Baseline Knee Extension Is Associated With Volumetric Femoral Cartilage Loss in the Central Region of the Mid-lateral and External Medial Femoral Condyles: Data From the Osteoarthritis Initiative

Abstract

Objective

Data evaluating knee flexion contracture (FC)-associated regional changes on femoral articular cartilage are lacking. We compared regional femoral articular cartilage outcomes of people with knee osteoarthritis (OA) with and without FC using quantitative MRI data.

Methods

Articular cartilage of the medial and lateral femoral condyles were segmented into internal, central, and external subregions on MRI. Goniometry measured knee extension. We tested for regional differences in cartilage thickness and percent denuded bone (i.e., 0mm cartilage thickness) in the presence or absence of FC, and for associations between cartilage outcomes with quantitative knee extension range of motion (ROM) using a linear model for 596 participants.

Results

For FC versus no FC, cartilage thickness in the central lateral subregion was higher (2.36±0.42mm vs. 2.29±0.43mm; p<0.05), with higher percent denuded bone in the central lateral (0.92±3.5% vs. 0.39±2.2%; p<0.05) and central medial subregions (4.61±12.88% vs. 3.17±11.66%; p<0.05). Lost knee extension was associated with increased percent denuded bone in the internal lateral (r=0.095; p<0.05), central lateral (r=0.90; p<0.05), and central medial subregions (r=0.117; p<0.01) but with increased central lateral cartilage thickness (r=0.110; p<0.01). After correcting for clinical factors, an association between lost knee extension and increased percent denuded bone remained in the central lateral femur [β=0.059; (95% CI 0.003–0.114)].

Conclusion

Conclusion: Lost knee extension was associated with increased percent denuded bone in the central lateral and external medial femur. Interventions to maintain and/or restore knee ROM may benefit femoral cartilage health. Longitudinal studies evaluating the impact of lost knee ROM on femoral cartilage are warranted.

Introduction

Osteoarthritis (OA) is a degenerative joint disease associated with loss of articular cartilage, a highly specialized viscoelastic tissue that provides protection from compressive forces to subchondral bone through load distribution, as well as low-friction movement between articular surfaces.^1,2 The mechanical behaviour of cartilage depends on the presence of collagen (predominantly type II), proteoglycans, and water content. ³ As OA advances, the structure and function of articular cartilage becomes progressively compromised.^2,3 The breakdown of the cartilage matrix begins in the superficial zone, further progressing into deeper zones, including the middle and deep zones, as OA advances. ² The mechanical properties of articular cartilage experience adverse affects, including reduction of its ability to withstand tension (reduced tensile modulus and stiffness), and as well as shear. ² As a result, cartilage begins to experience fibrillation at the articular surface and depletion of the proteoglycan extracellular matrix, alteration in the concentrations of critical trace elements within the cartilage matrix (e.g. iron, copper, zinc, and others) and increase in water content.^2-4 Such changes result in a catabolic state with the joint, including increased matrix metalloproteinase release and activity, release of inflammatory markers such as IL-1 and TGF-beta, adverse changes in major signaling pathways (Wnt/β-catenin, Notch, Ihh, FGF), chondrocyte hypertrophy and apoptosis, as well as neo-angiogenesis into the normally-avascular articular cartilage tissue.^1-3 The end result is a cyclically-perpetuating cascade, promoting cartilage degradation and OA progression.^2-5

The knee is the most common large joint affected by OA in the lower extremity,^6,7 which may be due to the high weight-bearing demands on that joint. Knee OA is often accompanied by pain, stiffness, swelling, loss of function, and decreased range of motion (ROM).^8,9 Lack of full knee extension is termed a flexion contracture (FC) and is present in about one-third of individuals with knee OA.^8-10 A cyclic effect has been proposed whereby FC promotes cartilage degeneration and vice versa.^11-13 The combination of knee OA and knee FC is associated with increased pain, functional impairments, and more rapid progression to joint replacement compared to those with OA without FC.^8,9,11,14,15

