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. Author manuscript; available in PMC: 2025 Mar 1.
Published in final edited form as: Med Sci Sports Exerc. 2023 Oct 5;56(3):411–417. doi: 10.1249/MSS.0000000000003318

Physical Activity Associates with T1rho MRI of Femoral Cartilage Following Anterior Cruciate Ligament Reconstruction

Hope C Davis-Wilson 1,2,3, Louise M Thoma 4,5, Jason R Franz 6, J Troy Blackburn 3,4,7, Lara Longobardi 8, Todd A Schwartz 4,9, Anthony C Hackney 10, Brian Pietrosimone 3,4,7
PMCID: PMC10922225  NIHMSID: NIHMS1934629  PMID: 37796166

Abstract

Purpose:

Less physical activity has been associated with systemic biomarkers of cartilage breakdown following anterior cruciate ligament reconstruction (ACLR). Yet, previous research lacks analysis of deleterious cartilage compositional changes and objective physical activity following ACLR. The purpose of this study was to determine the association between physical activity quantified via accelerometer-based measures of daily steps and time in moderate-to-vigorous physical activity (MVPA), and T1rho magnetic resonance imaging (MRI) of the femoral articular cartilage, a marker of proteoglycan density in individuals with ACLR.

Methods:

Daily steps and MVPA were assessed over 7 days using an accelerometer worn on the hip in 26 individuals between 6–12 months following primary unilateral ACLR. Resting T1rho MRI were collected bilaterally, and T1rho MRI inter-limb ratios (ILR: ACLR limb/contralateral limb) were calculated for lateral and medial femoral condyle regions of interest. We conducted univariate linear regression analyses to determine associations between T1rho MRI ILRs and daily steps and MVPA with and without controlling for sex.

Results:

Greater T1rho MRI ILR of the central lateral femoral condyle, indicative of less proteoglycan density in the ACLR limb, was associated with greater time in MVPA (R2=0.178, P=0.032). Sex-adjusted models showed significant interaction terms between daily steps and sex in the anterior (P=0.025), central (P=0.002), and posterior (P=0.002) medial femoral condyle.

Conclusions:

Lesser physical activity may be a risk factor for maintaining cartilage health following ACLR; additionally, the relationship between physical activity and cartilage health may be different between males and females.

Keywords: MODERATE TO VIGOROUS PHYSICAL ACTIVITY, MVPA, DAILY STEPS, ACCELEROMETRY, CARTILAGE COMPOSITION, POST TRAUMATIC KNEE OSTEOARTHRITIS

INTRODUCTION

Individuals who sustain anterior cruciate ligament (ACL) injury and undergo ACL reconstruction (ACLR) are at a high risk of developing posttraumatic knee osteoarthritis (PTOA), with two-thirds of individuals developing PTOA within two decades of initial ACL injury (1). While the development of PTOA is complex, aberrant loading of joint tissues has been hypothesized to play a major role in PTOA pathogenesis (2–5). Previous studies indicate that both excessive (6, 7) and insufficient loading (4, 8, 9) may lead to deleterious changes in joint tissue health, suggesting that determining optimal joint loading following injury is critical for prescribing effective treatments for preventing PTOA. Specifically, lesser lower extremity loading (measured with peak vertical ground reaction force [vGRF]) during walking is associated with diminished proteoglycan density within the femoral articular cartilage in the first six months following ACLR (5). Similarly, lesser peak tibiofemoral contact forces during early stance phase six months post-ACLR are associated with greater likelihood of radiographic PTOA five years post-ACLR (10). Conversely, others have reported that greater peak vGRF during early stance phase is associated with greater proteoglycan density of the tibiofemoral cartilage in participants undergoing ACLR (11). It is unclear why similar studies yield different results. It is possible that loading measurements captured in a research laboratory do not represent habitual loading in real-world settings.

Measuring daily steps utilizing accelerometry-based physical activity may provide unique and important information regarding the relationship between habitual loading that occurs with physical activity and cartilage composition following ACLR. Previous studies (5, 9, 11) have primarily focused on the link between the magnitude of lower extremity loading over a single step but not the number of steps taken daily, which may account for discrepancies between studies that have evaluated the link between both insufficient and excessive loading and cartilage health (4, 6–9). Physical activity can be estimated with accelerometer-based measures of daily steps and time spent in moderate-to-vigorous physical activity (MVPA) (12). A previous cross-sectional study found that individuals post-ACLR engage in fewer daily steps and fewer minutes in MVPA compared to age- and sex-matched uninjured controls (12), with females less likely to meet national MVPA guidelines compared to healthy participants (13). Reductions in daily steps and time in MVPA following ACLR decrease the total volume of loading placed on knee joint tissues (14); however, it is unknown if daily steps and time in MVPA are related to knee joint tissue health. Daily steps and time spent in MVPA may be modifiable factors to monitor following ACLR to sustain cartilage health and prevent or delay development of PTOA.

