Functional investigation of bone implant viability using radiotracers in a new model of osteonecrosis

OBJECTIVES: Conventional imaging methods are excellent for the morphological characterization of the consequences of osteonecrosis; however, only specialized techniques have been considered useful for obtaining functional information. To explore the affinity of radiotracers for severely devascularized bone, a new mouse model of isolated femur implanted in a subcutaneous abdominal pocket was devised. To maintain animal mobility and longevity, the femur was harvested from syngeneic donors. Two technetium-99m-labeled tracers targeting angiogenesis and bone matrix were selected. METHODS: Medronic acid and a homodimer peptide conjugated with RGDfK were radiolabeled with technetium-99m, and biodistribution was evaluated in Swiss mice. The grafted and control femurs were evaluated after 15, 30 and 60 days, including computed tomography (CT) and histological analysis. RESULTS: Radiolabeling achieved high (>95%) radiochemical purity. The biodistribution confirmed good blood clearance 1 hour after administration. For 99mTc-hydrazinonicotinic acid (HYNIC)-E-[c(RGDfK)2, remarkable renal excretion was observed compared to 99mTc-methylene diphosphonate (MDP), but the latter, as expected, revealed higher bone uptake. The results obtained in the control femur were equal at all time points. In the implanted femur, 99mTc-HYNIC-E-[c(RGDfK)2 uptake was highest after 15 days, consistent with early angiogenesis. Regarding 99mTc-MDP in the implant, similar uptake was documented at all time points, consistent with sustained bone viability; however, the uptake was lower than that detected in the control femur, as confirmed by histology. CONCLUSIONS: 1) Graft viability was successfully diagnosed using radiotracers in severely ischemic bone at all time points. 2) Analogously, indirect information about angiogenesis could be gathered using 999mTc-HYNIC-E-[c(RGDfK)2. 3) These techniques appear promising and warrant further studies to determine their potential clinical applications.

Preclinical Study of Cell Therapy for Osteonecrosis of the Femoral Head with Allogenic Peripheral Blood-Derived Mesenchymal Stem Cells

PURPOSE: To explore the value of transplanting peripheral blood-derived mesenchymal stem cells from allogenic rabbits (rPBMSCs) to treat osteonecrosis of the femoral head (ONFH). MATERIALS AND METHODS: rPBMSCs were separated/cultured from peripheral blood after granulocyte colony-stimulating factor mobilization. Afterwards, mobilized rPBMSCs from a second passage labeled with PKH26 were transplanted into rabbit ONFH models, which were established by liquid nitrogen freezing, to observe the effect of rPBMSCs on ONFH repair. Then, the mRNA expressions of BMP-2 and PPAR-γ in the femoral head were assessed by RT-PCR. RESULTS: After mobilization, the cultured rPBMSCs expressed mesenchymal markers of CD90, CD44, CD29, and CD105, but failed to express CD45, CD14, and CD34. The colony forming efficiency of mobilized rPBMSCs ranged from 2.8 to 10.8 per million peripheral mononuclear cells. After local transplantation, survival of the engrafted cells reached at least 8 weeks. Therein, BMP-2 was up-regulated, while PPAR-γ mRNA was down-regulated. Additionally, bone density and bone trabeculae tended to increase gradually. CONCLUSION: We confirmed that local transplantation of rPBMSCs benefits ONFH treatment and that the beneficial effects are related to the up-regulation of BMP-2 expression and the down-regulation of PPAR-γ expression.

Effect of Arterial Deprivation on Growing Femoral Epiphysis: Quantitative Magnetic Resonance Imaging Using a Piglet Model

