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Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy 1/2014

01.01.2014 | Knee

Is gender influencing the biomechanical results after autologous chondrocyte implantation?

verfasst von: Peter C. Kreuz, Sebastian Müller, Christoph Erggelet, Arvind von Keudell, Thomas Tischer, Christian Kaps, Philipp Niemeyer, Anja Hirschmüller

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 1/2014

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Abstract

Purpose

The influence of gender on the biomechanical outcome after autologous chondrocyte implantation (ACI) including isokinetic muscle strength measurements has not been investigated. The present prospective study was performed to evaluate gender-specific differences in the biomechanical function 48 months after ACI.

Methods

Fifty-two patients (mean age 35.6 ± 8.5 years) that met our inclusion criteria, underwent ACI with Bioseed C® and were evaluated with the KOOS score preoperatively, 6, 12 and 48 months after surgery. At final follow-up, 44 out of the 52 patients underwent biomechanical evaluation with isokinetic strength measurements of both knees. All data were evaluated separately for men and women and compared for each time interval using the Mann–Whitney U test.

Results

Clinical scores improved significantly over the whole study period (p < 0.05). Male patients demonstrated significantly better scores during the follow-up in the KOOS score (p < 0.05). Isokinetic strength measurements after 48 months revealed a significant strength deficit of the treated knee in all test modes compared to the healthy extremity (p < 0.05). Furthermore, male patients achieved significantly higher strength values compared to female patients (p < 0.05).

Conclusions

ACI is a viable treatment option for full-thickness chondral defects in the knee of both genders. Isokinetic muscle strength measures are significantly worse in women (p < 0.05), but physiological and may play a role for the explanation of gender-specific results after ACI.

