PM R XXX (2015) 1-8
www.pmrjournal.org
Original Research
Knee Flexion Contractures in Patients with Osteoarthritis: Clinical Features and Histologic Characterization of the Posterior Capsule Thomas Mark Campbell, MD, MSc, Guy Trudel, MD, MSc, Odette Laneuville, PhD
Abstract Objective: To (1) identify demographic and clinical factors associated with knee flexion contracture (KFlC) in the setting of osteoarthritis (OA) and (2) histologically compare the posterior knee capsule of patients with OA with and without KFlC. Design: Cross-sectional study. Setting: Primary care, including private and institutional practice. Patients: Thirteen patients with primary OA and KFlC and 8 patients with primary OA without KFlC. Methods: We compared the KFlC and non-KFlC groups to identify demographic and clinical factors associated with KFlC. We examined the histology of the posterior knee capsules of 9 patients with KFlC and 6 without. Main Outcome Measurements: Patient demographic and clinical factors. For histology we measured the proportional composition of collagenous, adipose, and synovial tissues; fibroblast and adipocyte cellularity; and synovial thickness. Results: Patients with contracture had longer duration of OA, reduced flexion of the surgical knee, and reduced extension of the contralateral knee (P ¼ .04, .05) (Table 2, Figure 1B). The number of fibroblasts (Figure 1C) was similar between the 2 groups (P > .05), whereas there was a greater number of adipocytes per HPF in the contracture group (28.8 versus 22.2, Figure 1D). Discussion We studied factors associated with KFlC in patients with severe knee OA before TKA and characterized the capsular changes at the tissue and cellular level. We found a significant association between KFlC and longer duration of knee OA, loss of flexion of the surgical knee, and loss of extension of the contralateral knee. Histologically, capsule tissue from knees with contracture contained more collagenous, more adipose, and less
Table 2 Histologic characteristics of the contracture and noncontracture groups Characteristic 2
Sample area (size of biopsy), mm % Adipose % Collagenous % Synovial intima % Other tissue Synovial thickness, no. of cells Average no. of fibroblasts/HPF (2 100 fields) Average no. of adipocytes/HPF (2 50 fields) Data shown are mean (and range). HPF ¼ high-powered field. * P ¼ .048.
Contracture Group (n ¼ 9)
Noncontracture Group (n ¼ 6)
11.2 14.2 70.4 2.3 15.4 5.2 28.6 28.8
19.3 8.9 57.0 13.0 24.4 3.8 26.0 22.2
(2.5-26.4) (0-61.9) (39.6-88.8) (0-5.5) (0.5-29.81) (0-10) (4.5-50) (0-32)*
(7.9-55.4) (0-40.1) (15.6-83.8) (0.4-55.0) (1.2-43.1) (3-6.5) (6-73.5) (0-26)
T.M. Campbell et al. / PM R XXX (2015) 1-8
5
Figure 1. Tissue composition pie graphs and photomicrographs of stained sections of posterior knee capsule from patients with osteoarthritis with or without knee flexion contracture. (A) Pie graphs showing mean relative tissue composition of capsule tissue samples. Left, contracture; right, noncontracture. (B) Top left, 20 magnification trichrome: contracture sample showing mainly collagenous tissue composition. Bottom left, 20 magnification, inset 100 magnification hematoxylin and eosin: contracture sample showing collagenous, adipose, synovial, and other tissue; inset: synovial border 3e4 cells thick. Top right, 20 magnification trichrome: noncontracture sample showing heterogeneous tissue composition. Bottom right, 20 magnification, inset 100 magnification hematoxylin and eosin: noncontracture sample showing marked synovial proliferation; inset: synovial border 4-6 cells thick. (C) Left, 400 magnification: contracture sample showing fibroblast cellularity within collagenous tissue. Right, 400 magnification: noncontracture sample showing similar fibroblast cellularity as contracture sample. (D) Left, 200 magnification: contracture sample showing adipocyte cellularity. Right, 200 magnification: noncontracture sample showing similar adipocyte cellularity as contracture sample.
