Is barefoot regional plantar loading related to self-reported foot pain in patients with midfoot osteoarthritis

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1 Osteoarthritis and Cartilage xxx (2011) 1e7 Is barefoot regional plantar loading related to self-reported foot pain in patients with midfoot osteoarthritis S. Rao y *, J.F. Baumhauer z, D.A. Nawoczenski x y Department of Physical Therapy, New York University, NY 10012, USA z Department of Orthopedics, University of Rochester Medical Center, Rochester, NY, USA x Center for Foot and Ankle Research, Department of Physical Therapy, Ithaca College e Rochester Center, Rochester, NY, USA article info summary Article history: Received 19 July 2010 Accepted 16 April 2011 Keywords: Arthritis Midfoot Plantar pressure Objective: While recent evidence suggests that foot pain may be related to mechanical stress, quantitative data elucidating the role of regional plantar loading in foot pain in individuals with midfoot osteoarthritis (OA) are lacking. Therefore the authors objective is to examine regional plantar loading and self-reported foot pain in patients with midfoot OA compared to asymptomatic, matched control subjects. Method: Fifty subjects, 30 patients with midfoot OA and 20 control subjects participated in this study. Self-reported function was assessed using the Foot Function Index e Revised (FFI-R). Plantar loading during barefoot walking at self-selected, monitored walking speed was quantified using an EMED pedobarograph. Between-group differences in FFI-R score and plantar loading were assessed using an independent t-test and the ManneWhitney U-test respectively. The relationship between FFI-R score and plantar loading was assessed using Spearman rank correlation. A k-means cluster analysis was used to identify potential sub-groups of patients through regional plantar loading. Results: The key findings of this study showed that patients with midfoot OA reported significantly higher FFI-R scores, and higher heel and medial midfoot compared to control subjects. Medial midfoot pressureetime integral was positively associated with FFI-R Pain Subscale Score (r ¼ 0.524, P < 0.01). Based on the adequacy index, the two-cluster solution was deemed most appropriate. Conclusion: This study demonstrated that patients with midfoot OA sustain increased magnitude and duration of regional plantar loading during walking compared to matched control subjects. Our findings support the theory that regional mechanical stress may be associated with symptoms in patients with midfoot OA. Future studies should assess whether interventions designed to reduce plantar loading are effective in relieving foot pain, and preventing progression of symptoms in patients with midfoot OA. Ó 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. Introduction The incidence and progression of osteoarthritis (OA), characterized by progressive loss of articular cartilage and attendant pain and disability, has been linked to mechanical stress sustained during weight-bearing activities of daily living 1,2. Increasing evidence indicates that mechanical stress plays an important role in cartilage homeostasis because chondrocytes function as mechanical transducers and respond to their mechanical milieu by upregulating synthetic activity or increasing the production of inflammatory cytokines and matrix-degrading enzymes 3e5. Progressive cartilage breakdown is accompanied by increasing * Address correspondence and reprint requests to: S. Rao, Department of Physical Therapy, New York University, 380 2nd Ave, 4th Floor, New York, NY 10010, USA. Tel: ; Fax: address: smita.rao@nyu.edu (S. Rao). disease severity 6, pain and disability 7. While the role of mechanical stress and patients self-reported pain and disability has been assessed in patients with OA of the knee joint, few studies have assessed mechanical stress in patients who have arthritis in the joints of the foot. OA of the tarso-metatarsal joints (midfoot) has emerged as a challenging problem due to its high potential for foot pain and chronic secondary disability. Individuals with midfoot OA experience foot pain which limits their participation in walking and weight-bearing activities. Midfoot injuries affect approximately 55,000 people per year 8 and are commonly seen in the athletic population 9. Despite their seemingly low incidence, they are particularly concerning because as many as 20% are missed or misdiagnosed 10. In recent years, these injuries have increased with alarming incidence as a consequence of plantar impact sustained in restrained motor vehicle trauma 11. Additionally, as our population ages, chronic increased joint loads sustained with high heeled /$ e see front matter Ó 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. doi: /j.joca

2 2 S. Rao et al. / Osteoarthritis and Cartilage xxx (2011) 1e7 footwear may be linked to the development of midfoot OA 12. Irrespective of the mechanism of trauma, midfoot OA has been reported to be inevitable sequelae of significant tarsometatarsal joint disease 11,13. Recent evidence from a variety of clinical populations suggests that foot pain may be related to mechanical stress, quantified as regional plantar loading 14. Mechanical stress, combined with local and central sensitization of neural pathways, may interact with inflammatory mediators and contribute to pain perception in patients with OA 15. Additionally, regional loading may influence net joint reaction forces and moments, and lead to abnormal articular (joint) stress 12,16. Burns et al. (2005) reported a significant positive relationship between total foot pressure time integral and foot pain in patients with rigid high arches secondary to pes cavus foot deformity 