Epidemiología, farmacología y caracterización clínica de la osteonecrosis de los maxilares. Un estudio retrospectivo de 70 casos / Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases

Introducción y objetivos: Los bisfosfonatos son fármacos con un amplio espectro de indicaciones cuya principal capacidad es la inhibición de la función osteoclástica. En el año 2003 se ha descrito una complicación asociada a su empleo, la osteonecrosis de los maxilares por bisfosfonatos (ONMB). Los objetivos del presente estudio son identificar los casos recogidos de ONMB en un hospital de tercer nivel durante 8 años, evaluando las principales variables en relación con la enfermedad, el bisfosfonato empleado y los factores de riesgo locales o generales que pudieran actuar como desencadenante en la patogénesis de la ONMB. Material y método: Se procedió a la selección los pacientes diagnosticados de ONMB en un centro de referencia para una población de 1.100.000 habitantes. Las variables analizadas se dividieron en 3 grupos: pacientes, fármaco (incluyendo el análisis de la dosis aplicada y la ponderación dosis/potencia) y osteonecrosis. Resultados: Se recogieron 70 casos (44 mujeres y 26 varones), con una media de 66,8 años. Dieciocho pacientes habían recibido un aminobisfosfonato oral y 52 por vía intravenosa. El tiempo medio de administración fue de 26,53 meses. En el 67,1% de los pacientes se pudo identificar un factor local desencadenante, siendo el más frecuente la exodoncia (48,6%). Aunque la exposición ósea estaba presente en el 75,7% de los casos, 8 enfermos padecieron una osteonecrosis sin exposición, manifestando la presencia de dolor y/o fístula crónica. El 58,6% experimentaron una resolución completa con un tiempo medio de control de 16,28 meses. Conclusiones: El 25% de las ONMB en nuestra serie se relacionaron con la administración de un bisfosfonato oral, especialmente el alendronato. El ácido zoledrónico es el agente que menos miligramos precisa para desarrollar la enfermedad. La exposición ósea solitaria fue el dato clínico más habitual, afectando especialmente a sectores posteriores mandibulares en pacientes con enfermedad metastásica (AU)

Background and objectives: Bisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8 years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. Material and method: Patients diagnosed with BRONJ in a centre of reference for a population of 1,100,000 inhabitants were selected. Variables analysed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. Results: Seventy cases were studied —44 women and 26 men—, with a mean age of 66.8 years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53 months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28 months. Conclusions: 25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease (AU)

Epidemiology, pharmacology and clinical characterization of bisphosphonate-related osteonecrosis of the jaw. A retrospective study of 70 cases.

BACKGROUND AND OBJECTIVES: Bisphosphonates are widely prescribed drugs whose principal capacity is inhibiting the osteoclast function. In 2003 a complication related to their administration, bisphosphonate-related osteonecrosis of the jaw (BRONJ), was described. The objectives of this study were to identify diagnosed cases of BRONJ in a third-level hospital over 8 years, evaluating the main features in relation to the disease, the bisphosphonate and the presence of local or general risk factors that could trigger the BRONJ. METHODS: Patients diagnosed with BRONJ in a centre of reference for a population of 1,100,000 inhabitants were selected. Variables analysed were classified into 3 groups: patients, bisphosphonate (focusing on dose and weighting dose/potency) and osteonecrosis. RESULTS: Seventy cases were studied -44 women and 26 men-, with a mean age of 66.8 years. Eighteen patients received bisphosphonates orally and 52, intravenously. The mean time of administration was 26.53 months. In 67.1% of the patients it was possible to identify a local trigger, with the most common being tooth extraction (48.6%). Bone exposure was present in 89.2% of the cases, while 12 patients developed BRONJ without exposed bone, with only pain and/or chronic sinus tracts. Complete resolution was achieved in 58.6% of the patients, with a mean time of control of 16.28 months. CONCLUSIONS: 25% of the BRONJ cases were related to the administration of oral bisphosphonates, especially alendronate. Zoledronic acid was the bisphosphonate that required the fewest milligrams to induce osteonecrosis. Single bone exposure was the most common clinical finding, especially in the molar mandibular region in patients with metastatic disease.