6
OA Knee Flexion Contracture
shorter [27]. Disadvantages of ambulating on legs of unequal lengths include altered center of pressure [28], increased energy requirements [29], and pain in other joints [27]. Patients flexing the knee opposite to the OA knee during gait compensate for the leg length discrepancy. The reduced length of the contralateral leg during ambulation restores equal (but shorter) leg length and effectively corrects the gait abnormality. To our knowledge however, direct kinematic and physiologic comparison of these gait patterns to determine which would be least energy-demanding has not been performed. The potential disadvantage of this postural adjustment is the permanent loss of extension range in the contralateral knee, as we found in our patients [27,28]. Genetically, evidence for a predisposition to decreased ROM comes from a study in which different rat strains were subjected to immobilization of the knee joint [30]. Dark Agouti and Fisher 344 strains developed more severe contractures than Augustus Copenhagen Irish and Brown Norway strains. Some patients with OA may display individual variation in the expression of genes or gene pathways contributing to contracture formation and experience bilateral knee contractures. At the opposite end of the spectrum, increased joint ROM caused by genetically determined capsular laxity has been well described: syndromes caused by genetic deficiencies related to collagen expression and synthesis, such as Marfan syndrome, increase normal capsule extensibility and resulting ROM [31]. Altered gene expression in the capsule can play an important role in joint ROM and also might help explain why our subjects with KFlCs also had reduced flexion. Our findings suggest that preventing a discrepancy in leg length might preserve ROM in the contralateral knee. Otherwise, patients whose contracture can be corrected at TKA will paradoxically present with a postoperative contracture in the opposite knee. A contracture in the non-TKA knee causes a functionally shorter leg, possibly increasing the risk for a repeat contracture in the TKA knee and, thus, a poor outcome [8]. It is not current standard clinical practice to monitor the ROM of both knees in patients with OA or to measure functional leg length. Correction of leg length discrepancy via the use of shoe lifts has been shown to be effective in reducing energy expenditure in other populations [32]. In patients with OA who will be undergoing TKA, pre- or postoperative correction for leg length discrepancy by the use of heel or shoe lifts may constitute a simple and inexpensive treatment to preserve function and improve surgical outcome with large health care system returns, and our study supports undertaking such an investigation. We found a greater proportion of fibrotic tissue in OA joint capsule from knees with a contracture than
those without a contracture. This novel clinical finding is consistent with results from animal models of contracture suggestive of a fibrotic process in the posterior capsule [25]. The observed decreased proportion of synovial tissue in knees with contractures agrees with findings of shortened synovial intima and decreased synovial proliferation markers in the posterior capsule of rat knee joints with contractures [26]. A knee contracture decreases the available ROM. This may reduce inflammation by preventing contact between degenerated articular cartilage surfaces and decreasing exposure of the synovium to inflammatory mediators [14,15]. Reduced inflammation may reduce synovial proliferation [33]. We could not determine the relative contribution of the OA disease process and/or of the reduced joint mobility attributable to the antalgic ROM arc to our histologic findings. Our preliminary data, however, show that the proportions of tissue types may characterize contracture development. Interestingly, whereas contracture samples had a statistically significantly greater number of adipocytes per HPF, the relative proportion of adipose was not different between the 2 groups, suggesting a larger number of smaller adipocytes. A limitation to our preliminary study is the small sample size. The exclusion criterion of knee arthroscopy was necessary to rule out previous capsular injury (eg, surgical portals) but limited recruitment, because