While knee FC was associated with a generalized progression of OA-associated articular changes, ¹⁶ there may also be a regional effect on the articular cartilage. ¹⁷ Campbell et al. (2023, 2024) reported that among individuals with knee OA and FC, the anterior region of the tibial articular surface demonstrated a greater percentage of denuded bone (defined as bone with 0% cartilage thickness), possibly due to unloading of that region of the tibial articular surface with increasingly flexed knee positioning.^11,18 In these studies, however, femoral cartilage was not evaluated, citing the biomechanical influence of the patellofemoral joint as a possible confounder to the analysis.^11,18 A separate study by Suzuki et al. (2013) evaluated femoral cartilage losses by dividing the articular surface of the knee joint into eight anatomical regions and evaluated cartilage degeneration macroscopically during open surgery at the time of total knee arthroplasty (TKA) in individuals with knee OA. ¹⁹ This study reported that restricted knee flexion ROM was significantly correlated with levels of knee cartilage degeneration in the patella as well as the lateral and posterior medial femoral condyles, the latter of which is a non-weight bearing region of the femur. ¹⁹ Together, these studies suggested that while femoral cartilage may be negatively impacted by knee FC, the effect of FC on this articular surface may differ from that of the tibia due to the polyarticular nature of the femur and the femur’s larger articulating surface.^11,18,20 Thus, a better understanding of how knee ROM impacts femoral cartilage loss in OA may provide further insight into OA pathophysiology and treatment options.

To our knowledge, no study has evaluated the association between FC and regional loss of cartilage in the distal femur using quantitative MRI data. This represents an important knowledge gap in our understanding about how knee FC may contribute to the total joint progression of OA. Therefore, this study sought to evaluate for an association between knee FC and regional femoral cartilage loss in the tibiofemoral joint. We tested the hypothesis that lost knee extension was associated with preferential articular cartilage loss within the central weight bearing regions of the femur in people with knee OA. To test this hypothesis, we used clinical and quantitative MRI femoral cartilage scoring data from the OA Initiative Database (OAI).

Materials and Methods

Data sources and patient selection

The entire OAI database comprises 4796 participants aged 45–79 years who were recruited between February 2004 and May 2006. ²¹ All participants provided written informed consent. For the present study, unilateral femoral cartilage data from 600 participants included in the Foundation for the National Institutes of Health (FNIH) nested case–control study were analyzed. ²² This sample was selected by the FNIH to determine the biomarkers with the greatest predictive and concurrent validity in addition to knee OA progression responsiveness. ²² This sample of 600 knees (one knee per participant) included knees with KL grade 1-3 and selected four groups: 1) Cases = knees with both radiographic and pain progression (n = 196), as well as control knees without this combination (n = 406) with control knees including: 2) knees with radiographic but not pain progression, 3) knees with pain but not radiographic progression, and 4) knees with neither radiographic nor pain progression. For better covariate balance among the groups, the knees selected for the four groups were frequency matched using KL grade strata 1–3 and BMI strata <25, 25–27.5, 27.5–30, 30–35 and ≥35 kg/m².^22,23 As we had no data upon which to perform a sample size calculation for our study, we included all 596 of the 600 participants that had knee extension and MRI data available. Given the cross-sectional nature of the data, observed relationships derived from our analysis are associative, and do not imply causation. Data from the OAI can be publicly accessed at https://data-archive.nimh.nih.gov/oai/. For our study, the clinical datasets (version 0.2.3) and enrolees datasets (version 25) were used. The MRI dataset OAI kMRI_FNIH_QCart_Chondrometrics00 (version 0.1 01/16/2015) was selected based on the availability of regional quantitative cartilage measurements and rigorous quality control.^17,24

Contracture definition, and clinical and radiographic assessments

Baseline physical examination data was used to determine maximum knee extension. For these measurements, a detailed standardized protocol was used as described previously.^8,9,21 Specifically, participants were placed in the supine position with their ankle supported on a foam roller and the ipsilateral knee extended to their full capacity.^8,9,21 Knee extension angle measurements were taken using a goniometer with the fulcrum positioned at the knee joint line, the upper arm pointed towards the greater trochanter and the lower arm pointed towards the lateral malleolus.^8,9,21 High inter-rater reliability has been previously demonstrated using this method.^20,25 The normal knee joint ROM varies from full extension to 135 degrees of flexion. ²⁶ Normal knee joint extension ranges from 0° to 5° of hyperextension. ¹⁰ Here, a knee FC was defined as the inability to extend the knee to 0°.^10,20 Thus, a straight, fully extended knee was defined as 0 degrees, hyperextension was given a positive value, and an inability to extend the knee to 0 degrees was defined as a knee FC and given a negative value.^8,9

