Terapia con células madre en la osteonecrosis de la cabeza femoral / Stem Cell Therapy in Osteonecrosis of the Femoral Head

RESUMEN Objetivos: Describir el efecto terapéutico del uso de células madre en el manejo de la osteonecrosis de la cabeza femoral. Métodos: Se realizó una búsqueda en las distintas bases de datos como Pubmed/MEDLINE, BVS y Cochrane de los últimos 10 años, incluyéndose estudios relevantes de metaanálisis, ensayos clínicos y revisiones. Además, se revisó la página electrónica oficial de la Organización Mundial de la Salud para referencias adicionales. Las palabras de búsqueda fueron: "("Stem Cells" OR "Stem Cell Transplantation"[Mesh] OR "Mesenchymal Stem Cell Transplantation"[Mesh] OR Hematopoietic Stem Cell Transplantation"[Mesh] OR Cell-and Tissue-Based Therapy"[Mesh] "Multipotent Stem Cells"[Mesh] OR "Embryonic Stem Cells"[Mesh]) AND ("Osteonecrosis"[Mesh] OR "Femur Head Necrosis"[Mesh] "osteonecrosis of the femoral head" OR "Femoral head"). Incluimos un total de 7 estudios. 2 metaanálisis, 2 artículos de revisión, 2 ensayos clínicos controlados y aleatorizados y un estudio de evidencia. Resultados: Todos los estudios evidenciaron que la terapia con células madre en el manejo de la osteonecrosis de la cabeza femoral es segura y efectiva. El tratamiento combinado de descompresión central más implantación de células madre mostró mayor efectividad. Conclusiones: La terapia con células madre es una opción terapéutica para tratar la osteonecrosis de la cabeza femoral, sobre todo en etapas tempranas. La combinación de descompresión central más la infiltración de células madre en la zona necrótica produce mejoría de la sintomatología y contiene el progreso de la enfermedad(AU)

ABSTRACT Objectives: To describe the therapeutic effect of the stem cell use in managing osteonecrosis of the femoral head. Methods: A search was carried out in the different databases as Pubmed / MEDLINE, BVS and Cochrane for the last 10 years, including relevant meta-analysis studies, clinical trials and reviews. In addition, the official website of the World Health Organization was checked for additional references. The search words were: "(" Stem Cells "OR" Stem Cell Transplantation "[Mesh] OR" Mesenchymal Stem Cell Transplantation "[Mesh] OR Hematopoietic Stem Cell Transplantation" [Mesh] OR Cell-and Tissue-Based Therapy "[ Mesh] "Multipotent Stem Cells" [Mesh] OR "Embryonic Stem Cells" [Mesh]) AND ("Osteonecrosis" [Mesh] OR "Femur Head Necrosis" [Mesh] "osteonecrosis of the femoral head" OR "Femoral head"). We include a total of 7 studies, 2 meta-analyzes, 2 review articles, 2 controlled and randomized clinical trials, and one evidence study. Findings: All the studies showed that stem cell therapy in managing osteonecrosis of the femoral head is safe and effective. The combined treatment of central decompression plus stem cell implantation showed greater effectiveness. Conclusions: Stem cell therapy is a therapeutic option to treat osteonecrosis of the femoral head, especially in the early stages. The combination of central decompression plus the infiltration of stem cells in the necrotic area produces an improvement in the symptoms and contains the progress of the disease(AU)

Outcome of childhood leukaemia survivors and necrosis of the femoral head treated with autologous mesenchymal stem cells.

PURPOSE: Corticoid-induced osteonecrosis (ON) of femoral head can lead to severe hip joint impairment and hip replacement, with negative impact in young survivors of acute lymphoblastic leukaemia (ALL) with long life expectancy. We aim to improve quality of life in these patients with a novel approach. METHODS/PATIENTS: Based on the regenerative capacities of mesenchymal stem cells (MSCs), we performed locally implanted autologous cell therapy in two adolescents suffering of bilateral femoral ON. This required a simple, minimally invasive surgical procedure. RESULTS: Both patients experienced significant pain relief and restoration of gait kinematic values. Radiographic evaluation showed cessation of hip collapse. No toxicities/complications were observed after a 4-year follow-up. CONCLUSIONS: Our preliminary results suggest that autologous MSCs can be considered as a novel treatment for children and young adults with ON after overcoming ALL. It may avoid hip replacement and improve quality of life of leukaemia survivors.