arthroscopy is a common procedure before TKA. Studying a larger sample may identify additional clinical risk factors for contracture and confirm those identified in the current study. A larger sample size may also reveal statistically significant differences in tissue proportions. Because our subjects had end-stage OA as well as multiple factors that can contribute to contracture (eg, presence of osteophytes, altered capsule), it was not possible to determine whether the changes in the capsule were the primary source of contracture or whether the contracture was secondary to another mechanical cause. We limited our histologic analysis to the posterior capsule and therefore cannot comment on changes in or contributions from other portions of the capsule (eg, anterior capsule changes in subjects who lacked full knee flexion). Our sample size did not allow statistical algorithms such as binomial logistic regression to further examine the effects of demographic features on contracture. Bonferroni correction eliminated all statistically significant variables and was not reported in our analysis. Conclusion In this preliminary study, we describe risk factors for KFlC in patients with OA before TKA, as well as corresponding histologic changes in the posterior knee capsule. To our knowledge, this is the first report of such findings. The clinical features of duration of OA,
T.M. Campbell et al. / PM R XXX (2015) 1-8
loss of flexion of the surgical knee, and loss of extension of the contralateral knee could potentially be used to stratify patients with knee OA with respect to risk of KFlC development. The proportions of tissue types may be correlated with contracture development and/or severity and could help generate prognostic tools for contracture in OA patients. These results support further research using a larger sample size to confirm these findings. Acknowledgments We thank Dr. Mathew Quon for assistance with radiography; Dr. Alain Stintzi, Dr. Zhara Montazeri, Dr. Julian Little, and Dr. Robert J. Feibel for project direction; Professor Philip Conaghan for manuscript advice; Louise Pelletier and the University of Ottawa Pathology Department, Elizabeth Coletta, Ying Nie Ping, Dr. Natalie Bunimov, and Ge ´nome Que ´bec for technical support; Sarah Plamondon and Anna Fazekas for assistance with patient recruitment and ethics approval; Gloria Baker for assistance with manuscript preparation; and Dr. Geoffrey Dervin, Dr. Robert J. Feibel, Dr. Paul Kim, Dr. Peter Thurston, and Dr. Paul Edgar Beaule ´ for tissue collection. References 1. Trudel G, Uhthoff HK. Contractures secondary to immobility: is the restriction articular or muscular? An experimental longitudinal study in the rat knee. Arch Phys Med Rehabil 2000;81:6-13. 2. Clavet H, He ´bert PC, Fergusson D, Doucette S, Trudel G. Joint contracture following prolonged stay in the intensive care unit. CMAJ 2008;178:691-697. 3. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998;41: 1343-1355. 4. Ritter MA, Lutgring JD, Davis KE, Berend ME, Pierson JL, Meneghini RM. The role of flexion contracture on outcomes in primary total knee arthroplasty. J Arthroplasty 2007;22:1092-1096. 5. Centers for Disease Control and Prevention/National Center for Health Statistics. FastStats: Inpatient surgery. Secondary FastStats: Inpatient surgery. 2010. Available from: http://www.cdc. gov/nchs/fastats/insurg.htm. Accessed May 30, 2013. 6. Perry J, Antonelli D, Ford W. Analysis of knee-joint forces during flexed-knee stance. J Bone Joint Surg Am 1975;57:961-967. 7. Potter PJ, Kirby RL, MacLeod DA. The effects of simulated kneeflexion contractures on standing balance. Am J Phys Med Rehabil 1990;69:144-147. 8. Trudel G, Laneuville O, Uhthoff HK. Joint contractures. Clin Orthop Relat Res 2007;456:2. 9. Anouchi YS, McShane M, Kelly FJ, Elting J, Stiehl J. Range of motion in total knee replacement. Clin Orthop Relat Res 1996; 331:87-92. 10. Laskin RS, Beksac B. Stiffness after total knee arthroplasty. J Arthroplasty 2004;19(4 Suppl):41-46. 11. Keeney JA, Clohisy JC, Curry M, Maloney WJ. Revision total knee arthroplasty for restricted motion. Clin Orthop Relat Res 2005;440: 135-140. 12. Mihalko WM, Whiteside LA. Bone resection and ligament treatment for flexion contracture in knee arthroplasty. Clin Orthop Relat Res 2003:141-147.
