The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 86, Issue 6

Scientific Articles | June 01, 2004

Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow Cells: A 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

5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case

Article

Comments (2)

text A A A

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.

Figures in this Article

Aseptic nontraumatic osteonecrosis is a painful disorder of the hip that often leads, in its final stage, to femoral head collapse, osteoarthritis, and the need for total hip replacement. Glucocorticoid use and alcohol abuse are among the most widely recognized risk factors for osteonecrosis in white individuals¹. Core decompression of the hip is the most widespread procedure used to treat early stages of osteonecrosis of the femoral head². Notwithstanding the fact that this procedure has been used for more than three decades, its efficacy remains controversial^3,4. Accordingly, a more pathophysiological approach to the treatment of osteonecrosis may be more appropriate. Different pathophysiological mechanisms have been postulated for this disease, including fat emboli⁵, microvascular tamponade of the blood vessels of the femoral head by marrow fat⁶, retrograde embolization of the marrow fat⁷, and microfracture of trabecular bone⁸. The levels of activity and the number of mesenchymal stem cells in both the hematopoietic and the stromal compartments of the bone marrow have been shown to be depressed in patients with osteonecrosis of the femoral head⁹, suggesting that this might be a disease of bone cells and/or mesenchymal cells. The capacity of osteoblastic cells to replicate is decreased in the proximal part of the femur of patients with osteonecrosis of the femoral head¹⁰. This finding raised the possibility that bone marrow containing stromal cells, which have many of the characteristics of the stem cells for mesenchymal tissues including bone, could be implanted into a necrotic lesion of the femoral head. Moreover, Hernigou et al.¹¹ reported the case of a patient who had been treated successfully with autologous bone-marrow implantation for osteonecrosis of the humeral head, secondary to sickle-cell disease. On the basis of this experience, we began a two-year prospective, controlled, double-blind pilot study on the effect of implantation of autologous bone-marrow mononuclear cells into the necrotic lesion in femoral heads with early osteonecrosis.

Materials and Methods

Patients

Patients were considered eligible for the study if they had stage-I or II osteonecrosis of the femoral head according to the system of the Association Research Circulation Osseous (ARCO)¹². According to this system, normal radiographic findings in the femoral head were classified as ARCO stage-I osteonecrosis; trabecular bone remodeling within the femoral head, as stage II; and subchondral collapse of the femoral head, as stage III. We excluded patients with evidence of a malignant disorder during the past five years. The study was approved by the ethical committee of the hospital, and informed consent was obtained from the patients. Osteonecrosis was diagnosed with magnetic resonance imaging¹³. The primary outcomes that were assessed were safety, clinical symptoms, and disease progression. Clinical symptoms included pain and other joint symptoms. Disease progression included an analysis of the stage of osteonecrosis and the volume of the osteonecrotic lesion at the time of the final follow-up. Since there were no published data on this particular procedure, as far as we know, we could not predetermine the number of hips that would be needed for adequate power in this study. Accordingly, we carried out this pilot study. Seventeen patients were recruited. Four patients were excluded, and thirteen patients (six women and seven men) were able to complete the study. There were no missing data. Demographic data are listed in Table I. At baseline, the stages of osteonecrosis, the age of the patients, the clinical symptoms, and the volume of osteonecrosis for the two groups were not found to be significantly different, with the numbers available.

View Larger

TABLE I Demographic Data and Baseline Characteristics of the Hips

Characteristics*	Control Group	Bone-Marrow-Graft Group
No. of hips	8	10
Age†(yr)	48.8 ± 11.2	40.9 ± 9.8
Time to diagnosis†(mo)	4.6 ± 0.6	5.2 ± 0.9
Etiology of osteonecrosis
Corticosteroid use	6	8
Alcohol abuse	1	1
Idiopathic	1	1
Visual analog pain scale†(mm)	34.6 ± 10.1	37.8 ± 8.4
Lequesne index†	5.4 ± 1.5	7.7 ± 1.5
WOMAC score†	21 ± 5	30 ± 5
ARCO stage I	1	1
ARCO stage II	7	9
Volume of osteonecrosis/volume of femoral head†(%)	16.7 ± 4.6	15.6 ± 1.5

WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index, and ARCO = Association Research Circulation Osseous. †The values are given as the mean and the standard error of the mean.

