RESUMO
BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.
Assuntos
Conservadores da Densidade Óssea , Fraturas do Fêmur , Fraturas Espontâneas , Fraturas Mandibulares , Osteomielite , Osteoporose Pós-Menopausa , Osteoporose , Feminino , Humanos , Pessoa de Meia-Idade , Difosfonatos/efeitos adversos , Alendronato/efeitos adversos , Osteoporose Pós-Menopausa/complicações , Osteoporose Pós-Menopausa/tratamento farmacológico , Osteoporose Pós-Menopausa/induzido quimicamente , Conservadores da Densidade Óssea/efeitos adversos , Fraturas Mandibulares/cirurgia , Fraturas Mandibulares/induzido quimicamente , Fraturas Mandibulares/tratamento farmacológico , Osteoporose/induzido quimicamente , Osteoporose/tratamento farmacológico , Fraturas Espontâneas/induzido quimicamente , Fraturas Espontâneas/diagnóstico por imagem , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/cirurgia , Osteomielite/tratamento farmacológicoRESUMO
INTRODUCTION: bisphosphonates are used for the management of postmenopausal osteoporosis with high risk of fracture, glucocorticoid-induced osteoporosis, Paget's disease and hypercalcemia; as well as an adjuvant for the management of hyperparathyroidism. Bisphosphonates have been associated with previously unknown adverse effects, including atypical femur fractures. OBJECTIVE: to analyze the relationship of the history of bisphosphonate (BF) use as a risk factor for presenting atypical femur fractures (AFF). MATERIAL AND METHODS: patients aged 40 years or older from two hospital centers seen from 2009 to 2018 for femur fracture were included. The radiographic studies of 441 records were reviewed, from which the fracture site was defined. Subtrochanteric (SF) and diaphyseal (DF) femur fractures were analyzed applying the criteria of the second report of the American Society for Bone and Mineral Research for case definition of AFF. Finally, the consumption of bisphosphonates in these groups was investigated to estimate a measure of association. RESULTS: of the 441 clinical records, 98 (22.2%) were male and 343 (77.7%) were female with a mean age of 77.8 (40-103) years. Fifty-nine FS/FD were identified, of which 53% (31 records) were categorized as AFF. BF use was determined in 80.6% of patients with AFF and 3.57% in FS/FD. BF use was significantly associated with the presence of AFF (OR: 112, p 0.000, CI 95%: 12.6-1001). CONCLUSIONS: BF use significantly increases the risk of presenting AFF. AFF in patients who used BF occurred after a minimum consumption of 24 months.
INTRODUCCIÓN: los bifosfonatos se usan para el manejo de osteoporosis postmenopáusica con riesgo elevado de fractura, osteoporosis inducida por glucocorticoides, enfermedad de Paget e hipercalcemia; así como coadyuvante para manejo del hiperparatiroidismo. Los bifosfonatos se han asociado a efectos adversos previamente desconocidos dentro de los que se encuentran fracturas de fémur de trazo atípico. OBJETIVO: analizar la relación del antecedente de uso de bifosfonatos (BF) como factor de riesgo para presentar fracturas atípicas de fémur (FAF). MATERIAL Y MÉTODOS: se incluyeron pacientes de 40 años o más de dos centros hospitalarios atendidos desde 2009 a 2018 por fractura de fémur. Se revisaron los estudios radiográficos de 441 registros, de los cuales se definió el sitio de fractura. Se analizaron las fracturas de fémur subtrocantéricas (FS) y diafisarias (FD) aplicando los criterios del segundo reporte de la American Society for Bone and Mineral Research para la definición de caso de FAF. Finalmente, se indagó el consumo de bifosfonatos en estos grupos para para estimar una medida de asociación. RESULTADOS: de los 441 registros clínicos, 98 (22.2%) fueron del sexo masculino y 343 (77.7%) del femenino, con edad promedio de 77.8 (40-103) años. Se identificaron 59 FS/FD, de las cuales 53% (31 registros) fueron catalogadas FAF. El consumo de BF se determinó en 80.6% de pacientes con FAF y en 3.57% con FS/FD. El uso de BF se asoció significativamente con la presencia de FAF (OR: 112, p 0.000, IC 95%: 12.6-1001). CONCLUSIONES: el uso de BF aumenta significativamente el riesgo de presentar FAF. Las FAF en pacientes que usaron BF se presentó tras un consumo mínimo de 24 meses.
