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A Randomized Trial Comparing Autologous Chondrocyte Implantation with MicrofractureFindings at Five Years
Gunnar Knutsen, MD1; Jon Olav Drogset, MD, PhD2; Lars Engebretsen, MD, PhD3; Torbjørn Grøntvedt, MD, PhD2; Vidar Isaksen, MD1; Tom C. Ludvigsen, MD3; Sally Roberts, PhD4; Eirik Solheim, MD, PhD5; Torbjørn Strand, MD5; Oddmund Johansen, MD, PhD1
1 Department of Orthopaedic Surgery, University of Tromsø, University Hospital North Norway, 9038 Tromsø, Norway. E-mail address for G. Knutsen: gunnar.knutsen@unn.no
2 University of Trondheim, Trondheim University Hospital, 7006 Trondheim, Norway
3 Department of Orthopaedic Surgery, University of Oslo, Ullevål University Hospital, 0407 Oslo, Norway
4 Robert Jones and Agnes Hunt Orthopaedic Hospital, Oswestry, Shropshire SY10 7AG, United Kingdom
5 Deaconess University Hospital Bergen, 5009 Bergen, Norway
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from the Norwegian Ministry of Health. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
A commentary is available with the electronic versions of this article, on our web site (www.jbjs.org) and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).
Investigation performed at the University Hospital North Norway and University of Tromsø, Tromsø, Trondheim University Hospital, Trondheim, Deaconess University Hospital Bergen, Bergen, Ullevål University Hospital Oslo, Oslo, Norway, and the Robert Jones and Agnes Hunt Orthopaedic Hospital, Shropshire, United Kingdom

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2007 Oct 01;89(10):2105-2112. doi: 10.2106/JBJS.G.00003
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Abstract

Background: The optimal treatment for cartilage lesions has not yet been established. The objective of this randomized trial was to compare autologous chondrocyte implantation with microfracture. This paper represents an update, with presentation of the clinical results at five years.

Methods: Eighty patients who had a single chronic symptomatic cartilage defect on the femoral condyle in a stable knee without general osteoarthritis were included in the study. Forty patients were treated with autologous chondrocyte implantation, and forty were treated with microfracture. We used the International Cartilage Repair Society, Lysholm, Short Form-36, and Tegner forms to collect clinical data, and radiographs were evaluated with use of the Kellgren and Lawrence grading system.

Results: At two and five years, both groups had significant clinical improvement compared with the preoperative status. At the five-year follow-up interval, there were nine failures (23%) in both groups compared with two failures of the autologous chondrocyte implantation and one failure of the microfracture treatment at two years. Younger patients did better in both groups. We did not find a correlation between histological quality and clinical outcome. However, none of the patients with the best-quality cartilage (predominantly hyaline) at the two-year mark had a later failure. One-third of the patients in both groups had radiographic evidence of early osteoarthritis at five years.

Conclusions: Both methods provided satisfactory results in 77% of the patients at five years. There was no significant difference in the clinical and radiographic results between the two treatment groups and no correlation between the histological findings and the clinical outcome. One-third of the patients had early radiographic signs of osteoarthritis five years after the surgery. Further long-term follow-up is needed to determine if one method is better than the other and to study the progression of osteoarthritis.

Level of Evidence: Therapeutic Level I. See Instructions to Authors for a complete description of levels of evidence.

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Gunnar Knutsen, M.D.
    Posted on November 09, 2007
    Dr. Knutsen et al. respond to Dr. Cole
    University of Tromso, University Hospital North Norway, 9038 Tromso, NORWAY

    We appreciate the interest by Dr. Cole in our recent article and we agree that our results can not be generalized to the full spectrum of patients who present with cartilage injuries. We have reported size, location of defects, and clinical data for the enrolled patients.

    Only defects on the weight bearing medial and lateral femoral condyles were included and that has to be considered when our results are interpreted. Far more patients would have been needed in our study to justify stratification into several subgroups. Further, our cohort of patients having relative large chronic defects has to be kept in mind. Clearly, there is a need for additional studies. Even longer follow up is needed in our study and we are aware of other ongoing randomized trials that could increase the evidence base in this difficult field.

    Our group published the two year results in 2004[1]. We reported that microfracture patients with a lesion smaller than 4 cm² had significantly better clinical results than did those with a bigger defect (p<0.003). We did not find this association between the size of the defect and the clinical outcome in the autologous chondrocyte implantation group (p> 0.89). At the five year follow up we tested the interaction between the size of defects, clinical results, and treatment group (p = 0.053). There was, at five years, a tendency for patients with smaller defects in the microfracture group to get better clinical results. This tendency was not present for the ACI group.