Add to My JBJS

TABLE I Demographic Data and Baseline Characteristics of the Hips

Characteristics*	Control Group	Bone-Marrow-Graft Group
No. of hips	8	10
Age†(yr)	48.8 ± 11.2	40.9 ± 9.8
Time to diagnosis†(mo)	4.6 ± 0.6	5.2 ± 0.9
Etiology of osteonecrosis
Corticosteroid use	6	8
Alcohol abuse	1	1
Idiopathic	1	1
Visual analog pain scale†(mm)	34.6 ± 10.1	37.8 ± 8.4
Lequesne index†	5.4 ± 1.5	7.7 ± 1.5
WOMAC score†	21 ± 5	30 ± 5
ARCO stage I	1	1
ARCO stage II	7	9
Volume of osteonecrosis/volume of femoral head†(%)	16.7 ± 4.6	15.6 ± 1.5

WOMAC = Western Ontario and McMaster Universities Osteoarthritis Index, and ARCO = Association Research Circulation Osseous. †The values are given as the mean and the standard error of the mean.

Five patients had bilateral involvement. Two hips had stage-I osteonecrosis, and sixteen hips had stage-II osteonecrosis. Ten patients (fourteen hips) had osteonecrosis as a result of corticosteroid therapy, and one patient (two hips) had alcohol-induced osteonecrosis. For one patient (two hips), no etiological factor was determined. All patients were symptomatic. The eighteen hips were allocated to treatment with either a core decompression (the control group) or to core decompression and implantation of autologous bone-marrow mononuclear cells (the bone-marrow-graft group). All patients were blind to the treatment assignment. The hips were not randomized. The surgeon performed both procedures (bonemarrow implantation or a core decompression) on an alternating basis. For patients with bilateral involvement, the surgeon chose which hip to treat first. The first hip to treat was alternately the right and then the left hip. To control for bias, the surgeon never examined the patients before or after the procedure and was the only person to know the group assignment. For ethical reasons, the patient was informed specifically of this procedure and knew that the surgeon could be called in case of complications or side effects. Investigators who assessed the outcomes were blind to group assignment. Recruitment began in January 1999, and all patients were followed for twenty-four months.

Core Decompression

With the patient under general anesthesia, a 5-mm incision was made through the skin and the fascia at the level of the greater trochanter. A 3-mm trephine (inner diameter) (Collin, Paris, France) was used as described by Hauzeur et al.^14,15. The trephine was introduced manually under fluoroscopic control through the greater trochanter into the necrotic lesion. The direction of the trephine was adjusted in the intertrochanteric region so that it was pointing toward the necrotic area. The tip of the trephine was placed at a distance of 2 to 3 mm from the articular cartilage (Fig. 1). No other areas of the necrotic lesion were penetrated with the trephine.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 1: Profile radiograph of the hip made at the time of the operation. The 3-mm trephine was introduced by hand under fluoroscopy through the greater trochanter into the anterosuperior region of the femoral head. The trephine was placed into the osteonecrotic zone within 2 to 3 mm of the subchondral bone. The mononuclear cells were injected through the trephine into the necrotic zone.