Proteoglycans are an integral component of the articular cartilage extracellular matrix and provide osmotic properties that contribute to the ability of the cartilage to resist compressive loads (15). Diminished proteoglycan density of articular cartilage is an early composition change associated with PTOA development (16), suggesting that higher proteoglycan density may be beneficial. T1rho magnetic resonance imaging (MRI) relaxation times are inversely associated with proteoglycan density (17, 18) and have been used in vivo to estimate articular cartilage composition following ACLR (11, 19, 20). Greater T1rho MRI relaxation times indicate lesser proteoglycan density and have been found in the femoral cartilage of ACLR limbs compared to contralateral limbs (21) and limbs of uninjured controls (19) within 12 months following ACLR. T1rho MRI relaxation times are influenced by joint loading, undergoing transient increases during unloading (22) and decreasing throughout the day due to loading during daily activities (23). Recent literature suggests that higher patient-reported physical activity levels associate with lesser proteoglycan density after ACLR, indicating higher physical activity levels may be detrimental to cartilage health (24). However, self-reported measures of physical activity are known to overestimate true physical activity levels compared to objective measures (25), and we hypothesize that evaluating objective physical activity outcomes rather than self-reported may yield different results. Therefore, the next logical step in this area of research is to evaluate the association between proteoglycan density of the articular cartilage and objectively measured physical activity following ACLR. The primary purpose of the current study was to determine the association between daily steps, time spent in MVPA, and T1rho MRI relaxation times in individuals between 6–12 months post-ACLR. We hypothesized that lesser T1rho MRI relaxation times (i.e., greater proteoglycan density) of femoral articular cartilage would be associated with greater daily steps and greater time in MVPA.

METHODS

Design

Individuals with a bone-patellar-tendon-bone ACLR autograft completed two laboratory testing sessions on separate days as part of this cross-sectional study. Demographic variables, self-reported meniscal injury, and patient-reported outcomes related to knee function (Knee Injury and Osteoarthritis Outcomes Score [KOOS]) and sport participation (Tegner Scale) were collected during the initial session (Table 1). Daily steps and time in MVPA were assessed using an ActiGraph GT9X Link triaxial accelerometer worn outside of the laboratory for a 7-day period, which began the day following the initial session. Resting T1rho MRI relaxation times were collected on the injured ACLR limb followed by the uninjured contralateral limb during the second session (27±22 days after the initial session). The Institutional Review Board at the approved all methods, and all participants (and parental guardians for adolescent participants) provided written consent before participation.

Table 1.

Descriptive and Outcome Variables

Entire Cohort (N=26) Males (n=10) Females (n=16)
Age (years) 21±4 24±5 19±3 *
Height (m) 1.70±0.10 1.79±0.09 1.64±0.06 *
Mass (kg) 72.0±13.3 82.1±12.5 65.6±9.6 *
Body Mass Index (kg/m2) 24.9±2.9 25.5±2.0 24.5±3.4
Months post-ACLR 8±1 9±2 7±1 *
Self-reported meniscal injury Yes = 10
No = 7
Unknown = 9		 Yes = 6
No = 1
Unknown = 3		 Yes = 4
No = 6
Unknown = 6
KOOS Symptoms 80.6±12.1 79.6±11.8 81.2±12.7
KOOS Pain 87.3±7.6 89.4±8.5 85.9±7.0
KOOS Activities of Daily Living 94.6±6.5 96.5±4.7 93.4±7.3
KOOS Sports 71.7±18.9 75.5±17.1 69.4±20.1
KOOS Quality of Life 58.9±17.3 58.7±23.2 59.0±13.3
Tegner Scale 5.5±1.9 6±2 5±2
Daily steps 7678±2327 7968±2421 7496±2328
Moderate-Vigorous Physical Activity (minutes/day) 59.6±25.4 69±25 54±25
ActiGraph Average Daily Wear Time 14.1±1.1 hours/day 14.1±0.8 hours/day 14.2±1.3 hours/day
ActiGraph Total Daily Wear Time 81.1±14.4 hours 84.8±14.6 hours 78.8±14.3 hours
ActiGraph Number of Valid Days 5.7±0.9 days 6.0±0.9 days 5.6±0.9 days
Anterior MFC MRI T1rho ILR Involved (ms) 58.2±4.6 60.7±2.8 56.6±4.9 *
Contralateral (ms) 53.9±3.4 54.3±3.3 54.6±3.6
Interlimb ratio 1.08±0.09 1.12±0.08 1.06±0.10
Central MFC T1rho MRI ILR Involved (ms) 55.3±4.3 56.6±3.7 54.6±4.5
Contralateral (ms) 51.9±3.9 52.6±2.7 51.4±4.4
Interlimb ratio 1.07±0.11 1.08±0.09 1.07±0.12
Posterior MFC MRI T1rho ILR Involved (ms) 54.9±3.7 55.6±2.9 54.4±4.1
Contralateral (ms) 52.9±3.0 53.6±3.0 52.5±3.1
Interlimb ratio 1.04±0.08 1.04±0.07 1.04±0.09
Anterior LFC MRI T1rho ILR Involved (ms) 56.1±4.5 57.1±2.2 55.5±5.5
Contralateral (ms) 49.8±4.3 49.9±3.3 49.8±4.9
Interlimb ratio 1.13±0.11 1.15±0.08 1.12±0.13
Central LFC MRI T1rho ILR Involved (ms) 55.4±4.2 57.5±3.7 54.1±4.0 *
Contralateral (ms) 53.0±3.7 53.1±3.8 52.8±3.8
Interlimb ratio 1.05±0.10 1.09±0.13 1.03±0.08
Posterior LFC MRI T1rho ILR Involved (ms) 56.2±4.1 59.3±2.5 54.2±3.7 *
Contralateral (ms) 55.3±3.6 56.0±3.9 54.8±3.5
Interlimb ratio 1.02±0.09 1.06±0.10 0.99±0.08 *
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ACLR – anterior cruciate ligament reconstruction, KOOS – Knee Injury and Osteoarthritis Outcomes Score, MRI – magnetic resonance imaging, MFC – medial femoral condyle, LFC – lateral femoral condyle, ILR- interlimb ratio

