Medication-Related Osteonecrosis of the Jaw: A Cross-Sectional Study on the Prevalence of Cutaneous Manifestations and the Primary Care Physician's Role in its Early Diagnosis.

BACKGROUND: Medication-related osteonecrosis of the jaw (MRONJ) is a side effect in patients undergoing treatment with bone-modifying agents (BMA) for cancer or osteoporosis. Although most cases are treated by oral medicine specialists, some cases may present extraorally as a fistula in the skin or erythematous swelling localized to the jaw area, causing these patients to consult a primary care physician. This study examined the prevalence and clinical characteristics of extraoral manifestations of MRONJ in a large cohort to raise awareness among primary care physicians of this entity, enabling prompt diagnosis and treatment. METHODS: Medical records were retrieved of patients diagnosed with MRONJ between 2003 and June 2020 in the Oral Medicine Unit of The Sheba Medical Center, Israel. Data relating to demographics, medical background, type of BMA, and clinical presentation were collected. RESULTS: In total, 515 patients (378 women [73%] and 137 men [27%]; mean age: 65 years, range: 32-94 years) met the inclusion criteria, among whom 84 (16.5%) presented with extraoral manifestations of MRONJ. Of these 84 patients, 21 (24.7%) presented with extraoral fistulas. Extraoral manifestations were strongly correlated with MRONJ of the mandible (n = 67; P = .0006). CONCLUSIONS: MRONJ is a significant side effect of BMA therapy. Although MRONJ mostly presents intraorally, some patients may initially present with extraoral manifestations of erythematous swelling or fistulas localized to the jaw area. Primary care physicians should consider MRONJ as a differential diagnosis in such patients.

Rapid onset of osteonecrosis of the jaw in patients switching from bisphosphonates to denosumab.

OBJECTIVE: The aim of this study was to determine whether osteonecrosis of the jaw (ONJ) developed more rapidly in patients who switched from bisphosphonates (BP) treatment to denosumab than in patients who received only denosumab. STUDY DESIGN: This was a retrospective cohort study conducted at a tertiary referral center. Thirty-one patients with ONJ met the inclusion criteria. RESULTS: Twenty-two patients who had been on BP were switched to denosumab (BP + D), whereas 9 patients received only denosumab. Both groups were similar for the known ONJ risk factors, that is, age, diabetes mellitus, and smoking. The number and cumulative doses of denosumab before the onset of ONJ symptoms were significantly lower among the BP + D group compared with the denosumab-only group (P = .025 and .018, respectively). In the BP + D group, ONJ symptoms developed in 9 patients (41%) following the administration of ≤3 denosumab doses compared with ONJ developing in only 1 patient (11%) who was naïve to BP. ONJ developed spontaneously without any known triggering event in 72.7% of patients in the BP + D group and in 77.8% of patients in the denosumab-only group. CONCLUSIONS: Denosumab-induced ONJ might develop rapidly in patients previously treated with BP. ONJ developed spontaneously in most patients treated with denosumab. In light of our sample being small, there is need for further investigation on our conclusions.

Involvement of the maxillary sinus in bisphosphonate-related osteonecrosis of the jaw: Radiologic aspects.

BACKGROUND: The use of bisphosphonates is very common among patients with osteoporosis and multiple myeloma as well as those with bone metastases from various malignancies. The benefits of bisphosphonates are well recognized, but it became evident during the past decade that these medications portend the major adverse effect of osteonecrosis of the jaw, known as bisphosphonate-related osteonecrosis of the jaw. OBJECTIVE: Our aim was to evaluate the specific manifestations of bisphosphonate use on the maxillary sinus in patients with documented bisphosphonate-related osteonecrosis of the jaw. METHODS: A retrospective review of all the patients diagnosed between October 2003 to August 2014 as having bisphosphonate-related osteonecrosis of the jaw in a large university-affiliated tertiary care medical center. The records of 173 patients diagnosed as having bisphosphonate-related osteonecrosis of the jaw during the study period were retrieved. The available head and neck computed tomographic images were analyzed for cases of involvement of the maxilla. MAIN OUTCOME MEASURES: Manifestations of bisphosphonate-related osteonecrosis of the jaw as observed on physical examination and on imaging studies. RESULTS: Seventy-one patients (41%) had involvement of the maxilla, 86 patients (49%) had involvement of the mandible, and 16 patients (9%) had involvement of both the maxilla and the mandible. Computerized tomography studies were available for 50 patients with involvement of the maxilla: 36 (72%) had evidence of maxillary sinus opacification (in comparison, the incidence of maxillary sinus opacification as an incidental finding in the general population is reported to be 19%, p < 0.0001). Sixteen patients (32%) had evidence of oroantral fistula, and five patients (10%) had oronasal fistula. CONCLUSION: In addition to its well-established effects on the mandible and maxilla, bisphosphonate-related osteonecrosis of the jaw significantly affected the maxillary sinus. Its radiologic manifestations should be recognized by clinicians and especially by otolaryngologists.