Bone-Marrow Grafting

The bone-marrow harvesting was performed during the same operative session as the core decompression. About 400 mL of marrow was obtained from the anterior iliac crest (see Appendix). Mononuclear cells were sorted on a Spectra cell separator (777006-300; Cobe, Lakewood, Colorado) and concentrated to a mean final volume (and standard error of the mean) of 51 ± 1.8 mL, which was injected through the trephine that was placed into the necrotic zone¹⁶. The mean number of leukocytes injected was 2.0 ± 0.3 × 10⁹, including 1.0% ± 0.2% of CD34⁺ cells, which are precursors of hematopoietic cells. Fibroblast colony-forming units were used as an indicator of stromal cell activity⁹. The mean number of fibroblast colony-forming units was 92 ± 9/10⁷ cells. The sorted bone-marrow mononuclear cells contained lymphocytoid cells (mean, 29% ± 2.2%), monocytoid cells (4% ± 1%), and myeloid cells (6% ± 1.3%).

Clinical Evaluation

Patients were assessed preoperatively and at three, six, twelve, and twenty-four months postoperatively. Pain was measured with use of a visual analog scale¹⁷. The severity of hip disease was gauged with use of the algofunctional index of Lequesne et al.¹⁸. Symptoms of osteonecrosis were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)¹⁹.

At each visit, patients were assessed for possible side effects of treatment.

Radiographic Evaluation

Anteroposterior and frog-leg lateral radiographs and magnetic resonance images of the affected hip were made at the time of each clinical assessment. Radiographic progression of the osteonecrosis was measured according to the ARCO staging system¹². All radiographs were analyzed by a single reader who was unaware of treatment assignments. The measurements of the magnetic resonance images were prepared on 3-mm coronal T1-weighted scans with use of a separate computer workstation (Easy Vision; Philips, Best, The Netherlands). The contours of the necrotic lesion and the femoral head were drawn on each slice. The volume of the femoral head and the osteonecrotic zone was then calculated by the computer workstation. The relative volume of the necrotic lesion was calculated as a percentage of the entire femoral head²⁰. To evaluate the reliability of this method, the magnetic resonance images were analyzed by two different observers, each unaware of treatment assignments. The first observer took two sets of measurements from each magnetic resonance image of the hip, and the second observer took one. This process resulted in 270 separate determinations.

Statistical Analysis

Continuous variables are described as the mean and the standard error of the mean.

We assessed the change over time with respect to the visual analog scale, the Lequesne index, the WOMAC score, and the volume of the necrotic lesion in both groups. Nonparametric Friedman tests were used. These tests were followed by the use of Wilcoxon paired samples in order to compare the baseline data with the values obtained at three, six, twelve, and twenty-four months. The reliability of the magnetic resonance imaging measurements was calculated with use of correlation coefficients of reliability²¹. Intraobserver reliability was estimated with use of the readings of the first observer. Interobserver reliability was estimated by taking the first reading of the first observer and the unique reading of the second one. A Kaplan-Meier survivorship analysis was used to compare the progression to subchondral fracture (stage III). The rates of survival of the femoral head for the two treatment groups, that is, the duration between the time of enrollment in the study and the end point (collapse of the femoral head), were compared with the log-rank test. The rates of survival within the subgroups of patients who had bilateral osteonecrosis were also compared. A Cox regression model was used with the rate of survival as a dependent variable and with the group and the patient as explained variables. SPSS statistical software (version 11.0; SPSS, Chicago, Illinois) was used.

