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Scientific Articles:
Gunnar Knutsen, Jon Olav Drogset, Lars Engebretsen, Torbjørn Grøntvedt, Vidar Isaksen, Tom C. Ludvigsen, Sally Roberts, Eirik Solheim, Torbjørn Strand, and Oddmund Johansen
A Randomized Trial Comparing Autologous Chondrocyte Implantation with Microfracture. Findings at Five Years
J Bone Joint Surg Am 2007; 89: 2105-2112 [Abstract] [Full text] [PDF]
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Electronic letters published:

[Read Letter to the Editor] Dr. Knutsen et al. respond to Dr. Cole
Gunnar Knutsen, M.D., Jon Olav Drogset, MD, PhD, Lars Engebretsen, MD, PhD, Torbjorn Grontvedt, MD, PhD, Tom C. Ludvigsen, MD, Eirik Solheim, MD, PhD, Torbjorn Strand, MD, and Oddmund Johansen, MD, PhD.   (13 November 2007)
[Read Letter to the Editor] Microfracture versus Autologous Chondrocyte Implantation for Cartilage Injuries
Brian J. Cole, M.D.   (13 November 2007)

Dr. Knutsen et al. respond to Dr. Cole 13 November 2007
Previous Letter to the Editor Top
Gunnar Knutsen, M.D.,
Orthopaedic Surgeon
University of Tromso, University Hospital North Norway, 9038 Tromso, NORWAY,
Jon Olav Drogset, MD, PhD, Lars Engebretsen, MD, PhD, Torbjorn Grontvedt, MD, PhD, Tom C. Ludvigsen, MD, Eirik Solheim, MD, PhD, Torbjorn Strand, MD, and Oddmund Johansen, MD, PhD.

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Re: Dr. Knutsen et al. respond to Dr. Cole

gunnar.knutsen{at}unn.no Gunnar Knutsen, M.D., et al.

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 cm˛ 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.
Microfracture versus Autologous Chondrocyte Implantation for Cartilage Injuries 13 November 2007
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Brian J. Cole, M.D.,
Attending Orthopedic Surgeon
Rush University Medical Center, Chicago, IL

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Re: Microfracture versus Autologous Chondrocyte Implantation for Cartilage Injuries

bcole{at}rushortho.com Brian J. Cole, M.D.

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.