17. In patients with acquired flat foot deformity and hindfoot pain, Ellis et al. noted increased lateral midfoot pressure 18 and concomitant degenerative changes at the subtalar joint, following surgical correction of flat foot deformity 19. Compared to asymptomatic control subjects, patients with OA of the first metatarsophalangeal joint (hallux rigidus/limitus), demonstrated higher plantar loads under the great toe region 20,21. Taken together, these studies suggest that increased regional plantar loads may contribute to mechanical overloading and consequently, to foot pain in patients with foot pathology. While growing evidence confirms the presence of elevated regional plantar loading and foot pain in patients with rheumatoid arthritis compared to control subjects, within-group analyses in studies examining the relationship between regional plantar loading and foot pain have reported conflicting results. One recent report found greater lateral forefoot loading in patients with rheumatoid arthritis and higher Health Assessment Questionnaire (HAQ) score (less disability, less pain) compared to patients with lower HAQ score 22. These results may suggest that patients with lower HAQ score (more disability, more pain) may adopt an antalgic loading strategy characterized by lower plantar loading. In contrast, two other studies have reported that elevated plantar loading is associated with increasing foot pain 23,24, in agreement with the premise that foot pain is related to mechanical overloading. These conflicting results may indicate that patients with foot pain may demonstrate either an antalgic strategy (increasing pain associated with lower loading) or a mechanical overloading strategy (increasing pain associated with higher loading), and underscore gaps in current knowledge elucidating the relationship between regional plantar loading and foot pain. Further, while regional plantar loading has been identified as a key determinant in mediating foot pain, previous studies have been limited to patients with neurogenic foot problems or inflammatory arthritis. Midfoot OA differs from neurogenic foot pain and inflammatory arthritis both in the etiology, as well as location of pain. Quantitative data elucidating the role of regional plantar loading in foot pain in individuals with midfoot OA are lacking. Walking has been ranked as the highest priority for improvement by patients seeking specialized care for foot and ankle disorders 25. In order to design the most effective intervention and minimize secondary disability in patients with midfoot OA, investigations that critically evaluate factors contributing to foot pain during functional activities are essential. Based on these data, corrective intervention may be designed and instituted to optimize patients function. The purpose of our study was to examine regional plantar loading and self-reported foot pain in patients with midfoot OA compared to asymptomatic, matched control subjects using between-group comparisons. In addition, we sought to examine the relationship between plantar loading and selfreported foot pain, using linear correlations and within-group analysis of clusters. Methods Subjects The sample comprised 50 subjects, 30 patients with midfoot OA and 20 asymptomatic control subjects, matched in age, sex and body mass index. All procedures were approved by the Institutional Review Boards of Ithaca College and the University of Rochester. Patients were recruited from the Outpatient Orthopedic Clinic at the University of Rochester Medical Center. All data were collected at the Movement Analysis Lab, Center for Foot and Ankle Research, at the Department of Physical Therapy, Ithaca College e Rochester Center, Rochester, NY, USA. Inclusion and exclusion criteria All patients presented with unilateral foot pain localized to the medial tarso-metatarsal region, and aggravated by weight bearing. The diagnosis of isolated midfoot OA was confirmed by radiographic evidence of degenerative changes at one or more tarsometatarsal joints on antero-posterior and lateral weight-bearing radiographs. All patients diagnosed with midfoot OA were invited to participate in this study with the following exclusion criteria: (1) injury or surgery of the lower extremity within the past 6 months, (2) other conditions such as stroke that may affect walking, or (3) use of assistive devices such as a cane or walker. Sixty-eight patients with medial foot pain were screened and 32 met the inclusion criteria. Twenty-five patients had a history of injury or surgery to the index lower extremity over the last 6 months, six patients had diabetes, five patients used an assistive device (cane) during walking. Of the 32 patients who met the inclusion criteria, two refused to participate for logistical reasons (lived more than 2 h away). Since the purpose of this study was to examine regional plantar loading and foot pain in patients with midfoot OA compared to matched control subjects, medial midfoot average pressure served as the primary outcome measure. Based on normative data from previous reports using similar methodology to evaluate medial midfoot 26,27, a priori power analysis indicated that group sizes of 18 and 18 are needed to achieve 81% power to detect a moderate effect size (Cohen s d ¼ 0.55) with a significance level (alpha) of 0.05, using a two-sided ManneWhitney test. Radiographic assessment Degenerative changes were assessed using medial longitudinal arch alignment, quantified as the calcaneal-first metatarsal angle (Fig. 1) on the lateral radiograph 28,29, and Kellgren Lawrence grades Fig. 1. Weight bearing lateral radiograph depicting calcaneal-first metatarsal angle, used to characterize medial longitudinal arch alignment.