Results

Overall, a significant decrease in the level of pain was detected in the bone-marrow-graft group after twenty-four months (p = 0.021). The mean scores on the visual analog scale decreased from 37.8 ± 8.4 mm at baseline to 15.1 ± 7.3 mm at three months (p = 0.013), 18.5 ± 6.2 mm at six months (p = 0.017), 23.4 ± 6.7 mm at twelve months (p = 0.066), and 16.3 ± 6.8 mm at twenty-four months (p = 0.017) for the bone-marrow-graft group (Fig. 2). No significant reduction in pain (measured with a visual analog scale) was found in the control group after twenty-four months (p = 0.646), with the numbers available. Overall, patients treated with bone-marrow implantation also demonstrated a marked decrease in joint symptoms after twenty-four months, according to the scores on the Lequesne index (p = 0.001) and the WOMAC index (p = 0.013). In the bone-marrow-graft group, the Lequesne index decreased from a mean of 7.7 ± 1.5 at baseline to 3.6 ± 1.3 at three months (p = 0.011), 3.0 ± 1.1 at six months (p = 0.007), 2.6 ± 1.1 at twelve months (p = 0.008), and 2.2 ± 1 at twenty-four months (p = 0.012) (Fig. 2). In addition, the mean WOMAC score fell from 30 ± 5 at baseline to 13 ± 6 at three months (p = 0.011), 18 ± 7 at six months (p = 0.059), 12 ± 5 at twelve months (p = 0.009), and 12 ± 5 at twenty-four months (p = 0.013) in the bone-marrow-graft group. With the numbers available, no significant decrease in the joint symptoms was detected, according to the scores on the Lequesne index (p = 0.609) and the WOMAC index (p = 0.142), for the control subjects at twenty-four months.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 2: A comparison of the bone-marrow-graft group (solid line) and the control group (dashed line) with respect to the evolution of the scores on the visual analog scale (VAS), the Lequesne index, and the WOMAC index over time. The results are shown as the mean and the standard error of the mean. One asterisk (p < 0.05) and two asterisks (p < 0.01) indicate a significant difference compared with baseline.

At twenty-four months, five of the eight hips in the control group had deteriorated to stage III, whereas only one of the 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 at twelve months (log-rank test, p = 0.038) and twenty-four months (log-rank test; p = 0.016) (Fig. 3).

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 3: Survivorship curves for the bone-marrow-graft group (solid line) and the control group (dashed line), with the collapse of the femoral head (ARCO stage III) as the end point. Kaplan-Meier survivorship analysis showed a significant difference between the two groups with respect to the distributions of the time to collapse at twelve months (log-rank test, p = 0.038) and twenty-four months (log-rank test, p = 0.016).

Two patients in the control group underwent unilateral total hip replacement. No total hip replacement had been performed in the bone-marrow-graft group at twenty-four months.

Overall, the ratio of the volume of the necrotic lesion to the volume of the whole femoral head significantly decreased in the bone-marrow-graft group after twenty-four months (p = 0.001). In the hips treated with bone-marrow grafting, this ratio decreased from a mean of 15.6% ± 1.5% at baseline to 12.5% ± 1.2% at three months (p = 0.009), 12.3% ± 2.5% at six months (p = 0.074), 12.0% ± 1.5% at twelve months (p = 0.005), and 10.1% ± 1.6% at twenty-four months (p = 0.005) (Figs. 4 and 5). In the hips treated with core decompression alone, this ratio increased from a mean of 16.7% ± 4.6% at baseline to 18.3% ± 4.5% at three months (p = 0.310), 17.7% ± 4.5% at six months (p = 0.726), 18.1% ± 4.8% at twelve months (p = 0.326), and 20.6% ± 4.1% at twenty-four months (p = 0.036). The reliability coefficient for the ratio of the necrotic lesion to the whole femoral head was 0.959 when measured by one observer, whereas it was 0.776 when measured by two different observers²¹. These high levels of correlation suggest that the method described was reliable enough to be clinically useful.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 4: A comparison of the bone-marrow-graft group (solid line) and the control group (dashed line) with respect to the evolution of the volume of the necrotic lesion over time. The results are shown as the mean and the standard error of the mean. One asterisk (p < 0.05) and two asterisks (p < 0.01) indicate a significant difference compared with baseline.

View Large | Download Slide(.ppt)
Add to My JBJS

Fig. 5: Coronal T1-weighted magnetic resonance imaging scans of two hips showing a reduction in the volume of osteonecrosis (arrow) after bone-marrow implantation (A) and an increase in the volume of osteonecrosis (arrow) in the hip of a control subject after two years (B).

Neither bone-marrow grafting nor core decompression caused major side effects. Two patients complained of pain at the site of the bone-marrow aspiration. In one patient, the bacteriological culture of the bone marrow showed coagulase-negative staphylococci. The patient was treated with antibiotics, and no clinical evidence of infection developed. Another patient presented with a hematoma at the site of the core decompression that resolved spontaneously.