*

Significantly different from male cohort (P < 0.05)

Participants

We included individuals who underwent unilateral ACLR using a bone-patellar-tendon-bone autograft within the 6–12 months prior to data collection and had physician approval to return to participation in physical activity. We excluded individuals less than 6 months post-ACLR to ensure that participants had returned to physical activity participation. We excluded individuals greater than 12 months post-ACLR to reduce covariance in loading outcomes due to time from injury (26). Individuals between the ages of 16–35 years with a BMI ≤ 35 kg/m2 were included. Individuals were excluded if they were currently pregnant, had been previously diagnosed with any form of inflammatory arthritis, needed multi-ligament reconstruction, or had a previous history of ACLR on either limb. Individuals were excluded from MRI if they had a history of cochlear implant or claustrophobia. Descriptive data are provided in Table 1. We estimated moderate associations would be detected between T1rho MRI relaxation times and daily steps as well as T1rho MRI relaxation times and MVPA based on previous data evaluating the association (R2 = 0.37) between daily steps and change in T1rho MRI relaxation times in uninjured healthy individuals (23). Therefore, we needed 26 participants to detect statistical significance with 80% power for a multiple linear regression model with an R2 of this magnitude with an alpha level set at 0.05 (G*Power, v3.1.9.2) (27).

Objectively Measured Physical Activity

At the end of the testing session, participants were given an ActiGraph GT9X Link triaxial accelerometer. The ActiGraph GT9X Link is a valid device to quantify physical activity in free-living conditions (28, 29). Participants wore the accelerometer over the right anterior superior iliac spine for seven consecutive days immediately following the study visit. A valid data collection period consisted of a minimum of 4 days (3 weekdays and 1 weekend day) of wear for no less than 10 hours per day (30). The participants returned the monitor after the wear period, at which time the data were assessed for fidelity and consistency with wear guidelines.

Average daily steps and time spent in MVPA per day were processed and analyzed using ActiLife software (v6.13.3). ActiGraph data was collected at 100 Hz and processed in 1-minute epochs. Total wear time was validated using Choi et al. (30) recommendations (zero-count threshold during a nonwear time interval, 90-min time window for consecutive zero/nonzero counts, allowance of 2-min interval of nonzero counts for detection of artifactual movements) to ensure each participant wore the ActiGraph for at least 4 days for 10 hours per day. Freedson Adult VM3 cut points were used to categorize physical activity as light (<2690 counts/minute), moderate (2690–6166 counts/minute), vigorous (6167–9642 counts/minute), or very vigorous (>9642 counts/minute) based on the number of activity counts per minute during wear time (31). Cut points were then used to calculate MVPA (>2690 counts/minute) (31). Freedson cut points demonstrate moderate to high agreement at identifying sufficient MVPA in young adults (32). Daily steps were assessed using vertical acceleration data measured with the ActiGraph monitor. Outcome variables were then averaged over the number of valid wear days to create a daily average (12).

Magnetic Resonance Image Acquisition

T1rho MRI were acquired on the ACLR limb followed by the uninjured contralateral limb using a Siemens Magnetom Prisma 3T scanner and a 4-channel Siemens large flex coil (516 mm x 224 mm, Siemens, Munich, Germany). Upon arrival at the biomedical imaging center, participants remained seated for 45 minutes to unload the knee cartilage (33). We used a T1rho prepared three-dimensional Fast Low Angle Shot (FLASH) with a spin-lock power at 500Hz, five different spin-lock durations (40, 30, 20, 10, 0 ms) and a voxel size of 0.8 mm x 0.4 mm x 3 mm (field of view= 288 mm, slice thickness=3.0 mm, 160 × 320 matrix, gap= 0 mm, flip angle=10°, echo-train duration time= 443 ms, phase encode direction of anterior/posterior) (34). Before segmentation, an affine registration technique was used to register the ACLR limb image to the uninjured limb image using the 3-D Slicer software (35). After the affine registration, a nonrigid deformable, voxel-by-voxel intensity-based registration technique was applied to account for specific interlimb differences of specific tissues (e.g., bone and cartilage), which allowed for an accurate alignment of the ACLR limb to the uninjured limb.

Segmentation of the Articular Cartilage

The articular cartilage in the medial and lateral condyles of the femur was manually segmented using ITK-SNAP software (36) on a T1rho MRI acquired during the 0 ms spin-lock duration. Manual segmentation of the articular cartilage has strong reliability in our laboratory for all regions of interest (ROI) (intra-rater reliability, N=8, ICC = 0.80–0.97; inter-segmentor reliability, N=10, ICC = 0.75–0.98).(21) The medial and lateral femoral condyles (MFC and LFC) were further sub-sectioned into three regions of interest (ROIs), based upon the location of the meniscus in the sagittal plane (21). The three ROI that were sub-sectioned represent load-bearing regions of the femoral condyle and included: 1) the cartilage overlying the posterior horn of the meniscus (Posterior MFC/LFC), 2) the central portion of the cartilage that lies between the anterior and posterior horns of the meniscus (Central MFC/LFC), and 3) the cartilage corresponding with the anterior horn of the meniscus (Anterior MFC/LFC) (34).