MRI analysis

OAI-obtained cartilage thickness and percent denuded bone data for this study relied on 3-Tesla 3D sagittal double-echo steady-state imaging, as described previously. ²³ Segmentation of the femoral cartilage surfaces was performed by seven readers who had received continuous training for ≥ 5 years, with one reader measuring each knee at baseline. ²³ Segmentation was performed in both the sagittal and coronal planes (Figure 1). For our analysis, we included all available quantitative MRI femoral cartilage scoring data. The subchondral bone and articular cartilage areas of the central (tibiofemoral articulating) region of the femur were manually traced as described previously.^23,27,28 Briefly, manual tracings of the total subchondral bone area and the cartilage-joint surface area of this central region of the medial femur and the lateral femur were performed to complete the regional segmentation into internal, central, and external subregions^23,27,28 (Figure 1). Test-retest variability for segmentation tracing was reported as having a standard deviation between 0.0% and 0.2%. ²⁹ Articular cartilage thickness or denuded bone (0mm thickness) was measured for each segmented region. Test-retest variability for articular cartilage thickness measurement was reported as having a standard deviation between 1.3% and 5.3%, depending on the region. ²⁹

Figure 1.

A) Sagittal view of the portion of the femoral cartilage that was analyzed which has been labelled as the cMF and represents the anterior 60% of the region between the trochlear notch and the pMF. While this image shows the MF, the same process was done with the LF. B) Caudal view of the segmentation of the femoral regions of both the MF and LF into EX, CEN, and IN sub-regions. C) Cartilage plates analyzed in the coronal view, further demonstrating how the subregions of each femoral region were obtained.

CEN, central, cMF, central medial femoral condyle; EX, external; IN, internal; LF, lateral femur; MF, medial femur; pMF, posterior medial femoral condyle

Statistical analysis

Normality of outcome data was assessed using the Shapiro-Wilk test. The data failed to meet a normal distribution, thus the Mann–Whitney U test for non-parametric data was used to test for the presence of intergroup differences for percentage denuded bone and cartilage thickness. A p-value of <0.05 was defined as statistically significant. The Spearman correlation coefficient was used to determine correlations between MRI parameters and knee extension (a continuous variable measured in degrees). A linear regression model was selected to determine the separate effect sizes of the presence of knee FC (a categorical variable) and knee extension (a quantitative variable) on findings that were statistically significant in the uncorrected correlation analysis. Separate analyses were performed for FC and knee extension in order to avoid one confounding the other. We corrected for covariates that were previously reported to influence clinical outcomes in the setting of knee FC, including sex, age, BMI, knee alignment, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Kellgren and Lawrence (KL) radiologic score.^8,30 We included potential additional confounding factors as covariates in the model: Physical Activity Scale for the Elderly (PASE) score, history of knee injury and previous treatment with joint injection in the model. All data analyses were conducted using SPSS 23.0 (SPSS, Chicago, IL).

Results

Participant knee extension and demographic data

Of the included 596 participants, 199 had a knee FC while 397 achieved full knee extension. A significant difference was identified between the two groups with respect to sex, but none of the other demographic factors (Table 1). Participants with knee FC had significantly worse WOMAC pain, function, and stiffness compared to those without a FC (Table 1).

Table 1.

Participant demographics

Demographic	Mean (SD)
Age (years)
No FC	61.21 (0.44)
FC	62.29 (0.65)
Sex (% female)
No FC	61.96*
FC	52.26
BMI (kg/m2)
No FC	30.51 (0.24)
FC	31.13 (0.34)
Maximum Knee Extension (°)
No FC	-1.83 (0.13)
FC	4.40 (0.19)
Knee Alignment Angle (°)
No FC	-0.23 (0.18)
FC	-0.56 (0.27)
KL Grade
No FC	2.22 (0.03)
FC	2.30 (0.05)
WOMAC Pain
No FC	2.14 (0.15) **
FC	2.95 (0.24)
WOMAC Function
No FC	7.34 (0. 49) ***
FC	11.32 (0.83)
WOMAC Stiffness
No FC	1.44 (0.08) **
FC	1.85 (0.11)

BMI, Body mass index; FC, Flexion Contracture; KL, Kellgren-Lawrence; SD, Standard deviation; WOMAC, Western Ontario and McMaster Universities Osteoarthritis Index.

^*p < 0.05.

^**p < 0.01.

^***p < 0.001.