Level of evidence

II.
Literatur
2.
Zurück zum Zitat Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895PubMedCrossRef Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331(14):889–895PubMedCrossRef
3.
Zurück zum Zitat Brun P, Dickinson SC, Zavan B, Cortivo R, Hollander AP, Abatangelo G (2008) Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation. Arthrits Res Ther 10(6):R132CrossRef Brun P, Dickinson SC, Zavan B, Cortivo R, Hollander AP, Abatangelo G (2008) Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation. Arthrits Res Ther 10(6):R132CrossRef
4.
Zurück zum Zitat Della Villa S, Kon E, Filardo G, Ricci M, Vincentelli F, Delcogliano M, Marcacci M (2010) Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes? Am J Sports Med 38(1):68–77PubMedCrossRef Della Villa S, Kon E, Filardo G, Ricci M, Vincentelli F, Delcogliano M, Marcacci M (2010) Does intensive rehabilitation permit early return to sport without compromising the clinical outcome after arthroscopic autologous chondrocyte implantation in highly competitive athletes? Am J Sports Med 38(1):68–77PubMedCrossRef
5.
Zurück zum Zitat Dunkel L (2006) Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol 25:207–216CrossRef Dunkel L (2006) Use of aromatase inhibitors to increase final height. Mol Cell Endocrinol 25:207–216CrossRef
6.
Zurück zum Zitat Erggelet C, Kreuz PC, Mrosek EH, Schagemann JC, Lahm A, Ducommun PP, Ossendorf C (2010) Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions in the knee. Arch Orthop Trauma Surg 130(8):957–964PubMedCrossRef Erggelet C, Kreuz PC, Mrosek EH, Schagemann JC, Lahm A, Ducommun PP, Ossendorf C (2010) Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions in the knee. Arch Orthop Trauma Surg 130(8):957–964PubMedCrossRef
7.
Zurück zum Zitat Gikas PD, Morris T, Carrington R, Skinner J, Bentley G, Briggs T (2009) A correlation between the timing of biopsy after autologous chondrocyte implantation and the histological appearance. J Bone Joint Surg 91-B:1172–1177CrossRef Gikas PD, Morris T, Carrington R, Skinner J, Bentley G, Briggs T (2009) A correlation between the timing of biopsy after autologous chondrocyte implantation and the histological appearance. J Bone Joint Surg 91-B:1172–1177CrossRef
8.
Zurück zum Zitat Goldring MB, Goldring SR (2007) J Cell Physiol. Osteoarthritis 213(3):626–634 Goldring MB, Goldring SR (2007) J Cell Physiol. Osteoarthritis 213(3):626–634
9.
Zurück zum Zitat Granata KP, Padua DA, Wilson SE (2002) Gender differences in active musculoskeletal stiffness. Part II. Quantification of leg stiffness during functional hopping tasks. J Electromoyogr Kinesiol 12(2):127–135CrossRef Granata KP, Padua DA, Wilson SE (2002) Gender differences in active musculoskeletal stiffness. Part II. Quantification of leg stiffness during functional hopping tasks. J Electromoyogr Kinesiol 12(2):127–135CrossRef
10.
Zurück zum Zitat Griffin LY, Albohm MJ, Arendt EA et al (2006) Understanding and preventing noncontact anterior cruciate ligament injuries: a review of the Hunt valley II meeting, January 2005. Am J Sports Med 34(9):1512–1532PubMedCrossRef Griffin LY, Albohm MJ, Arendt EA et al (2006) Understanding and preventing noncontact anterior cruciate ligament injuries: a review of the Hunt valley II meeting, January 2005. Am J Sports Med 34(9):1512–1532PubMedCrossRef
11.
Zurück zum Zitat Gudas R, Kalesinskas RJ, Kimtys V, Stankevicius E, Toliusis V, Bernotavicius G, Smailys A (2005) A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 21(9):1066–1075PubMedCrossRef Gudas R, Kalesinskas RJ, Kimtys V, Stankevicius E, Toliusis V, Bernotavicius G, Smailys A (2005) A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee joint in young athletes. Arthroscopy 21(9):1066–1075PubMedCrossRef
12.
Zurück zum Zitat Harmon KG, Ireland ML (2000) Gender differences in noncontact anterior cruciate ligament injuries. Clin Sports Med 19:287–302PubMedCrossRef Harmon KG, Ireland ML (2000) Gender differences in noncontact anterior cruciate ligament injuries. Clin Sports Med 19:287–302PubMedCrossRef
13.