Assuntos
Fraturas do Fêmur , Osteoporose , Humanos , Masculino , Feminino , Idoso , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/diagnóstico por imagem , Fatores de Risco , Diáfises , Estudos RetrospectivosRESUMO
Presentamos el primer reporte de caso en paciente adulto con virus de la inmunodeficiencia humana (VIH + ) con fractura por fragilidad en fémur proximal asociada al uso de terapia antirretroviral (TARV) con fumarato de disoproxilo de tenofovir (FDT) en Chile. Actualmente, los pacientes diagnosticados con VIH inician tratamiento precoz con TARV, lo que implica mayor cantidad de años de exposición a los fármacos de la terapia. El tiempo de exposición acumulado al FDT se ha asociado a disminución de la densidad mineral ósea y falla renal progresiva, pudiendo el paciente desarrollar síndrome de Fanconi adquirido y osteomalacia, con riesgo aumentado de fractura. Presentamos el caso de un hombre de 44 años, VIH+ , evaluado en urgencia tras caída a nivel que resultó en fractura patológica del fémur proximal. Los exámenes de ingreso destacaron hipocalemia, hipocalcemia, hipofosfatemia e hipovitaminosis D. Se realizó manejo multidisciplinario, con suspensión del FDT, un cambio en la TARV, y suplementación con calcio y carga de vitamina D. Se realizó reducción cerrada y fijación con clavo cefalomedular largo, que evolucionó favorablemente con rehabilitación motora precoz; el paciente recuperó su funcionalidad previa, y se observó consolidación ósea a las 12 semanas. La aparición de dolor osteomuscular en pacientes VIH+ en TARV debe levantar alta sospecha clínica de efecto adverso a medicamento; el seguimiento de estos pacientes debe incluir el control seriado de la función renal y de los niveles séricos de calcio y fósforo. La búsqueda y sospecha de estas complicaciones permitiría una intervención precoz, mejorando la condición de los pacientes y previniendo fracturas patológicas.
We present the first case report of a human immunodeficiency virus (HIV)-positive adult patient with a fragility fracture of the proximal femur associated with antiretroviral therapy (ART) with tenofovir disoproxil fumarate (TDF) in Chile. Currently, patients diagnosed with HIV start ART early, resulting in more years of exposure to these drugs. The accumulated exposure time to TDF has been associated with a decreased bone mineral density and progressive renal failure, potentially leading to acquired Fanconi syndrome, osteomalacia, and an increased risk of fracture. We present a case of a 44-year-old, HIV-positive man assessed at the emergency room after a fall from standing height which resulted in a proximal femoral pathological fracture. Laboratory findings at admission revealed hypokalemia, hypocalcemia, hypophosphatemia, and hypovitaminosis D. Multidisciplinary management was performed, with TDF discontinuation, ART change, and supplementation with calcium and vitamin D. Closed reduction and fixation with a long cephalomedullary nail was successful, with early motor rehabilitation, functional recovery, and bone consolidation at 12 weeks. Musculoskeletal pain in HIV-positive patients on ART must raise the clinical suspicion of an adverse drug effect; the follow-up of these subjects must include serial monitoring of renal function and serum calcium and phosphorus levels. Screening and suspicion of such complications would enable an early intervention, improving the patients' condition and preventing pathological fractures.
Assuntos
Humanos , Masculino , Adulto , Fármacos Anti-HIV/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/terapia , Tenofovir/efeitos adversos , Vitamina D/uso terapêutico , Pinos Ortopédicos , Cálcio/uso terapêutico , Redução Fechada , Fixação Intramedular de Fraturas/instrumentaçãoAssuntos
Humanos , Feminino , Idoso de 80 Anos ou mais , Difosfonatos/administração & dosagem , Difosfonatos/efeitos adversos , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico , Osteoporose/complicações , Preparações Farmacêuticas , Densidade Óssea , Densidade Óssea/efeitos dos fármacos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Quadril/induzido quimicamenteRESUMO
Las fracturas asociadas al consumo crónico de bifosfonatos son cuadros descritos recientemente en la literatura médica, que presentan altas tasas de seudoartrosis. Presentamos un caso de rescate de seudoartrosis de fractura femoral subtrocantérica atípica por bifosfonatos asociada a falla del material de osteosíntesis, tratada finalmente con clavo endomedular cervicodiafisario e injerto estructural de peroné. El tratamiento con clavo cervicodiafisario más injerto autólogo está indicado para la seudoartrosis en fracturas femorales asociadas a bifosfonatos. Nivel de Evidencia: IV.