3 S. Rao et al. / Osteoarthritis and Cartilage xxx (2011) 1e7 3 Table I Summary of radiographic characteristics in patients with midfoot arthritis Joint Median Kellgren Lawrence grade on lateral radiographs Percent of patients with Kellgren Lawrence grade of 1 and higher Joint Median Kellgren Lawrence grade on anterioreposterior radiographs Tarso-metatarsal first tarso-metatarsal Naviculo-cuneiform second tarso-metatarsal Talo-navicular Inter-tarsal Subtalar Inter-metatarsal Calcaneo-cuboid Percent of patients with Kellgren Lawrence grade of 1 and higher on lateral and anterioreposterior radiographs 30. A single rater obtained all radiographic measurements. Personal identifiers were eliminated from radiographs and three blinded readings (i.e., the rater was not allowed to refer to the previous reading) of each measurement were made. Intra-rater reliability was examined using Intraclass Correlation Coefficient (ICC) (Model (3,3)) 31,32. Excellent intra-rater reliability, reflected in ICC(3,3) of 0.96, 0.95 and 0.93, for calcaneal-first metatarsal angle, lateral and anterioreposterior tarsometatarsal Kellgren Lawrence grade respectively, was noted. Lower arch alignment was noted in patients with midfoot OA. Patients with midfoot OA demonstrated calcaneal-first metatarsal angle of 145 [standard deviation (SD: 8)] compared to normative values of 132 (SD: 11) 28,29. Median Kellgren Lawrence grades and percentage of patients showing degenerative changes at each articulation (Kellgren Lawrence grade 1 and higher) are reported in Table I. Control group Asymptomatic subjects were recruited from the community using fliers, screened by a single trained physical therapist (SR) for lower extremity pain and/or dysfunction, and were matched for age, gender and BMI to patients with midfoot OA. Demographic characteristics of the study and control group are summarized in Table II. Self-reported pain and foot function The Foot Function Index e Revised (FFI-R) was used to assess self-reported pain and foot function. The FFI-R is the revised version 33 of an anatomically-specific outcomes instrument with previously established validity, testeretest reliability, internal consistency and responsiveness 33e37. The FFI-R assesses selfreported foot function the following dimensions: pain, activity limitation, disability and psychosocial issues. Psychometric properties of the FFI-R have been tested using Rasch analysis, and established on a sample of 92 patients, of whom slightly over twothirds (63/92, 69%) reported having degenerative arthritis 33. Given its robust psychometric properties, the FFI-R was selected to assess the subjects in this study. Plantar loading Plantar loading during barefoot walking at self-selected, monitored walking speed was quantified using an EMED pedobarograph (Novel Inc, St Paul, MN). The capacitative pedobarograph was Table II Mean (SD) summary of demographic characteristics Midfoot arthritis Control group P value Age (years) 62 (7) 58 (7) Body mass index (kg/m 2 ) 29.7 (5.7) 29.3 (4.3) Sex (M:F) 2:28 1:19 e Walking speed (m/s) 0.71 (0.20) 0.74 (0.17) embedded flush with the walkway. Plantar loading data were acquired at 50 Hz and at a spatial resolution of four sensors per square centimeter. Patients walked at self-selected speed, monitored to 5% using an infra-red timing system (Brower Inc, UT). Control subjects speed was matched to patients walking speed, because walking speed is known to influence magnitude of plantar loading 38. Prior to data collection, all subjects were encouraged to attempt practice trials to establish walking speed. Subjects were allowed as many practice trials as they needed prior to data collection. Starting position was standardized to avoid targeting and to ensure clean foot contact on the pedobarograph. Using a mid-gait protocol, a minimum of three and maximum of five steps were collected to ensure adequate reliability 39,40. Data were analyzed using Novel Projects software (Novel Inc, St Paul, MN). The foot was divided into the following regions of interest or masks,defined as a percent of foot length and width: heel, medial and lateral midfoot, medial and lateral forefoot, and great toe. Given the location of pain in patients with midfoot OA, loading characteristics at the medial midfoot were the primary focus of analysis. In addition, the heel, medial and lateral forefoot masks were used for a secondary evaluation of