Zurück zum Zitat Hewett TE, Myer GD, Ford KR, Heidt RS Jr, Colosimo AJ, McLean SG, van den Bogert AJ, Paterno MV, Succop P (2005) Biomechanical measures of neuromuscular control and valgus loading of the knee predict anterior cruciate ligament injury risk in female athletes: a prospective study. Am J Sports Med 33:492–501PubMedCrossRef Hewett TE, Myer GD, Ford KR, Heidt RS Jr, Colosimo AJ, McLean SG, van den Bogert AJ, Paterno MV, Succop P (2005) Biomechanical measures of neuromuscular control and valgus loading of the knee predict anterior cruciate ligament injury risk in female athletes: a prospective study. Am J Sports Med 33:492–501PubMedCrossRef
14.
Zurück zum Zitat Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432–463PubMedCrossRef Hunziker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage 10:432–463PubMedCrossRef
15.
Zurück zum Zitat Jenei-Lanzl Z, Straub RH, Dienstknecht T, Huber M, Hager M, Grässel S, Kujat R, Angele MK, Nerlich M, Angele P (2010) Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling. Arthritis Rheum 62(4):1088–1096PubMedCrossRef Jenei-Lanzl Z, Straub RH, Dienstknecht T, Huber M, Hager M, Grässel S, Kujat R, Angele MK, Nerlich M, Angele P (2010) Estradiol inhibits chondrogenic differentiation of mesenchymal stem cells via nonclassic signaling. Arthritis Rheum 62(4):1088–1096PubMedCrossRef
16.
Zurück zum Zitat Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Südkamp NP, Niemeyer P (2012) Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med 40(1):58–67PubMedCrossRef Jungmann PM, Salzmann GM, Schmal H, Pestka JM, Südkamp NP, Niemeyer P (2012) Autologous chondrocyte implantation for treatment of cartilage defects of the knee: what predicts the need for reintervention? Am J Sports Med 40(1):58–67PubMedCrossRef
17.
Zurück zum Zitat Karimian E, Sävendahl L (2011) Estrogen signaling in growth plate cartilage. Endocr Dev 21:42–51PubMedCrossRef Karimian E, Sävendahl L (2011) Estrogen signaling in growth plate cartilage. Endocr Dev 21:42–51PubMedCrossRef
18.
Zurück zum Zitat Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O (2007) A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 89(10):2105–2112PubMedCrossRef Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O (2007) A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am 89(10):2105–2112PubMedCrossRef
19.
Zurück zum Zitat Kon E, Filardo G, Berruto M, Benazzo F, Zanon G, Della Villa S, Marcacci M (2011) Articular cartilage treatment in high-level male soccer players: a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantation versus microfracture. Am J Sports Med 39(12):2549–2557PubMedCrossRef Kon E, Filardo G, Berruto M, Benazzo F, Zanon G, Della Villa S, Marcacci M (2011) Articular cartilage treatment in high-level male soccer players: a prospective comparative study of arthroscopic second-generation autologous chondrocyte implantation versus microfracture. Am J Sports Med 39(12):2549–2557PubMedCrossRef
20.
Zurück zum Zitat Kreuz PC, Erggelet C, Steinwachs MR, Krause SJ, Lahm A, Niemeyer P, Ghanem N, Uhl M, Südkamp N (2006) Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger? Arthroscopy 22(11):1180–1186PubMedCrossRef Kreuz PC, Erggelet C, Steinwachs MR, Krause SJ, Lahm A, Niemeyer P, Ghanem N, Uhl M, Südkamp N (2006) Is microfracture of chondral defects in the knee associated with different results in patients aged 40 years or younger? Arthroscopy 22(11):1180–1186PubMedCrossRef
21.
Zurück zum Zitat Kreuz PC, Müller S, Freymann U, Erggelet C, Niemeyer P, Kaps C, Hirschmüller A (2011) Repair of focal cartilage defects with scaffold-assisted autologous chondrocyte grafts: clinical and biomechanical results 48 months after transplantation. Am J Sports Med 39(8):1697–1705PubMedCrossRef Kreuz PC, Müller S, Freymann U, Erggelet C, Niemeyer P, Kaps C, Hirschmüller A (2011) Repair of focal cartilage defects with scaffold-assisted autologous chondrocyte grafts: clinical and biomechanical results 48 months after transplantation. Am J Sports Med 39(8):1697–1705PubMedCrossRef
22.
Zurück zum Zitat Kreuz PC, Steinwachs M, Erggelet C, Krause SJ, Ossendorf C, Maier D, Ghanem N, Uhl M, Haag M (2007) Classification of graft hypertrophy after autologous chondrocyte implantation of full-thickness chondral defects in the knee. Osteoarthritis Cartilage 15(12):1339–1347PubMedCrossRef Kreuz PC, Steinwachs M, Erggelet C, Krause SJ, Ossendorf C, Maier D, Ghanem N, Uhl M, Haag M (2007) Classification of graft hypertrophy after autologous chondrocyte implantation of full-thickness chondral defects in the knee. Osteoarthritis Cartilage 15(12):1339–1347PubMedCrossRef