Fractures associated with chronic use of bisphosphonates are recently described entities, with high rates of nonunion. We report a case of nonunion rescue of an atypical subtrochanteric bisphosphonate femoral fracture associated with osteosynthesis failure, which was finally treated using an intramedullary nail and structural fibular graft. Treatment with autologous graft and neck-nail is indicated for nonunion in femoral fractures associated with bisphosphonates. Level of Evidence: IV.
Assuntos
Humanos , Idoso , Transplante Ósseo , Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Pseudoartrose , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the experience of a single tertiary care teaching hospital with the association between use of bisphosphonates and atypical femoral fractures, and to identify potential risk factors and chronologic incidence. DESIGN: Retrospective review. SETTING: Tertiary-care teaching hospital. PATIENTS: Thirty-two patients with a total of 43 fractures met inclusion criteria. INTERVENTION: Treatment for atypical femur fractures. MAIN OUTCOME MEASUREMENTS: Radiographic assessments, duration of bisphosphonate therapy, prodromal symptoms, associated medications/comorbidities. RESULTS: Thirty-one female patients and 1 male patient, with a total of 43 fractures, with an average age of 71.0 (47-92 years) ± 11.01 years at time of fracture, had an average duration of bisphosphonate therapy of 7.57 (1-12 years) ± 3.07 years. Prodromal thigh pain was reported in 20 of 43 fractures (46.5%). Eleven of the forty-three (25.5%) fractures occurred between 2001 and 2005. From 2006 to May 2011, however, 32/43 (74.5%) were reported. Beta-blockers, ACE/ARBs, and Statins (43.8%) were the most common concomitant medications, whereas Levothyroxine (21.8%), H-2 blockers (15.6%), and Glucocorticoids (12.5%) were less common. CONCLUSIONS: There is an increasing trend of atypical femur fractures in the current adult population. Bisphosphonate therapy beyond 7 years may place patients at increased risk. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Assuntos
Difosfonatos/efeitos adversos , Fraturas do Fêmur/epidemiologia , Fraturas do Fêmur/cirurgia , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/prevenção & controle , Conservadores da Densidade Óssea/efeitos adversos , Comorbidade , Fraturas do Fêmur/induzido quimicamente , Hospitais de Ensino/estatística & dados numéricos , Humanos , Incidência , Fraturas por Osteoporose/induzido quimicamente , Pennsylvania/epidemiologia , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricosRESUMO
We describe four cases of atypical femoral fractures treated at the Department of Endocrinology, Hospital de Clínicas, Federal University of Paraná (SEMPR) which, although characteristic of this type of fracture, presented clinical peculiarities that should be considered and serve as a warning in these patients, such as: late diagnosis with maintenance of bisphosphonates; absence of co-morbidities with excellent result; failure of fracture healing; use of anabolic medication after the fracture and the use of bone turnover markers at the follow up.
Assuntos
Difosfonatos/efeitos adversos , Fraturas do Fêmur/induzido quimicamente , Osteocalcina/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Densidade Óssea , Remodelação Óssea/fisiologia , Colágeno Tipo I/metabolismo , Diagnóstico Tardio , Difosfonatos/uso terapêutico , Feminino , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Fixação Intramedular de Fraturas/métodos , Consolidação da Fratura , Humanos , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/tratamento farmacológico , Peptídeos/metabolismo , Radiografia , Fatores de Risco , Fatores de TempoRESUMO
The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a "drug holiday," which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks.