Discussion

Our study shows that implantation of bone-marrow mononuclear cells in the osteonecrotic zone appears to be an effective treatment for early stages of osteonecrosis of the femoral head. Implantation of bone-marrow cells decreased the pain and other joint symptoms caused by the osteonecrosis and delayed the progression of the disease to the point of subchondral fracture (stage III) during the twenty-four-month follow-up period.

Many studies have suggested that the likely outcome of osteonecrosis of the femoral head (and, more particularly, the evolution to collapse) is influenced by the size of the lesion, the extent to which the weight-bearing portion of the femoral head is involved²², the stage of the osteonecrosis, and the cause of the osteonecrosis²³. However, the most important factor in predicting the outcome of stage-I or II osteonecrosis of the hip is probably the size of the necrotic lesion. Steinberg et al.²⁴ reported that four of thirteen hips that had core decompression and bone-grafting for the treatment of lesions that involved between 15% and 30% of the femoral head required total hip replacement. In contrast, only one of fourteen hips with lesions that involved <15% of the femoral head required replacement. In our study, no significant difference was detected between the control group and the bone-marrow-graft group with respect to the volume of osteonecrosis preoperatively. Therefore, we believe that the patients were similar with regard to the prognosis of the osteonecrosis. Furthermore, the method used to determine the lesion size (magnetic resonance imaging) provides an accurate measure of the volume of both the necrotic segment and the femoral head, a finding confirmed by substantial degrees of intraobserver and interobserver reproducibility.

The progression of the disease was significantly different between the two groups as only one of the ten hips in the bone-marrow-graft group collapsed. This finding is markedly better than that in another series on the natural history of osteonecrosis in which forty-six of seventy hips progressed to stage III²². As far as we know, there are no data on the effect of core decompression with use of a 3-mm trephine on the evolution of osteonecrosis. Conversely, core decompression of the hip with use of an 8-mm trephine is still the most common procedure used to treat the early stages of the disease. Nevertheless, there remains some controversy about its ability to influence the outcome of osteonecrosis. Mont et al. assessed forty-two studies in which a total of 1206 hips were treated with core decompression and 819 had various nonoperative interventions²⁵. Three hundred and forty-five of the 466 hips treated prior to collapse resolved satisfactorily following core decompression, and 182 of the 819 hips that had nonoperative interventions had a satisfactory result. Since we used a 3-mm trephine, our results need to be compared with the results obtained for core decompression with a larger trephine.

A minimum follow-up period of twenty-four months was chosen because collapse of the femoral head generally occurs over this span of time. It also occurs with greater frequency in the first twelve months following the initial diagnosis²². Although the findings of this study are promising, their interpretation is limited by the constraints imposed by the relatively small number of patients and the short duration of follow-up.

The bone marrow was injected through the trephine that was placed into the necrotic zone. Although some of the bone-marrow cells might have leaked through the trephine or into the circulation of the proximal aspect of the femur, the greatest part of the bone marrow remained in the area of osteonecrosis or in the femoral head as shown by radionuclide labeling, which was performed in two patients. So far we have been unable to define, using imaging techniques, the exact location of the bone marrow after the injection. Larger trials and the use of other techniques are needed to confirm and to fully understand our results.

