Osteonecrosis of the jaw in patients with multiple myeloma treated with zoledronic acid

Abstract

Intravenous bisphosphonates-the potent inhibitors of osteoclast-mediated bone resorption are among the most commonly prescribed drugs in the management of multiple myeloma (MM). Zoledronic acid (ZA) is a new generation potent intravenous bisphosphonate that has been approved for the treatment and prevention of bone lesions, and/or hypercalcemia associated with MM. Osteonecrosis of the jaw (ONJ) is an emerging serious side effect of the new generation bisphosphonates with a growing number of reports related to this pathological entity. ONJ usually appears following oral surgical and dental procedures but sometimes occur spontaneously. These cases are mostly seen and treated by dentists and oral surgeons. The aim of this study was to discuss the frequency, characteristics, risk factors, management and histopathological features of ZA induced ONJ based on the literature and illustrated with five own cases. Thirty-two patients with MM who received ZA for a median period of 26.5 +/- 18.7 months (min: 5 months, max: 76 months) were evaluated. ONJ was detected in five patients and mean drug duration time was 34 months. The frequency was 15% and the patients were usually symptomatic. There was no significant difference in terms of the duration of ZA in patients with and without ONJ. Management of these established cases were performed with medical treatment, minor debridement, sequestrectomy, and combining bone resection with autologous platelet rich plasma. Our data indicate that ZA therapy has a major role in the development of ONJ a fact that should be considered by physicians treating MM patients.

Platelet-Rich Plasma in Treatment of Zoledronic Acid-Induced Bisphosphonate-related osteonecrosis of the jaws

“…Cetiner et al described a case of Zoledronate-associated BRONJ after tooth exodontia in a 68-year-old man with multiple myeloma treated with surgical debridement plus PRP, showing a good outcome after six months follow-up (34, 47). It should be noted that PRP pH value ranges between 6.5 and 6.7, which is more acidic than blood (7.0 - 7.2), and therefore it is expected to be less favorable for bacterial growth (27, 34).…”

Osteonecrosis of the Jaw Developed in Mice

“…ONJ is initially defined as an exposed jawbone in the oral cavity for more than 8 weeks even after appropriate intervention therapies in patients with current or past BP treatment (3,4). An increasing number of case reports suggest that considerable variations exist in the clinical manifestations of ONJ, ranging from radiographic bone pathology without ulcerative oral mucosal lesions to localized swelling with persistent fistula formation (5)(6)(7).…”

IL-17–Mediated M1/M2 Macrophage Alteration Contributes to Pathogenesis of Bisphosphonate-Related Osteonecrosis of the Jaws

“…The incidence of BRONJ in cancer patients receiving high doses of intravenous BP such as zoledronic acid (ZA) and pamidronate (%) ranged from 0.8~12%, a rate much higher than that in patients with osteoporosis on oral BP treatment. Among the cancer group, highest prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been reported in patients with multiple myeloma, followed by breast and prostate cancer (4–7). To date, even though several risk factors, including invasive dental procedure, infection, mechanical trauma to the jaw bone, and concomitant use of immunosuppressive and chemotherapy drugs, have been implicated in the etiology of BRONJ (4, 5), its underlying mechanisms remains largely unknown.…”