Percentage of denuded bone and cartilage thickness for those with and without knee flexion contracture

The percentage of denuded bone was significantly higher in the central subregion of the medial and lateral femoral condyles among participants with FC compared to participants without FC (4.61±12.88% vs 3.17±11.66%; 0.92±3.5% vs 0.39±2.2%, respectively; both p<0.05; Table 2). There was no significant difference in the percentage of denuded bone within the external and internal regions of either medial or lateral femoral condyles (p>0.05 for all; Table 2). Mean cartilage thickness was greater within the central region of the lateral femoral condyle in participants with versus without FC (2.36±0.42mm vs 2.29±0.43mm; p<0.05; Table 2). There was no significant difference in mean cartilage thickness between the two groups within the central aspect of the medial femoral condyle, or the external and internal aspects of either femoral condyle (p>0.05; Table 2).

Table 2.

Percentage of denuded bone and cartilage thickness for participants with and without knee flexion contracture

​	Mean (SD):
	% Denuded Bone	Cartilage Thickness, mm
Lateral Femoral Condyle
Center
No FC	0.39 (2.2)	2.29 (0.43)
FC	0.92 (3.5)*	2.36 (0.42)*
External
No FC	0.36 (2.16)	1.64 (0.34)
FC	0.59 (2.98)	1.68 (0.35)
Internal
No FC	1.90 (0.36)	1.47 (6.00)
FC	1.92 (0.36)	2.56 (7.88)
Medial Femoral Condyle
Center
No FC	3.17 (11.66)	1.88 (0.54)
FC	4.61 (12.88)*	1.87 (0.58)
External
No FC	3.30 (10.83)	1.28 (0.31)
FC	4.74 (13.69)	1.32 (0.36)
Internal
No FC	1.30 (5.19)	1.92 (0.43)
FC	1.41 (5.90)	1.96 (0.42)

FC, Flexion contracture; SD, Standard deviation.

*p < 0.05 for FC versus no FC using the Mann–Whitney U test.

Associations between percentage denuded bone, cartilage thickness, and quantitative knee extension

Lack of full knee extension was associated with a greater percentage of denuded bone in the central subregions of the lateral (r=0.90; p<0.05) and medial femoral condyles (r=0.117; p<0.01) as well as the internal subregion of the lateral femoral condyle (r=0.095; p<0.05). Conversely, lack of full knee extension range was associated with greater mean cartilage thickness (r=0.110; p<0.01) in the central subregion of the lateral femoral condyle (Table 3).

Table 3.

Spearman Correlations between percent denuded bone, cartilage loss, and knee extension

​	Correlation Co-efficient:
	% Denuded Bone	Cartilage Thickness, mm
Lateral Femoral Condyle
Center – Central LF	0.090*	0.110**
External – Central LF	0.053	0.049
Internal – Central LF	0.095*	0.076
Medial Femoral Condyle
Center – Central MF	0.117**	-0.048
External – Central MF	0.076	0.025
Internal – Central MF	0.073	0.055

LF, Lateral femur; MF, Medial femur.

*p < 0.05.

**p < 0.01.

Association between knee extension and percentage denuded bone following linear regression

Lack of full knee extension was associated with increased percentage denuded bone in the central lateral femoral condyle [β=0.059; (95% CI 0.003 – 0.114); Table 4] and the external medial femoral condyle [β=0.237; (95% CI 0.014 – 0.460); Table 4] after correcting for demographics, knee alignment, KL severity, activity score, previous injury and/or joint injection (Supplementary Tables 1 and 2).

Table 4.

Linear model evaluating significant association between percentage of denuded bone and cartilage loss with knee extension

​	Effect size of knee FC [95% CI]	Effect size of lost knee extension [95% CI]
Lateral Femur
Center Cartilage thickness	0.039 [-0.31 - 0.108]	0.004 [-0.004 - 0.013]
Center % denuded bone	0.396 [-0.072 - 0.864]	0.059 [0.003 - 0.114]*
External Cartilage thickness	-0.003 [-0.058 – 0.053]	0.000 [-0.007 – 0.006]
External % denuded bone	0.158 [-0.272 – 0.587]	0.015 [-0.036 – 0.066]
Internal Cartilage thickness	0.003 [-0.054 – 0.060]	0.003 [-0.004 – 0.010]
Internal % denuded bone	0.888 [-0.279 – 2.055]	0.111 [-0.027, 0.250]
Medial Femur
Center Cartilage thickness	-0.011 [-0.091 – 0.070]	-0.005 [-0.015, 0.004]
Center % denuded bone	0.965 [-1.058 - 2.998]	0.214 [-0.025 - 0.454]
External Cartilage thickness	0.030 [-0.022 – 0.081]	0.002 [-0.005 – 0.008]
External % denuded bone	0.864 [-1.019 – 2.748]	0.237 [0.014 – 0.460]*
Internal Cartilage thickness	0.017 [-0.048 – 0.081]	0.002 [-0.005 – 0.010]
Internal % denuded bone	-0.172 [-1.113 - 0.768]	0.030 [-0.082 - 0.142]

CI, Confidence interval.