23.
Zurück zum Zitat Kreuz PC, Steinwachs M, Erggelet C, Lahm A, Krause S, Ossendorf C, Meier D, Ghanem N, Uhl M (2007) Importance of sports in cartilage regeneration after autologous chondrocyte implantation: a prospective study with a 3-year follow-up. Am J Sports Med 35(8):1261–1268PubMedCrossRef Kreuz PC, Steinwachs M, Erggelet C, Lahm A, Krause S, Ossendorf C, Meier D, Ghanem N, Uhl M (2007) Importance of sports in cartilage regeneration after autologous chondrocyte implantation: a prospective study with a 3-year follow-up. Am J Sports Med 35(8):1261–1268PubMedCrossRef
24.
Zurück zum Zitat Loken S, Ludvigsen T, Hoysveen T, Holm I, Engebretsen L, Reinholt FP (2009) Autologous chondrocyte implantation to repair knee cartilage injury: ultrastructural evaluation at 2 years and long-term follow-up including muscle strength measurements. Knee Surg Sports Traumatol Arthrosc 17:1278–1288PubMedCrossRef Loken S, Ludvigsen T, Hoysveen T, Holm I, Engebretsen L, Reinholt FP (2009) Autologous chondrocyte implantation to repair knee cartilage injury: ultrastructural evaluation at 2 years and long-term follow-up including muscle strength measurements. Knee Surg Sports Traumatol Arthrosc 17:1278–1288PubMedCrossRef
25.
Zurück zum Zitat Mandelbaum BR, Silvers HJ, Watanabe DS, Knarr JF, Thomas SD, Griffin LY, Kirkendall DT, Garrett W (2005) Effectiveness of a neuromuscular and proprioceptive training program in preventing anterior cruciate ligament injuries in female athletes: 2-year follow-up. Am J Sports Med 33(7):1003–1010PubMedCrossRef Mandelbaum BR, Silvers HJ, Watanabe DS, Knarr JF, Thomas SD, Griffin LY, Kirkendall DT, Garrett W (2005) Effectiveness of a neuromuscular and proprioceptive training program in preventing anterior cruciate ligament injuries in female athletes: 2-year follow-up. Am J Sports Med 33(7):1003–1010PubMedCrossRef
26.
Zurück zum Zitat Miller AEJ, MacDougall JD, Tarnopolsky MA, Sale DG (1993) Gender differences in strength and muscle fiber characteristics. Eur J Appl Physiol 66:254–262CrossRef Miller AEJ, MacDougall JD, Tarnopolsky MA, Sale DG (1993) Gender differences in strength and muscle fiber characteristics. Eur J Appl Physiol 66:254–262CrossRef
27.
Zurück zum Zitat Peterson L, Brittberg M, Kiviranta I, Akerlund EL, Lindahl A (2002) Autologous chondrocyte transplantation: biomechanics and long-term durability. Am J Sports Med 30(1):2–12PubMed Peterson L, Brittberg M, Kiviranta I, Akerlund EL, Lindahl A (2002) Autologous chondrocyte transplantation: biomechanics and long-term durability. Am J Sports Med 30(1):2–12PubMed
28.
Zurück zum Zitat Peterson L, Vasiliadis HS, Brittberg M, Lindahl A (2010) Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 38(6):1117–1124PubMedCrossRef Peterson L, Vasiliadis HS, Brittberg M, Lindahl A (2010) Autologous chondrocyte implantation: a long-term follow-up. Am J Sports Med 38(6):1117–1124PubMedCrossRef
29.
Zurück zum Zitat Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD (1998) Knee Injury and Osteoarthritis Outcome Score (KOOS)-development of a self-administered outcome measure. J Orthop Sports Phys Ther 28(2):411–418CrossRef Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD (1998) Knee Injury and Osteoarthritis Outcome Score (KOOS)-development of a self-administered outcome measure. J Orthop Sports Phys Ther 28(2):411–418CrossRef
30.
Zurück zum Zitat Saris D, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP, TIG/ACT/01/2000&EXT study group (2009) Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(Suppl 1):10S–19S Saris D, Vanlauwe J, Victor J, Almqvist KF, Verdonk R, Bellemans J, Luyten FP, TIG/ACT/01/2000&EXT study group (2009) Treatment of symptomatic cartilage defects of the knee: characterized chondrocyte implantation results in better clinical outcome at 36 months in a randomized trial compared to microfracture. Am J Sports Med 37(Suppl 1):10S–19S
31.
