RESUMEN
Bisphosphonates are widely used for the treatment of postmenopausal osteoporosis; however, they cause several long-term side effects, necessitating the investigation of local ways to improve osseointegration in compromised bone tissue. The purpose of this study was to evaluate peri-implant bone repair using implants functionalized with zoledronic acid alone (OVX ZOL group, n = 11), zoledronic acid + teriparatide (OVX ZOL + TERI group, n = 11), and zoledronic acid + ruterpy (OVX ZOL + TERPY group, n = 11) compared to the control group (OVX CONV, n = 11). Analyses included computer-assisted microtomography, qualitative histologic analysis, and real-time PCR analysis. Histologically, all functionalized surfaces improved peri-implant repair, with the OVX ZOL + TERI group standing out. Similar results were found in computerized microtomography analysis. In real-time PCR analysis, however, the OVX ZOL and OVX ZOL + TERPY groups showed better results for bone formation, with the OVX ZOL + TERPY group standing out, while there were no statistical differences between the OVX CONV and OVX ZOL + TERI groups for the genes studied at 28 postoperative days. Nevertheless, all functionalized groups showed a reduced rate of bone resorption. In short, all surface functionalization groups outperformed the control group, with overall better results for the OVX ZOL + TERI group.
Asunto(s)
Osteoporosis , Ácido Zoledrónico , Animales , Ratas , Femenino , Ácido Zoledrónico/administración & dosificación , Ácido Zoledrónico/farmacología , Osteoporosis/tratamiento farmacológico , Microtomografía por Rayos X , Oseointegración/efectos de los fármacos , Conservadores de la Densidad Ósea/administración & dosificación , Conservadores de la Densidad Ósea/farmacología , Conservadores de la Densidad Ósea/uso terapéutico , Sistemas de Liberación de Medicamentos/métodos , Difosfonatos/administración & dosificación , Osteogénesis/efectos de los fármacosRESUMEN
PURPOSE: This systematic review aimed to determine the effects of maternal exposure to bisphosphonates (BPs) during pregnancy on neonatal outcomes. It aimed to disclosfe the impact of BPs on neonates and identify aspects that require further investigation. METHODS: A comprehensive search of PubMed, Science Direct, LILACS, EMBASE, and Web of Science was conducted until August 2022, with no time restrictions. The selection criteria included studies published in English that evaluated pregnant women who were exposed to BPs. RESULTS: From an initial pool of 2169 studies, 13 met the inclusion criteria for this systematic review. These studies collectively included 106 women (108 pregnancies) who were exposed to BPs either before orduring pregnancy. A summary of the key characteristics of the selected studies and the risk of bias assessment are provided. Exposure to BPs occurs at various stages of pregnancy, with different indications for BP treatment. The most frequently reported neonatal outcomes were spontaneous abortion, congenital malformations, hypocalcemia, preterm birth, and low birth weight. CONCLUSION: Although previous reports have linked BPs before or during pregnancy with adverse neonatal outcomes, these associations should be interpreted with caution. Given the complexity of these findings, further research is necessary to provide more definitive insights to guide clinical decisions regarding the use of BPs in pregnant women.
Asunto(s)
Conservadores de la Densidad Ósea , Difosfonatos , Resultado del Embarazo , Humanos , Embarazo , Femenino , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Difosfonatos/administración & dosificación , Recién Nacido , Conservadores de la Densidad Ósea/efectos adversos , Conservadores de la Densidad Ósea/uso terapéutico , Conservadores de la Densidad Ósea/administración & dosificación , Aborto Espontáneo/inducido químicamente , Aborto Espontáneo/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Nacimiento PrematuroRESUMEN
El síndrome de dolor regional complejo (SDRC) es una patología poco frecuente, caracterizada por dolor crónico y cambios locales del sitio afectado. Ocurre en forma posterior a un traumatismo, o, menos frecuentemente, sin desencadenante claro. El diagnóstico se realiza de forma clínica, evaluando la presencia de hallazgos típicos detallados en los criterios de Budapest, como el dolor continuo y desproporcionado, y síntomas y signos típicos, como edema, asimetría térmica y disminución del rango de movilidad. Los estudios por imágenes, así como la radiografía, la resonancia magnética o el centellograma óseo de 3 fases, también brindan información valiosa, sobre todo en los casos que se presentan con más dudas, y para realizar diagnóstico diferencial de otras patologías. En este sentido, la medición de la densidad mineral ósea por absorciometría dual de rayos X (DXA) se presenta también como herramienta de utilidad, no solo en la fase diagnóstica, al evidenciar la mayor desmineralización del miembro afectado, sino también en la evaluación de la respuesta terapéutica a bifosfonatos. Presentamos el caso de una paciente con SDRC del miembro inferior, donde la densitometría ósea resultó de gran utilidad en su manejo clínico. (AU)