comparative regional loading, or load transfer 41. Plantar loading data was analyzed using Novel Win softwareô (St Paul, MN). The following dependent variables were evaluated:, contact time and pressure time integral. Average pressure was defined as the mean of the highest pressures sustained within each mask and expressed in kilopascals (kpa). Contact time was defined as the duration of loading for each mask and expressed in % stance. Pressure time integral was defined as the area under the peak pressure within each mask and expressed in kilopascals.seconds (kpa.s). These definitions of dependent variables used to characterize plantar loading are consistent with definitions used in previous studies 17,42,43. Statistical analysis All dependent variables were assessed for normality, using the KolmogoroveSmirnov test, and variance homogeneity, using Levene s test. Subsequently, independent t-tests, not assuming equal variance, were used to assess statistical significance of differences in FFI-R scores in patients with midfoot OA compared to asymptomatic control subjects. The statistical significance of between-group comparisons in regional plantar loading was assessed using the ManneWhitney U-test. Differences between groups were considered significant if P < Correlations were assessed using Spearman rank correlation. A k-means cluster analysis was used to identify potential clusters (sub-groups of patients) present in the midfoot OA patient cohort. K-means analysis applies an optimization approach to minimize the sum of the squared Euclidean distances between observations and their group mean over multiple features of the dataset 44. K-means cluster analysis is an exploratory data analysis technique and may be valuable in studies that assess plantar loading because k-means analysis allows us to simultaneously

4 4 S. Rao et al. / Osteoarthritis and Cartilage xxx (2011) 1e7 Table III Mean (95% confidence interval) FFI-R scores in patients with midfoot OA and matched control subjects. Higher score indicates worse function explore multiple features (masks) of a dataset. K-means clustering was performed using in each mask: heel, medial and lateral midfoot, medial and lateral forefoot and great toe. Two, three, four and five cluster solutions and analysis of variance (ANOVA) tables were computed. Subsequently, the adequacy index, computed as mean square error between-clusters divided by the mean square error within-clusters, was used to determine the optimum number of clusters in the dataset. The best solution (number of clusters) was the solution that maximized adequacy index 44. Lastly, to understand the implications of cluster membership, FFI-R Pain Subscale Score and in each mask were computed for each of the sub-groups. All statistical testing was performed in SPSS v16 (SPSS, Chicago). Results Midfoot arthritis Control group 95% confidence intervals P value Pain (17,29) <0.001 Disability (18,28) <0.001 Activity limitation (14,31) <0.001 Psychosocial issues (10,21) <0.001 Total score (16,26) <0.001 midfoot. Contact time was higher in the heel, medial and lateral midfoot, and medial forefoot regions in patients with midfoot OA compared to asymptomatic control subjects (Table IV). Pressure time integral was higher in the heel, medial and lateral midfoot, and medial forefoot regions in patients with midfoot OA compared to asymptomatic control subjects (Table IV). Correlations There was a significant positive correlation between medial midfoot pressureetime integral and FFI-R Pain Subscale Score (r ¼ 0.524, P < 0.01) and between medial midfoot and FFI-R Pain Subscale Score (r ¼ 0.448, P < 0.01). However, medial midfoot pressure-time integral and medial midfoot were highly correlated (r ¼ 0.927, P ¼ 0.01). Cluster analysis Based on the adequacy index, the two-cluster solution was deemed most appropriate for this cohort of patients with midfoot OA. Graphical depiction of the adequacy index and bivariate scatter plots of the two-cluster solution are presented in Fig. 2. Mean (SD) FFI-R Pain Subscale Score, and Average Pressure sustained at the Heel, Medial and Lateral Midfoot, Medial and Lateral Forefoot and Self-reported pain and foot function Patients with midfoot OA reported significantly higher FFI-R Total Scores compared to matched control subjects (Table III). An examination of subscale scores revealed that patients with midfoot OA scored significantly higher