions in thesymptomatic anterior cruciate ligament-deficient knee. Arthroscopy: J. Arthro-scopic Relat. Surg. 19, 685–690.

Papannagari, R., Gill, T.J., DeFrate, L.E., Moses, J.M., Petruska, A.J., Li, G., 2006. In vivokinematics of the knee after anterior cruciate ligament reconstruction: aclinical and functional evaluation. Am. J. Sports Med. 34, 2006–2012.

Raynauld, J.P., Martel-Pelletier, J., Berthiaume, M.J., Beaudoin, G., Choquette, D.,Haraoui, B., Tannenbaum, H., Meyer, J.M., Beary, J.F., Cline, G.A., Pelletier, J.P.,2006. Long term evaluation of disease progression through the quantitativemagnetic resonance imaging of symptomatic knee osteoarthritis patients:correlation with clinical symptoms and radiographic changes. Arthritis Res.Ther. 8, R21.

Renstrom, P., Ljungqvist, A., Arendt, E., Beynnon, B., Fukubayashi, T., Garrett, W.,Georgoulis, T., Hewett, T.E., Johnson, R., Krosshaug, T., Mandelbaum, B., Micheli, L.,Myklebust, G., Roos, E., Roos, H., Schamasch, P., Shultz, S., Werner, S., Wojtys, E.,Engebretsen, L., 2008. Non-contact ACL injuries in female athletes: an InternationalOlympic Committee current concepts statement. Br. J. Sports Med. 42, 394–412.

Salmon, L.J., Russell, V.J., Refshauge, K., Kader, D., Connolly, C., Linklater, J.,Pinczewski, L.A., 2006. Long-term outcome of endoscopic anterior cruciateligament reconstruction with patellar tendon autograft: minimum 13-yearreview. Am. J. Sports Med. 34, 721–732.

Scanlan, S.F., Chaudhari, A.M., Dyrby, C.O., Andriacchi, T.P., 2010. Differences in tibialrotation during walking in ACL reconstructed and healthy contralateral knees. J.Biomech. 43, 1817–1822.

Sutter, E.G., Widmyer, M.R., Utturkar, G.M., Spritzer, C.E., Garrett, W.E., DeFrate, L.E.,2013. Effects of ACL deficiency on localized tibiofemoral cartilage strains afterdynamic activity. Trans. Orthop. Res. Soc. 59, 191.

Tashman, S., Araki, D., 2013. Effects of anterior cruciate ligament reconstruction onin vivo, dynamic knee function. Clin. Sports Med. 32, 47–59.

Tashman, S., Collon, D., Anderson, K., Kolowich, P., Anderst, W., 2004. Abnormalrotational knee motion during running after anterior cruciate ligament recon-struction. Am. J. Sports Med. 32, 975–983.

Tashman, S., Kolowich, P., Collon, D., Anderson, K., Anderst, W., 2007. Dynamicfunction of the ACL-reconstructed knee during running. Clin. Orthop. Relat. Res.454, 66–73.

Taylor, K.A., Terry, M.E., Utturkar, G.M., Spritzer, C.E., Queen, R.M., Irribarra, L.A.,Garrett, W.E., DeFrate, L.E., 2011. Measurement of in vivo anterior cruciateligament strain during dynamic jump landing. J. Biomech. 44, 365–371.

Tochigi, Y., Vaseenon, T., Heiner, A.D., Fredericks, D.C., Martin, J.A., Rudert, M.J.,Hillis, S.L., Brown, T.D., McKinley, T.O., 2011. Instability dependency of osteoar-thritis development in a rabbit model of graded anterior cruciate ligamenttransection. J. Bone Joint Surg. Am. 93, 640–647.

Van de Velde, S.K., Bingham, J.T., Hosseini, A., Kozanek, M., DeFrate, L.E., Gill, T.J., Li,G., 2009. Increased tibiofemoral cartilage contact deformation in patients withanterior cruciate ligament deficiency. Arthritis Rheum. 60, 3693–3702.

Van Ginckel, A., Verdonk, P., Victor, J., Witvrouw, E., 2013. Cartilage status inrelation to return to sports after anterior cruciate ligament reconstruction. Am.J. Sports Med. 41, 550–559.

Widmyer, M.R., Utturkar, G.M., Leddy, H.A., Coleman, J.L., Spritzer, C.E., Moorman3rd, C.T., Defrate, L.E., Guilak, F., 2013. High body mass index is associated withincreased diurnal strains in the articular cartilage of the knee. Arthritis Rheum.65, 2615–2622.

Wu, X., Kondragunta, V., Kornman, K.S., Wang, H.Y., Duff, G.W., Renner, J.B., Jordan, J.M., 2013. IL-1 receptor antagonist gene as a predictive biomarker of progressionof knee osteoarthritis in a population cohort. Osteoarthritis Cartilage 21,930–938.

E.C. Okafor et al. / Journal of Biomechanics 47 (2014) 96–101 101