T1rho MRI Relaxation Time Quantification

Voxel by voxel T1rho relaxation maps were constructed from a five-image sequence using a MatLab program (MatLab R2020a, MathWorks, Natick, MA, USA) with the following equation: S(TSL) = S0 exp(−TSL/T1rho), where TSL is the duration of the spin-lock time, S0 is signal intensity when TSL = 0, S is the signal intensity, and T1rho is the T1 relaxation time in the rotating frame. The previous segmentation image was transposed over the T1rho image to establish T1rho MRI relaxation times for each ROI (34). A mean of the T1rho MRI relaxation times for each ROI was calculated using the ITK-SNAP software (36). Higher T1rho MRI relaxation times are interpreted as tissue consisting of lower proteoglycan density (37). For our analyses, we calculated T1rho MRI as an interlimb ratio (ILR) determined as the T1rho MRI relaxation time for the ROI of the ACLR limb normalized to the same ROI in the uninjured contralateral limb (T1rho ILR= ACLR limb/uninjured limb), as described previously (5, 34). Normalizing T1rho relaxation times in cross-sectional studies allows for estimation of individual differences in injured limb cartilage composition and accounts for between-subject variability (5). T1rho MRI ILR values greater than 1.00 demonstrate greater T1rho MRI relaxation times on the ACLR limb compared to the uninjured contralateral limb, indicative of lower relative proteoglycan density in the ACLR limb.

Statistical Analysis

All data were visually assessed for potential statistical outliers using boxplots. Data points ≥ 3x the interquartile range would be flagged as statistical outliers and removed from subsequent analyses. Means and standard deviations were calculated for all continuous variables, with counts and frequencies for non-continuous variables.

For the primary analyses, separate univariate linear regression models were constructed to determine the unique associations between each of daily steps and time in MVPA with T1rho MRI ILR separately for each ROI (Anterior MFC, Central MFC, Posterior MFC, Anterior LFC, Central LFC, Posterior LFC). Separate regression equations were constructed with T1rho MRI ILR for each ROI as the dependent variable and either daily steps or time in MVPA were individually evaluated as independent variables in separate models. We evaluated R2 and unstandardized beta (β) for the criterion variable attributable to each predictor variable.

Post Hoc Analysis

Sex has been shown to influence biological PTOA outcomes following ACLR (38, 39). Therefore, as an exploratory post hoc analysis separate linear models were fit for each physical activity independent variable (daily steps and MVPA) with each T1hrho MRI ILR ROI (dependent variables). Each model included 1) the main effect of the physical activity variable, 2) the main effect of sex (male or female), and 3) the interaction between the physical activity variable and sex. The inclusion of this interaction term allowed for determination of whether the association between physical activity and T1rho MRI ILR differed between males and females. Independent t-tests were conducted for all descriptive and outcome variables between males and females before the post-hoc analyses. Descriptive and outcome variables for the entire cohort, and separately for males and females, are shown in Table 1. Statistical significance was determined a priori as P ≤ 0.05, no adjustments were performed for multiple comparisons, and all statistical analyses were performed using R (v3.6.1).

RESULTS

No outliers were identified for any outcome variables. Men demonstrated greater age (t24=2.92, p=0.007), height (t24=5.35, p<0.001), mass (t24=3.79, p=0.001), months post-ACLR (t24=2.43, p=0.023), T1rho MRI relaxation times in the anterior MFC (t24=2.42, p=0.024), central LFC (t24=2.17, p=0.040), and posterior LFC in the ACLR limb (t24=3.88, p=0.001), and greater T1rho MRI ILR in the posterior LFC (t24=2.18, p=0.039) compared to females (Table 1).

Primary Analyses – Associations within the Entire Cohort

Greater T1rho MRI ILR (lesser proteoglycan density for the ACLR limb) for the central LFC was associated with greater time in MVPA (R2=0.178, β=0.002, p=0.032, Table 2, Figure 1). No significant associations existed between T1rho MRI ILR and daily steps (R2 range: < 0.001 to 0.071, all p>0.05, Table 2) or time in MVPA (R2 range: < 0.001 to 0.118, all p>0.05, Table 2) for other ROIs.

Table 2.

Associations Between Physical Activity and T1rho Interlimb Ratios in Individuals with ACLR

Daily Steps MVPA (minutes/day)
Anterior MFC T1rho ILR R2=0.021 R2=0.118
β= <0.001 β= 0.001
P=0.479 P=0.086
Central MFC T1rho ILR R2=0.014 R2=0.001
β= <0.001 β= <0.001
P=0.569 P=0.883
Posterior MFC T1rho ILR R2=0.012 R2= <0.001
β= <0.001 β= <0.001
P=0.600 P=0.972
Anterior LFC T1rho ILR R2=0.025 R2=0.045
β= <0.001 β= 0.001
P=0.298
P=0.437 P=0.298
Central LFC T1rho ILR R2=0.071 R2=0.178
β= <0.001 β= 0.002
P=0.190 P=0.032 *
Posterior LFC T1rho ILR R2=<0.001 R2=0.011
β= <0.001 β= <0.001
P=0.959 P=0.617
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ACLR – anterior cruciate ligament reconstruction, MVPA – Moderate to Vigorous Physical Activity, MRI – magnetic resonance imaging, MFC – medial femoral condyle, LFC – lateral femoral condyle, ILR – interlimb ratio

*

Significantly different from male cohort (P < 0.05)

Figure 1.