Sinus mucosal thickening in bisphosphonate-related osteonecrosis of the jaws: a case-control study.

Osteonecrosis of the jaws is a clinically significant complication of bisphosphonate (BP) medications. Otherwise, the effects of BPs on oral soft tissue or cells remain unknown. The main objective of the present study was to determine whether the presence of sinus mucosal thickening was significantly related to BP-related osteonecrosis of the jaw (BRONJ). A case-control study was conducted on 32 patients who underwent treatment of BRONJ with conventional radiological investigations (panoramic radiographs) and computed tomography. The results indicated that patients with BRONJ had a 5.57-fold greater probability of presenting sinus mucosal thickening than controls. Although the existence of this thickening was more common in patients with advanced-stage disease or low levels of C-telopeptide-cross-linked type I collagen, no significant difference was observed between cases and controls. While considering the limitations inherent in the design and number of cases analyzed in our study, patients with osteonecrosis of the jaw were found to have a 5.57-fold greater probability of presenting sinus mucosal thickening (>3 mm) than healthy subjects.

Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: A pilot study comparing fibrin rich in growth factors and teriparatide

OBJECTIVES: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. MATERIAL AND METHODS: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. RESULTS: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bisphosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. CONCLUSIONS: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ

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Bisphosphonate-related osteonecrosis associated with dental implants: a microcomputed tomography study.

PURPOSE: The aims of this study were to quantify bone mineral density (BMD) and trabecular architecture of sequestra in patients with bisphosphonate-related osteonecrosis of the jaw (BRONJ) associated with dental implants and to assess if there are differences between trabecular bone in "implant loading-triggered" and "implant surgery-triggered" BRONJ. MATERIALS AND METHODS: Bone sequestra of 2 patients diagnosed with BRONJ associated with dental implants were scanned using high-resolution microcomputed tomography (microCT). Images were obtained at a voltage of 50 kV and 800 µA, and the specimens were scanned at 180 degrees with a single rotation step of 0.3, 1-mm aluminum filter, and a pixel size of 12 µm. The morphometric parameters examined were: BMD, ratio of bone volume/tissue volume (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp), connectivity density (Conn.D, mm), degree of anisotropy, and the structural model index. RESULTS: BMD and BV/TV were higher in bone sequestration than in healthy bone. Tb.Sp was lower and Tb.N and Tb.Th were higher in the BRONJ group. Conn.D and Tb.N values were significantly high in implant surgery-triggered sequestrum but substantially low in sequestra caused by loading as compared with those of the control sample. CONCLUSIONS: MicroCT is useful for assessing bone sequestration of BRONJ associated to dental implants. The necrotic bone is similar to that described in conventional BRONJ.

Alternative treatments for oral bisphosphonate-related osteonecrosis of the jaws: a pilot study comparing fibrin rich in growth factors and teriparatide.

OBJECTIVE: The aim of this study is to describe and compare the evolution of recurrent bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients treated with plasma rich in growth factors or teriparatide. MATERIAL AND METHODS: Two different types of treatments were applied in patients diagnosed of recurrent BRONJ in a referral hospital for 1.100.000 inhabitants. In the group A, plasma rich in growth factors was applied during the surgery. In the group B, the treatment consisted in the subcutaneous administration of teriparatide. All the cases of BRONJ should meet the following conditions: recurrent BRONJ, impossibility of surgery in stage 3 Ruggiero classification and absence of diagnosed neoplastic disease. Clinical and radiographic evolution of the patients from both groups was observed. RESULTS: Nine patients were included, 5 in group A and 4 in group B. All the patients were women on oral bisphosphonate therapy for primary osteoporosis (5 patients) or osteoporosis-related to the use of corticosteroids (4 patients). Alendronate was the most common oral bisphosphonate associated with BRONJ in our study (four patients in group A and two in group B). The mean age was 72,8 years in the group A and 73,5 years in the group B. All the patients from group A showed a complete resolution of their BRONJ. Only one patient in the group B showed the same evolution. CONCLUSION: In our series, the plasma rich in growth factors showed better results than the teriparatide in the treatment of recurrent BRONJ.

