Osteonecrosis of the jaw (ONJ): diagnosis and management in 2015

Abstract

Osteonecrosis of the jaw (ONJ) has been associated with the use of aminobisphosphonates and denosumab. The vast majority (>90%) of cases occur in the oncology patient population receiving high doses of intravenous bisphosphonates or subcutaneous denosumab. The incidence of ONJ in the osteoporosis patient population is very low and is estimated at 1-90 per 100,000 patient-years of exposure. In the oncology patient population the incidence appears to be related to dose and duration of exposure, and prevalence has been estimated to be as high as 18.6%. A number of risk factors in addition to antiresorptive therapy have been identified. These include the presence of periodontal disease, oral surgical procedures with extractions or implants, radiation therapy, chemotherapy, diabetes, glucocorticoid use, and smoking. Antiangiogenic agents appear to contribute to the risk of ONJ, however, data at this time are limited and further evidence is required prior to confirming a causal relationship. ONJ may be prevented with optimization of oral hygiene, the use of oral antimicrobial mouth rinses, as well as systemic antibiotic therapy. Individuals not responding to conservative management or in the advanced stages of ONJ may be considered for surgery, as data over the past several years have demonstrated surgical success in this patient population. Case reports have indicated that teriparatide may enhance healing. A number of experimental therapies are being evaluated and include the use of bone marrow stem cell intralesional transplantation, local application of platelet-derived growth factor, hyperbaric oxygen, tissue grafting, and low-level laser therapy. This paper summarizes the current research as well as the international consensus on the diagnosis and management of ONJ.

Drug-induced osteonecrosis of the jaw: the state of the art

“…Among the concomitant medical issues besides periodontal disease or other oral conditions, rheumatoid arthritis and diabetes were also reported, while the most commonly used medication affecting bone metabolism was glucocorticoid therapy (9). Several effects of glucocorticoids may contribute to increased risk of ONJ, such as inhibition of the osteoblast function, increased osteoblast and osteocyte apoptosis, increased bone resorption, immunosuppression, impaired wound healing and increased risk of local infection (2).…”

“…Thus, it is quite natural to consider the suppression of bone resorption and of bone turnover as possible mechanisms in the development of ONJ. Furthermore, the risk of ONJ increases with both the cumulative dose and the duration of exposure to the treatment (2,3,15). This pathogenetic hypothesis would explain the appearance of ONJ through an excessive inhibition of bone remodeling and therefore resulting in an impaired osteoclast activity, too inadequate to allow the healing of the extraction socket (2).…”

“…Furthermore, the risk of ONJ increases with both the cumulative dose and the duration of exposure to the treatment (2,3,15). This pathogenetic hypothesis would explain the appearance of ONJ through an excessive inhibition of bone remodeling and therefore resulting in an impaired osteoclast activity, too inadequate to allow the healing of the extraction socket (2). The studies cited above are consistent with this hypothesis, although ONJ has never been reported in other conditions associated with low bone turnover.…”

“…Teriparatide may be considered a conservative treatment choice for those with osteoporosis and without cancer or prior radiation therapy to bone (2,3,21). Subjects with stage 3 ONJ may be considered for surgery with osteotomy of the affected area (2, 3).…”

“…It was reported for the first time in 2003 (1), when 36 cancer patients receiving treatment with pamidronate or zoledronate developed a painful bone exposure of the mandible, of the maxilla or both, unresponsive to surgical and medical treatment. Since then, several case reports have been published as well as retrospective and limited prospective data, showing that more than 90% of the cases of ONJ occurred in oncologic patients who were receiving high doses of antiresorptive therapy (2).…”