Figure 1.

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Greater minutes in moderate-vigorous physical activity (MVPA) associates with greater T1rho interlimb ratios in the central lateral femoral condyle (LFC) in individuals with an anterior cruciate ligament reconstruction (ACLR).

Post Hoc Analysis – Interaction Between Daily Steps and Sex

There was a significant interaction with sex with the association between daily steps and T1rho MRI ILR of the anterior, central, and posterior MFC (Table 3). Daily steps, sex, and their interaction explained between 30% and 38%, respectively, of the T1rho MRI ILR for anterior, central, and posterior MFC in post-hoc linear models (Table 3). Females who engaged in greater daily steps demonstrated lesser T1rho MRI IRL (higher proteoglycan density of the ACLR limb), and males who engaged in greater daily steps demonstrated greater T1rho MRI IRL (lower proteoglycan density of the ACLR limb). There was no significant interaction between sex and daily steps with respect to T1rho MRI ILR of the anterior, central, and posterior LFC (Table 3).

Table 3.

Linear Associations between Physical Activity, the Interaction Between Physical Activity and Sex, and T1rho ILRs

Daily Steps MVPA (minutes/day)
R2 P-value Daily steps by sex interaction
P-value		 R2 P-value Daily steps by sex interaction
P-value
Anterior MFC T1rho ILR 0.303 0.044 * 0.025 * 0.293 0.051 0.068
Central MFC T1rho ILR 0.359 0.019 * 0.002 * 0.245 0.097 0.014 *
Posterior MFC T1rho ILR 0.381 0.013 * 0.002 * 0.214 0.143 0.023 *
Anterior LFC T1rho ILR 0.061 0.703 0.449 0.061 0.702 0.449
Central LFC T1rho ILR 0.161 0.266 0.548 0.307 0.041 * 0.099
Posterior LFC T1rho ILR 0.174 0.230 0.690 0.176 0.225 0.604
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ILR – Interlimb ratio, MVPA – Moderate to Vigorous Physical Activity, MFC – Medial Femoral Condyle, LFC – Lateral Femoral Condyle

*

Statistically significant (P ≤ 0.05)

Post Hoc Analysis – Interaction Between MVPA and Sex

There was a significant interaction between male sex and greater MVPA for greater T1rho MRI ILR (lesser proteoglycan density of the ACLR limb) of the central and posterior MFC in post-hoc linear models (Table 3); however, the overall models were not statistically significant. The overall model for the central LFC remained statistically significant; however, there was no significant interaction between sex and MVPA with respect to T1rho MRI ILRs (Table 3). No other interaction terms were significant for T1rho MRI ILRs (Table 3).

DISCUSSION

Contrary to our primary hypotheses, greater time in MVPA (i.e., greater physical activity) associated with greater T1rho MRI ILR (i.e., lesser proteoglycan density in the ACLR limb) in the central LFC in individuals post-ACLR. Our results agree with a recent preliminary study which found that high physical activity levels associate with worse MRI outcomes of cartilage quality very early (1-month) post-ACL injury (40). Daily steps did not significantly associate with T1rho MRI ILR in any ROI in the unadjusted model; however, sex may influence the association between daily steps and T1rho MRI ILRs of the anterior, central, and posterior MFC. Results from our cohort suggest that females who engaged in greater daily steps demonstrated lesser T1rho MRI ILRs of the anterior, central, and posterior MFC (indicative of greater proteoglycan content in the ACLR limb), while males who engaged in greater daily steps demonstrated greater T1rho MRI ILRs in the anterior, central, and posterior MFC (indicative of lesser proteoglycan content in the ACLR limb). The influence that sex has on the association between physical activity and cartilage composition reflects the need to determine sex-specific optimal joint loading following ACLR, as both insufficient and excessive physical activity may be linked to deleterious changes in joint tissue health within the first 12 months following ACLR (10, 11).

To our knowledge, this is the first study to evaluate the association between accelerometer-based measures of physical activity and femoral articular cartilage proteoglycan density following ACLR. However, ACL injuries often occur in young and physically active individuals (41), and the participants with an ACLR in our cohort engaged in 61±23 minutes per day of MVPA, or approximately 7 hours/ week of MVPA, 8±2 months post-ACLR. ACSM guidelines suggest that healthy adults should aim for 150 min/week of MVPA; completing 7 hours/week of MVPA while recovering from injury could potentially be a high amount for the typical recreational athlete. While our study is cross-sectional in nature and cannot determine causality, a high amount of time spent in MVPA may negatively affect femoral cartilage composition in specific individuals within 12 months of ACLR. Average MVPA for our ACLR cohort (60±25 min/d) was similar to individuals with ACLR from a previous study who were of similar age and BMI (79±24 min/d) suggesting our sample is representative of our target population (12). Uninjured controls of similar age and BMI engaged in 94±22 min/d of MVPA (12), suggesting our cohort was less active than an uninjured group. Future research is needed to determine the optimal MVPA in the first 12 months following ACLR. This highlights the need for a larger study to evaluate the relationship between physical activity and T1rho MRI ILR while accounting for any potential covariates.