Zurück zum Zitat Schinhan M, Gruber M, Vavken P, Dorotka R, Samouh L, Chiari C, Gruebl-Barabas R, Nehrer S (2012) Critical-size defect induces unicompartmental osteoarthritis in a stable ovine knee. J Orthop Res 30(2):214–220PubMedCrossRef Schinhan M, Gruber M, Vavken P, Dorotka R, Samouh L, Chiari C, Gruebl-Barabas R, Nehrer S (2012) Critical-size defect induces unicompartmental osteoarthritis in a stable ovine knee. J Orthop Res 30(2):214–220PubMedCrossRef
32.
Zurück zum Zitat Schneider U, Rackwitz L, Andereya S, Siebenlist S, Fensky F, Reichert J, Läer I, Barthel T, Rudert M, Nöth U (2011) A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am J Sports Med 39(12):2558–2565PubMedCrossRef Schneider U, Rackwitz L, Andereya S, Siebenlist S, Fensky F, Reichert J, Läer I, Barthel T, Rudert M, Nöth U (2011) A prospective multicenter study on the outcome of type I collagen hydrogel-based autologous chondrocyte implantation (CaReS) for the repair of articular cartilage defects in the knee. Am J Sports Med 39(12):2558–2565PubMedCrossRef
33.
Zurück zum Zitat Schroeppel JP, Crist JD, Anderson HC, Wang J (2011) Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histol Histopathol 26(3):377–394PubMed Schroeppel JP, Crist JD, Anderson HC, Wang J (2011) Molecular regulation of articular chondrocyte function and its significance in osteoarthritis. Histol Histopathol 26(3):377–394PubMed
34.
Zurück zum Zitat Semmler JG, Kutzscher DV, Enoka RM (1999) Gender differences in the fatigability of human skeletal muscle. J Neurophysiol 82:3590–3593PubMed Semmler JG, Kutzscher DV, Enoka RM (1999) Gender differences in the fatigability of human skeletal muscle. J Neurophysiol 82:3590–3593PubMed
35.
Zurück zum Zitat Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19:477–484PubMedCrossRef Steadman JR, Briggs KK, Rodrigo JJ, Kocher MS, Gill TJ, Rodkey WG (2003) Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19:477–484PubMedCrossRef
36.
Zurück zum Zitat Steinwachs M, Kreuz PC (2007) Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy 23(4):381–387PubMedCrossRef Steinwachs M, Kreuz PC (2007) Autologous chondrocyte implantation in chondral defects of the knee with a type I/III collagen membrane: a prospective study with a 3-year follow-up. Arthroscopy 23(4):381–387PubMedCrossRef
37.
Zurück zum Zitat Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP, TIG/ACT/01/2000&EXT study group (2011) Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters. Am J Sports Med 39(12):2566–2574CrossRef Vanlauwe J, Saris DB, Victor J, Almqvist KF, Bellemans J, Luyten FP, TIG/ACT/01/2000&EXT study group (2011) Five-year outcome of characterized chondrocyte implantation versus microfracture for symptomatic cartilage defects of the knee: early treatment matters. Am J Sports Med 39(12):2566–2574CrossRef
38.
Zurück zum Zitat Victor J, Labey L, Wong P, Innocenti B, Bellemans J (2010) The influence of muscle load on tibiofemoral knee kinematics. J Orthop Res 28(4):419–428PubMed Victor J, Labey L, Wong P, Innocenti B, Bellemans J (2010) The influence of muscle load on tibiofemoral knee kinematics. J Orthop Res 28(4):419–428PubMed
39.
Zurück zum Zitat Wojtys EM, Huston LJ, Schock HJ, Boylan JP, Ashton-Miller JA (2003) Gender differences in muscular protection of the knee in torsion in size-matched athletes. J Bone Joint Surg 85(5):782–789PubMed Wojtys EM, Huston LJ, Schock HJ, Boylan JP, Ashton-Miller JA (2003) Gender differences in muscular protection of the knee in torsion in size-matched athletes. J Bone Joint Surg 85(5):782–789PubMed
40.
Zurück zum Zitat Zhong M, Carney DH, Boyan BD, Schwartz Z (2011) 17ß-estradiol regulates rat growth plate chondrocyte apoptosis through a mitochondrial pathway not involving nitric oxide or MAPKs. Endocrinology 152(1):82–92PubMedCrossRef Zhong M, Carney DH, Boyan BD, Schwartz Z (2011) 17ß-estradiol regulates rat growth plate chondrocyte apoptosis through a mitochondrial pathway not involving nitric oxide or MAPKs. Endocrinology 152(1):82–92PubMedCrossRef
Metadaten
Titel
Is gender influencing the biomechanical results after autologous chondrocyte implantation?
verfasst von
Peter C. Kreuz
Sebastian Müller
Christoph Erggelet
Arvind von Keudell
Thomas Tischer
Christian Kaps
Philipp Niemeyer
Anja Hirschmüller
Publikationsdatum
01.01.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 1/2014
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-012-2280-3

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