Complex regional pain syndrome (CRPS) is a rare pathology, characterized by chronic pain and local changes of the affected site. It occurs after trauma or, less frequently, without a clear trigger. The diagnosis is made clinically, evaluating the presence of typical findings detailed in the Budapest criteria, such as continuous and disproportionate pain, and typical signs and symptoms, like edema, thermal asymmetry, and decreased range of motion. Imaging studies, such as radiography, magnetic resonance imaging, or 3-phase bone scintigraphy also provide valuable information, especially in cases that present with more doubts, and to make a differential diagnosis with other pathologies. In this regard, the measurement of bone mineral density by dual X-ray absorptiometry (DXA) is also a useful tool, not only in the diagnostic phase, by showing the greater demineralization of the affected limb, but also in the evaluation of the therapeutic response to bisphosphonates. We present the case of a patient with CRPS of the lower limb, where bone densitometry was very useful in her clinical management. (AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Síndromes de Dolor Regional Complejo/diagnóstico , Síndromes de Dolor Regional Complejo/patología , Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Densitometría , Densidad Ósea , Síndromes de Dolor Regional Complejo/diagnóstico por imagen , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Dolor Crónico/etiologíaRESUMEN
ABSTRACT BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still the most prevalent type of osteonecrosis with clinical relevance. In Brazil, bisphosphonate use is high but there is a lack of epidemiological studies on BRONJ. OBJECTIVE: To determine the clinical profile of BRONJ in a Brazilian population through an integrative review. DESIGN AND SETTING: Integrative review of BRONJ in a Brazilian population. METHODS: Cases and clinical research on Brazilians with BRONJ between 2010 and 2019, indexed in PubMed/MEDLINE, Scopus, Web of Science and LILACS were reviewed. Age, sex, type and time of bisphosphonate intake, administration route, related diseases, region of the BRONJ, diagnostic criteria, staging, triggering factor and type of treatment were analyzed. RESULTS: Fifteen articles on 128 subjects were included. Most patients were women (82.03%); the mean age was 63 years. Intravenous zoledronic acid was mostly used (62.50%), for breast cancer treatment (46.87%). The main localization of BRONJ was the mandible (54.68%), associated mainly with tooth extractions (45.98%). The diagnostic criteria were clinical (100%) and radiographic (89.06%), mostly in stage II (68.08%). The surgical treatments were sequestrectomy (37.50%) and platelet-rich plasma (PRP) (36.71%). Microbial control was done using chlorhexidine (93.75%) and infection control using clindamycin (53.90%). CONCLUSIONS: BRONJ had higher prevalence in Brazilian women receiving treatment for breast cancer and osteoporosis. The mandible was the region most affected with a moderate stage of BRONJ, particularly when there were histories of tooth extraction and peri-implant surgery. Sequestrectomy with additional drugs and surgical therapy was the treatment most accomplished.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Extracción Dental , Difosfonatos/efectos adversos , Conservadores de la Densidad Ósea/efectos adversos , Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Osteoporosis/tratamiento farmacológico , Brasil , Neoplasias de la Mama/tratamiento farmacológico , Atención Odontológica , Resultado del Tratamiento , Inhibidores de la Angiogénesis , Difosfonatos/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico por imagenRESUMEN
