Denosumab Related Osteonecrosis of the Jaw with Spontaneous Necrosis of the Soft Palate: Report of a Life Threatening Case

Abstract

Bisphosphonates have been used for years in the treatment of patients with distant bony metastasis and in the prevention of osteoporosis. One of main side effects of these medications is the development of bisphosphonate related osteonecrosis of the jaw (BRONJ) in a small subset of patients. A new class of medications with a shorter half-life, known as receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors, was introduced with the hopes of avoiding this side effect. However, reports of osteonecrosis of the jaw after the use of RANKL inhibitors have also been documented. We report on a patient who developed a life threatening osteonecrosis of the jaw with sepsis shortly after switching from a bisphosphonate to a RANKL inhibitor for osteoporosis treatment. This patient developed several soft tissue defects including spontaneous necrosis of the soft palate. To our knowledge this is the first time this presentation has been described.

Osteonecrosis of the Jaw (ONJ) in Osteoporosis Patients: Report of Delayed Diagnosis of a Multisite Case and Commentary about Risks Coming from a Restricted ONJ Definition

“…However, an increasing number of ONJ cases in osteoporosis and rheumatoid arthritis patients were observed in later years after receiving bisphosphonates therapy [ 31 , 41 , 42 , 43 , 44 ]. The same observation was more recently reported for denosumab: few ONJ cases were reported in trials, but an increasing number of cases are published on osteoporosis patients after more or less prolonged treatment with denosumab alone or bisphosphonates switched to denosumab [ 40 , 45 , 46 , 47 , 48 ].…”

“…However, we know that life-threatening or lethal drug-induced ONJ cases have been observed not only in cancer and myeloma [ 33 , 34 , 35 , 36 ] but also in osteoporotic patients [ 37 , 38 , 39 , 40 ] due to infectious complications; consequently, a diagnosis delay has to be avoided as much as possible.…”

New Molecules Modulating Bone Metabolism – New Perspectives in the Treatment of Osteoporosis

“…Kamimura et al (2017) showed inhibition of bone resorption and an increase in lumbar and hip BMD after one year of treatment with denosumab in patients unresponsive to bisphosphonate. Nevertheless, similar to bisphosphonates, a certain limitation of long-term denosumab treatment may be the reduced renewal of bone mass with subsequent osteonecrosis of the jaw and/or atypical femoral fractures (Qaisi et al 2016).…”

Bone necrosis associated with the use of bisphosphonates: Case report

“…9,10 For diagnosis of this disease, 3 elements should be present -the patient received or receives drugs from the BP group, exposure of dead bone tissue in the upper or lower jaw was observed (longer than 8 weeks), and the patient was not treated with the use of radiotherapy in the area of the head and neck. 11 In 2014, AAOMS (The American Association of Oral and Maxillofacial Surgeons) recommended the change of this term to "medication-related osteonecrosis of the jaw (MRONJ)". 12 Osteonecrosis associated with the use of bisphosphonates can occur intrinsically, but usually is connected with invasive dental procedures, i.e.…”

“…Interestingly, it is more common among patients with cancer (about 0.7-6.7%) than in patients treated for osteoporosis (0.04-0.2%). 11,12 This disease more often affects the lower jaw than the maxilla. Risk factors mainly include: injuries associated with treatment in dental surgery, use of mismatched prosthetic restorations, presence of bone exostosis, odontogenic inflammations, poor oral hygiene, coexisting diabetes, simultaneous chemotherapy and/or steroid treatment, malnutrition and smoking.…”