OBJECTIVE: To investigate the usefulness of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion MRI for the evaluation of femoral head ischemia. MATERIALS AND METHODS: Unilateral femoral head ischemia was induced by selective embolization of the medial circumflex femoral artery in 10 piglets. All MRIs were performed immediately (1 hour) and after embolization (1, 2, and 4 weeks). Apparent diffusion coefficients (ADCs) were calculated for the femoral head. The estimated pharmacokinetic parameters (Kep and Ve from two-compartment model) and semi-quantitative parameters including peak enhancement, time-to-peak (TTP), and contrast washout were evaluated. RESULTS: The epiphyseal ADC values of the ischemic hip decreased immediately (1 hour) after embolization. However, they increased rapidly at 1 week after embolization and remained elevated until 4 weeks after embolization. Perfusion MRI of ischemic hips showed decreased epiphyseal perfusion with decreased Kep immediately after embolization. Signal intensity-time curves showed delayed TTP with limited contrast washout immediately post-embolization. At 1-2 weeks after embolization, spontaneous reperfusion was observed in ischemic epiphyses. The change of ADC (p = 0.043) and Kep (p = 0.043) were significantly different between immediate (1 hour) after embolization and 1 week post-embolization. CONCLUSION: Diffusion MRI and pharmacokinetic model obtained from the DCE-MRI are useful in depicting early changes of perfusion and tissue damage using the model of femoral head ischemia in skeletally immature piglets.

Eficácia na remoção da necrose óssea térmica: realizada por implantes osseointegráveis com câmaras coletoras / Removal effectiveness of thermal osteonecrosis: performed by osseointegrated implants with collecting chambers

Durante a confecção do alvéolo, promove-se o aumento da temperatura da broca devido à fricção, aquecendo o tecido ósseo adjacente e seus componentes celulares, podendo provocar a Necrose Óssea Térmica. A necrose óssea térmica deteriora a porção orgânica do tecido ósseo (tanto matriz óssea como as células), bem como as células diferenciadas e indiferenciadas presentes na circulação sanguínea e medula óssea local. Alguns trabalhos demonstraram que o aquecimento ósseo acima de 47oC por 1 minuto provoca tal fenômeno. Atualmente existem variações na técnica de perfuração com objetivo de diminuir o grau de aquecimento e aumentar as taxas de sucesso dos tratamentos reabilitadores. Sabemos que nem todos os profissionais são cautelosos em utilizar materiais de qualidade e que mesmo os materiais com qualidade, após repetido uso, perdem a eficácia. Seria ideal que o implante osseointegrável gerenciasse a remoção destas áreas de necrose óssea térmica, independentemente da execução correta da técnica de perfuração e da qualidade das brocas. Com isso, garantiríamos que o tecido ósseo poderia se reparar ao redor dos implantes da melhor maneira possível. Neste trabalho avaliamos a eficácia de 3 modelos de implante com câmaras coletoras funcionais diferentes, em tecido ósseo de minipig. O implante com câmara coletora interna demonstrou-se 37,22% mais eficaz que o implante com câmaras externas e 3 arestas cortantes, quando os alvéolos eram confeccionados sem irrigação e com brocas desgastadas. O implante com câmaras coletoras externas e 4 arestas também demonstrou-se eficaz, porém manteve 83,75% das células viáveis enquanto que no grupo com câmaras internas este resultado foi de 91,39%.

The manufacture of the alveolus can increase the temperature of the drill due to friction heating the adjacent bone tissue and its cellular components, this phenomenon is known by thermal osteonecrosis. The thermal osteonecrosis deteriorates the organic portion of bone (bone matrix and cells), as well as undifferentiated and differentiated cells circulating in the blood and bone marrow. Some studies have demonstrated that bone heating above 47oC for 1 minute causes this phenomenon. Currently there are variations in drilling technique aiming to reduce the heating degree and increase the success rates of rehabilitation treatments. We know that not all professionals are cautious of using quality materials and even the materials with quality after repeated use, lose their effectiveness. Would be ideal that implants manages and removes these areas with thermal osteonecrosis, regardless of the technique of implementing the drilling and the quality of drills. With this, we ensure that bone tissue could possibly repair around implants in the best way. In this study we evaluated the efficacy of 3 implant models with different functional collecting chambers in minipigs bone tissue. The implant with internal collection chamber proved to be 37.22% more effective than the implant with external chambers and three sharp edges, when the alveolus were manufactured without irrigation and uncut drills. The implant with external collecting chambers and four sharp edges also showed an effective but 83.75% of the cells remained viable while in the group with internal chambers this result was 91.39%.