Autologous Platelet Concentrates as Treatment for Avascular Necrosis of Femoral Head in a Dog.

Avascular necrosis of the femoral head is a developmental disturbance that generally affects young dogs of small breeds and produces ischemic necrosis of the femoral head resulting in an incongruous and malformed joint. The most common treatment is the excisional arthroplasty of the head and femoral neck. The aim of this study is to describe the treatment of avascular necrosis in a Yorkshire dog using intra-articular injections of autologous platelet concentrate. Evaluations were made at 0, 15, 30, 60, and 120 days of treatment, describing the following parameters: clinical gait analysis, perimetry, goniometry, and radiographic evaluations. The results obtained in this case suggest that the autologous platelet concentrate may be an alternative for the treatment of avascular necrosis of the femoral head in dogs.

Analysis of Cell Therapies Used in Clinical Trials for the Treatment of Osteonecrosis of the Femoral Head: A Systematic Review of the Literature.

BACKGROUND: Osteonecrosis of the femoral head (ONFH) is associated with regional loss of cells within bone, often resulting in pain and mechanical collapse. Our purpose was to analyze the cell-therapies used in clinical trials for the treatment of ONFH with regard to (1) cell-sources, (2) collection techniques, (3) cell-processing, (4) qualitative and quantitative characterizations, and (5) delivery methods. METHODS: A systematic review of the current literature on the use of cell therapies for the treatment of ONFH was performed. Studies with a level-of-evidence III or higher were evaluated. A total of 1483 articles were screened. Eleven studies met the criteria to be included in this review. RESULTS: Ten studies used bone-marrow, and 1 study used blood as the cell-source. Nine studies used freshly isolated tissue-derived nucleated cells from bone-marrow, mixed bone marrow-derived nucleated cells, 1 study used mixed blood-derived nucleated cells, and 1 study used culture-expanded cells derived from bone marrow aspirate. Cell dose varied from 2-million to 3-billion cells. Qualitative cell characterization of injected cells using surface markers was done by 5 studies using CD34. Two studies assayed the cell-population using a colony-forming-unit assay. CONCLUSION: There is a lack of standardization with respect to the quantitative and qualitative characterization of methods for cell-harvest, cell-processing, and cell-transplantation/delivery. Cell-therapy holds promise as a means of restoring local cell populations that are made deficient because of injury or disease. However, the orthopedic community and patients will benefit greatly by a greater investment in blinded, randomized, controlled trials and clinical effectiveness trials that embrace rigorous standards.

Efficacy of autologous stem cell-based therapy for osteonecrosis of the femoral head in sickle cell disease: a five-year follow-up study.

INTRODUCTION: Stem cell therapy with bone marrow-derived mononuclear cells (BMMCs) is an option for improving joint function in osteonecrosis of the femoral head (ONFH). Bone marrow-derived mesenchymal stromal cell (MSC) numbers and their osteogenic differentiation are decreased in patients with ONFH. However, whether this decrease also extends to the early stages of ONFH in sickle cell disease (SCD) is still unclear. METHODS: We conducted a phase I/II, non-controlled study to determine efficacy and safety of BMMC implantation using a minimally invasive technique in SCD patients with ONFH. Eighty-nine patients were recruited and followed up for 60 months after surgery. Clinical and radiographic findings were assessed, and data were completed by in vitro analysis. RESULTS: At the final follow-up (60 months) there was a significant improvement in clinical joint symptoms and pain relief as measured by the Harris Hip Score (P = 0.0005). In addition, after the BMMC implantation procedure, radiographic assessment showed disease stabilization and only 3.7 % of the treated patients did not achieve a satisfactory clinical result. The amount of fibroblast colony-forming units was 28.2 ± 13.9 per 1 million BMMCs after concentration. Flow cytometry analysis showed a significantly higher number of hematopoietic stem/endothelial progenitor cell markers in concentrated BMMCs when compared with bone marrow aspirate, indicating an enrichment of these cell types. Isolated MSCs from SCD patients with pre-collapse ONFH maintained the replicative capacity without significant loss of their specific biomolecular characteristics, multi-differentiation potential, and osteogenic differentiation activities. Cytokines and growth factors (interleukin-8, transforming growth factor-beta, stromal cell-derived factor-1alpha and vascular endothelial growth factor) that mediate endogenous bone regeneration were also produced by expanded MSCs from SCD patients. CONCLUSION: The autologous BMMC implantation with a minimally invasive technique resulted in significant pain relief and halted the progression of early stages of ONFH in SCD patients. MSCs from SCD patients display biological properties that may add to the efficiency of surgical treatment in ONFH. In summary, our results indicate that infusion of BMMCs enriched with stem/progenitor cells is a safe and effective treatment for the early stages of ONFH in SCD patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02448121; registered 15 May 2015.

