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-I (prospective cohort study). See Instructions to Authors for a complete description of levels of evidence.

Treatment of osteonecrosis of the femoral head with implantation of autologous bone-marrow cells. A pilot study.

The bone marrow edema (BME) pattern of signal intensity changes on magnetic resonance (MR) images (decreased on T1-weighted and increased on T2-weighted) is a nonspecific finding encountered with several entities, including transient osteoporosis of the hip, transient BME syndrome, osteonecrosis, trauma, infection, and infiltrative neoplasm. Transient osteoporosis, an unusual but distinct syndrome characterized by self-limited pain and radiographically evident osteopenia, can be distinguished from other causes of the BME pattern, particularly osteonecrosis, on the basis of clinical findings and the development of radiographically evident focal osteopenia within 8 weeks after the onset of pain. This is an important distinction, since all patients with transient osteoporosis recover completely, without intervention. The term transient BME syndrome can be used to describe any patient in whom a reversible BME pattern is seen on MR images. Although the transient BME syndrome is also self-limited and quite likely related to transient osteoporosis, the authors believe that to avoid confusion, this nonspecific term should be reserved only for patients who do not develop radiographically evident osteopenia.

MR imaging of bone marrow edema pattern : transient osteoporosis, transient bone marrow edema syndrome, or osteonecrosis

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.

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

Osteonecrosis is common and represents loss of blood supply to a region of bone. Common sites affected include the femoral head, humeral head, knee, femoral/tibial metadiaphysis, scaphoid, lunate, and talus. Symptomatic femoral head osteonecrosis accounts for 10,000-20,000 new cases annually in the United States. In contradistinction, metadiaphyseal osteonecrosis is often occult and asymptomatic. There are numerous causes of osteonecrosis most commonly related to trauma, corticosteroids, and idiopathic. Imaging of osteonecrosis is frequently diagnostic with a serpentine rim of sclerosis on radiographs, photopenia in early disease at bone scintigraphy, and maintained yellow marrow at MR imaging with a serpentine rim of high signal intensity (double-line sign) on images obtained with long repetition time sequences. These radiologic features correspond to the underlying pathology of osseous response to wall off the osteonecrotic process and attempts at repair with vascularized granulation tissue at the reactive interface. The long-term clinical importance of epiphyseal osteonecrosis is almost exclusively based on the likelihood of overlying articular collapse. MR imaging is generally considered the most sensitive and specific imaging modality both for early diagnosis and identifying features that increase the possibility of this complication. Treatment subsequent to articular collapse and development of secondary osteoarthritis typically requires reconstructive surgery. Malignant transformation of osteonecrosis is rare and almost exclusively associated with metadiaphyseal lesions. Imaging features of this dire sequela include aggressive bone destruction about the lesion margin, cortical involvement, and an associated soft-tissue mass. Recognizing the appearance of osteonecrosis, which reflects the underlying pathology, improves radiologic assessment and is important to guide optimal patient management.

From the Radiologic Pathology Archives Imaging of Osteonecrosis: Radiologic-Pathologic Correlation

Six major and seven minor diagnostic criteria have been developed by the Japanese Investigation Committee for osteonecrosis of the femoral head (ONFH). We have carried out a multicentre study to clarify these. We studied prospectively 277 hips in 222 patients, from six hospitals, who had ONFH and other hip pathology and from whom histological material was available. We identified five criteria with high specificity: 1) collapse of the femoral head without narrowing of the joint space or acetabular abnormality on radiographs, including the crescent sign; 2) demarcating sclerosis in the femoral head without narrowing or acetabular abnormality; 3) a 'cold-in-hot' appearance on the bone scan; 4) a low-intensity band on T1-weighted images (band pattern); and 5) evidence of trabecular and marrow necrosis on histological examination. With any combination of two of these criteria, the sensitivity and specificity of the diagnosis were 91% and 99%, respectively.

Diagnostic criteria for non-traumatic osteonecrosis of the femoral head. A multicentre study.

To attest the validity of magnetic resonance imaging (MRI) to evaluate the pathophysiology in nontraumatic osteonecrosis (ON) of the femoral head, we attempted to correlate the different MRI patterns with the histology in cases of early stages. We used not only the T1 and T2 pulse sequences, but also the T1 sequence after gadolinium-DTPA to demonstrate the presence of vascularization. Studying 24 core biopsies from 16 hips (9 patients), we explored the MRI presentations that corresponded to the main histologic findings of the different trabecular bone and bone marrow conditions. Histologic findings including trabecular bone necrosis and bone marrow necrosis represented by amorphous eosinophilic debris presented a low T1 signal intensity without enhancement after intravenous gadolinium injection and a low T2 signal intensity. Trabecular bone necrosis associated with mummified fat cells presented a normal T1 and T2 signal intensity. Trabecular bone necrosis with fibrosis filling the intertrabecular spaces had a low T1 signal intensity that was enhanced by gadolinium and had an intermediate T2 signal intensity. Bands of fibrosis without trabecular bone as seen in fracture zones showed a low T1 signal intensity that was enhanced by gadolinium with a high T2 signal intensity. Thickened trabecular bone with fibrosis as found in creeping substitution areas had also a low T1 signal enhanced by gadolinium, but the T2 signal intensity was low. Farther from the necrotic area, despite normal trabecular bone, we found some patchy necrosis of the bone marrow without any modification of the normal T1 and T2 MRI patterns.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship between magnetic resonance imaging and histologic findings by bone biopsy in nontraumatic osteonecrosis of the femoral head.

To better define the magnetic resonance imaging (MRI) features during transient osteoporosis of the hip, we carried out sequential MRI of 8 patients with transient osteoporosis of the hip showing the typical radiographic pattern of diffuse osteoporosis of the femoral head. These cases displayed the same MRI changes in the femoral head and neck characterized by low signal intensity on the T1 weighted images and high signal intensity on the T2 weighted images. The MRI signal became normal within 11 months, but surprisingly, migration of the MRI abnormalities was observed during the course of the disease in 5 cases: abnormal MRI signals were first observed in the anterior area, then migrated to the posterior part, while a normal MRI signal reappeared in the anterior part. We conclude that MRI seems to show some particular features in transient osteoporosis of the hip, which normalize after a few months of evolution; this could represent a migration of MRI abnormalities. Such findings could help in the differential diagnosis of hip diseases such as aseptic bone necrosis.

Study of magnetic resonance imaging in transient osteoporosis of the hip.

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Relationship between magnetic resonance imaging and histologic findings by bone biopsy in nontraumatic osteonecrosis of the femoral head.

Study of magnetic resonance imaging in transient osteoporosis of the hip.