Eficácia na remoção da necrose óssea térmica: realizada por implantes osseointegráveis com câmaras coletoras / Removal effectiveness of thermal osteonecrosis: performed by osseointegrated implants with collecting chambers

Durante a confecção do alvéolo, promove-se o aumento da temperatura da broca devido à fricção, aquecendo o tecido ósseo adjacente e seus componentes celulares, podendo provocar a Necrose Óssea Térmica. A necrose óssea térmica deteriora a porção orgânica do tecido ósseo (tanto matriz óssea como as células), bem como as células diferenciadas e indiferenciadas presentes na circulação sanguínea e medula óssea local. Alguns trabalhos demonstraram que o aquecimento ósseo acima de 47oC por 1 minuto provoca tal fenômeno. Atualmente existem variações na técnica de perfuração com objetivo de diminuir o grau de aquecimento e aumentar as taxas de sucesso dos tratamentos reabilitadores. Sabemos que nem todos os profissionais são cautelosos em utilizar materiais de qualidade e que mesmo os materiais com qualidade, após repetido uso, perdem a eficácia. Seria ideal que o implante osseointegrável gerenciasse a remoção destas áreas de necrose óssea térmica, independentemente da execução correta da técnica de perfuração e da qualidade das brocas. Com isso, garantiríamos que o tecido ósseo poderia se reparar ao redor dos implantes da melhor maneira possível. Neste trabalho avaliamos a eficácia de 3 modelos de implante com câmaras coletoras funcionais diferentes, em tecido ósseo de minipig. O implante com câmara coletora interna demonstrou-se 37,22% mais eficaz que o implante com câmaras externas e 3 arestas cortantes, quando os alvéolos eram confeccionados sem irrigação e com brocas desgastadas. O implante com câmaras coletoras externas e 4 arestas também demonstrou-se eficaz, porém manteve 83,75% das células viáveis enquanto que no grupo com câmaras internas este resultado foi de 91,39%.

The manufacture of the alveolus can increase the temperature of the drill due to friction heating the adjacent bone tissue and its cellular components, this phenomenon is known by thermal osteonecrosis. The thermal osteonecrosis deteriorates the organic portion of bone (bone matrix and cells), as well as undifferentiated and differentiated cells circulating in the blood and bone marrow. Some studies have demonstrated that bone heating above 47oC for 1 minute causes this phenomenon. Currently there are variations in drilling technique aiming to reduce the heating degree and increase the success rates of rehabilitation treatments. We know that not all professionals are cautious of using quality materials and even the materials with quality after repeated use, lose their effectiveness. Would be ideal that implants manages and removes these areas with thermal osteonecrosis, regardless of the technique of implementing the drilling and the quality of drills. With this, we ensure that bone tissue could possibly repair around implants in the best way. In this study we evaluated the efficacy of 3 implant models with different functional collecting chambers in minipigs bone tissue. The implant with internal collection chamber proved to be 37.22% more effective than the implant with external chambers and three sharp edges, when the alveolus were manufactured without irrigation and uncut drills. The implant with external collecting chambers and four sharp edges also showed an effective but 83.75% of the cells remained viable while in the group with internal chambers this result was 91.39%.

Eruption sequestrum - case report and histopathological findings

Eruption sequestrum is an uncommon disturbance in eruption and consists of small fragments of calcified tissue overlying the crowns of erupting permanent molar teeth, especially at the time of eruption of the mandibular first molars. This paper reports a case of unilateral eruption sequestrum in a 7-year-old Brazilian boy and describes its histopathological findings. A white small fragment, 0.5 cm in diameter, with hard consistency, irregular shape and located on the occlusal surface of the erupting mandibular left first molar was excised. Microscopic examination revealed large trabeculae with empty lacunae and a minimal amount of existing spongy bone consisting of acute inflammatory cells (neutrophils). Signs of necrosis were found on the periphery. The histological analysis was consistent with non-vital bone and the diagnosis of eruption sequestrum was established. Clinical and radiographic follow-up visits scheduled at short intervals and then every 6 months revealed normal postoperative conditions.