BACKGROUND: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is still the most prevalent type of osteonecrosis with clinical relevance. In Brazil, bisphosphonate use is high but there is a lack of epidemiological studies on BRONJ. OBJECTIVE: To determine the clinical profile of BRONJ in a Brazilian population through an integrative review. DESIGN AND SETTING: Integrative review of BRONJ in a Brazilian population. METHODS: Cases and clinical research on Brazilians with BRONJ between 2010 and 2019, indexed in PubMed/MEDLINE, Scopus, Web of Science and LILACS were reviewed. Age, sex, type and time of bisphosphonate intake, administration route, related diseases, region of the BRONJ, diagnostic criteria, staging, triggering factor and type of treatment were analyzed. RESULTS: Fifteen articles on 128 subjects were included. Most patients were women (82.03%); the mean age was 63 years. Intravenous zoledronic acid was mostly used (62.50%), for breast cancer treatment (46.87%). The main localization of BRONJ was the mandible (54.68%), associated mainly with tooth extractions (45.98%). The diagnostic criteria were clinical (100%) and radiographic (89.06%), mostly in stage II (68.08%). The surgical treatments were sequestrectomy (37.50%) and platelet-rich plasma (PRP) (36.71%). Microbial control was done using chlorhexidine (93.75%) and infection control using clindamycin (53.90%). CONCLUSIONS: BRONJ had higher prevalence in Brazilian women receiving treatment for breast cancer and osteoporosis. The mandible was the region most affected with a moderate stage of BRONJ, particularly when there were histories of tooth extraction and peri-implant surgery. Sequestrectomy with additional drugs and surgical therapy was the treatment most accomplished.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos/cirugía , Conservadores de la Densidad Ósea/efectos adversos , Difosfonatos/efectos adversos , Extracción Dental , Inhibidores de la Angiogénesis , Osteonecrosis de los Maxilares Asociada a Difosfonatos/diagnóstico por imagen , Osteonecrosis de los Maxilares Asociada a Difosfonatos/etiología , Conservadores de la Densidad Ósea/administración & dosificación , Brasil , Neoplasias de la Mama/tratamiento farmacológico , Atención Odontológica , Difosfonatos/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis/tratamiento farmacológico , Resultado del TratamientoRESUMEN
The aim was to evaluate bone repair and gingival tissue repair in osteopenic rats. Fifteen female wistar rats were included; in all of them ovariectomy was realized to induce osteopenia; after 45 days, the animals were submitted to 2 surgical techinques 1) dental extraction of the upper central incisor with no socket preservation and 2) 5 mm cranial defect in the calvarium; 5 rats were included in the control group (G1) withput alendronate application; in the group 2 (G2) was used subcutenous alendronate (0.5 mg/kg) once for three weeks and then was realizd the both surgical techniques. In group 3 (G3), after ovariectomy was realized the both dental extraction and the calvarium defect and after that was realized the alendronate protocol. In each group, after six week was realized euthanasia and descriptive histological analysis of the surgical areas involved. In bone formation of the 5 mm cranial defect was observed with good progression in the 3 experimental models and no modification in quality of bone repair was observed. For the gingival tissue in the extraction socket, no differences were observed between G1 and G3. On other hand, in G2 a thinner and reduced gingival epithelium was found. Our results showed that alendronate was not an obstacle for bone repair; deficiencies in re-epithelialization of oral mucosa show the impact of alendronate before dental extraction.
El objetivo fue evaluar la reparación ósea y gingival en ratas con osteopenia. Quince ratas wistar hembras fueron incluidas; en todas ellas se realizo ovarectomia y fue realizada la inducción de osteopenia; después de 45 días, los animales fueron sometidos a dos técnicas quirúrgicas 1) extracciones dentales del incisivo central superior sin preservación alveolar y 2) creación de un defecto craneano de 5 mm en la calota; 5 animales fueron incluidos como grupo control (G1) sin la aplicación de alendronato; en el grupo 2 (G2) se utilizó alendronato subcutáneo (0,5 mg/kg) una vez a la semana durante 3 semanas. En el grupo 3 (G3), después de la ovarectomia se realizó la exodoncia y el defecto en el cráneo y después de ello se inicio el protocolo con alendronato. En cada grupo, después de seis semanas se realizó la eutanasia con descripción histológica de los hallazgos. En el hueso formado en el defecto craneano de 5 mm se observó una adecuada progresión de reparación en los 3 modelos experimentales y no se observó cambios importantes en el modelo de reparación. Para el tejido gingival en el sitio de extracción, no se observaron diferencias entre el grupo G1 y G3. Por otra parte, el G2 presentó un tejido mas delgado con reducción del epitelio gingival; nuestros resultados demuestran que el alendronato no fue un obstáculo en la reparación ósea; deficiencias en la re epitelización de la mucosa oral muestran el impacto del alendronato después de la exodoncia.