    We have, in our first paper, reported that with the same power, we would have needed 120 biopsies to find a significant difference between the two groups. Our study was, as mentioned, not adequately powered to find a significant difference between the two groups regarding histology. However, we reported a tendency (p = 0.08) for the ACI procedure to result in more hyaline repair cartilage that the microfracture procedure.

    Reference:

    1. Knutsen G, Engebretsen L, Ludvigsen TC, Drogset JO, Grontvedt T, Solheim E et al.: Autologous chondrocyte implantation compared with microfracture in the knee. A randomized trial. J Bone Joint Surg Am 2004, 86-A: 455-464.

    Brian J. Cole, M.D.
    Posted on October 30, 2007
    Microfracture versus Autologous Chondrocyte Implantation for Cartilage Injuries
    Rush University Medical Center, Chicago, IL

    To The Editor:

    I read the recently published article “A Randomized Trial Comparing Autologous Chondrocyte Implantation (ACI) with Microfracture: Findings at Five Years".(1) While the results are enlightening, I am concerned that they may not be generalized to the full spectrum of patients who present with cartilage injuries.

    The authors report that the overall 2- and 5- year mean scores are not significantly different between the two treatment groups, however sub- analyses of the 2- year follow-up demonstrated that treatment of smaller lesions with microfracture yielded better clinical results than treatment of larger lesions, an effect not observed in the ACI group. Other studies have reported that lesion size can negatively affect clinical outcomes after microfracture (2-4), a finding not observed with ACI(5-7). Unfortunately, the authors of the current paper failed to elaborate on the effect of defect size for each treatment group.

    In addition, the study did not assess the use of microfracture or ACI in the trochlea. Cartilage defects in the patella-femoral joint remain a difficult problem. Results from one microfracture study suggest that lesion location may affect clinical outcome over time(8). My own experience is consistent with this finding.

    While the study showed no significant differences between the groups with regard to histology, this conclusion should also be interpreted with caution, given that the authors correctly acknowledged that the study was not adequately powered to find a difference between the two groups. Nevertheless, trends suggest that patients treated with ACI had superior histology scores. This is important because the current paper suggests that hyaline-like repairs were less likely to fail.

    While the results from this study provide a benchmark to which results from other studies will be compared, they should be confirmed with additional well designed studies that evaluate defect size, location, and histology at an even more comprehensive level.

    In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Genzyme. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

    References:

    1. Knutsen G, Drogset JO, Engebretsen L, Grontvedt T, Isaksen V, Ludvigsen TC, Roberts S, Solheim E, Strand T, Johansen O. A randomized trial comparing autologous chondrocyte implantation with microfracture. Findings at five years. J Bone Joint Surg Am. 2007;89:2105-2112.

    2. Gudas R, Kalesinskas RJ, Kimtys V, et al. A prospective randomized clinical study of mosaic osteochondral autologous transplantation versus microfracture for the treatment of osteochondral defects in the knee join in young athletes. Arthroscopy. September 2005 2005;21(9):1066-1075.

    3. Mithoefer K, Williams RJ, Warren RF, et al. The microfracture technique for the treatment of articular cartilage lesions in the knee. A prospective cohort study. The Journal of Bone and Joint Surgery. 2005;87(9):1911-1120.

    4. Mithoefer K, Williams RJ, Warren RF, et al. High-impact athletics after knee articular cartilage repair: A prospective evaluation of the microfracture technique. The American Journal of Sports Medicine. September 2006 2006;34(9):1413-1418.

    5. Browne JE, Anderson AF, Arciero R, et al. Clinical outcome of autologous chondrocyte implantation at 5 years in US subjects. Clinical Orthopaedics and Related Research. 2005;436:237-245.

    6. Mandelbaum B, Browne JE, Fu F, et al. Treatment outcomes of autologous chondrocyte implantation for full-thickness articular cartilage defects of the trochlea. American Journal of Sports Medicine. 2007;35(6):915-921.

    7. Micheli LJ, Moseley JB, Anderson AF, et al. Articular cartilage defects in children & adolescents: treatment with autologous chondrocyte implantation. Journal of Pediatric Orthopaedics. 2006;26(4):455-460.

    8. Kreuz PC, Steinwachs MR, Erggelet C, et al. Results after microfracture of full-thickness chondral defects in different compartments in the knee. Osteoarthritis and Cartilage. November 2006 2006;14(11):1119- 1125.

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