Sequestro de erupção é um distúrbio raro da erupção e consiste de pequenos fragmentos de tecido calcificado que envolvem as coroas dos dentes molares permanentes em erupção, principalmente no momento da erupção dos primeiros molares inferiores. O objetivo deste trabalho é relatar um caso unilateral de sequestro de erupção em um menino brasileiro de 7 anos de idade e descrever seus achados histopatológicos. Um fragmento branco e pequeno, de 0,5 cm de diâmetro, com consistência dura, de forma irregular e localizado na superfície oclusal do primeiro molar inferior esquerdo em erupção foi excisado. O exame microscópico revelou trabéculas grandes com lacunas vazias e uma quantidade mínima de osso esponjoso existente consistindo de células inflamatórias agudas (neutrófilos). Na periferia, sinais de necrose foram evidenciados. A análise histológica foi consistente com osso não-vital e o diagnóstico de sequestro de erupção foi estabelecido. Exames clínicos e radiográficos em intervalos curtos e posteriormente semestrais revelaram condições pós-operatórias normais.

Ressonância magnética da osteonecrose do joelho: estudo de 19 casos / Magnetic resonance imaging of knee osteonecrosis: a study of 19 cases

OBJETIVO: Descrever os achados epidemiológicos, clínicos e de ressonância magnética da osteonecrose das porções distal do fêmur e proximal da tíbia. MATERIAIS E MÉTODOS: Avaliação de 19 pacientes (12 mulheres e 7 homens), sem história prévia de fatores causais, com achados à ressonância magnética sugestivos de osteonecrose do platô tibial ou côndilo femoral. RESULTADOS: Verificou-se a presença de anormalidades osteocondrais em 63,1 por cento dos casos e em 73,6 por cento destes houve associação com lesão meniscal ipsilateral. Houve também importante associação com edema na medular óssea em correspondência (grau III em 16 casos). CONCLUSÃO: A ressonância magnética demonstrou ser um método não invasivo com boa sensibilidade no diagnóstico da osteonecrose do joelho, bem como das lesões associadas, sendo mais frequente nas mulheres (63 por cento dos casos).

OBJECTIVE: To describe epidemiological, clinical and magnetic resonance imaging findings of osteonecrosis in the distal femur and proximal tibia. MATERIALS AND METHODS: Evaluation of 19 patients (12 women and 7 men), with no previous history of causative factors, with magnetic resonance imaging findings suggestive of osteonecrosis in the tibial plateau or femoral condyle. RESULTS: Osteochondral abnormalities were observed in 63.1 percent of the cases; in 73.6 percent of them, such abnormality was associated with ipsilateral meniscal lesion. Also, a significant association with bone marrow edema (grade III in 16 cases) was observed. CONCLUSION: Magnetic resonance imaging has demonstrated to be a noninvasive method with good sensitivity in the diagnosis of knee osteonecrosis as well as of associated lesions which are most frequently found in women (63 percent of cases).

Complicaciones en el tratamiento de las fracturas del húmero proximal / Complications in the treatment of fractures of the proximal humerus

Las complicaciones propias al tratamiento quirúrgico de las fracturas del húmero proximal son la rigidez articular, la necrosis aséptica de la cabaeza humeral, la consolidación de la fractura en posición defectuosa del foco fracturario. Se describe cada una de ellas y la manera más adecuada para prevenirlas.

Osteonecrosis asociada al uso de bifosfonatos: A propósito de un caso clínico / Osteonecrosis associated with the use of biphosphonates: Case report

Biphosphonates reduce the risk of skeletal events and are currently part of standards of therapy in myeloma. Recently, zoledronate and pamidronate have been linked to osteonecrosis of the jaw, specially after surgical dental procedures. We report a 84 year-old man with multiple myeloma who developed spontaneous osteonecrosis of both jaws, after 36 months of therapy with zoledronate with a cumulative dose of 136 mg. We discuss the pathogenic mechanisms, and review the recommendations on prevention and management of this new complication for neoplastic patients under prolonged therapy with biphosphonates.