The use of pedicled buccal fat pad combined with sequestrectomy in bisphosphonate-related osteonecrosis of the maxilla

The use of pedicled buccal fat pad flap (BFP) has proved of value for the closure of oroantral and oronasal communications and is a well-established tool in oral and maxillofacial surgery. Otherwise, the perceived limitations of surgical therapy for bisphosphonate-related osteonecrosis of the jaws (BRONJ) have been widely discussed, and recommendations have largely been made to offer aggressive surgery only to stage 3 patients refractary to conservative management. Oroantral communication may be a common complication after sequestrectomy and bone debridement in upper maxillary BRONJ. We report a case series of stage 3 recalcitrant maxillary BRONJ surgically treated with extensive sequestrectomy and first reconstruction using pedicled BFP. All the cases presented an uneventful postoperative healing was uneventful without dehiscence, infection, necrosis or oroantral communication. We postulate that managing initially the site with BFP and primary closure may ensure a sufficient blood supply and adequate protection for an effective bone-healing response to occur. This technique may represent a mechanic protection and an abundant source of adipose-derived adult stem cells after debridement in upper maxillary BRONJ. We evaluate in this work results, advantages and indications of this technique (AU)

Hematoma de suelo oral asociado al síndrome coronario agudo / Haematoma of the floor of the mouth associated to acute myocardial infarction

Presentamos el caso de un paciente varón de 80 años de edad, ingresado en nuestro hospital por un síndrome coronario agudo tratado con alteplasa, tras lo cual desarrolló un hematoma de suelo oral espontáneo. Describimos tanto el tratamiento recibido como las medidas preventivas para evitar su aparición (AU)

We report the case of an 80-year-old man who developed a haematoma in the floor of the mouth after receiving alteplase in the treatment of an acute myocardial infarction. Both the treatment received and appropriate preventive measures to avoid such haematomas are described (AU)

[Haematoma of the floor of the mouth associated to acute myocardial infarction]. / Hematoma de suelo oral asociado al síndrome coronario agudo.

We report the case of an 80-year-old man who developed a haematoma in the floor of the mouth after receiving alteplase in the treatment of an acute myocardial infarction. Both the treatment received and appropriate preventive measures to avoid such haematomas are described.

Multiple myeloma and bisphosphonate-related osteonecrosis of the mandible associated with dental implants.

Multiple myeloma (MM) is a malignant plasma cell disorder and more than 30% of patients with this pathology develop osteolytic lesions in the jaw. Either pamidronate or zoledronic acid is recommended in patients with MM who have one or more lytic lesions. However, bisphosphonate-related osteonecrosis of the jaws (BRONJ) has been described as a complication associated with their use. Otherwise, the use of endosseous implants in oral rehabilitation is a well-established procedure, with good long-term success although systemic factors may affect the bone healing around dental implants. We report the first case reported of MM adjacent to a mandibular dental implant in a patient who developed BRONJ in the same area after intravenous zoledronate treatment. We discuss possible pathogeny of this particular and interesting phenomena.