7
13. Firestone TP, Krackow KA, Davis JD 4th, Teeny SM, Hungerford DS. The management of fixed flexion contractures during total knee arthroplasty. Clin Orthop Relat Res 1992:221-227. 14. Pritzker KPH. Pathology of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis. 1st ed. New York: Oxford University Press; 1998; 56-57. 15. Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: A histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis 1988;47: 300-307. 16. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039-1049. 17. Norkin CC, White DJ. Measurement of Joint Motion: A Guide to Goniometry. 3rd ed. Philadelphia: FA Davis Company; 2003. 18. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494-502. 19. Hinman RS, May RL, Crossley KM. Is there an alternative to the fullleg radiograph for determining knee joint alignment in osteoarthritis? Arthritis Rheum 2006;55:306-313. 20. Kraus VB, Vail TP, Worrell T, McDaniel G. A comparative assessment of alignment angle of the knee by radiographic and physical examination methods. Arthritis Rheum 2005;52:1730-2735. 21. Campbell TM, Trudel G, Wong KK, Laneuville O. Genome-wide gene expression analysis of the posterior capsule in patients with osteoarthritis and knee flexion contracture. J Rheumatol 2014;41: 2232-2239. 22. Uhthoff HK, Coletta E, Trudel G. Intramuscular fat accumulation and muscle atrophy in the absence of muscle retraction. Bone Joint Res 2014;3:117-122. 23. Egan KP, Brennan TA, Pignolo RJ. Bone histomorphometry using free and commonly available software. Histopathology 2012;61: 1168-1173. 24. Prasad K, Prabhu GK. Image analysis tools for evaluation of microscopic views of immunohistochemically stained specimen in medical researchda review. J Med Syst 2012;36:2621-2631. 25. Matsumoto F, Trudel G, Uhthoff HK. High collagen type I and low collagen type III levels in knee joint contracture: An immunohistochemical study with histological correlate. Acta Orthop Scand 2002;73:335-343. 26. Trudel G, Jabi M, Uhthoff HK. Localized and adaptive synoviocyte proliferation characteristics in rat knee joint contractures secondary to immobility. Arch Phys Med Rehabil 2003;84: 1350-1356. 27. Friberg O. Clinical symptoms and biomechanics of lumbar spine and hip joint in leg length inequality. Spine (Phila Pa 1976) 1983;8: 643-651. 28. Mahar RK, Kirby RL, MacLeod DA. Simulated leg-length discrepancy: Its effect on mean center-of-pressure position and postural sway. Arch Phys Med Rehabil 1985;66:822-824. 29. Delacerda FG, Wikoff OD. Effect of lower extremity asymmetry on the kinematics of gait. J Orthop Sports Phys Ther 1982;3:105-107. 30. Laneuville O, Zhou J, Uhthoff HK, Trudel G. Genetic influences on joint contractures secondary to immobilization. Clin Orthop Relat Res 2007;456:36-41. 31. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991;352:337-339. 32. Abdulhadi HM, Kerrigan DC, LaRaia PJ. Contralateral shoe-lift: Effect on oxygen cost of walking with an immobilized knee. Arch Phys Med Rehabil 1996;77:670-672. 33. Wijbrandts CA, Remans PH, Klarenbeek PL, et al. Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients. Arthritis Rheum 2008;58:3330-3339.
8
OA Knee Flexion Contracture
Disclosure T.M.C. Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa, Ottawa, ON, Canada. Address correspondence to: T.M.C.; e-mail: [email protected] Disclosure: nothing to disclose G.T. Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa, Ottawa, ON, Canada Disclosure: nothing to disclose
O.L. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada Disclosure: nothing to disclose This work was funded by Canadian Institutes of Health Research grant MOP97831 to Drs. Trudel and Laneuville. Submitted for publication February 18, 2014; accepted December 1, 2014.