Post-hoc analyses suggest that the association between daily steps and T1rho MRI ILRs in the anterior, central, and posterior MFC are moderated by sex. It should be noted that males in our cohort engaged in a statistically nonsignificant greater time in MVPA (69±21 min/d) compared to females (54±23 min/d, Cohen’s d=0.60), which may explain some difference in the association between daily steps and T1rho outcomes between males and females. This agrees with previous literature suggesting males are more likely to meet ACSM physical activity guidelines than females post-ACLR (13). While it remains unknown how much time in MVPA is considered excessive within the first 12 months following ACLR, it is possible that higher average MVPA in males contributed to the stronger association between greater daily steps and greater T1rho MRI ILR in the MFC. Conversely, females demonstrated that fewer daily steps were associated with greater T1rho MRI ILR in the MFC. It is possible that the differing relationship between daily steps and cartilage composition found between sexes could be influenced by physiological factors such as hormonal influences (42), behavioral differences (e.g., sex differences in physical activity engagement) (13), or other psychosocial factors. For example, females tend to demonstrate lower self-efficacy following ACLR compared to males (43), which could influence physical activity levels, movement patterns, and other factors related to articular cartilage composition. Our post-hoc analyses were exploratory in nature and cannot conclude which factors are driving the difference found between males and females. Differences in our cohort between men and women like age and time since ACLR may influence results as well. Our study further highlights the need for future research that systematically identifies factors that influence physical activity and cartilage composition as a person recovers from ACLR.

The association between physical activity and cartilage composition may impact how clinicians approach rehabilitation in the first 12 months following ACLR. Overall daily walking, measured with daily steps, and exercise intensity, measured with time spent in MVPA, should be monitored as individuals rehabilitate following ACLR. In agreement with our results, Friedman et al. found higher patient-reported activity levels (Marx activity scores) associated with greater T1rho cartilage compositional degeneration 3 years following ACLR (24). Due to the cross-sectional nature of our study, it remains unknown how time spent in MVPA changes throughout ACLR rehabilitation. Further longitudinal research is needed to understand how time in MVPA may contribute to insufficient or excessive lower extremity loading during the first 12 months following ACLR.

The current study was the first to demonstrate associations between daily steps, time in MVPA, and proteoglycan density of femoral articular cartilage in individuals post-ACLR; however, there are some limitations to our work. We focused our current analysis on T1ρ relaxation times of the femoral articular cartilage as femoral compartments have been reported to demonstrate early T1ρ relaxation times changes (44) and greater osteophyte formation(45). Future work should expand analyses to the tibia to determine the effect of different physical activity levels on tibial cartilage t1ρ relaxation times. Age, height, mass, and months post-ACLR were significantly different between males and females (Table 1), but due to our sample size, we did not include these outcomes as covariates in the linear regression models to avoid overfitting the models, which is a limitation of the current study. Our sample size was limited, and results from the current study suggest additional research should evaluate sex differences in physical activity and proteoglycan density in larger sample sizes. Our design was cross-sectional, so we can not imply causation, and we did not include an uninjured control group. It is possible that those with better knee joint health can better tolerate high physical activity levels; however, to our knowledge it remains unknown how knee joint health and physical activity levels correlate in those without a knee injury. It is unknown if there is an optimal range of proteoglycan density following ACLR, and this should be addressed in future work. Lastly, mechanism of injury was not collected in the current study; however, contact vs. non-contact injuries may influence MRI outcomes. There is still a need for a longitudinal study to evaluate physical activity and cartilage composition following ACLR.

CONCLUSIONS

In conclusion, greater time in MVPA associates with lesser proteoglycan density in the central LFC in the ACLR limb in individuals post-ACLR. Males who engaged in greater daily steps demonstrated lesser proteoglycan density in the anterior, central, and posterior portions of the MFC in the ACLR limb compared to the contralateral limb. Females who engaged in greater daily steps demonstrated greater proteoglycan density in the anterior, central, and posterior MFC of the ACLR limb compared to the contralateral limb. Physical activity is an important, modifiable risk factor to consider for sustaining cartilage health following ACLR, as both excessive and insufficient loading may be detrimental following ACLR. Our results suggest the need to study further how sex-specific physical activity intervention strategies within the first year following ACLR may impact cartilage health.

Acknowledgments

The results of this study are presented clearly, honestly, and without fabrication, falsification, or inappropriate data manipulation. The results of the present study do not constitute endorsement by the American College of Sports Medicine.

Funding Source:

The current study was funded by a grant from the National Institutes of Health National Institute of Arthritis & Musculoskeletal and Skin Diseases (R21 AR074094) and the American College of Sports Medicine Doctoral Student Research Grant.

Footnotes

Conflict of Interest

There are no professional relationships with companies or manufacturers who will benefit from the results of the present study to disclose.

