Osteonecrosis of the jaw and oral bisphosphonate treatment

BACKGROUND: Bisphosphonates are becoming recognized increasingly as having a significant impact on dental therapies. This case report describes adverse clinical sequelae and successful treatment following periodontal surgery in a dental patient receiving bisphosphonate treatment. CASE DESCRIPTION: A 78-year-old woman experienced a nonhealing interproximal wound subsequent to a minor periodontal procedure performed to facilitate restoration of an adjacent tooth. Her medical history revealed that she had been taking an oral bisphosphonate every day for the previous five years for treatment of osteoporosis. After three months of periodic débridement and meticulous oral home care, one of the authors recovered a large piece of necrotic bone. The wound healed after the author performed surgery at the site. CLINICAL IMPLICATIONS: Dentists should exercise caution when considering surgical procedures for patients with a history of oral bisphosphonate use. Thorough treatment of nonhealing wounds in these patients can lead to favorable outcomes.     

Osteonecrosis of the jaw in patients transitioning from bisphosphonates to denosumab treatment for osteoporosis

Antiresorptive-related osteonecrosis of the jaw (ARONJ) is a rare but severe side effect of antiresorptive treatment with bisphosphonates or RANKL-antibody denosumab in patients with malignant diseases or osteoporosis. Whilst osteonecrosis of the jaw (ONJ) related to the administration of bisphosphonates (BPs) has been investigated for more than 1 decade now, only few data are available on denosumab-related ONJ, especially in patients with osteoporosis. From 2008 to 2016, 52 osteoporosis patients were treated with ARONJ in the Department of Oral and Maxillofacial Surgery, University Medical Center Freiburg, Germany. In all patients, a surgical regimen consisting of complete removal of necrotic bone, primary wound closure and perioperative i.v. antibiotic therapy was applied. Of the 52 patients, 38 developed ARONJ after BP monotherapy; in 11 patients, antiresorptive therapy had been transitioned from BPs to denosumab and 3 patients had received denosumab monotherapy. From July 2013, when the first patient with ONJ and transitioning therapy from BPs to denosumab presented to our department, to October 2016, we found recurrences in 17.6% of the patients with BP monotherapy and in 45.5% of the patients with transitioning therapy from BPs to denosumab. Transitioning antiresorptive therapy from BPs to denosumab may be an additional risk factor for developing ARONJ. In these patients, treatment of ARONJ-lesions seems to provoke more complications. An additional dental screening before transitioning should be initiated. Further studies are needed to evaluate if a first-line treatment with denosumab decreases the incidence of ARONJ in patients with osteoporosis and simplifies its treatment.     

Osteonecrosis of the jaws and bisphosphonate therapy

Bisphosphonates are a class of agents used to treat osteoporosis and malignant bone metastases. The efficacy of these agents in treating and preventing the significant skeletal complications associated with these conditions has had a major positive impact for patients and is responsible for their widespread use in medicine. Despite these benefits, osteonecrosis of the jaws has recently emerged as a significant complication in a subset of patients receiving these drugs. Based on a growing number of case reports and institutional reviews, bisphosphonate therapy may cause exposed and necrotic bone that is isolated to the jaw. This complication usually presents following simple dento-alveolar surgery, and can cause a significant adverse effect on the quality of life for most patients. The pathogenesis for this complication appears to be related to the profound inhibition of osteoclast function and bone remodeling.     

Radical surgical treatment of bisphosphonate related osteonecrosis of the jaw

We describe a case of a 64-year-old female diagnosed with multiple myeloma in 2001. She was treated with pamidronate and subsequently zolodronic acid before developing spontaneous bisphosphonate related osteonecrosis (BRONJ) of the left maxilla in December 2008. Over the next two years the BRONJ was treated conservatively but gradually became more symptomatic. About three years after her last dose of zolodronic acid with her symptoms increasing, she underwent radical surgical excision of all diseased bone and flap reconstruction. The patient is now six months postoperative and symptom free.     

Osteonecrosis and spontaneous exfoliation of dental implants associated with oral bisphosphonate therapy: a case report

Bisphosphonates (BPs) have long been used for the treatment of osteoporosis and diseases like bone malignancies, active Paget's disease of bone, severe osteogenesis imperfecta and fibrous dysplasia among others. They bond highly to the bone surface and inhibit bone resorption. As BPs have a long half-life in bone because of their irreversible binding to bone, patients retain their risk profile even after drug cessation. This property also explains the complications wherein the cessation of bone resorption leads to halt in bone turnover. Usually with alendronate the risk of bisphosphonate-related osteonecrosis of jaw (BRONJ) wears off after 12 months. Reporting of the development of BRONJ is commonly associated with the intravenous BPs. Invasive surgical procedure associated with the placement of implants has been shown to be a major reason for the occurrence or initiation of BRONJ in susceptible patients. The prognosis of implants placed in the jaws of patients under or past BP medication is still uncertain. The present case report describes a patient on long-term oral BP therapy with spontaneous exfoliation of implant supported bone due to osteonecrosis.     