www.pmrjournal.org
Original Research
Knee Flexion Contractures in Patients with Osteoarthritis: Clinical Features and Histologic Characterization of the Posterior Capsule Thomas Mark Campbell, MD, MSc, Guy Trudel, MD, MSc, Odette Laneuville, PhD
Abstract Objective: To (1) identify demographic and clinical factors associated with knee flexion contracture (KFlC) in the setting of osteoarthritis (OA) and (2) histologically compare the posterior knee capsule of patients with OA with and without KFlC. Design: Cross-sectional study. Setting: Primary care, including private and institutional practice. Patients: Thirteen patients with primary OA and KFlC and 8 patients with primary OA without KFlC. Methods: We compared the KFlC and non-KFlC groups to identify demographic and clinical factors associated with KFlC. We examined the histology of the posterior knee capsules of 9 patients with KFlC and 6 without. Main Outcome Measurements: Patient demographic and clinical factors. For histology we measured the proportional composition of collagenous, adipose, and synovial tissues; fibroblast and adipocyte cellularity; and synovial thickness. Results: Patients with contracture had longer duration of OA, reduced flexion of the surgical knee, and reduced extension of the contralateral knee (P ¼ .04, .05) (Table 2, Figure 1B). The number of fibroblasts (Figure 1C) was similar between the 2 groups (P > .05), whereas there was a greater number of adipocytes per HPF in the contracture group (28.8 versus 22.2, Figure 1D). Discussion We studied factors associated with KFlC in patients with severe knee OA before TKA and characterized the capsular changes at the tissue and cellular level. We found a significant association between KFlC and longer duration of knee OA, loss of flexion of the surgical knee, and loss of extension of the contralateral knee. Histologically, capsule tissue from knees with contracture contained more collagenous, more adipose, and less
Table 2 Histologic characteristics of the contracture and noncontracture groups Characteristic 2
Sample area (size of biopsy), mm % Adipose % Collagenous % Synovial intima % Other tissue Synovial thickness, no. of cells Average no. of fibroblasts/HPF (2 100 fields) Average no. of adipocytes/HPF (2 50 fields) Data shown are mean (and range). HPF ¼ high-powered field. * P ¼ .048.
Contracture Group (n ¼ 9)
Noncontracture Group (n ¼ 6)
11.2 14.2 70.4 2.3 15.4 5.2 28.6 28.8
19.3 8.9 57.0 13.0 24.4 3.8 26.0 22.2
(2.5-26.4) (0-61.9) (39.6-88.8) (0-5.5) (0.5-29.81) (0-10) (4.5-50) (0-32)*
(7.9-55.4) (0-40.1) (15.6-83.8) (0.4-55.0) (1.2-43.1) (3-6.5) (6-73.5) (0-26)
T.M. Campbell et al. / PM R XXX (2015) 1-8
5
Figure 1. Tissue composition pie graphs and photomicrographs of stained sections of posterior knee capsule from patients with osteoarthritis with or without knee flexion contracture. (A) Pie graphs showing mean relative tissue composition of capsule tissue samples. Left, contracture; right, noncontracture. (B) Top left, 20 magnification trichrome: contracture sample showing mainly collagenous tissue composition. Bottom left, 20 magnification, inset 100 magnification hematoxylin and eosin: contracture sample showing collagenous, adipose, synovial, and other tissue; inset: synovial border 3e4 cells thick. Top right, 20 magnification trichrome: noncontracture sample showing heterogeneous tissue composition. Bottom right, 20 magnification, inset 100 magnification hematoxylin and eosin: noncontracture sample showing marked synovial proliferation; inset: synovial border 4-6 cells thick. (C) Left, 400 magnification: contracture sample showing fibroblast cellularity within collagenous tissue. Right, 400 magnification: noncontracture sample showing similar fibroblast cellularity as contracture sample. (D) Left, 200 magnification: contracture sample showing adipocyte cellularity. Right, 200 magnification: noncontracture sample showing similar adipocyte cellularity as contracture sample.