on all the subscales (Pain, Activity Limitation, Disability and Psychosocial Issues) of the FFI-R compared to matched control subjects (Table III). Plantar loading Average pressure was higher in the heel and medial midfoot regions in patients with midfoot OA compared to asymptomatic control subjects (Table IV). Similar trends were noted at the lateral Table IV Mean (SD), contact time and pressure time integral during barefoot walking, in patients with midfoot arthritis compared to matched asymptomatic control subjects Midfoot arthritis Control group P value Average pressure (kpa) Heel (51.3) 90.0 (30.8) Medial midfoot 32.8 (16.1) 21.6 (16.2) Lateral midfoot 60.4 (33.2) 47.1 (32.0) Medial forefoot (73.2) (62.9) Lateral forefoot (73.9) (77.7) Great toe (98.0) (98.5) Contact time (% stance) Heel 69.5 (9.4) 57.2 (11.5) Medial midfoot 50.8 (18.2) 29.1 (24.2) Lateral midfoot 67.0 (14.9) 53.7 (12.4) Medial forefoot 80.0 (6.9) 77.2 (5.0) Lateral forefoot 86.1 (4.5) 84.2 (3.3) Great toe 73.1 (14.5) 72.8 (15.2) Pressure time integral ((kpa)*s) Heel (103.7) 76.1 (26.2) Medial midfoot 32.8 (18.7) 17.8 (23.0) Lateral midfoot 67.4 (34.8) 41.6 (29.6) Medial forefoot (117.6) (55.0) Lateral forefoot (105.0) (63.2) Great toe (131.7) (82.6) Fig. 2. (Top) Graph depicting adequacy index (ordinate) vs number of clusters (abscissa) indicating that the two-cluster solution is appropriate. (Bottom) Bivariate scatter plots showing two-cluster solution obtained using the following features: in heel (h_avgp), medial midfoot (mmid_avgp), lateral midfoot (lmid_avgp), medial forefoot (mfore_avgp), lateral forefoot (lfo_avgp), great toe (halx_avgp).

5 S. Rao et al. / Osteoarthritis and Cartilage xxx (2011) 1e7 5 Table V Mean (SD) FFI-R Pain Subscale Score, and median Kellgren Lawrence grade in the higher function (n ¼ 10) and lower function (n ¼ 10) clusters Cluster Pain Subscale FFI-R Heel average pressure Medial midfoot Lateral midfoot Medial forefoot Lateral forefoot Great toe Kellgren Lawrence grade n ¼ (13) (26.3) 37.5 (17.0) 61.3 (24.2) (55.0) (79.9) (58.3) 3.1 (0.8) n ¼ (13) (68.8) 24.4 (10.7) 58.9 (47.0) (71.9) (66.3) (69.2) 3.0 (0.6) Great Toe for the two-cluster solution are presented in Table V. K-means clustering identified two subgroups, Cluster 1 (higher medial midfoot group (n ¼ 20)) and Cluster 2 (lower medial midfoot average group (n ¼ 10)). Cluster 1 (n ¼ 20) showed higher medial midfoot, higher FFI-R Pain Subscale scores, and lower heel and forefoot pressure compared to Cluster 2 (n ¼ 10). Discussion Increasing evidence indicates that mechanical stress plays an important role in cartilage breakdown and clinical outcomes in individuals with knee OA. However, limited objective data are available examining the relationship between mechanical stress and self-reported function in patients with arthritis in their foot. The key findings of our study showed that patients with midfoot OA report significant pain and disability, reflected as higher scores on the FFI-R Pain Subscale and Total Scores, compared to asymptomatic control subjects. In addition, patients with midfoot OA demonstrated elevated magnitude and duration of regional plantar loading, evidenced as increased medial midfoot, contact time, and pressure time integral. To our knowledge, these results are the first to support the theory that regional plantar loading is related to symptoms in patients with midfoot OA. These findings emphasize the significant disability experienced by patients with midfoot OA and suggest potential mechanisms by which mechanical stress may contribute to patients clinical symptoms and self-reported pain. Our cohort of patients with midfoot OA reported moderate to severe foot pain in weight-bearing activities of daily living compared to asymptomatic matched controls, evidenced as significantly higher FFI-R Pain Subscale Scores. Consistent with previous reports of foot function in patients with midfoot OA compared to asymptomatic matched controls, our patients also demonstrated significant activity limitation and reduction in overall foot function 45,46. The preponderance of female patients (28/30) in our study, is consistent with previous studies examining patients with midfoot OA as well as other types of arthritis affecting the foot 45,47. Contrary to our expectation that the majority of patients would present with post-traumatic midfoot OA 8, none of our patients recalled a major traumatic