Osteonecrosis of the jaw as an adverse bisphosphonate event: three cases of bone metastatic prostate cancer patients treated with zoledronic acid

Bisphosphonates offer a significant improvement in the quality of life for cancer patients; these potent inhibitors of bone resorption have been shown to markedly reduce the morbidity frequently resulting from bone metastases. Despite the success of bisphosphonates as therapeutic agents, however, toxicity in the form of osteonecrosis of the jaw (ONJ) is a rare complication whose incidence rate has climbed in recent years. ONJ is defined as an unexpected development of necrotic bone in the oral cavity, and is commonly associated with administration of the bisphosphonates Pamidronate and Zoledronate. Clinical features include local pain, soft-tissue swelling, and/or loose teeth; ONJ is also often correlated with previous dental procedures, such as tooth extractions, during biphosphonate therapy. Although additional risk factors-such as corticosteroids, chemotherapy, radiotherapy, trauma or infection-exhibit etiological associations with ONJ, the real pathobiology has not yet been fully elucidated. Here we report our findings on all 2005 OJN cases presented at our institution resulting from bone metastatic prostate cancer treated with zoledronic acid. The incidence of ONJ is nearly 3% (3 out of 104) in these patients.     

Osteonecrosis of the jaw related to sunitinib

Case Report

A 59-year-old male patient was referred to the hospital with exposed bone measuring 10?mm in diameter in the posterior, left-side region of the lower jaw. Two months previous, the first molar had been extracted. The patient had contracted renal cell carcinoma and had been treated by nephrectomy in 2003. Soft tissue metastases occurred. After initial therapy with interferon and vinblastine, a relapse occurred and the therapy was changed to sorafenib, followed by sunitinib. Osteonecrosis of the lower jaw appeared 1?year after initial and exclusive therapy with sunitinib.

Conclusions

Bisphosphonates had never been applied. With increasing application of multi-kinase inhibitors, complications due to osteonecrosis could occur more frequently.     

Osteonecrosis of the jaw related to everolimus: a case report

Antiresorptive agent-related osteonecrosis of the jaw results in appreciable morbidity in affected patients. Nowadays many physicians prescribe an antiangiogenic agent for the management of malignant metastases. Everolimus is a serine–threonine kinase that acts as an inhibitor of mammalian target of rapamycin, which results in reduced growth of cells, angiogenesis, and survival of cells. We report the first case to our knowledge of osteonecrosis of the jaw that seemed to result from the additive effect of everolimus.     

Denture-related osteonecrosis of the maxilla associated with oral bisphosphonate treatment

BACKGROUND: Bisphosphonates are a class of agents used to treat various systemic conditions. Despite the benefits of bisphosphonates, osteonecrosis of the jaws is an important complication in a subset of patients who receive this drug treatment. CASE DESCRIPTION: A 66-year-old woman was referred to an oral surgeon at a private surgical center because of a pressure wound in the margins of a removable maxillary denture. The patient reported that she had received oral alendronate sodium treatment for eight years. A clinical examination revealed a palatal ulcer with exposed necrotic gray bone at its center. The clinician performed an excisional biopsy and separated two palatal rotational flaps to enable an adequate blood supply to reach the operated-on area. CLINICAL IMPLICATIONS: This report, together with growing evidence in the literature, serves to alert treating physicians and dental practitioners about the potential complication of maxillary and mandibular bone necrosis in patients receiving bisphosphonate therapy.     

Osteonecrosis of the jaw in a patient receiving cabozantinib

Since the discovery of bisphosphonate‐related osteonecrosis of the jaw, there has been increasing evidence in recent years of osteonecrosis induced by drugs other than bisphosphonates, mainly agents with antiangiogenic and antiosteoclastic activity. Mandibular osteonecrosis was observed in a 51‐year‐old female with medullary thyroid cancer receiving cabozantinib, a new tyrosine kinase inhibitor having antiangiogenic activity. The bone necrosis appeared after a dental extraction. The clinical, radiographic and histologic picture of a chronic non‐healing extraction socket was consistent with drug‐induced osteonecrosis of the jaw. Healing was achieved by segmental ostectomy. The osteonecrosis was likely associated with a vascular endothelial growth factor (VEGF) pathway inhibition, implying inhibition of angiogenesis and hampering of the local host defence mechanisms.     

Osteonecrosis of the jaw among cancer patients in Denmark: risk and prognosis

Osteonecrosis of the jaw (ONJ) is a serious complication of anti-resorptive therapy used in the treatment of multiple myeloma and cancerous bone metastases. In this study, patients with either multiple myeloma or solid tumours with a simultaneous or subsequent record of anti-resorptive treatment or bone metastases were identified using population-based medical registries. These patients were followed for the outcome of ONJ. Considering death as a competing risk, the cumulative incidence of ONJ was estimated, overall and by cancer site. Patients who developed ONJ were followed for the outcome of death overall and by several risk factors for ONJ. A total of 33,975 cancer patients fulfilling the inclusion criteria were identified; 233 incidents of ONJ and a cumulative incidence of 1.9% (95% confidence interval 1.6–2.3%) over a maximum follow-up time of 7.5 years were observed. The 5-year cumulative incidence was 1.3% (95% confidence interval 1.2–1.6%) and varied by cancer site. There were 126 deaths among cancer patients with ONJ over a maximum follow-up time of 6.4 years, resulting in a 5-year mortality of 91% (95% confidence interval 81–97%). Mortality among patients with ONJ varied by cancer site, osteonecrosis stage, and by history of trauma to the mucosa.