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Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow CellsA Pilot Study
Valérie Gangji, MD1; Jean-Philippe Hauzeur, MD, PhD1; Celso Matos, MD1; Viviane De Maertelaer, PhD2; Michel Toungouz, MD, PhD1; Micheline Lambermont, PharmD1
1 Department of Rheumatology and Physical Medicine (V.G. and J.-P.H.), Department of Radiology (C.M.), and the Cellular and Molecular Therapy Unit (M.T. and M.L.), Erasme University Hospital, 808 Route de Lennik, 1070 Brussels, Belgium. E-mail address for V. Gangji: vgangji@ulb.ac.be
2 Department of Biostatistics, Institut de Recherche Interdisciplinaire en Biologie Humaine et Moleculaire, School of Medicine, Université Libre de Bruxelles, 808 Route de Lennik, 1070 Brussels, Belgium
View Disclosures and Other Information
The authors did not receive grants or outside funding in support of their research or preparation of this manuscript. They did not receive 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, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.
Investigation performed at the Department of Rheumatology and Physical Medicine, the Department of Radiology, and the Cellular and Molecular Therapy Unit, Erasme University Hospital, Brussels, Belgium

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2004 Jun 01;86(6):1153-1160
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Abstract

Background: Aseptic nontraumatic osteonecrosis of the femoral head is a disorder that can lead to femoral head collapse and the need for total hip replacement. Since osteonecrosis may be a disease of mesenchymal cells or bone cells, the possibility has been raised that bone marrow containing osteogenic precursors implanted into a necrotic lesion of the femoral head may be of benefit in the treatment of this condition. For this reason, we studied the implantation of autologous bone-marrow mononuclear cells in a necrotic lesion of the femoral head to determine the effect on the clinical symptoms and the stage and volume of osteonecrosis.

Methods: We studied thirteen patients (eighteen hips) with stage-I or II osteonecrosis of the femoral head, according to the system of the Association Research Circulation Osseous. The hips were allocated to a program of either core decompression (the control group) or core decompression and implantation of autologous bone-marrow mononuclear cells (the bone-marrow-graft group). Both patients and assessors were blind with respect to treatment-group assignment. The primary outcomes studied were safety, clinical symptoms, and disease progression.

Results: After twenty-four months, there was a significant reduction in pain (p = 0.021) and in joint symptoms measured with the Lequesne index (p = 0.001) and the WOMAC index (p = 0.013) within the bone-marrow-graft group. At twenty-four months, five of the eight hips in the control group had deteriorated to stage III, whereas only one of the ten hips in the bone-marrow-graft group had progressed to this stage. Survival analysis showed a significant difference in the time to collapse between the two groups (p = 0.016). Implantation of bone-marrow mononuclear cells was associated with only minor side effects.

Conclusions: Implantation of autologous bone-marrow mononuclear cells appears to be a safe and effective treatment for early stages of osteonecrosis of the femoral head. Although the findings of this study are promising, their interpretation is limited because of the small number of patients and the short duration of follow-up. Further study is needed to confirm the results.

Level of Evidence: Therapeutic study, Level II-1 (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

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    References

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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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    Valérie Gangji
    Posted on November 26, 2004
    Dr. Gangji responds to Dr. Radke
    Rheumatology and physical Medicine department, Hôpital Erasme

    To the editor,

    In our study(1), the two year survival rate was 50 % for the control group (core decompression only) compared to 90 % in the bone marrow graft group. Because of a small number of patients and the use of a 3 mm inner diameter trephine, our results cannot be compared to large review studies showing encouraging results with core decompression.

    Concerning the efficacy of core decompression, the optimistic conclusion of Radke et al needs to be discussed. We found two randomized and controlled studies on the effect of core decompression (2,3). In the first trial, 61 % of the hips treated by core decompression did not show radiological progression where as only 39 % had no radiological progression in the control group (3). In the other study, the results were not in favour of core decompression since 78 % and 79 % of the hips progressed to subchondral fracture in the control and the core decompression groups respectively, after 24 months of follow up (2).

    For the classical core decompression achieved with a 8 to 10 mm trephine (4), a meta-analysis concludes that the efficacy of core decompression was only demonstrated for stage 1 osteonecrosis (5) . Radke et al used a 2 mm wire to make ten perforations into the necrotic area. This technique might be interesting but is but not validated (6). To our knowledge, there are no data to prove that such a method constitutes an "ideal technique".