Pathological mandibular fracture after simple molar extraction in a patient with osteogenesis imperfecta treated with alendronate

Osteogenesis imperfecta (OI), is a heterogeneous group of inherited disorders of connective tissue characterized by bone fragility. Patients with this disease frequently suffer fractures, over 80% of the extremities due to the more intensive mechanical load. Fractures of the facial bones occur very infrequently. Several studies have provedthat bisphosphonate therapy may be effective in reducing fracture risk in OI patients. We report here an unusual case of pathological mandibular fracture following simple molar extraction in an adult patient with OI type I andoral alendronic acid treatment. Extraction was atraumatical and without bone removal . Fracture was treated by internal fixation by plate osteosynthesis and additional mandibulomaxillary fixation (MMF). Bone healing after fracture treatment was completely normal and no clinical signs of osteoneocrosis were observed. To the best of our knowledge, this is an unusual complication even in this type of patients. Particular care is necessary is these patients during oral surgery, even when they have been treated and controlled (AU)

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Pathological mandibular fracture after simple molar extraction in a patient with osteogenesis imperfecta treated with alendronate.

Osteogenesis imperfecta (OI), is a heterogeneous group of inherited disorders of connective tissue characterized by bone fragility. Patients with this disease frequently suffer fractures, over 80% of the extremities due to the more intensive mechanical load. Fractures of the facial bones occur very infrequently. Several studies have proved that bisphosphonate therapy may be effective in reducing fracture risk in OI patients. We report here an unusual case of pathological mandibular fracture following simple molar extraction in an adult patient with OI type I and oral alendronic acid treatment. Extraction was atraumatical and without bone removal. Fracture was treated by internal fixation by plate osteosynthesis and additional mandibulomaxillary fixation (MMF). Bone healing after fracture treatment was completely normal and no clinical signs of osteoneocrosis were observed. To the best of our knowledge, this is an unusual complication even in this type of patients. Particular care is necessary is these patients during oral surgery, even when they have been treated and controlled.

Clinical experiences with bisphosphonate-associated osteonecrosis of the jaws: analysis of 21 cases.

PURPOSE: The aim of the present study was to analyze the clinical presentation, risk factors, radiologic features, histopathologic and microbiological findings, treatment, and evolution of bisphosphonate-associated osteonecrosis of the jaws (BONJ). METHODS: This study made a retrospective review of 21 patients who underwent treatment and diagnosis of BONJ during 2004 to 2007 in a tertiary health care center reference for 1,100,000 inhabitants. RESULTS: The mean patient age at the time of presentation was 65.1 years. Of the 21 patients observed, 19 (90.4%) were receiving intravenous zoledronate. Of the 21 patients, 15 were treated with bisphosphonates for bone metastasis (71.4%), 5 for multiple myeloma (23.8%), and 1 for rheumatoid arthritis (4.7%). In 17 patients, the lesions occurred in the mandible. Fifteen patients had previous tooth extractions at the same site of bone necrosis. CONCLUSION: In our series, most patients improved with conservative surgical debridement. Prospective clinical trials would enable clinicians to make accurate judgments about risk, treatment, and outcome for patients with BONJ.

Oral bisphosphonates-associated osteonecrosis in rheumatoid arthritis

Adverse effects associated with the use of bisphosphonates are infrequent and consist of pyrexia, renal function impairment, and hypocalcemia. Bisphosphonates-associated osteonecrosis of the jaws is an uncommon but potentially serious complication of intravenous bisphosphonate therapy in cancer patients. The degree of risk for osteonecrosis in patients taking oral bisphosphonates, such as alendronate, is uncertain and warrants careful monitoring. Oral bisphosphonates-associated osteonecrosis can occur in patients with rheumatoid arthritis. We report a case of mandibular osteonecrosis in a patient who received alendronate for 3.8 years. The pathology im- proved after bisphosphonate therapy discontinuation and sequestrectomy. To our knowledge there are only three cases published in the literature relating bisphosphonates-associated osteonecrosis of the jaws in patients with rheumatoid arthritis. All the cases published, including our case, have reported association between methotrex-ate, prednisone and alendronate sodium (Fosamax®) therapy. Corticosteroid therapy and dental surgery could increase the risk of developing bisphosphonates-associated osteonecrosis of the jaws in these patients (AU)