CC
A 52-year-old postmenopausal female is referred for evaluation by her restorative dentist for “oral rehabilitation” using dental implants.
Subcutaneous drug–induced osteonecrosis of the jaws
The most commonly used subcutaneous drug approved to treat osteoporosis and is also known to cause osteonecrosis of the jaws is denosumab (Prolia). Denosumab is a monoclonal antibody, hence the word ending in “mab.” Denosumab inhibits RANK (reactor activator of nuclear κB) ligand and by doing so inhibits the development of osteoclasts in the bone marrow, as well as in the circulation and tissue spaces and while resorbing bone. Therefore, it has a much greater antiosteoclastic effect than even a bisphosphonate. Therefore, drug–induced osteonecrosis of the jaws (DIONJ) cases solely caused by denosumab occur sooner and are more extensive. Moreover, if the patient has previously taken a bisphosphonate and was switched to denosumab, the alveolar bone now loaded with the bisphosphonate readily becomes exposed with the switch to denosumab. This is caused by denosumab’s targeting the osteoclast precursors in the bone marrow ( Fig. 13.1 ).
However, denosumab cases can be effectively managed with the knowledge that they do not bind to bone as do the bisphosphonates. They have a half-life of only 26 days, which lends treatment protocols to a short drug holiday of 3 months before and 3 months after an alveolar bone surgery.
HPI
The patient is a 52-year-old female who was referred by her restorative dentist. This patient had a neglected dentition with mobility and significant periodontal bone loss about her few remaining teeth. She now presents with an edentulous maxilla, a lone standing left mandibular canine (tooth #22), and exposed bone in the area of the right mandibular canine (tooth #27) ( Fig. 13.2 ). She relates that she took alendronate (Fosamax) 70 mg/week for 4 years for “severe osteoporosis” (T score = 4.2 and one vertebral fracture). When her treating physician identified no improvement by her every-2-year dual x-ray absorptiometry scan (a radiographic analysis of bone density), she was switched to denosumab (Prolia) 60 mg subcutaneously every 6 months as per US Food and Drug Administration (FDA) approval. She has no comorbidities other than Hashimoto’s thyroiditis for which she takes Synthroid.
PMHX/PDHX/medications/allergies/SH/FH
Examination
The exposed bone in the mandible is nonmobile as is tooth #22. Although there is granulation tissue present, there is no pus. Both the maxillary and mandibular ridges are irregular because of areas of more severe bone loss and past extractions. There is no exposed bone, and there is no drainage.
Oral and maxillofacial
Imaging
A cone-beam computed tomography scan shows no osteolysis but moderate demineralization in the exposed alveolar bone. The maxillary sinuses are appropriately pneumatized with no evidence of sinusitis.
Assessment
Stage I drug-induced osteonecrosis of the maxilla secondary to alendronate therapy.
The exposed bone limited one quadrant represents stage I. The previous use of a bisphosphonate followed by a RANK ligand inhibitor is the underlying cause of this rapidly appearing exposed bone. The treatment plan will require a drug holiday. Therefore, discussion must occur with her treating physician about drug holidays. Moreover, because she has severe osteoporosis, an alternative osteoporosis medication will be likely required during the drug holiday. If she did not have a diagnosis of severe osteoporosis with a vertebral compression fracture, either no alternative osteoporosis medication would have been acceptable, or vitamin D 3 and calcium or raloxifene (Evista) could be substituted. However, because of her “severe osteoporosis,” the use of an anabolic osteoporosis drug that adds new bone rather than retains old bone is needed.
Specific to the drug holiday, this case will require a 9-month drug holiday before the procedure rather than the 3-month drug holiday for a denosumab-only case followed by 3 months after the procedure. If a bisphosphonate with its 11.2-year half-life was used at any time in the patient’s osteoporosis treatment, then the drug holiday must be the one appropriate for the bisphosphonate.
Treatment
- A.
Osteoporosis Management and Drug Holiday
-
The treating physician was happy to place this patient on our recommended drug holiday and chose to continue treating her with rhPTH1-34 (Forteo). Recombinant human parathyroid hormone 1-34 (rhPTH 1-34) is an anabolic agent that builds new bone rather than retains old bone as do bisphosphonates and denosumab. It has no known cases of DIONJ and has no mechanism to produce DIONJ. It is also FDA approved specifically for “severe osteoporosis.” As an alternative, rhPTH 1-80, Tymlos, or romosozumab (Evenity), can be used.
-
- B.
The Dental and Oral and Maxillofacial Treatment Plan:
-
During the 9-month drug holiday, radiographs identified an involucrum around a sequestrum encompassing the exposed bone ( Fig. 13.3 ). The office-based procedure easily removed the exposed bone because it became mobile during the drug holiday. The bone was leveled and contoured, and four implants were placed into the remaining mandibular bone as well as six implants into the maxilla together with bilateral sinus lift procedures. After the drug holiday has been taken to the appropriate time, all commonly used alveolar bone surgeries, sinus lift procedures, and grafting procedures can be done with a minimal risk for exposed bone. The graft material used is the choice of the surgeon with none contraindicated by the history of DIONJ-causing drugs.
-
