CC
A 57-year-old female is referred by her oncologist for progressively advancing bone exposure in her mandible.
Subcutaneous drug–induced osteonecrosis of the jaws
The subcutaneous oncology drug used to reduce cancer-stimulated osteolysis and pathologic fractures is denosumab 120 mg sub cutaneous every month (Xgeva). Denosumab is an inhibitor of RANK (reactor activator of nuclear κB) ligand, which is the ligand that activates osteoclasts in bone remodeling. However, denosumab acts on the bone marrow osteoclast precursors, significantly reducing their numbers, and acts on the mature circulating osteoclasts and even those actively resorbing bone. Although this effect indeed works to reduce cancer-stimulated bone resorption and pathologic fractures, its profound effect of reducing the total osteoclast population and its bone marrow replacements has created the most severe and most extensive drug-induced osteonecrosis of the jaws (DIONJ).
In contrast to bisphosphonates, which have a strong affinity to bind to bone, thus exhibiting a 11.2-year half-life in bone, denosumab does not bind to bone and therefore has a half-life in the bone marrow plasma of only 26 days. The clinical importance of this is that a 3-month drug holiday before a procedure followed by another 3-month drug holiday after the procedure is useful in treating almost every denosumab-exposed patient.
HPI
This 57-year-old female presents with several photographs taken at the start of the exposed bone 18 months earlier ( Figs. 14.1 and 14.2 ). An initial oral examination today indicates a loss of all the teeth present at the time of the last photograph, 6 months ago, and exposed necrotic bone of the entire alveolar process of the mandible ( Fig. 14.3 ).
This patient is currently being treated for active multiple myeloma with lenalidomide (Revlimid), bortezomib (Velcade), and prednisone. Her oncologist has deferred a bone marrow transplant partially because of the exposed bone and bouts of infection as well as her currently active multiple myeloma.
She related that she received zoledronate 4 mg intravenously monthly for 4 years. Because of two vertebral compression fractures, her oncologist switched her to subcutaneous denosumab 120 mg monthly. Just after the second dose of denosumab 18 months ago, exposed bone appeared in the anterior mandible ( Fig. 14.1 ). With continued denosumab use, the exposed bone area extended to all of her remaining dentition (see Fig. 14.3 ). About 6 months ago, these teeth “were exfoliated,” or “fell out,” leaving her with the extensive alveolar bone exposure seen today ( Fig. 14.4 ). She reports that in the past year, she has had several bouts of severe pain and swelling, one requiring a hospital admission for intravenous antibiotics.
PMHX/PDHX/medications/allergies/SH/FH
This patient’s past medical history is significant for hypertension, osteoporosis, and insomnia. She currently takes amlodipine–benazepril, atenolol, and dapagliflozin for her hypertension and uses zolpidem for sleep each night. Her vital signs are stable with a blood pressure of 138/87 mm Hg. She is a never smoker and has a stated allergy to penicillin that she reports as “shortness of breath.”
She is currently receiving lenalidomide, bortezomib, and prednisone for her multiple myeloma IGa type, which is at 2400 mg/dL (reference range, 60–400 mg/dL).
Examination
The oral examination today identifies exposed sockets and alveolar bone from the left second molar area to the right second molar area. The exposed bone is nonmobile but is tender to the touch. In the anterior area, a slight suppurative exudate came to be expressed. The maxilla is partially edentulous with moderate periodontal bone loss and 1+ mobility of the remaining teeth.
Oral and maxillofacial
Imaging
A cone-beam computed tomography scan shows osteolysis mainly focused on the intercortical bone area of the mandible ( Fig. 14.5 ). There is no evidence of osteolysis to the inferior border or that of a pathologic fracture.