event leading to their midfoot symptoms. While our study sample is similar in terms of etiology and patient demographics, to that reported in more recent reports 45,46, the absence of major trauma combined with the gender distribution, may be indicative of the potential role of chronic increased joint loads accompanying poor footwear choices 48 in the development of midfoot OA. The magnitudes of pressure time integral sustained in the control group during barefoot walking are in agreement with previous reports of pressure time integral in asymptomatic subjects 26,27. The magnitude of pressure time integral sustained at the heel and forefoot in patients with midfoot OA is consistent with previous reports of pressure time integral sustained during barefoot walking in asymptomatic subjects 26,27, as well as in subjects with chronic rheumatoid arthritis 24. However, the magnitude of medial midfoot pressure time integral as well as medial midfoot sustained during barefoot walking in patients with midfoot OA was higher than that reported in previous studies 24,26,27. Increased medial midfoot loading in asymptomatic subjects 49 and in individuals with arthritis of the talo-navicular and navicular-first cuneiform joints 50 has been linked with low arch alignment. Increased medial midfoot loading may be related to motion, such as calcaneal pronation, that occurs at proximal joints 51. However, recent evidence does not support this contention 52. Using an in vivo three-dimensional kinematic model of the foot, motion of the first metatarsal and calcaneus was assessed during barefoot walking. No between-group differences were noted in calcaneal eversion in patients with midfoot arthritis compared to matched control subjects 52. In addition to arch alignment and pronation, several reports have suggested that disease severity, quantified using radiographs, is related to midfoot plantar loading. In patients with hindfoot pain, Ellis et al. noted increased lateral midfoot loading 18 and subtalar arthritis 18. In patients with rheumatoid arthritis, increased joint erosion, determined using the Larsen score, was accompanied by increased forefoot plantar loading 23,42. Consistent with the literature, our findings may suggest that increased medial midfoot plantar loading may be linked with pain experienced by patents with midfoot OA. In agreement with the mechanical overloading theory, a modest positive association between medial midfoot plantar loading and patients self-reported pain score was noted. Regional plantar loading explained about 28% of the variance in patients pain. In a study involving patients with painful pes cavus, Burns et al. found that pressure time integral accounted for 24% of the variance in foot pain 17. In patients with rheumatoid arthritis, previous studies have noted that the magnitude of forefoot plantar loading accounts for 10e30% of the variance in patients self-reported pain 14,24. Taken together, the results of our study combined with previous findings, suggest that regional plantar loading may account for approximately one third of the variance in self-reported foot pain, and support the contention that mechanical stress may be related to patients symptoms. In an attempt to identify potential clusters (sub-groups of patients) present in the midfoot OA patient cohort, k-means analysis was used as an exploratory data analysis technique 44. Previous studies evaluating plantar loading in patients with foot pain have assessed one foot region at a time 17,22,24. The chief limitation of this approach (assessing one foot region at a time) is that it does not take into account changes in load distribution that may occur concurrently over multiple regions of the foot. As a novel solution to this problem, we used k-means cluster analysis to simultaneously assess plantar loading in multiple regions of the foot. Using k-means cluster analysis, we discerned two subgroups within our cohort of patients with midfoot OA. Cluster 1 (n ¼ 20) showed higher medial midfoot, higher FFI-R Pain Subscale Scores, and lower heel and forefoot pressure compared to Cluster 2 (n ¼ 10). These clusters are consistent with the regional mechanical overloading theory and may represent different load redistribution strategies. Mechanical stress, through its effect on cartilage homeostasis and breakdown, may contribute to the development and progression of osteoarthritic changes 3.