Asunto(s)
Animales , Femenino , Ratas , Enfermedades Óseas Metabólicas/tratamiento farmacológico , Regeneración Ósea/efectos de los fármacos , Alendronato/administración & dosificación , Encía/efectos de los fármacos , Osteonecrosis/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Enfermedades Óseas Metabólicas/complicaciones , Ovariectomía , Ratas Wistar , Difosfonatos/administración & dosificaciónRESUMEN
Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the head and neck with potential for aggressive and locally destructive behaviour. Lesions of the maxilla tend to expand more than those of the mandible due to the thinner cortices and spongy tissue of this location. Surgical removal is the most common treatment; however, it may be disfiguring in aggressive cases, especially for lesions located in the maxilla. Alternative treatments, such as intralesional corticosteroid injections, have been performed with satisfactory results. We report a case of a 12-year-old female patient with a CGCG of the left maxilla that was treated with 40 doses of intralesional triamcinolone acetonide infiltrations combined with alendronate sodium and calcium carbonate. Clinical and imaging follow-up over 12 years demonstrates improvement in the patient's condition.
Asunto(s)
Corticoesteroides/administración & dosificación , Difosfonatos/administración & dosificación , Granuloma de Células Gigantes/tratamiento farmacológico , Granuloma de Células Gigantes/patología , Enfermedades Maxilares/tratamiento farmacológico , Enfermedades Maxilares/patología , Alendronato/administración & dosificación , Antiinflamatorios/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Carbonato de Calcio/administración & dosificación , Niño , Femenino , Estudios de Seguimiento , Humanos , Inyecciones Intralesiones , Tiempo , Triamcinolona Acetonida/administración & dosificaciónRESUMEN
El propósito de la terapia en el desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica (IRC) consiste en restaurar el balance mineral, y, en la osteoporosis, mantener o aumentar la masa ósea. Ambas terapias tratan de evitar la fractura ósea. La mayoría de los osteoactivos están contraindicados en la insuficiencia renal crónica avanzada (estadios 4 y 5), y las terapias son empíricas. Algunos autores opinan que sin anomalías bioquímicas del desorden del metabolismo óseo mineral asociado a la enfermedad renal crónica avanzada se podría intentar el tratamiento estándar para la osteoporosis. Antes de intentar la terapia osteoactiva se debe corregir el desorden mineral óseo que pudiera presentarse asociado a la IRC, y en la indicación del tipo de osteoactivo se sugiere seleccionar al paciente según su estado óseo. Se aconseja que la administración de los antirresortivos se realice a dosis menores con respecto a los que tienen mejor función renal junto con aportes adecuados de calcio y vitamina D, antes y durante el tratamiento para prevenir el riesgo de severas hipocalcemias y un efecto óseo excesivo. Se presenta el caso clínico de una mujer de 65 años, con diagnóstico de osteoporosis de etiología multifactorial, fractura de pelvis, múltiples fracturas vertebrales e insuficiencia renal crónica avanzada, entre otras comorbilidades, y probable enfermedad ósea adinámica. Recibió inicialmente terapia con teriparatide y luego con denosumab, complicándose con hipocalcemia asintomática. (AU)
The purpose of therapy for the bone mineral metabolism disorder associated with chronic kidney disease is to restore the mineral balance; and to maintain or increase bone mass in osteoporosis. The goal of both types of therapy is to avoid bone fractures. Most antiosteoporotic drugs are contraindicated in advanced chronic renal failure (CRF) stages 4 and 5, and the therapies are empirical. Some authors believe that without biochemical abnormalities of the mineral bone metabolism disorder associated with advanced chronic kidney disease, standard treatment for osteoporosis could be attempted. Before attempting antiosteoporotic therapy, the bone mineral disorder that may be associated with CRF must be corrected, and in the indication of the type drug it is suggested that the patient be selected according to their bone status. It is advised that the administration of anti-resorptives be performed at lower doses in individuals with poor renal function compared to those with better renal function together with adequate calcium and vitamin D, before and during treatment to prevent the risk of severe hypocalcemia, and an excessive bone effect. We present the clinical case of a 65-year-old woman with a diagnosis of osteoporosis of multifactorial etiology, pelvic fracture, multiple vertebral fractures and advanced chronic renal failure, among other comorbidities and probable adynamic bone disease. The patient received initial therapy with teriparatide and followed by denosumab administration and exhibited asymptomatic hypocalcemia. (AU)
Asunto(s)