Osteonecrosis in patients with acquired immunodeficiency syndrome (AIDS): report of two cases and review of the literature

Um aumento na incidência de anormalidades no metabolismo ósseo-mineral (osteopenia/osteoporose) tem sido observado em pacientes com síndrome de imunodeficiência humana adquirida (SIDA). Relatamos dois casos de osteonecrose em pacientes com SIDA. Ambos os pacientes estavam recebendo terapia anti-retroviral de alta potência (HAART) e apresentavam um ou mais fatores de risco conhecidos para osteonecrose. Nós revisamos a literatura e discutimos a patogênese, diagnóstico, prevenção e tratamento desta patologia em pacientes com SIDA.

Tratamento da osteonecrose do côndilo femoral pela mosaicoplastia: descriçäo da técnica cirúrgica / Treatment of the osteonecrosis of the femoral condyle by mosaicplasty: description of the surgical technique

Os autores apresentam um caso de osteonecrose no côndilo femoral lateral de um paciente de 23 anos de idade. Ressaltam os aspectos clínicos da patologia e detalhes técnicos da mosaicoplastia como opçäo terapêutica.

Avascular necrosis of the femoral and humeral heads in the sickle cell disease: Experience at Qatif central hospital, Saudi Arabia

To estimate the frequency of avascular necrosis of femoral heads [ANFH] and humeral heads [ANHH] in sickle cell disease patients. Retrospective study. A secondary care hospital, which is the main referral hospital in Qatif area. Eastern Province of Saudi Arabia. A total of 105 patients, native to the Qatif area with sickle cell disease; 59 patients were males; 46 patients were females; mean age was 22.3 years, [range 5-70 years]. Review of radiographs of femoral and humeral heads. Main outcome measures: Presence of avascular necrosis of femoral and humeral heads. Abnormalities were graded according to Ficat's classification of ANFH. The frequency of ANFH was 41.9%, and that of ANHH was 47.6%. The disease was bilateral in 63.6% and 84% of patients with ANFH and ANHH respectively; 72.7% of patients with ANFH had also ANHH. The frequencies of ANFH and ANHH as reported in this study from Qatif area are much higher than previously reported from the Eastern Province of Saudi Arabia

Imagen por resonancia magnética de la cadera / MRI of the hip

Se analizan la anatomía y algunas de las manifestaciones patológicas de la articulación de la cadera en la Imagen por Resonancia Magnética, entre las que se destacan la osteoartropatía degenerativa, la enfermedad de Paget, la necrosis avascular, la artritis reumatoide y los tumores, haciendo notar la utilidad de la Radiología convencional y las aportaciones adicionales que da la IRM al diagnóstico.

Osteonecrosis en pacientes con lupus eritematoso sistémico / Osteonecrosis in patiens with systemic lupus erythematosus

La Osteonecrosis (ON) sigue siendo una complicación de patogenia obscura y la de tipo ortopédico más frecuente en pacientes con Lupus Eritematoso Sistémico (LES). Este estudio retrospectivo fue realizado con el objeto de determinar la incidencia de esta complicación entre nuestros pacientes y para tratar de precisar factores de riesgo con miras a adoptar medidas preventivas futuras. De 112 pacientes con 4 ó más criterios de LES estudiados durante un lapso de 10 años, en 6 (4 hembras y 2 varones) se estableció el diagnóstico de ON por criterios clínicos y radiológicos. Las edades de los pacientes estuvieron en un rango de 14 a 37 años (media:24,6) y el tiempo de evolución entre comienzo aparente del LES hasta los primeros síntomas de ON varió entre 12 a 120 meses (media:44,33). El diagnóstico de ON fue realizado en avanzado estadio radiológico, estando la articulación coxofemoral afectada en todos. Aunque el carácter retrospectivo del estudio no nos permitió conclusiones estadísticas, los resultados sugieren que 2 ó más de los principales factores evaluados deben ser considerados como riesgo de ON en pacientes con LES, sobre todo, dosis de 30mgs. o más de Prednisona diaria por un período mayor de 12 meses, enfermedad persistentemente activa, sobrepeso e historia de trauma articular accidental u ocupacional. Nos permitimos recomendar la evaluación radiológica de la cadera a todo paciente con LES al momento del diagnóstico y luego por lo menos una vez al año. Los pacientes con factores de riesgo deben ser vigilados más estrechamente y los mismos corregidos a la medida de lo posible