Recent advances in our understanding of the pathophysiology of osteonecrosis suggest that a decrease in the mesenchymal stem-cell pool of the proximal aspect of the femur might not provide enough osteoblasts to meet the needs of bone-remodeling in the early stage of the disease⁹. An insufficiency of osteogenic cells could explain the inadequate repair mechanism that, it is postulated, leads to femoral head collapse. The effectiveness of bone-marrow mononuclear cells may be related to the availability of stem cells endowed with osteogenic properties, arising from an increase in the supply of such cells to the femoral head through bone-marrow implantation. Indeed, in the very early stages of osteonecrosis, providing sufficient repair capacity through the implantation of osteogenic cells could make these lesions reversible^26,27. In our study, the ratio of the volume of the necrotic lesion decreased by a mean of 35% in the bone-marrow-graft group, whereas it increased by a mean of 23% in the control group. This finding suggests that necrotic lesions might be reversible to some extent. Another possible explanation for the therapeutic effect of bone-marrow implantation is that injected marrow stromal cells secrete angiogenic cytokines resulting in increased angiogenesis and subsequent improvement in osteogenesis. One study has suggested that the efficacy of such implantation was due to a supply of endothelial progenitor cells included in the CD34⁺ fraction as well as to multiple angiogenic factors (vascular endothelial growth factors, basic fibroblast growth factor, and angiopoietin-1) released from the CD34⁺ fractions²⁸.

In summary, we have shown the efficacy and apparent safety of the implantation of bone-marrow mononuclear cells in the early stages of osteonecrosis of the femoral head in a small number of patients. This promising new approach for the treatment of osteonecrosis could benefit from the recent advances made in the field of stem-cell biology, including the use of subpopulations of progenitors with greater therapeutic potential.

Appendix

A description of the details of the bone-marrow harvest and grafting procedure is available with the electronic versions of this article, on our web site at (go to the article citation and click on "Supplementary Material") and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

Acknowledgements

Note: The authors thank Professor Appelboom and Dominique Egrise for revising the manuscript, Dr. Azadeh Sattari and Dr. Bernard Stallenberg for reading the radiographs, and Dr. Olivier Pradier for marrow-cell counting.

References

Ficat P, Arlet J.Ischémie et nécrose osseuse. L'exploration fonctionnelle de la circulation intraosseuse et ses applications. Paris: Masson; 1977. Necroses de la tete femorale; p 67-87.67 1977

Steinberg ME, Larcom PG, Stafford BB, Hosick WB, Corces A, Bands RE, Hartmann KM. Treatment of osteonecrosis of the femoral head by core decompression, bone grafting, and electrical stimulation. In: Urbaniak JR, Jones JP, editors. Osteonecrosis: etiology, diagnosis, and treatment. Rosemont, IL: American Academy of Orthopaedic Surgeons; 1997. p 293-9.293 1997

Stulberg BN, Davis AW, Bauer TW, Levine M, Easley K. Osteonecrosis of the femoral head. A prospective randomized treatment protocol. Clin Orthop.1991;268: 140-51.268140 1991 [PubMed]

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: 870-4.77870 1995

Jones JP Jr. Fat embolism and osteonecrosis. Orthop Clin North Am.1985;16: 595-633.16595 1985 [PubMed]

Wang GJ, Sweet DE, Reger SI, Thompson RC. Fat-cell changes as a mechanism of avascular necrosis of the femoral head in cortisone-treated rabbits. J Bone Joint Surg Am.1977;59: 729-35.59729 1977

Simkin PA, Downey DJ. Hypothesis: retrograde embolization of marrow fat may cause osteonecrosis. J Rheumatol.1987;14: 870-2.14870 1987

Laurent J, Meunier P, Courpron P, Edouard C, Bernard J, Vignon G. [Research on the pathogenesis of aseptic necrosis of the femoral head. Evaluation of the constitutional bony factors in 35 cases of iliac crest biopsy]. Nouv Presse Med.1973;2: 1755-60. French.21755 1973 [PubMed]

Hernigou P, Beaujean F, Lambotte JC. Decrease in the mesenchymal stemcell pool in the proximal femur in corticosteroid-induced osteonecrosis. J Bone Joint Surg Br.1999;81: 349-55.81349 1999 [CrossRef]

Gangji V, Hauzeur JP, Schoutens A, Hinsenkamp M, Appelboom T, Egrise D. Abnormalities in the replicative capacity of osteoblastic cells in the proximal femur of patients with osteonecrosis of the femoral head. J Rheumatol.2003;30: 348-51.30348 2003 [PubMed]