REFERENCES

  • 1.Luc B, Gribble PA, Pietrosimone BG. Osteoarthritis prevalence following anterior cruciate ligament reconstruction: a systematic review and numbers-needed-to-treat analysis. J Athl Train. 2014;49(6):806–19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Hart HF, Culvenor AG, Collins NJ, et al. Knee kinematics and joint moments during gait following anterior cruciate ligament reconstruction: a systematic review and meta-analysis. Br J Sports Med. 2016;50(10):597–612. [DOI] [PubMed] [Google Scholar]
  • 3.Webster KE, Feller JA, Wittwer JE. Longitudinal changes in knee joint biomechanics during level walking following anterior cruciate ligament reconstruction surgery. Gait Posture. 2012;36(2):167–71. [DOI] [PubMed] [Google Scholar]
  • 4.Pietrosimone B, Blackburn JT, Harkey MS, et al. Greater mechanical loading during walking is associated with less collagen turnover in individuals with anterior cruciate ligament reconstruction. Am J Sports Med. 2016;44(2):425–32. [DOI] [PubMed] [Google Scholar]
  • 5.Pfeiffer SJ, Spang J, Nissman D, et al. Gait mechanics and T1ρ MRI of tibiofemoral cartilage 6 months after ACL reconstruction. Med Sci Sports Exerc. 2019;51(4):630–9. [DOI] [PubMed] [Google Scholar]
  • 6.Kumar D, Manal KT, Rudolph KS. Knee joint loading during gait in healthy controls and individuals with knee osteoarthritis. Osteoarthritis Cartilage. 2013;21(2):298–305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 7.Meireles S, Wesseling M, Smith CR, Thelen DG, Verschueren S, Jonkers I. Medial knee loading is altered in subjects with early osteoarthritis during gait but not during step-up-and-over task. PLoS One. 2017;12(11):e0187583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 8.Luc-Harkey BA, Franz JR, Hackney AC, Blackburn JT, Padua DA, Pietrosimone B. Lesser lower extremity mechanical loading associates with a greater increase in serum cartilage oligomeric matrix protein following walking in individuals with anterior cruciate ligament reconstruction. Clin Biomech (Bristol, Avon). 2018;60:13–9. [DOI] [PubMed] [Google Scholar]
  • 9.Pietrosimone B, Loeser RF, Blackburn JT, et al. Biochemical markers of cartilage metabolism are associated with walking biomechanics 6-months following anterior cruciate ligament reconstruction. J Orthop Res. 2017;35(10):2288–97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Wellsandt E, Gardinier ES, Manal K, Axe MJ, Buchanan TS, Snyder-Mackler L. Decreased knee joint loading associated with early knee osteoarthritis after anterior cruciate ligament injury. Am J Sports Med. 2016;44(1):143–51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Teng HL, Wu D, Su F, et al. Gait characteristics associated with a greater increase in medial knee cartilage T1rho and T2 relaxation times in patients undergoing anterior cruciate ligament reconstruction. Am J Sports Med. 2017;45(14):3262–71. [DOI] [PubMed] [Google Scholar]
  • 12.Bell DR, Pfeiffer KA, Cadmus-Bertram LA, et al. Objectively measured physical activity in patients after anterior cruciate ligament reconstruction. Am J Sports Med. 2017;45(8):1893–900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Kuenze C, Lisee C, Pfeiffer KA, et al. Sex differences in physical activity engagement after ACL reconstruction. Phys Ther Sport. 2019;35:12–7. [DOI] [PubMed] [Google Scholar]
  • 14.Maly MR, Robbins SM, Stratford PW, Birmingham TB, Callaghan JP. Cumulative knee adductor load distinguishes between healthy and osteoarthritic knees-a proof of principle study. Gait Posture. 2013;37(3):397–401. [DOI] [PubMed] [Google Scholar]
  • 15.Roughley PJ, Lee ER. Cartilage proteoglycans: structure and potential functions. Microsc Res Tech. 1994;28(5):385–97. [DOI] [PubMed] [Google Scholar]
  • 16.Rautiainen J, Nissi MJ, Salo EN, et al. Multiparametric MRI assessment of human articular cartilage degeneration: correlation with quantitative histology and mechanical properties. Magn Reson Med. 2015;74(1):249–59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Duvvuri U, Charagundla SR, Kudchodkar SB, et al. Human knee: in vivo T1(rho)-weighted MR imaging at 1.5 T--preliminary experience. Radiology. 2001;220(3):822–6. [DOI] [PubMed] [Google Scholar]
  • 18.Regatte RR, Akella SVS, Borthakur A, Kneeland JB, Reddy R. Proteoglycan depletion-induced changes in transverse relaxation maps of cartilage: comparison of T2 and T1rho. Acad Radiol. 2002;9(12):1388–94. [DOI] [PubMed] [Google Scholar]
  • 19.Li X, Kuo D, Theologis A, et al. Cartilage in anterior cruciate ligament-reconstructed knees: MR imaging T1{rho} and T2--initial experience with 1-year follow-up. Radiology. 2011;258(2):505–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Su F, Hilton JF, Nardo L, et al. Cartilage morphology and T1rho and T2 quantification in ACL-reconstructed knees: a 2-year follow-up. Osteoarthritis Cartilage. 2013;21(8):1058–67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Pietrosimone B, Nissman D, Padua DA, et al. Associations between cartilage proteoglycan density and patient outcomes 12months following anterior cruciate ligament reconstruction. Knee. 2018;25(1):118–29. [DOI] [PubMed] [Google Scholar]