Humanos , Femenino , Anciano , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/tratamiento farmacológico , Fracturas Óseas/prevención & control , Osteoporosis/terapia , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/complicaciones , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/metabolismo , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/terapia , Vitamina D/administración & dosificación , Vitamina D/uso terapéutico , Calcio/administración & dosificación , Calcio/uso terapéutico , Alendronato/uso terapéutico , Teriparatido/administración & dosificación , Teriparatido/efectos adversos , Teriparatido/uso terapéutico , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Difosfonatos/uso terapéutico , Cinacalcet/uso terapéutico , Ácido Risedrónico/uso terapéutico , Denosumab/administración & dosificación , Denosumab/efectos adversos , Denosumab/uso terapéutico , Hipocalcemia/prevención & controlRESUMEN
RESUMEN: El balance óseo está mediado por una regulación inmunoendócrina, siendo éste un complejo proceso. Entre las acciones llevadas a cabo para mantener la densidad y estructura del esqueleto son variadas las farmacoterapias utilizadas. Diversos estudios han demostrado que tanto Alendronato (AL) y Vitamina E (E) contribuyen a la inhibición de la reabsorción ósea. El objectivo de este trabajo fue estudiar el efecto de la administración combinada de (AL) por vía subcutánea y (E) se administró tres veces por semana también por vía subcutánea con una dosificación de 20 mg/kg de peso corporal. La fórmula farmacéutica fue de 0,5 mg/kg de peso corporal para AL, y 20 mg/kg de vitamina E. El efecto se evaluó en ratas machos Wistar (n=108), de 90 ± 20 g, divididas en 4 grupos. Se realizó la exodoncia de los primeros molares inferiores. La droga se inyectó en forma subcutánea en tiempos 0, 7, 15 y 30 días post cirugía. Las imágenes de las mandíbulas fueron adquiridas mediante radiovisiógrafo, en cada tiempo experimental y fueron analizadas con el Software Image ProPlus versión 4,1 de Media Cibernetics. Estudios estadísticos: no paramétrico: prueba de Kruskal-Wallis Resultados: El grupo C (que registró la media de intensidad más baja), se diferenció significativamente de los grupos E y A-E (p<0,001), no así del grupo que utilizó únicamente Al (p=0,070; p>0,05). Los grupos Al, E y el combinado Al-E no se diferenciaron significativamente entre sí (p>0,05 en todos los casos). Los datos evaluados sirven para mostrar una tendencia favorable en relación al efecto beneficioso de la combinación de AL y vitamina E.
ABSTRACT: The bone balance is mediated by an immunoendocrine regulation, this being a complex process. A number of pharmacotherapies are used among the actions taken to maintain the density and structure of the skeleton. Several studies have shown that both Alendronate (AL) and Vitamin E (E) contribute to the inhibition of bone resorption. Objective: To study the effect of combined administration of (LA) subcutaneously and (E) was administered three times per week also subcutaneously with a dosage of 20 mg / kg body weight. The pharmaceutical formulation was 0.5 mg / kg body weight for AL and 20 mg / kg vitamin E. The effect was evaluated in male Wistar rats (n = 108), 90 ± 20 g, divided into 4 groups. Extraction of the first lower molars was performed. The drug was injected subcutaneously at time 0, 7, 15 and 30 days post-surgery. The images of the jaws were acquired by radiovisiography, at each experimental time and were analyzed with Image ProPlus Software version 4.1 of Media Cibernetics. Statistical studies: non-parametric: Kruskal-Wallis test Group C (which recorded the lowest mean intensity) was significantly different from the E and AE groups (p <0.001), but not from the group that used only Al (P = 0.070, p> 0.05). The Al, E and combined Al-E groups did not differ significantly from each other (p> 0.05 in all cases). The data evaluated serve to show a favorable trend in relation to the beneficial effect of the combination of AL and vitamin E.
Asunto(s)
Animales , Ratas , Vitamina E/administración & dosificación , Remodelación Ósea/efectos de los fármacos , Alendronato/administración & dosificación , Radiografía Dental , Análisis de Varianza , Experimentación Animal , Difosfonatos/administración & dosificaciónAsunto(s)
Humanos , Masculino , Femenino , Difosfonatos/administración & dosificación , Fracturas Óseas/prevención & control , Denosumab/administración & dosificación , Osteoporosis/tratamiento farmacológico , Factores de Riesgo , Alendronato/administración & dosificación , Alendronato/uso terapéutico , Difosfonatos/uso terapéutico , Denosumab/uso terapéutico , Ácido Zoledrónico/administración & dosificaciónRESUMEN
Hypercalcemia in hypoparathyroidism has rarely been described. A 55 year-old male patient with primary hypoparathyroidism, left eye melanoma, and Noonan's syndrome, was referred to the endocrinology clinics due to hypoparathyroidism. Laboratories showed serum calcium of 7.8 mg/d, and phosphate 4.8 mg/dl, while using calcium carbonate 1200 mg and vitamin D3 600 IU daily. Calcitriol 0.25 mcg daily was started and calcium carbonate discontinued. Abdominopelvic CT scan and thoracolumbar MRI, showed metastasis to liver, pancreas, and osteolytic lesions in spine, humerus, and ribs. Liver biopsy confirmed metastatic melanoma. Eight weeks later, serum calcium increased to 12 mg/dl. PTH, vitamin D 1,25-OH and PTHrP levels were within the lower range of normal compatible with hypercalcemia of malignancy, secondary to osteolytic disease. Zoledronic acid was added to treat hypercalcemia and bone pain. Our case demonstrates a successful treatment and monitoring of hypocalcemia after administration of bisphosphonate in a patient with hypoparathyroidism.