6
OA Knee Flexion Contracture
shorter [27]. Disadvantages of ambulating on legs of unequal lengths include altered center of pressure [28], increased energy requirements [29], and pain in other joints [27]. Patients flexing the knee opposite to the OA knee during gait compensate for the leg length discrepancy. The reduced length of the contralateral leg during ambulation restores equal (but shorter) leg length and effectively corrects the gait abnormality. To our knowledge however, direct kinematic and physiologic comparison of these gait patterns to determine which would be least energy-demanding has not been performed. The potential disadvantage of this postural adjustment is the permanent loss of extension range in the contralateral knee, as we found in our patients [27,28]. Genetically, evidence for a predisposition to decreased ROM comes from a study in which different rat strains were subjected to immobilization of the knee joint [30]. Dark Agouti and Fisher 344 strains developed more severe contractures than Augustus Copenhagen Irish and Brown Norway strains. Some patients with OA may display individual variation in the expression of genes or gene pathways contributing to contracture formation and experience bilateral knee contractures. At the opposite end of the spectrum, increased joint ROM caused by genetically determined capsular laxity has been well described: syndromes caused by genetic deficiencies related to collagen expression and synthesis, such as Marfan syndrome, increase normal capsule extensibility and resulting ROM [31]. Altered gene expression in the capsule can play an important role in joint ROM and also might help explain why our subjects with KFlCs also had reduced flexion. Our findings suggest that preventing a discrepancy in leg length might preserve ROM in the contralateral knee. Otherwise, patients whose contracture can be corrected at TKA will paradoxically present with a postoperative contracture in the opposite knee. A contracture in the non-TKA knee causes a functionally shorter leg, possibly increasing the risk for a repeat contracture in the TKA knee and, thus, a poor outcome [8]. It is not current standard clinical practice to monitor the ROM of both knees in patients with OA or to measure functional leg length. Correction of leg length discrepancy via the use of shoe lifts has been shown to be effective in reducing energy expenditure in other populations [32]. In patients with OA who will be undergoing TKA, pre- or postoperative correction for leg length discrepancy by the use of heel or shoe lifts may constitute a simple and inexpensive treatment to preserve function and improve surgical outcome with large health care system returns, and our study supports undertaking such an investigation. We found a greater proportion of fibrotic tissue in OA joint capsule from knees with a contracture than
those without a contracture. This novel clinical finding is consistent with results from animal models of contracture suggestive of a fibrotic process in the posterior capsule [25]. The observed decreased proportion of synovial tissue in knees with contractures agrees with findings of shortened synovial intima and decreased synovial proliferation markers in the posterior capsule of rat knee joints with contractures [26]. A knee contracture decreases the available ROM. This may reduce inflammation by preventing contact between degenerated articular cartilage surfaces and decreasing exposure of the synovium to inflammatory mediators [14,15]. Reduced inflammation may reduce synovial proliferation [33]. We could not determine the relative contribution of the OA disease process and/or of the reduced joint mobility attributable to the antalgic ROM arc to our histologic findings. Our preliminary data, however, show that the proportions of tissue types may characterize contracture development. Interestingly, whereas contracture samples had a statistically significantly greater number of adipocytes per HPF, the relative proportion of adipose was not different between the 2 groups, suggesting a larger number of smaller adipocytes. A limitation to our preliminary study is the small sample size. The exclusion criterion of knee arthroscopy was necessary to rule out previous capsular injury (eg, surgical portals) but limited recruitment, because arthroscopy is a common procedure