Porous tantalum rods for treating osteonecrosis of the femoral head.

This study evaluated the outcomes of using porous tantalum rods for the treatment of osteonecrosis of the femoral head (ONFH). We performed core decompression and inserted porous tantalum implants in 149 patients (168 consecutive hips) with ONFH. Hips had large (65), medium (64), or small (39) lesions; 63 lesions were lateral, 68 were central, and 35 were medial. Conversion to total hip arthroplasty (THA) was the end point of this survey. A total of 130 cases (138 hips) were followed. The mean follow-up time was 38.46 ± 5.76 months; 43 hips (31%) were converted to or needed THA. Of the 43 hips requiring THA, 33 had large lesions, including 1 medial, 3 central, and 29 lateral lesions; 9 had medium, lateral lesions, and 1 hip had a small, lateral lesion. Bone grafting was used in 59 hips, with 3 hips failing; 40 of 79 hips without bone grafts failed. The sum distances between the tops of the rods and the lateral lesion boundaries (SDTL, mm) were measured in anteroposterior and lateral radiographs. In the failure and spared groups, the average SDTLs were 7.65 ± 2.759 and 0.83 ± 2.286 mm, respectively. The survival of porous tantalum rods used for treating early-stage ONFH was affected by the size and location of the lesion, whether or not a bone graft was used, as well as the distance between top of the rod and the lateral boundary of the lesion.

[Review of non-surgical treatment of avascular necrosis of the femoral head]. / Revisión del tratamiento no quirúrgico de la necrosis aséptica de la cabeza femoral.

Avascular necrosis of the femoral head is a frequent condition with an insidious presentation; it is initially asymptomatic and thus it is seldom diagnosed at the early stages. The purpose of this review is to update the status of the diagnosis and non-surgical treatment of avascular necrosis of the femoral head. This paper analyzes the natural history of the disease as well as the prognostic importance of early diagnosis and the identification of the extension and location of osteonecrosis. It also discusses the different nonsurgical treatment methods such as: high energy extracorporeal shock waves, electromagnetic pulsed fields, hyperbaric oxygen therapy, drugs, physical therapy, and regenerative medicine. The conclusion is that no method is effective in the advanced stages and there is great hope of treating this condition without surgery; however, progress needs to be made in research, particularly in the use of external biophysical agents and regenerative medicine. The gold standard of treatment is still surgical decompression of the femoral head at the stages in which no collapse has occurred. The prognosis apparently improves with the use of biophysical and regenerative medicine adjuvants.

Trapezoidal bony correction of the femoral neck in the treatment of severe acute-on-chronic slipped capital femoral epiphysis.

PURPOSE: To present the first technical description of a modified surgical technique for trapezoidal bony correction of the femoral neck in the treatment of slipped capital femoral epiphysis (SCFE), performed entirely by arthroscopy. METHODS: From December 2005 to January 2008, 5 patients with severe SCFE underwent trapezoidal femoral neck bone correction through arthroscopy. Their mean age at the time of surgery was 13.2 years. The time for postoperative follow-up ranged from a minimum of 12 months to a maximum of 39 months (mean, 26 months). The study analyzed data regarding the type of slip, degree of correction obtained, clinical and functional outcomes, and complications. RESULTS: Analysis with the modified Harris Hip Score criteria showed a mean of 17.2 points preoperatively and 86.6 points at the last assessment. The mean epiphyseal deviation ranged from 82° at the initial presentation to 14° postoperatively. There were no intraoperative complications, and there was 1 case of avascular necrosis. CONCLUSIONS: Arthroscopic treatment of SCFE resulted in correction of the angles of epiphyseal slip (from a mean epiphyseal-diaphyseal angle of 82° before surgery to 14° after surgery), with no immediate complications and 1 case of a late complication (avascular necrosis) in this 5-patient series. Clinical improvement was shown by a mean 69.4-point increase in the modified Harris Hip Score. LEVEL OF EVIDENCE: Level IV, therapeutic case series.