  • 22.Souza RB, Baum T, Wu S, et al. Effects of unloading on knee articular cartilage T1rho and T2 magnetic resonance imaging relaxation times: a case series. J Orthop Sports Phys Ther. 2012;42(6):511–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Taylor KA, Collins AT, Heckelman LN, et al. Activities of daily living influence tibial cartilage T1rho relaxation times. J Biomech. 2019;82:228–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Friedman JM, Su F, Zhang AL, et al. Patient-reported activity levels correlate with early cartilage degeneration after anterior cruciate ligament reconstruction. Am J Sports Med. 2021;49(2):442–9. [DOI] [PubMed] [Google Scholar]
  • 25.Celis-Morales CA, Perez-Bravo F, Ibañez L, Salas C, Bailey MES, Gill JMR. Objective vs. self-reported physical activity and sedentary time: effects of measurement method on relationships with risk biomarkers. PLoS One. 2012;7(5):e36345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Capin JJ, Khandha A, Zarzycki R, et al. Gait mechanics and tibiofemoral loading in men of the ACL-SPORTS randomized control trial. J Orthop Res. 2018;36(9):2364–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav Res Methods. 2007;39(2):175–91. [DOI] [PubMed] [Google Scholar]
  • 28.Quante M, Kaplan ER, Rueschman M, Cailler M, Buxton OM, Redline S. Practical considerations in using accelerometers to assess physical activity, sedentary behavior, and sleep. Sleep Health. 2015;1(4):275–84. [DOI] [PubMed] [Google Scholar]
  • 29.Valkenet K, Veenhof C. Validity of three accelerometers to investigate lying, sitting, standing and walking. PLoS One. 2019;14(5):e0217545. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30.Choi L, Liu Z, Matthews CE, Buchowski MS. Validation of accelerometer wear and nonwear time classification algorithm. Med Sci Sports Exerc. 2011;43(2):357–64. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 31.Sasaki JE, John D, Freedson PS. Validation and comparison of ActiGraph activity monitors. J Sci Med Sport. 2011;14(5):411–6. [DOI] [PubMed] [Google Scholar]
  • 32.Leinonen AM, Ahola R, Kulmala J, et al. Measuring physical activity in free-living conditions-Comparison of three accelerometry-based methods. Front Physiol. 2017;7:681. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Harkey MS, Blackburn JT, Hackney AC, et al. Comprehensively assessing the acute femoral cartilage response and recovery after walking and drop-landing: an ultrasonographic study. Ultrasound Med Biol. 2018;44(2):311–20. [DOI] [PubMed] [Google Scholar]
  • 34.Pfeiffer S, Harkey MS, Stanley LE, et al. Associations between slower walking speed and T1rho magnetic resonance imaging of femoral cartilage following anterior cruciate ligament reconstruction. Arthritis Care Res (Hoboken). 2018;70(8):1132–40. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.Fedorov A, Beichel R, Kalpathy-Cramer J, et al. 3D Slicer as an image computing platform for the Quantitative Imaging Network. Magn Reson Imaging. 2012;30(9):1323–41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Yushkevich PA, Piven J, Hazlett HC, et al. User-guided 3D active contour segmentation of anatomical structures: significantly improved efficiency and reliability. Neuroimage. 2006;31(3):1116–28. [DOI] [PubMed] [Google Scholar]
  • 37.Theologis AA, Haughom B, Liang F, et al. Comparison of T1rho relaxation times between ACL-reconstructed knees and contralateral uninjured knees. Knee Surg Sports Traumatol Arthrosc. 2014;22(2):298–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Davis HC, Spang JT, Loeser RF, et al. Time between anterior cruciate ligament injury and reconstruction and cartilage metabolism six-months following reconstruction. Knee. 2018;25(2):296–305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Lane AR, Harkey MS, Davis HC, et al. Body mass index and type 2 collagen turnover in individuals after anterior cruciate ligament reconstruction. J Athl Train. 2019;54(3):270–5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Wellsandt E, Kallman T, Golightly Y, et al. Knee joint unloading and daily physical activity associate with cartilage T2 relaxation times 1 month after ACL injury. J Orthop Res. 2022;40(1):138–49. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 41.Schub D, Saluan P. Anterior cruciate ligament injuries in the young athlete: evaluation and treatment. Sports Med Arthrosc Rev. 2011;19(1):34–43. [DOI] [PubMed] [Google Scholar]
  • 42.Bell DR, Blackburn JT, Norcross MF, et al. Estrogen and muscle stiffness have a negative relationship in females. Knee Surg Sports Traumatol Arthrosc. 2012;20(2):361–7. [DOI] [PubMed] [Google Scholar]
  • 43.Thomee P, Wahrborg P, Borjesson M, Thomee R, Eriksson BI, Karlsson J. Self-efficacy of knee function as a pre-operative predictor of outcome 1 year after anterior cruciate ligament reconstruction. Knee Surg Sports Traumatol Arthrosc. 2008;16(2):118–27. [DOI] [PubMed] [Google Scholar]
  • 44.Kumar D, Su F, Wu D, et al. Frontal plane knee mechanics and early cartilage degeneration in people with anterior cruciate ligament reconstruction: a longitudinal study. Am J Sports Med. 2018;46(2):378–87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 45.Culvenor AG, Collins NJ, Guermazi A, et al. Early knee osteoarthritis is evident one year following anterior cruciate ligament reconstruction: a magnetic resonance imaging evaluation. Arthritis Rheumatol. 2015;67(4):946–55. [DOI] [PubMed] [Google Scholar]

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