before TKA. Studying a larger sample may identify additional clinical risk factors for contracture and confirm those identified in the current study. A larger sample size may also reveal statistically significant differences in tissue proportions. Because our subjects had end-stage OA as well as multiple factors that can contribute to contracture (eg, presence of osteophytes, altered capsule), it was not possible to determine whether the changes in the capsule were the primary source of contracture or whether the contracture was secondary to another mechanical cause. We limited our histologic analysis to the posterior capsule and therefore cannot comment on changes in or contributions from other portions of the capsule (eg, anterior capsule changes in subjects who lacked full knee flexion). Our sample size did not allow statistical algorithms such as binomial logistic regression to further examine the effects of demographic features on contracture. Bonferroni correction eliminated all statistically significant variables and was not reported in our analysis. Conclusion In this preliminary study, we describe risk factors for KFlC in patients with OA before TKA, as well as corresponding histologic changes in the posterior knee capsule. To our knowledge, this is the first report of such findings. The clinical features of duration of OA,
T.M. Campbell et al. / PM R XXX (2015) 1-8
loss of flexion of the surgical knee, and loss of extension of the contralateral knee could potentially be used to stratify patients with knee OA with respect to risk of KFlC development. The proportions of tissue types may be correlated with contracture development and/or severity and could help generate prognostic tools for contracture in OA patients. These results support further research using a larger sample size to confirm these findings. Acknowledgments We thank Dr. Mathew Quon for assistance with radiography; Dr. Alain Stintzi, Dr. Zhara Montazeri, Dr. Julian Little, and Dr. Robert J. Feibel for project direction; Professor Philip Conaghan for manuscript advice; Louise Pelletier and the University of Ottawa Pathology Department, Elizabeth Coletta, Ying Nie Ping, Dr. Natalie Bunimov, and Ge ´nome Que ´bec for technical support; Sarah Plamondon and Anna Fazekas for assistance with patient recruitment and ethics approval; Gloria Baker for assistance with manuscript preparation; and Dr. Geoffrey Dervin, Dr. Robert J. Feibel, Dr. Paul Kim, Dr. Peter Thurston, and Dr. Paul Edgar Beaule ´ for tissue collection. References 1. Trudel G, Uhthoff HK. Contractures secondary to immobility: is the restriction articular or muscular? An experimental longitudinal study in the rat knee. Arch Phys Med Rehabil 2000;81:6-13. 2. Clavet H, He ´bert PC, Fergusson D, Doucette S, Trudel G. Joint contracture following prolonged stay in the intensive care unit. CMAJ 2008;178:691-697. 3. Felson DT, Zhang Y. An update on the epidemiology of knee and hip osteoarthritis with a view to prevention. Arthritis Rheum 1998;41: 1343-1355. 4. Ritter MA, Lutgring JD, Davis KE, Berend ME, Pierson JL, Meneghini RM. The role of flexion contracture on outcomes in primary total knee arthroplasty. J Arthroplasty 2007;22:1092-1096. 5. Centers for Disease Control and Prevention/National Center for Health Statistics. FastStats: Inpatient surgery. Secondary FastStats: Inpatient surgery. 2010. Available from: http://www.cdc. gov/nchs/fastats/insurg.htm. Accessed May 30, 2013. 6. Perry J, Antonelli D, Ford W. Analysis of knee-joint forces during flexed-knee stance. J Bone Joint Surg Am 1975;57:961-967. 7. Potter PJ, Kirby RL, MacLeod DA. The effects of simulated kneeflexion contractures on standing balance. Am J Phys Med Rehabil 1990;69:144-147. 8. Trudel G, Laneuville O, Uhthoff HK. Joint contractures. Clin Orthop Relat Res 2007;456:2. 9. Anouchi YS, McShane M, Kelly FJ, Elting J, Stiehl J. Range of motion in total knee replacement. Clin Orthop Relat Res 1996; 331:87-92. 10. Laskin RS, Beksac B. Stiffness after total knee arthroplasty. J Arthroplasty 2004;19(4 Suppl):41-46. 11. Keeney JA, Clohisy JC, Curry M, Maloney WJ. Revision total knee arthroplasty for restricted motion. Clin Orthop Relat Res 2005;440: 135-140. 12. Mihalko WM, Whiteside LA. Bone resection and ligament treatment for flexion contracture in knee arthroplasty. Clin Orthop Relat Res 2003:141-147.