The use of extracorporeal shock waves in the treatment of osteonecrosis of the femoral head: a systematic review.

Osteonecrosis is a progressive clinical condition with significant morbidity, which primarily affects weight-bearing joints and is characterized by the death of the bone, or part of it, because of insufficient circulation. The hip is the most common compromised joint. In osteonecrosis of the femoral head (ONFH), the collapse of the femoral head is a result of mechanically weak bone submitted to a load of weight, and can be associated with incapacitating pain and immobility. Both nonsurgical and surgical treatment options have been used with differing levels of success, and nonoperative treatment modalities such as bisphosphonates, statins, anticoagulants, and extracorporeal shock wave therapy (ESWT) for early-stage disease have been described, but exact indications have not been established yet. The aim of this study was to make a systematic review of the use of ESWT in the treatment of ONFH. MEDLINE, LILACS, and Scielo databases were searched using the keywords "shock wave", "osteonecrosis", "avascular necrosis", "aseptic necrosis" and "femoral head". The search period was between 1966 and 2009. Only five articles that fulfilled the previously established criteria were obtained. Of these five articles, two were randomized clinical trials, one open label study, one comparative prospective study, and one was a case report. The present review demonstrated that there are no controlled and double-blind studies about the efficacy of ESWT in the treatment of ONFH. On the other hand, the published noncontrolled studies appear to demonstrate some favorable result, which justifies new research in this area.

Tratamiento de la osteonecrosis de cabeza femoral / Treatment of femoral head osteonecrosis

Se realizó una revisión bibliográfica de actualización acerca del tratamiento de la osteonecrosis de cabeza femoral. El objetivo consiste en profundizar sobre los métodos de tratamiento en el estadio inicial y tardío. En el estadio inicial se hace referencia a la suspensión del apoyo, al tratamiento farmacológico, la oxigenación hiperbárica, la estimulación eléctrica y las perforaciones o trepanaciones de la cabeza femoral, mostrando en esta última resultados de diversos autores. En el tratamiento de las osteonecrosis en estadio avanzado o tardío se recomienda el uso de osteotomías, técnica de Merle D Aubigne; hemiartroplastia con copa, con prótesis parcial o artroplastia total de cadera(AU)

Tratamiento de la osteonecrosis de cabeza femoral / Treatment of femoral head osteonecrosis

Se realizó una revisión bibliográfica de actualización acerca del tratamiento de la osteonecrosis de cabeza femoral. El objetivo consiste en profundizar sobre los métodos de tratamiento en el estadio inicial y tardío. En el estadio inicial se hace referencia a la suspensión del apoyo, al tratamiento farmacológico, la oxigenación hiperbárica, la estimulación eléctrica y las perforaciones o trepanaciones de la cabeza femoral, mostrando en esta última resultados de diversos autores. En el tratamiento de las osteonecrosis en estadio avanzado o tardío se recomienda el uso de osteotomías, técnica de Merle D Aubigne; hemiartroplastia con copa, con prótesis parcial o artroplastia total de cadera

Osteonecrosis aséptica de la cabeza del fémur: desde la clínica / Femur head aseptic osteonecrosis: clinical view

La osteonecrosis aséptica de cabeza de fémur es una enfermedad de etiología multifactorial y tratamiento multidisciplinario. Presentamos nuestra casuística, enfatizando en los aspectos clínicos y etiopatogénicos. Consideramos que el médico generalista desempeña un rol trascendente en el diagnóstico precoz de esta enfermedad. (AU)

Osteonecrosis aséptica de la cabeza del fémur: desde la clínica / Femur head aseptic osteonecrosis: clinical view

La osteonecrosis aséptica de cabeza de fémur es una enfermedad de etiología multifactorial y tratamiento multidisciplinario. Presentamos nuestra casuística, enfatizando en los aspectos clínicos y etiopatogénicos. Consideramos que el médico generalista desempeña un rol trascendente en el diagnóstico precoz de esta enfermedad.