*p < 0.05.

Linear model corrected for age, sex, BMI, knee alignment, total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Kellgren and Lawrence (KL) radiologic score, Physical Activity Scale for the Elderly (PASE) score, history of knee injury and previous treatment with joint injection.

Discussion

Our study demonstrated larger areas of percent denuded bone in the central subregions of the lateral and medial femur among OAI participants with versus without FC. Interestingly, this was accompanied by a relative sparing of overall cartilage thickness in the central lateral femur. When analyzed as continuous data, less knee extension ROM was similarly found to be associated with increased percent denuded bone with increased cartilage thickness in the central lateral femur with further associations between less knee extension ROM and increased percent denuded bone in the internal lateral and central medial subregions. In keeping with previously-reported OAI data, ⁸ we also found a higher proportion of males in the FC groups versus the no FC group. After correcting for demographic factors (i.e., age, sex, and BMI), knee alignment, KL severity, activity score, previous knee injury and/or knee injection, we found an association between less knee extension ROM and increased percent denuded bone in the central lateral femur as well as the external medial femur. Due to the cross-sectional nature of the data, these relationships are considered associative.

We observed a greater percent denuded bone in the central subregions of the lateral and medial femur among OAI participants with FC. Though the absolute mean difference in the percentage of denuded bone between FC and non-FC participants may be small (<2%), full thickness cartilage defects of any size were reported as a risk factor for cartilage loss and progression to arthroplasty. ³¹ Paradoxically, we observed sparing of overall cartilage thickness in the central lateral femur. This finding of a larger focal defect surrounded by overall thicker cartilage suggests a highly-localized, focal site of cartilage injury. A differential regional effect of knee FC on the articular loading forces applied to the knee articular surface may help explain these findings. Both increased and decreased joint loading, i.e., overloading and unloading, can result in cartilage deterioration.^11,18 It is well-described that knee alignment (varus and valgus) alterations result in a force redistribution, placing increased load on the respective medial and lateral compartments of the joint.^32,33 These varus and valgus malalignment patterns were previously reported to be associated with increased medial and lateral OA progression, respectively, of the overloaded compartment.^32,33 After following individuals with knee OA for 18-months, Sharma et al. (2001) reported that those with varus and valgus deformities had an increased risk of medial and lateral OA progression as confirmed by radiographic joint space narrowing. ³⁴ In a study by the same group, varus malalignment was found to independently predict medial loss of cartilage and increased denuded bone as quantified using MRI imaging. ³⁵ Interestingly, knee alignment inconsistently predicted of cartilage loss in the present study (significant in our percent denuded bone in the central lateral femur analysis but not our external medial femur and less than half of the overall linear model outputs, see Supplementary Tables), necessitating additional explanation for our findings. During normal knee extension, the femoral condyles experience rotational movement in the terminal 10-20 degrees of extension.^20,36 A FC might result in a more posteriorly located center of gravity of the femoral condyle as they are unable to rotate through their full excursion, resulting in localized region-dependent alterations in articular loading anterior-to-posterior. When considering the sagittal plane, joint unloading was reported to result in accelerated, focused cartilage degeneration: rat knees immobilized at 135 degrees of flexion for up to 32 weeks were found to have increasing articular cartilage replacement with bone in the unloaded anterior tibial region, but not regions of tibiofemoral cartilage contact, thus supporting a protective effect of cartilage contact.^37,38 Similarly, Ni et al., (2016) showed that 8-weeks of immobilization at 150 degrees of flexion (unloading) as well as 8-weeks of high-intensity treadmill running (overloading) both resulted in catabolic gene expression and degenerative changes in femoral condylar cartilage in Winstar rats, including changes in gross and histologic cartilage appearance. ³⁹ These degenerative changes were more severe in the immobilized group, suggesting that different pathologic mechanisms in the immobilized group may have contributed to the cartilage changes as compared to the overloaded group. ³⁹ In the clinical setting, Suzuki et al., (2013) demonstrated that restricted knee flexion ROM was correlated with knee cartilage degeneration in the lateral and posteromedial femoral condyles among participants with OA. ¹⁹ In two separate observational studies in humans, lost knee extension was associated with cartilage loss in the unloaded anterior and middle medial tibial articular surface with preservation of cartilage in the posterior tibial region.^11,18 Guermazi et al. (2012) identified full-thickness cartilage defects (similar to our denuded bone outcome) in adults enrolled in the Framingham Osteoarthritis Study without knee osteoarthritis. ⁴⁰ Similarly, Everhart et al. (2019) reported full-thickness cartilage defects in participants of the OAI with OA radiographic KL grades 0 (no OA) or 1 (doubtful OA). ³¹ Though the “paradox” in our study resolved following our linear model analysis (with only two percentage denuded cartilage outcomes remaining significant), our and the results of the above studies suggest that in some individuals with knee OA, early articular cartilage loss may be focal yet severe, later proceeding to more diffuse cartilage loss. Reduced sagittal knee ROM could potentially influence this process by influencing local articular overloading and/or unloading.