Assuntos
Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Carcinoma/induzido quimicamente , Ensaios Clínicos como Assunto , Difosfonatos/uso terapêutico , Neoplasias Esofágicas/induzido quimicamente , Fraturas do Fêmur/induzido quimicamente , Humanos , Assistência de Longa Duração , Dor Musculoesquelética/induzido quimicamente , Osteonecrose/induzido quimicamente , Fatores de Proteção , Medição de Risco , Fatores de RiscoRESUMO
The objective this study was to summarize long-term risks associated with bisphosphonate therapy. Search of relevant medical publications for data from clinical trials, trial extensions, observational studies and post-marketing reports. Trial extensions and modifications did not reveal significant long-term safety issues. Observational data suggest at least as many benefits as risks. Post-marketing reports of musculoskeletal pain, osteonecrosis of the jaw and atypical femur fractures have been widely circulated in the lay press. Most focus on long-terms risks has been on osteonecrosis of the jaw and atypical femur fractures which occur in patients who have not received bisphosphonate therapy but may be more frequent (though still uncommon) in patients who have been on treatment for 5 years or longer. Lower-risk patients may be able to stop treatment after 3-5 years for a “drug holiday,” which mitigates these long-term risks; for higher risk patients, therapy through 6-10 years appears to be advisable and offers more benefits than risks.
O objetivo deste estudo foi resumir os riscos associados ao tratamento a longo prazo com bisfosfonatos. Foram pesquisadas as publicações médicas relevantes incluindo ensaios clínicos, extensões de ensaios clínicos, estudos observacionais e relatórios pós-comercialização (vigilância farmacológica). As extensões e modificações de ensaios clínicos não indicaram nenhuma situação de alarme quanto à segurança dos bisfosfonatos a longo prazo. Dados observacionais sugerem pelo menos tantos benefícios quanto riscos. Entretanto, relatos pós-comercialização de dor musculoesquelética, osteonecrose da mandíbula e fraturas de fêmur atípicas foram amplamente divulgados na imprensa leiga. O foco nos riscos a longo prazo do tratamento com bisfosfonatos tem sido pincipalmente a osteonecrose da mandíbula e as fraturas atípicas de fêmur. Essas últimas, embora mais frequentes (ainda que pouco comuns) em pacientes que receberam tratamento com bisfosfonatos por 5 anos ou mais, podem ocorrer em indivíduos não tratados com esses medicamentos. Pacientes com baixo risco de fratura podem potencialmente parar o tratamento depois de 3 a 5 anos (“drug holiday”). Esse procedimento reduz os riscos desses medicamentos a longo prazo. Não obstante, nos pacientes de maior risco a terapia por 6 a 10 anos parece ser aconselhável e oferece mais benefícios do que riscos.
Assuntos
Humanos , Conservadores da Densidade Óssea/efeitos adversos , Difosfonatos/efeitos adversos , Osteoporose/tratamento farmacológico , Fibrilação Atrial/induzido quimicamente , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/etiologia , Conservadores da Densidade Óssea/uso terapêutico , Ensaios Clínicos como Assunto , Carcinoma/induzido quimicamente , Difosfonatos/uso terapêutico , Neoplasias Esofágicas/induzido quimicamente , Fraturas do Fêmur/induzido quimicamente , Assistência de Longa Duração , Dor Musculoesquelética/induzido quimicamente , Osteonecrose/induzido quimicamente , Fatores de Proteção , Medição de Risco , Fatores de RiscoRESUMO
CLINICAL SCENARIO: One of your patients, a 59-year-old postmenopausal Asian woman (menopause, age 52), took hormone therapy for about one year for her menopause symptoms. When she was 54, her mother (age 80) suffered a hip fracture, and she requested a bone density test at her next gynecology visit. The t-score results were spine, -1.1; total hip, -1.8; and femoral neck, -2.1, all in the osteopenic range. After some discussion, she was started on alendronate 70 mg once a week, together with calcium and vitamin D. Follow-up dual-energy x-ray absorptiometry testing after 2 and 5 years of therapy showed increases in bone mineral density, resulting in t-score improvements of about 0.3 to 0.5 units (spine was now normal; femoral neck was -1.8). The Fracture Risk Assessment Tool estimated her 10-year risk of hip fracture to be 0.4% and her 10-year risk of any of 4 major osteoporotic fractures to be 7.5%. During her most recent gynecology visit, she expressed concern about unusual femoral fractures being linked to long-term use of alendronate. She asks if there is reason for her to stop using this drug.