Hernigou P, Bernaudin F, Reinert P, Kuentz M, Vernant JP. Bone-marrow transplantation in sickle-cell disease. Effect on osteonecrosis: a case report with a four-year follow-up. J Bone Joint Surg Am.1997;79: 1726-30.791726 1997 [PubMed]

ARCO (Association Research Circulation Osseous): Committee on Terminology and Classification. ARCO News.1992;4: 41-6.441 1992

Hauzeur JP, Pasteels JL, Schoutens A, Hinsenkamp M, Appelboom T, Chochrad I, Perlmutter N. The diagnostic value of magnetic resonance imaging in non-traumatic osteonecrosis of the femoral head. J Bone Joint Surg Am.1989;71: 641-9.71641 1989 [PubMed]

Hauzeur JP, Orloff S, Taverne-Verbanck J, Pasteels JL. Diagnosis of aseptic osteonecrosis of the femoral head by percutaneous transtrochanterian needle biopsy. Clin Rheumatol.1986;5: 346-58.5346 1986 [CrossRef]

Hauzeur JP, Sintzoff S Jr, Appelboom T, De Maertelaer V, Bentin J, Pasteels JL. Relationship between magnetic resonance imaging and histologic findings by bone biopsy in nontraumatic osteonecrosis of the femoral head. J Rheumatol.1992;19: 385-92.19385 1992 [PubMed]

Hernigou P, Beaujean F. Treatment of osteonecrosis with autologous bone marrow grafting. Clin Orthop.2002;405: 14-23.40514 2002 [CrossRef]

Frank AJ, Moll JM, Hort JF. A comparison of three ways of measuring pain. Rheumatol Rehabil.1982;21: 211-7.21211 1982 [CrossRef]

Lequesne MG, Mery C, Samson M, Gerard P. Indexes of severity for osteoarthritis of the hip and knee. Validation—value in comparison with other assessment tests. Scand J Rheumatol Suppl.1987;65: 85-9. Erratum in: Scand J Rheumatol. 1988;17:following 241. Scand J Rheumatol Suppl. 1988;73:1.6585 1987 [PubMed][CrossRef]

Bellamy N, Buchanan WW, Goldsmith CH, Campbell J, Stitt LW. Validation study of WOMAC: a health status instrument for measuring clinically important patient relevant outcomes to antirheumatic drug therapy in patients with osteoarthritis of the hip or knee. J Rheumatol.1988;15: 1833-40.151833 1988 [PubMed]

Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br.1995;77: 34-41.7734 1995

Fleiss JL.The design and analysis of clinical experiments. New York: Wiley; 1986. 1986

Ohzono K, Saito M, Takaoka K, Ono K, Saito S, Nishina T, Kadowski T. Natural history of nontraumatic avascular necrosis of the femoral head. J Bone Joint Surg Br.1991;73: 68-72.7368 1991 [PubMed]

Sugano N, Ohzono K, Masuhara K, Takaoka K, Ono K. Prognostication of osteonecrosis of the femoral head in patients with systemic lupus erythematosus by magnetic resonance imaging. Clin Orthop.1994;305: 190-9.305190 1994 [PubMed]

Steinberg ME, Bands RE, Parry S, Hoffman E, Chan T, Hartman KM. Does lesion size affect the outcome in avascular necrosis? Clin Orthop.1999;367: 262-71.367262 1999 [PubMed]

Mont MA, Carbone JJ, Fairbank AC. Core decompression versus nonoperative management for osteonecrosis of the hip. Clin Orthop.1996;324: 169-78.324169 1996 [PubMed][CrossRef]

Inoue A, Ono K. A histological study of idiopathic avascular necrosis of the head of the femur. J Bone Joint Surg Br.1979;61: 138-43.61138 1979