Asunto(s)
Hipercalcemia/etiología , Hipoparatiroidismo/fisiopatología , Melanoma/complicaciones , Ácido Zoledrónico/administración & dosificación , Conservadores de la Densidad Ósea/administración & dosificación , Calcitriol/administración & dosificación , Difosfonatos/administración & dosificación , Neoplasias del Ojo/patología , Humanos , Hipercalcemia/tratamiento farmacológico , Masculino , Melanoma/diagnóstico , Melanoma/patología , Persona de Mediana Edad , Síndrome de Noonan/fisiopatologíaRESUMEN
La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son caracteriÌsticos, aunque variables y de caraÌcter evolutivo. La gammagrafiÌa ósea es la teÌcnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnoÌstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)
Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)
Asunto(s)
Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Adulto , Adulto Joven , Displasia Fibrosa Ósea/etiología , Displasia Fibrosa Ósea/tratamiento farmacológico , Osteogénesis/genética , Osteomalacia/complicaciones , Anomalías Congénitas , Vitamina D/uso terapéutico , Osteosarcoma/etiología , Calcio/uso terapéutico , Hipofosfatemia/sangre , Quistes Óseos Aneurismáticos/etiología , Diagnóstico Diferencial , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Fracturas Óseas/patología , Células Madre Mesenquimatosas/patología , Manejo del Dolor , Displasia Fibrosa Monostótica/etiología , Displasia Fibrosa Ósea/genética , Displasia Fibrosa Ósea/sangre , Displasia Fibrosa Ósea/diagnóstico por imagen , Displasia Fibrosa Poliostótica/etiología , Displasia Fibrosa Poliostótica/diagnóstico por imagen , Displasia Fibrosa Craneofacial/etiología , Mutación/genéticaRESUMEN
BACKGROUND: Bisphosphonates (BF) rise proinflammatory markers and irreversibly bind to bone. Chronically, BF can lead to an inflammatory status and can increase the local oxidative stress in periodontium. Therefore, the objective of this study was to evaluate whether the chronic infusion of Zoledronic Acid (ZA) increases inflammatory markers in periodontium of rats. METHODS AND RESULTS: Chronically, infusion therapy was performed with ZA (0.04, 0.2 or 1 mg/kg or saline) by four doses in over a 70-day period to analyze periodontium of the first right inferior molar using histologic, histochemical (toluidine blue), and immunohistochemical (CD68, tumor necrosis factor-α (TNF-α), interleukin-1beta (IL-1ß), inducible nitric oxide synthase (iNOS) and nuclear factor kappa B (NF-kB)) tests. The experiment was replicated (ZA 0.2 mg/kg versus saline) for myeloperoxidase (MPO) assay and dose TNF-α, IL-1ß, malondialdehyde (MDA) and glutathione (GSH) in gingiva of the same tooth. Despite there is no alteration in mast cells (P = .608) and CD68 mononuclear-positive cells (P = .351), in the periodontium of the ZA-treated group, was observed an increase in the presence of inflammatory cells (P = .001) and cytoplasmic immunostaining for TNF-α (P = .003), IL-1b (P = .004), iNOS (P = .008), and NF-kB (P = .025). Levels of MPO (P < .001), TNF-α (P = .002), IL-1ß (P < .001), and GSH (P = .005) were augmented in gingiva of ZA-treated group but MDA (P = .993) levels and NF-kB nuclear staining (P = .923) were not altered. CONCLUSIONS: Chronic treatment with ZA increase proinflammatory cytokines and the number of inflammatory cells in periodontium of rats and GSH are expressed probably in a compensatory manner.
Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Imidazoles/administración & dosificación , Inflamación , Periodoncio/efectos de los fármacos , Periodoncio/inmunología , Animales , Biomarcadores/análisis , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar , Ácido ZoledrónicoRESUMEN
Purpose: To performed a histomorphometric and radiological study to evaluate the effects of alendronate sodium administered locally in mandibular bone defects created in rabbits. Methods: Two circular defects 5 mm in diameter were created bilaterally in the mandibular corpus of 20 New Zealand rabbits (i.e., four defects per animal). Each defect received one of four treatments: no treatment (EC group), alendronate irrigation (AL group), autogenous bone grafting (AG group), or alendronate irrigation with autogenous bone grafting (AL+AG group). Histomorphometric and radiological assessments were conducted at 4 and 8 weeks after surgery. Results: Between-group comparisons of the new bone area, the value of the AL+AG group was significantly lower thanthe remaining three groups at 4 weeks postoperatively. In all groups, the new bone area was significantly larger at 8 weeks than at 4 weeks. The residual graft area at 4 and 8 weeks was significantly higher in the AL+AG group than in the AG group, although it was significantly smaller at 8 weeks than at 4 weeks in both these groups. Conclusion: The use of alendronate sodium in conjunction with autogenous bone grafting improves the osteoconductive properties of the graft, enhances graft retention in the defect, and improves ossification.(AU)
Asunto(s)
Animales , Conejos , Difosfonatos/administración & dosificación , Difosfonatos/química , Cicatrización de Heridas , Conejos/anomalías , Conejos/anatomía & histología , Conejos/lesionesAsunto(s)
Humanos , Femenino , Anciano de 80 o más Años , Difosfonatos/administración & dosificación , Difosfonatos/efectos adversos , Osteonecrosis/inducido químicamente , Osteonecrosis/tratamiento farmacológico , Osteoporosis/complicaciones , Preparaciones Farmacéuticas , Densidad Ósea , Densidad Ósea/efectos de los fármacos , Fracturas del Fémur/inducido químicamente , Fracturas de Cadera/inducido químicamenteRESUMEN
BACKGROUND: Alendronate (ALN) is a nitrogen-bisphosphonate that may induce an anabolic effect on craniofacial bone repair when administrated in low doses. Based on this premise, this study analyzed the influence of prophylactic low doses of ALN on bone healing in defects created in rabbit mandible. METHODS: A 5 × 2-mm diameter deep defect was created in the calvaria of 28 rabbits. Fourteen of these rabbits received previously 50âµg/kg of 1% sodium ALN for 4 weeks, while the other rabbits received only 0.9% physiological saline solution (control). Animals were euthanized at 15 and 60 days postsurgery (n = 7), and the data were analyzed using histomorphometry and immunohistochemistry using the anti-CD34, bone morphogenetic protein -2 (BMP-2), and transforming growth factor (TGF)-ß1 antibodies. RESULTS: On the 15th day postsurgery, the specimens that received previous treatment with ALN demonstrated large vascular lumen and intense positivity to CD34 either concentrated in endothelium or cells spread among the reparative tissue. These results coincided with intense positivity for BMP-2+ cells and TGF-ß1 that was concentrated in both cells and perivascular area. In contrast, the control group revealed scarce cells that exhibited CD34, BMP-2+, and the TGF-ß1 was restricted for perivascular area on well-formed granulation tissue. These patterns of immunohistochemical result, especially found on the 15th day of analysis, seem to be responsible for the development of larger quantities of bone matrix in the specimens that receive ALN on the 60th day postsurgery. CONCLUSION: These preliminary results showed that the prophylactic administration of low doses of ALN might be an alternative to craniofacial bone craniofacial bone repair because it increases the immunopositivity for TGF-ß1 and consequently improves the CD34+ and BMP-2+ cells on reparative sites.
Asunto(s)
Alendronato/administración & dosificación , Regeneración Ósea/efectos de los fármacos , Difosfonatos/administración & dosificación , Mandíbula/fisiología , Mandíbula/cirugía , Cráneo/fisiología , Cráneo/cirugía , Animales , Antígenos CD34/metabolismo , Matriz Ósea/metabolismo , Proteína Morfogenética Ósea 2/metabolismo , Diferenciación Celular/efectos de los fármacos , Femenino , Inmunohistoquímica , Mandíbula/citología , Conejos , Cráneo/citología , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
OBJECTIVE: To test the hypothesis that intravenous (IV) bisphosphonate (BP) therapy thickens or alters the micromorphology of cementum and periodontal ligament (PDL) in cancer patients. STUDY DESIGN: Thirty-two teeth extracted from 24 cancer patients and separated into test (patients who have undergone IV BP therapy, n = 16) and control (patients naive to BP therapy, n = 16) groups were studied. Cementum thickness was measured in 3 different areas of the dental root with polarized light microscopy. PDL was assessed by optical light microscopy and the immunohistochemical expression of periostin. RESULTS: No significant difference was detected in cementum thickness (apical, P = .06; medium, P = .16; cervical, P = .18) between groups. The numbers of fibroblasts in PDL (P = .56), incremental lines of cementum (P = .51) and the immunohistochemical patterns of periostin expression in PDL (P = .68) did not differ between groups. CONCLUSION: IV BP therapy does not thicken cementum or change the micromorphology of PDL.