7
13. Firestone TP, Krackow KA, Davis JD 4th, Teeny SM, Hungerford DS. The management of fixed flexion contractures during total knee arthroplasty. Clin Orthop Relat Res 1992:221-227. 14. Pritzker KPH. Pathology of osteoarthritis. In: Brandt KD, Doherty M, Lohmander LS, eds. Osteoarthritis. 1st ed. New York: Oxford University Press; 1998; 56-57. 15. Revell PA, Mayston V, Lalor P, Mapp P. The synovial membrane in osteoarthritis: A histological study including the characterisation of the cellular infiltrate present in inflammatory osteoarthritis using monoclonal antibodies. Ann Rheum Dis 1988;47: 300-307. 16. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis. Classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039-1049. 17. Norkin CC, White DJ. Measurement of Joint Motion: A Guide to Goniometry. 3rd ed. Philadelphia: FA Davis Company; 2003. 18. Kellgren JH, Lawrence JS. Radiological assessment of osteoarthrosis. Ann Rheum Dis 1957;16:494-502. 19. Hinman RS, May RL, Crossley KM. Is there an alternative to the fullleg radiograph for determining knee joint alignment in osteoarthritis? Arthritis Rheum 2006;55:306-313. 20. Kraus VB, Vail TP, Worrell T, McDaniel G. A comparative assessment of alignment angle of the knee by radiographic and physical examination methods. Arthritis Rheum 2005;52:1730-2735. 21. Campbell TM, Trudel G, Wong KK, Laneuville O. Genome-wide gene expression analysis of the posterior capsule in patients with osteoarthritis and knee flexion contracture. J Rheumatol 2014;41: 2232-2239. 22. Uhthoff HK, Coletta E, Trudel G. Intramuscular fat accumulation and muscle atrophy in the absence of muscle retraction. Bone Joint Res 2014;3:117-122. 23. Egan KP, Brennan TA, Pignolo RJ. Bone histomorphometry using free and commonly available software. Histopathology 2012;61: 1168-1173. 24. Prasad K, Prabhu GK. Image analysis tools for evaluation of microscopic views of immunohistochemically stained specimen in medical researchda review. J Med Syst 2012;36:2621-2631. 25. Matsumoto F, Trudel G, Uhthoff HK. High collagen type I and low collagen type III levels in knee joint contracture: An immunohistochemical study with histological correlate. Acta Orthop Scand 2002;73:335-343. 26. Trudel G, Jabi M, Uhthoff HK. Localized and adaptive synoviocyte proliferation characteristics in rat knee joint contractures secondary to immobility. Arch Phys Med Rehabil 2003;84: 1350-1356. 27. Friberg O. Clinical symptoms and biomechanics of lumbar spine and hip joint in leg length inequality. Spine (Phila Pa 1976) 1983;8: 643-651. 28. Mahar RK, Kirby RL, MacLeod DA. Simulated leg-length discrepancy: Its effect on mean center-of-pressure position and postural sway. Arch Phys Med Rehabil 1985;66:822-824. 29. Delacerda FG, Wikoff OD. Effect of lower extremity asymmetry on the kinematics of gait. J Orthop Sports Phys Ther 1982;3:105-107. 30. Laneuville O, Zhou J, Uhthoff HK, Trudel G. Genetic influences on joint contractures secondary to immobilization. Clin Orthop Relat Res 2007;456:36-41. 31. Dietz HC, Cutting GR, Pyeritz RE, et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature 1991;352:337-339. 32. Abdulhadi HM, Kerrigan DC, LaRaia PJ. Contralateral shoe-lift: Effect on oxygen cost of walking with an immobilized knee. Arch Phys Med Rehabil 1996;77:670-672. 33. Wijbrandts CA, Remans PH, Klarenbeek PL, et al. Analysis of apoptosis in peripheral blood and synovial tissue very early after initiation of infliximab treatment in rheumatoid arthritis patients. Arthritis Rheum 2008;58:3330-3339.
8
OA Knee Flexion Contracture
Disclosure T.M.C. Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa, Ottawa, ON, Canada. Address correspondence to: T.M.C.; e-mail: [email protected] Disclosure: nothing to disclose G.T. Department of Medicine, The Ottawa Hospital Rehabilitation Centre, University of Ottawa, Ottawa, ON, Canada Disclosure: nothing to disclose
O.L. Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada Disclosure: nothing to disclose This work was funded by Canadian Institutes of Health Research grant MOP97831 to Drs. Trudel and Laneuville. Submitted for publication February 18, 2014; accepted December 1, 2014.