    The Association Research Circulation Osseous (ARCO) staging is a classification principally based on X-Ray. Magnetic resonance imaging (MRI) was added to assess preradiological stages. Furthermore, based on publications from Japan and USA pointing out the prognostic value of the size and the position of the necrotic lesion, the ARCO Committee added a subclassification using MRI and X-Ray for the location and the quantification of the lesion (7). However, the ARCO staging has never been validated. So far, only the classification of Steinberg was validated except for the subclasses A, B, C used to quantify the lesion (8). In our study, the location of the osteonecrotic lesion in relation to the weight bearing portion of the femoral head was measured by MRI and was comparable in the two groups at baseline. The volume of the lesion and of the femoral head was measured by drawing the contours of the necrotic lesion on each 3 mm coronal T1 weighted slice. Those measurements can not be compared to those reported in other studies (8-10). However, Hernigou et al compared the volume of the osteonecrotic lesion in stage 3 osteonecrosis to the anatomical measurements of the femoral heads using the same technique as ours (11). Like us, they demonstrated the accuracy of the measurement of the volume of the lesion using this technique. Moreover, since the volume of the lesion was similar at baseline in both groups, it could not have interfered with the outcome.

    References

    (1) Gangji V, Hauzeur JP, Matos C, De M, V, Toungouz M, Lambermont M. Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study. J Bone Joint Surg Am 2004; 86 -A(6):1153-1160.

    (2) Koo KH, Kim R, Ko GH, Song HR, Jeong ST, Cho SH. Preventing collapse in early osteonecrosis of the femoral head. A randomised clinical trial of core decompression. J Bone Joint Surg Br 1995; 77(6):870-874.

    (3) Stulberg BN, Davis AW, Bauer TW, Levine M, Easley K. Osteonecrosis of the femoral head. A prospective randomized treatment protocol. Clin Orthop 1991;(268):140-151.

    (4) Ficat P, Arlet J, Vidal R, Ricci A, Fournial JC. [Therapeutic results of drill biopsy in primary osteonecrosis of the femoral head (100 cases)]. Rev Rhum Mal Osteoartic 1971; 38(4):269-276.

    (5) Castro FP, Jr., Barrack RL. Core decompression and conservative treatment for avascular necrosis of the femoral head: a meta-analysis. Am J Orthop 2000; 29(3):187-194.

    (6) Radke S, Kirschner S, Seipel V, Rader C, Eulert J. Magnetic resonance imaging criteria of successful core decompression in avascular necrosis of the hip. Skeletal Radiol 2004; 33(9):519-523.

    (7) Gardeniers JWM. ARCO (Association Research Circulation Osseous) committee on terminology and classification. ARCO News 1993;(5):79-82.

    (8) Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br 1995; 77(1):34-41.

    (9) Cherian SF, Laorr A, Saleh KJ, Kuskowski MA, Bailey RF, Cheng EY. Quantifying the extent of femoral head involvement in osteonecrosis. J Bone Joint Surg Am 2003; 85-A(2):309-315.

    (10) Koo KH, Kim R. Quantifying the extent of osteonecrosis of the femoral head. A new method using MRI. J Bone Joint Surg Br 1995; 77(6):875 -880.

    (11) Hernigou P, Lambotte JC. Volumetric analysis of osteonecrosis of the femur. Anatomical correlation using MRI. J Bone Joint Surg Br 2001; 83(5):672-675.

    Stefan Radke
    Posted on August 09, 2004
    Treatment of Osteonecrosis with Autologous Marrow Cells.
    Department of orthopedic surgery, julius maximilians university wuerzburg

    To the Editor:

    In the recent article by Gangji et al, implantation of autologous bone marrow cells is compared to core decompression for the treatment of early stage osteonecrosis. Both treatment groups undergo core decompresson with a 3 mm hollow trephine and in one group, core decompression is supplemented by bone-marrow grafting. The two year survival rate for the control group is 50% compared to 90% in the bone marrow graft group. This demonstrates a positive effect of the bone marrow implantation on the osteonecrosis in comparison to core decompression with a 3 mm hollow trephine alone.

    However, the results for core decompression in this study are worse than the results generally achieved by core decompression [1,2,3], and can be attributed to a number of factors: the technique used by the authors; the radiographically based ARCO staging system which is less sensitive to subchondral fractures than an MRI based ARCO staging system [4]; the location of the osteonecrotic lesion in relation to the weight bearing surface (not mentioned); and the smaller volume percentage of the necrotic area.

    Although the short term results of this technique are good, it should be compared to the results and costs of core decompression performed with ideal technique and optimal evaluative criteria.

    1. RP Ficat, Idiopathic bone necrosis of the femoral head. Early diagnosis and treatment. JBJS Br 1985 67:6-9 2. ME Steinberg, GD Hayken, DR Steinberg. A quantitative system for staging avascular necrosis. JBJS Br 1995 77:34-41 3. AC Fairbank, D Bhatia, RH Jinnah, DS Hungerford. Long term results of core decompression for ischemic necrosis of the femoral head. JBJS Br 1995 77:42-49 4. S Radke, S Kirschner, V Seipel, C Rader, J Eulert. MRI prognostic criteria for core decompression in early stage osteonecrosis. Skeletal Radiol. 2004 Jun 23 [e-pub ahead of print]

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