Asunto(s)
Cemento Dental/efectos de los fármacos , Difosfonatos/administración & dosificación , Neoplasias/tratamiento farmacológico , Ligamento Periodontal/efectos de los fármacos , Moléculas de Adhesión Celular/metabolismo , Cemento Dental/anatomía & histología , Fibroblastos/metabolismo , Humanos , Inmunohistoquímica , Infusiones Intravenosas , Ligamento Periodontal/anatomía & histología , Ligamento Periodontal/citología , Extracción DentalRESUMEN
Estudios han demostrado que el aceite de oliva (O) con sus compuestos fenólicos tienen efectos positivos en diversos biomarcadores fisiológicos. Análisis previos han demostrado que los bisfosfonatos, son potentes inhibidores de la resorción ósea. Estudiar el efecto del tratamiento combinado de alendronato (AL) y pamidronato (PA) y de O sobre la regeneración ósea. Las fórmulas se dosificaron 0,5 mg/kg de peso para AL, y de 0,6 mg/kg de peso para PA. El O se administró en la dieta, 50 g/Kg. Cincuenta y cuatro ratas macho de la línea Wistar se dividieron en 6 grupos. El grupo control (C), recibió semanalmente 0,3 ml/100 g de solución salina vía subcutánea. El grupo (AL) recibió semanalmente por vía subcutánea en el miembro posterior izquierdo. El grupo (PA) se colocó igual que el grupo anterior. El grupo (O) fue tratado en la alimentación y en las áreas de la cirugía recibieron inyección subcutánea con solución fisiológica. El grupo (ALO) recibió tratamiento combinado con AL y O. El grupo (PAO) se trató igual al anterior. Se obtuvieron muestras de fémur en tiempos 15, 30, 60 y 90 días, que se incluyeron en solución fisiológica y mantenidos a -20 C. Los estudios estadísticos se realizaron a través del análisis de la variancia a dos y tres criterios de clasificación. Sólo el factor días influye significativamente sobre los valores. Las diferencias entre drogas no resultaron estadísticamente significativas. Tampoco se verificó interacción significativa entre los factores Droga y etapa. Los valores más elevados de fuerza de ruptura aplicada, se registraron a los 90 días. No se encontraron diferencias significativas en los ensayos biomecánicos, poniendo de manifiesto la acción sistémica de los fármacos. Estas acciones fueron benéficas al aumentar la rigidez.
Studies have shown that olive oil (O) with its phenolic compounds have positive effects on various physiological biomarkers. Previous analyzes have shown that bisphosphonates are potent inhibitors of bone resorption. The objective of this work was to study the effect of combined treatment with alendronate (AL) and pamidronate (PA) and O on bone regeneration. Formulas 0.5 mg/kg for AL dosed, and 0.6 mg/kg for PA. O was administered in the diet, 50 g/kg. Fifty-four male Wistar rats were divided into 6 groups. The control group (C) received weekly 0.3 mL/100 g of saline subcutaneously. Group (AL) received weekly subcutaneously in the left posterior limb. Group (PA) was placed as the previous group. Group (O) was treated in food and in the areas of surgery received subcutaneous injection with saline. The (ALO) group received combined treatment with Al and O. The group (PAO) was treated the same as before. Femur samples at times 15, 30, 60 and 90 days, were included in physiological solution and maintained at -20 °C were obtained. Statistical studies were conducted through analysis of variance to two and three classification criteria. The ANOVA showed that only days factor significantly influences the values of the variables (p <0.05). The differences between drugs were not statistically significant (p> 0.05). Nor was there significant drug interaction between factors and stage (p> 0.05) was verified. The highest values of force rupture applied occurred at 90 days. No significant differences were found in the biomechanical testing, demonstrating the systemic action of drugs. These actions were beneficial to increase rigidity.