Necrosis aséptica de la cadera: análisis comparativo de los resultados de dos métodos "descompresivos" / Aseptic hip necrosis: comparative analysis of the results of two "decompressive" methods

Se presenta el seguimiento comparativo a largo plazo (entre 5 y 15 años) de 2 procedimientos terapéuticos de la necrosis aséptica (NA) incipiente de la cabeza femoral en el adulto. Fueron comparados 2 métodos, uno realizado entre mediados de los años 60 hasta mediados de los años 70, el bloqueo metafisario descrito por M. Napolitano y N. Bloise de Napolitano, y el otro, que realizamos a partir de mediados de los años 70, las perforaciones múltiples (forage), preconizadas por Arlet y Ficat. Se estudiaron 14 caderas tratadas con el bloqueo metafisario y 42 tratadas con perforaciones múltiples (core decompression de los autores norteamericanos) y se comparó a ambos grupos con 6 caderas diagnosticadas con punción bajo TAC, todos los casos en estadio O, 1 o 2a de la clasificación de Arlet y Ficat. La comparación se realizó, por la discrepancia entre los métodos diagnósticos y puntuaciones clasificatorias de época, exclusivamente en base al parámetro de la necesidad de un segundo procedimiento para tratar la NA. Los resultados fueron: grupo bloqueos: no requirieron otro tratamiento el 21,42 por ciento de los pacientes a los 12,5 años de efectuado el bloqueo, mientras que requirieron tratamiento (osteotomía, reemplazo total de cadera [RTC] ) el grupo forage: no requirieron otro tratamiento el 16,66 por ciento de los pacientes a los 11,5 años y sí lo requirieron el 83,33 por ciento de los pacientes a los 5,8 años de la intervención ; grupo control: el 100 por ciento de los pacientes de este grupo fue tratado con RTC dentro de los 4,8 años de seguimiento. Se efectúan consideraciones acerca de la validez de estos resultados y se concluye que, en cierta forma, fue más efectivo el bloqueo que las perforaciones, siendo ambos efectivos frente al grupo control

Necrosis aséptica de la cadera: análisis comparativo de los resultados de dos métodos "descompresivos" / Aseptic hip necrosis: comparative analysis of the results of two \"decompressive\" methods

Se presenta el seguimiento comparativo a largo plazo (entre 5 y 15 años) de 2 procedimientos terapéuticos de la necrosis aséptica (NA) incipiente de la cabeza femoral en el adulto. Fueron comparados 2 métodos, uno realizado entre mediados de los años 60 hasta mediados de los años 70, el bloqueo metafisario descrito por M. Napolitano y N. Bloise de Napolitano, y el otro, que realizamos a partir de mediados de los años 70, las perforaciones múltiples (forage), preconizadas por Arlet y Ficat. Se estudiaron 14 caderas tratadas con el bloqueo metafisario y 42 tratadas con perforaciones múltiples (core decompression de los autores norteamericanos) y se comparó a ambos grupos con 6 caderas diagnosticadas con punción bajo TAC, todos los casos en estadio O, 1 o 2a de la clasificación de Arlet y Ficat. La comparación se realizó, por la discrepancia entre los métodos diagnósticos y puntuaciones clasificatorias de época, exclusivamente en base al parámetro de la necesidad de un segundo procedimiento para tratar la NA. Los resultados fueron: grupo bloqueos: no requirieron otro tratamiento el 21,42 por ciento de los pacientes a los 12,5 años de efectuado el bloqueo, mientras que requirieron tratamiento (osteotomía, reemplazo total de cadera [RTC] ) el grupo forage: no requirieron otro tratamiento el 16,66 por ciento de los pacientes a los 11,5 años y sí lo requirieron el 83,33 por ciento de los pacientes a los 5,8 años de la intervención ; grupo control: el 100 por ciento de los pacientes de este grupo fue tratado con RTC dentro de los 4,8 años de seguimiento. Se efectúan consideraciones acerca de la validez de estos resultados y se concluye que, en cierta forma, fue más efectivo el bloqueo que las perforaciones, siendo ambos efectivos frente al grupo control