Clinical Implications

Our study supports monitoring knee ROM as a routine component of knee OA assessment, as previously proposed for the preservation of tibial cartilage.^11,18 Early detection and treatment of lost knee extension, such as provision of evidence-based stretching and strengthening programs,^41,42 may benefit knee articular cartilage and improve knee OA outcomes. Longitudinal studies evaluating the effects of ROM on femoral cartilage health in OA are needed.

Study Limitations

The cross-sectional study design allows detection of associations between knee FC and femoral cartilage changes, but not causation. As such the mechanistic interpretations noted above are hypotheses requiring further validation in longitudinal studies. Our study is limited by the utilization of secondary data from the OAI cohort with a restricted generalizability to populations who are under-represented, such as individuals younger than 45-years or older than 79-years, individuals belonging to racial and ethnic groups other than those included in the OAI, as well as individuals with more severe OA (individuals with KL 4 were not included). Furthermore, the available OAI data is limited to the central femoral condylar region and does not include the anterior or posterior regions, precluding assessment of the femoral side of the patella-femoral joint, or the femoral articulation with the tibia with increasing knee flexion. Thus, the interpretation of our results is limited to the central region that was analyzed. OAI knee extension data is limited to that obtained by manual goniometric measurements. While a standardized protocol was used by trained OAI research staff, some degree of error in the measurement is possible. Reassuringly, Akizuki et al. reported that quantitative goniometer measurement error was random in nature (rather than systematic), suggesting that our large sample size should have reduced the mean error for the quantitative knee extension measurements (though possibly less-so for our dichotomous data), supporting our results. ⁴³ Additionally, knee alignment measurements (used as a covariate in our analysis) were measured as part of the physical exam using by trained research staff using a standardized protocol. ²¹ While alignment as measured by physical exam is highly correlated with the gold standard full-length radiographic method, absolute values may differ (mean difference <5°). ⁴⁴ The exploratory approach of our analysis used an uncorrected p<0.05 for our uncorrected analyses (Tables 2 and 3), which may have introduced a type I error at this stage of the analysis. The correlation data that we report (Table 3) shows only small correlations coefficients. While these correlations were statistically-significant, they are considered weak and suggest that lost knee extension explains only a small portion of the greater percentage of denuded bone, while other factors not included in our analysis as they were not available in our dataset (such as the presence of bone marrow lesions on MRI ⁷ ) may also influence our outcomes. Our biomechanical explanation for our findings remains speculative but suggests the need for novel methods of evaluating intra-articular compartmental loading forces in healthy joints as well as those subjected to altered ROM. Finally, for this initial quantitative study of FC association with femoral cartilage, we limited our analysis to the baseline OAI data. Further analysis of the longitudinal data may provide further valuable insight into femoral cartilage changes in the context of OA progression.

Conclusion

Knee FC was associated with an increase in percentage denuded bone in the mid-lateral and external medial femoral condyles. These data suggest that cartilage loss in the setting of knee FC may be regional, possibly due to altered compartmental loading due to lost knee extension. Femoral cartilage health may benefit from interventions aimed at maintaining and restoring knee ROM in OA. Longitudinal studies evaluating the impact on lost knee ROM on femoral cartilage and OA outcomes are needed.

ORCID iDs

Domenica Cirone https://orcid.org/0000-0003-3144-6016

T. Mark Campbell https://orcid.org/0000-0001-6328-9030

Ethical Consideratioons

All data included in this study were obtained from the OAI (NCT00080171), a multi-centre, prospective cohort study funded by the National Institutes of Health that focused on knee OA. Study approval was granted by the institutional review boards of all participating sites with the University of California, San Francisco, California, USA as the coordinating site (ethics approval number 10–00532).

Data Availability Statement

Data for this study is available upon reasonable request.*