Scientific letter
Maxillar osteonecrosis associated to denosumab in a patient with systemic mastocytosis
Osteonecrosis maxilar asociada a tratamiento con denosumab en una paciente con mastocitosis sistémica
José Darío Sánchez López
, Paolo Cariati, Miguel Pérez de Perceval Tara
Corresponding author
Servicio de Cirugía Oral y Maxilofacial, Hospital Universitario Virgen de las Nieves, Granada, Spain
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Sánchez López, Paolo Cariati, Miguel Pérez de Perceval Tara" "autores" => array:3 [ 0 => array:4 [ "nombre" => "José Darío" "apellidos" => "Sánchez López" "email" => array:1 [ 0 => "josed.sanchez.sspa@juntadeandalucia.es" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "Paolo" "apellidos" => "Cariati" ] 2 => array:2 [ "nombre" => "Miguel" "apellidos" => "Pérez de Perceval Tara" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Cirugía Oral y Maxilofacial, Hospital Universitario Virgen de las Nieves, Granada, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Osteonecrosis maxilar asociada a tratamiento con denosumab en una paciente con mastocitosis sistémica" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 972 "Ancho" => 750 "Tamanyo" => 36333 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Area of osteonecrosis and osteolysis in the left jaw with bone sequestrum (the arrow represents the lesion).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The systemic form of mastocytosis constitutes 10% of the total and can be classified into 4 different forms.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of a 46-year-old female patient with a previous history of hysterectomy due to myomas, having frequent episodes of urticaria treated with antihistamines, as well as frequent gastrointestinal pain, diarrhoea and gastroesophageal reflux. Haematology confirmed the diagnosis of mastocytosis by bone marrow fine-needle biopsy and immunophenotypic study with the presence of 0.01% of mast cells (CD117++/+++/CD34−/CD45++/CD203c+), with a weak aberrant CD25+, CD63+/++++het. Mutation of the c-kit gene was observed (D816V) in mast cells, but not in CD34 cells or eosinophils. Subsequently, she was referred to rheumatology due to osteopenia detected in a bone densitometry with risk of hip fracture. The treatment with bisphosphonates (BP) (pamidronate, etidronate, zoledronate, etc.) was discarded due to being harmful to the distal third of the oesophagus. For this reason, another antiresorptive agent, denosumab (Prolia® was chosen), (non-chimeric) human monoclonal antibody (IgG2), which binds with great affinity and specificity to the receptor activator of nuclear factor kappa-B ligand (RANKL), preventing the activation of its RANK receptor on the surface of the osteoclast precursors and in osteoclasts, inhibiting osteoclastic action and therefore causing a decrease in bone resorption.<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">2</span></a> A two-year treatment with denosumab (a subcutaneous dose every 6 months) was initiated, and the medication had to be discontinued when the patient experienced pain and suppuration in the upper left jaw, which is why she was referred to the oral and maxillofacial surgery service. On clinical examination, necrotic bone exposure was observed in the described location of approx. 2<span class="elsevierStyleHsp" style=""></span>cm in diameter, starting treatment with amoxicillin 1<span class="elsevierStyleHsp" style=""></span>g/8<span class="elsevierStyleHsp" style=""></span>h for one week and meticulous oral hygiene with 12% chlorhexidine mouthwash/3 times a day. An imaging study was also performed using computerized axial tomography (CAT) that showed extensive osteonecrosis of the jaw (ONJ) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). BP-related ONJ is widely collected in the scientific literature; some cases of ONJ have recently been described in relation to the use of denosumab, with Neuprez et al. reporting the first case of ONJ in a patient with osteoporosis after a dental extraction.<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">3</span></a> Although denosumab, unlike BP, lacks anti-angiogenic activity, 3 clinical trials with denosumab (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>52) showed an increased risk of developing osteonecrosis of the jaw compared to zoledronic acid (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>37), with a 1.4:1 ratio (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>0.05).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">4</span></a> Although the medical literature shows that the risk of developing ONJ in patients exposed to oral BP or denosumab in the treatment of osteoporosis is real, it continues to be low. The cases described are explained by the high number of patients (5.1 million over 55 years of age) exposed to these drugs. However, as denosumab does not incorporated into bone matrix, the cases of ONJ could cure with a higher success rate, as shown by the stabilization of the process in the case reported, where, after the administration of antibiotherapy and a meticulous oral hygiene, the symptoms have disappeared, exclusively persisting the intraoral necrotic bone exposure after one year of follow-up.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Sánchez López JD, Cariati P, Pérez de Perceval Tara M. Osteonecrosis maxilar asociada a tratamiento con denosumab en una paciente con mastocitosis sistémica. Med Clin (Barc). 2018;151:81–82.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 972 "Ancho" => 750 "Tamanyo" => 36333 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Area of osteonecrosis and osteolysis in the left jaw with bone sequestrum (the arrow represents the lesion).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:4 [ 0 => array:3 [ "identificador" => "bib0025" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mastocitosis ósea. Aproximación al diagnóstico" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M.B. 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