6 6 S. Rao et al. / Osteoarthritis and Cartilage xxx (2011) 1e7 Shape-based k-means cluster analysis has been previously used to classify subjects based on their plantar loading characteristics, with varying degrees of success in terms of providing clinically meaningful results 53,54. De Cock et al. used forefoot pressure time integral obtained during jogging to classify asymptomatic subjects into four foot types 53. K-means cluster analysis of the peak pressure curve was applied in symptomatic patients with rheumatoid arthritis and indicated the presence of three well-separated subgroups 54. However, classification of patients using k-means cluster analysis did not agree with a HAQ-based clinical classification 54. Whether the inclusion of plantar loading parameters from multiple regions of the foot in k-means analysis will improve agreement remains unknown and requires further study. Our results indicate that the inclusion of multiple regions of the foot is valuable in the assessment of patients with foot pain and pathology. Additionally, alternative multi-variate techniques such as principal components analyses may reduce the dimensionality of plantar loading parameters and may help characterize loading strategies that contribute to patients symptoms. The chief limitations of this study are its relatively small sample size and cross-sectional nature. Prospective studies are indicated to examine the time course of the evolution of foot pain and changes in plantar loading in patients with midfoot OA. Additional studies are indicated to assess whether anatomical subtypes exist within midfoot OA, based on anatomical location of joints affected. We assessed regional plantar loading during barefoot walking to avoid confounding effects due to footwear and shoe inserts. However, in individuals with foot pain, barefoot walking may have limited external validity. Patients with midfoot OA report symptoms during dynamic weight-bearing activities such as walking. For this reason, we assessed midfoot plantar loading during walking. However, normal force (the product of pressure and area) and dynamic loads through the forefoot, particularly during the propulsion phase of gait may also contribute to patients symptoms. Future investigations modeling biomechanical loads at the midfoot are indicated to assess net joint forces and moments at the tarso-metatarsal joints. Additional studies are indicated to quantify the direct relationship between regional plantar loading and articular stress sustained in the joints of the foot during weight-bearing activities. Conclusions This study demonstrated that patients with midfoot OA sustain increased magnitude and duration of regional plantar loading during walking compared to matched control subjects. Future studies should assess whether interventions designed to reduce plantar loading are effective in relieving foot pain and/or preventing progression of symptoms in patients with midfoot OA. Further analysis using k-means cluster analysis distinguished two sub-groups. Prospective studies are indicated to assess disease progression and response to intervention in these two subgroups. Contributions All authors were involved in study design, data analysis and manuscript preparation. The Corresponding Author (Smita Rao) was primarily responsible for seeking consent and collecting data, and is responsible for the integrity of the work as a whole, from inception to finished article. Role of the funding source The study sponsors played no role in the study design; collection; analysis or interpretation of data. Conflict of interest We, the authors of this manuscript, affirm that we have no financial affiliation (including research funding) or involvement with any commercial organization that has a direct financial interest in any matter included in this manuscript except as cited in the manuscript. Acknowledgments We would like to acknowledge funding support from the Arthritis Foundation and the American Orthopaedic Foot and Ankle Society. Supplementary data Supplementary data related to this article can be found online at doi: /j.joca References 1. Segal NA, Anderson DD, Iyer KS, et al. Baseline articular contact stress levels predict incident symptomatic knee osteoarthritis development in the MOST cohort. J Orthop Res 2009;27:1562e8. 2. Andriacchi TP, Mundermann A. The role of ambulatory mechanics in the initiation and progression of knee osteoarthritis. Curr Opin Rheumatol 2006;18:514e8. 3. Abramson SB, Attur M. Developments in the scientific understanding of osteoarthritis. 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