Hauzeur JP, Pasteels JL. Pathology of bone marrow distant from the sequestrum in nontraumatic aseptic necrosis of the femoral head. In: Arlet J, Mazières B, editors. Bone circulation and bone necrosis. Berlin: Springer; 1990. p 73-6.73 1990

Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Amano K, Kishimoto Y, Yoshimoto K, Akashi H, Shimada K, Iwasaka T, Imaizumi T; Therapeutic Angiogenesis using Cell Transplantation (TACT) Study Investigators. Therapeutic angiogenesis for patients with limb ischaemia by autologous transplantation of bone-marrow cells: a pilot study and a randomised controlled trial. Lancet.2002;360: 427-35.360427 2002 [PubMed][CrossRef]

Topics

bone marrow transplantation ; cancer staging ; head of femur ; femur head necrosis ; necrosis ; pain ; pilot projects ; bone marrow ; osteonecrosis ; transplantation

Username

Password

Access for Patients

Forgot Password?

Have a subscription to the print edition?

Not a Subscriber?

Buy this Article

Get online access for 30 days for $35

New to JBJS?

Subscribe to the online edition for 30 days for $75

Register for a FREE limited account to get full access to all CME activities, to comment on public articles, or to sign up for alerts.

Have a subscription to the print edition?

Current subscribers to The Journal of Bone & Joint Surgery in either the print or quarterly DVD formats receive free online access to JBJS.org.

Activate your online account now

Forgot your password?

Enter your username and email address. We'll send you a reminder to the email address on record.

Username:*

Email Address:*

Forgot your username or need assistance? Please contact customer service at subs@jbjs.org. If your access is provided
by your institution, please contact you librarian or administrator for username and password information. Institutional
administrators, to reset your institution's master username or password, please contact subs@jbjs.org

References

Accreditation Statement

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.

CME Activities Associated with This Article

Submit a Comment

Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discretion of JBJS editorial staff.

* = Required Field

Comment Author(s) * (if multiple authors, separate names by comma)

Example: John Doe

Affiliation & Institution*

Comment Title*

Comment*

Cancel

Posted on November 26, 2004

Dr. Gangji responds to Dr. Radke

Rheumatology and physical Medicine department, HÃ´pital 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]

Print
Email

Recipient(s) will receive an email with a link (good for 5 days) to 'Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow Cells: A Pilot Study'.
Your Name:*
Example: John Doe

Email Address:* CC Me:
Enter your valid email address. Example: jdoe@example.com

Recipient's Email Address:*

Separate multiple email address with semi-colons (up to 5).

Subject:* 's The Journal of Bone & Joint Surgery: 'Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow Cells: A Pilot Study'
Subject for your email.

Message:

(Optional, message will truncate at 1000 characters)

Processing your request... Please Wait...

Copyright © in the material you requested is held by The Journal of Bone & Joint Surgery, Inc. (unless otherwise noted). This email ability is provided as a courtesy, and by using it you agree that that you are requesting the material solely for personal, non-commercial use, and that it is subject to Journal of Bone & Joint Surgery, Inc.'s Terms of Use. The information provided in order to email this topic will not be used to send unsolicited email, nor will it be furnished to third parties. Please refer to The Journal of Bone & Joint Surgery Inc.'s Privacy Policy for further information.

Copyright © The Journal of Bone & Joint Surgery Inc. All rights reserved.
Share
Get Citation

Valérie Gangji, Jean-Philippe Hauzeur, Celso Matos, Viviane De Maertelaer, Michel Toungouz, Micheline Lambermont; Treatment of Osteonecrosis of the Femoral Head with Implantation of Autologous Bone-Marrow CellsA Pilot Study. The Journal of Bone & Joint Surgery. 2004 Jun;86(6):1153-1160.

Download citation file:

RIS (Zotero)

EndNote

BibTex

Medlars

ProCite

RefWorks

Reference Manager

Copyright © The Journal of Bone and Joint Surgery, Inc.
Rights & Permissions
Article Alerts

Processing your request... Please Wait.
Submit a Comment
Data Supplements