Tratamento da necrose avascular de cabeça do fêmur näo traumática, grau III de Ficat, pela osteotomia transtrocantérica de rotaçao, técnica de Sugioka / Sugioka's transtrochanteric rotational osteotomy for non-traumatic femoral head necrosis, Ficat grade III

O autor analisa o resultado de 18 osteotomias transtrocantéricas de rotaçao, técnica de Sugioka, realizadas entre 1986 e 1991 em 17 pacientes com necrose avascular da cabeça do fêmur nao traumática, com predominância de etiologia alcoólica (16 do sexo masculino e 1 do feminino), com acompanhamento médio de 65,5 meses. A idade variou de 26 a 46 anos, média de 36 anos. As necroses foram classificadas como de grau III de Ficat, com ângulo de necrose médio de 243 graus, na classificaçao de Kerboul. Conclui-se que as necroses com as características citadas, tratadas com a osteotomia transtrocantérica de rotaçao, apresentam 50 por cento de resultados clínicos e radiográficos satisfatórios.

Tratamiento de la Necrósis avascular de la cabeza femoral con injerto de pedículo ósteo-muscular (cuadrado femoral) / Treatment of the avascular necrosis of the femoral head with implant of ósteo-muscular pedículo (femoral square)

Doce pacientes con necrósis avascular de la cabeza femoral en etapas III-IV de Marcus y cols. (1973) fueron tratados quirúrgicamente; realizándose múltiples perforaciones sobre la cabeza femoral, remoción parcial del hueso necrótico, así como la transposición y anclaje de un injerto de pedículo ósteo-muscular (cuadrado femoral) dentro de la cabeza femoral. El 33.33 por ciento de los casos eran idiopáticos, 25 por ciento por luxaciones de cadera, 25 por ciento por fracturas intracapsulares femorales, 8.33 por ciento por Epifiosiolísis de cadera, 8,33 por ciento paciente esteroide-dependiente. La mayoría de los pacientes eran jóvenes con un promedio de edad de 39,16 años (rango: 20-52 años). El sexo predominante fue el masculino en una relación de 2:1 con respecto a las hembras. La sintomatología preoperatoria especialmente el dolor y nivel de actividad del paciente mejoró notablemente después de la intervención. El tiempo de seguimiento fue de 12 a 63 meses. Los resultados clínicos-radiológicos fueron: Buenos 66,66 por ciento; Regular: 16,66 por ciento y Malo: 16,66 por ciento de los casos en el período observado. La transposición de pedículo osteomuscular (cuadrado femoral) en el tratamiento de la necrósis avascular de la cabeza femoral en etapas tempranas es una excelente alternativa quirúrgica, especialmente en pacientes jóvenes

Avascular necrosis as a complication of septic arthritis of the hip in children.

Seventy-one hip joints in 69 infants and children with pyogenic arthritis were studied. Twenty joints (28%) with the radiographic characteristics of avascular necrosis were identified and the changes classified into 3 groups: Group 1 (infants up to the age of 6 months) had ischaemic changes characterized by the absence or delayed appearance of the epiphyseal ossification centre; Group 2 (children aged between 7 months and 5 years) showed disappearance of this centre whether followed by revascularization or not, with the shape of the cartilaginous femoral head preserved in either case; and in Group 3 (children 6-16 years of age) the femoral epiphysis was either totally or partially involved with increased bone density; collapse of the head may or may not have occurred. At follow-up for between 2 and 15 years, a trend towards more severe deformities was seen in the 11 hip joints of Group 3 when compared to the 9 hip joints in Groups 1 and 2. The opposite was observed in relation to less severe deformities. Early diagnosis and treatment of infection is mandatory in patients with pyogenic arthritis and increased intra-articular hydrostatic pressure, or those with septic thrombosis of the epiphyseal vessels, which could cause avascular necrosis (AVN).