Inferior alveolar neurosensory deficiency associated with placement of dental implants.

BACKGROUND: This study reports and analyzes a large series of patients with neurosensory deficiency related to the placement of dental implants (DIs) and resulting in liability claims (LCs). METHODS: From 1998 to 2009, there were 92 LCs related to persistent altered sensation post DI placements in Israel. Patients' demographics, year and source of LCs, interval between the procedure that resulted in a neurosensory deficiency and the LC, qualifications of the surgeon, preoperative imaging modality, DI length, available alveolar bone for DI placement, placement site, timing of DI placement (immediately after tooth extraction or after socket healing), and treatment after the diagnosis of neurosensory deficiency were recorded and analyzed. RESULTS: There were 21 cases during the first 5 years of the study (mean 4.2/year) and 63 cases (mean 12.6/year) over the following 5 years. Thirty LCs were issued during the second postoperative year and 15 LCs after >5 years. Most LCs (76%) involved procedures that were planned and performed according to radiographs and 24% after computed tomography. Sixty-five percent of the LCs were performed by general dental practitioners and 35% by specialists. More than one DI was performed during the surgical procedure that resulted in a neurosensory deficiency in 73 LCs (79.3%), and the DI was >10 mm in 55 (59.8%) cases. CONCLUSIONS: LCs for DIs that result in a neurosensory deficiency pose a legal risk to the practitioner long after the injury has occurred.

Serologic bone markers for predicting development of osteonecrosis of the jaw in patients receiving bisphosphonates.

PURPOSE: Osteonecrosis of the jaw is a well-documented side effect of bisphosphonate (BP) use. Attempts have recently been made to predict the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ). We prospectively investigated the predictive value of serum levels of C-terminal telopeptide of collagen I (CTX), bone-specific alkaline phosphatase, and parathyroid hormone for the development of BRONJ. PATIENTS AND METHODS: Data on the demographics, comorbidities, and BP treatment were collected from 78 patients scheduled for dentoalveolar surgery. Of the 78 patients, 51 had been treated with oral BPs and 27 had been treated with frequent intravenous infusions of BPs. Blood samples for CTX, bone-specific alkaline phosphatase, and parathyroid hormone measurements were taken preoperatively. Surgery was performed conservatively, and antibiotic medications were prescribed for 7 days. RESULTS: Of the 78 patients, 4 patients taking oral BPs (7.8%) and 14 receiving intravenous BPs (51.8%) developed BRONJ. A CTX level less than 150 pg/mL was significantly associated with BRONJ development, with an increased odds ratio of 5.268 (P = .004). The bone-specific alkaline phosphatase levels were significantly lower in patients taking oral BPs who developed BRONJ. The parathyroid hormone levels were similar in patients who did and did not develop BRONJ. CONCLUSION: The incidence of BRONJ after oral surgery involving bone is greater among patients receiving frequent, intravenous infusions of BPs than among patients taking oral BPs. Although the measurement of serum levels of CTX is not a definitive predictor of the development of BRONJ, it might have an important role in the risk assessment before oral surgery.

Bisphosphonate-related osteonecrosis of the jaw associated with dental implants.

PURPOSE: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a well-documented devastating side effect of long-term bisphosphonate (BP) use. There is scarce information in the literature on BRONJ associated with dental implants (DIs). The purpose of this study was to present a large series of cases of this association. PATIENTS AND METHODS: The files of all patients with BRONJ associated with DIs who were treated in the department of oral and maxillofacial surgery from 2003 to 2009 were reviewed. Data on demographics, medical background, type, and duration of BP treatment before the development of BRONJ, mode of therapy, and therapeutic outcome were retrieved. RESULTS: Of the 27 patients enrolled into the study, 11 (41%) developed BRONJ while taking oral BPs and 16 (59%) developed BRONJ associated with intravenous BPs. BRONJ developed after mean periods of 68 months (median, 60), 16.4 months (median, 13), and 50.2 months (median, 35) in patients on alendronate, zoledronic acid, and pamidronate, respectively. Only 6 patients developed BRONJ during the first 6 months after DI placement. When BP treatment had been started before DI placement, there was a mean duration of 16.2 months (median, 11) until the appearance of BRONJ development. Long-term antibiotics and only essential surgical procedures comprised the treatment of choice, and the response rate was considerably better for patients taking the oral type of BPs. There was no significant association between BRONJ and diabetes, steroid intake, or smoking habits. CONCLUSION: Patients undergoing BP treatment and who receive DIs require a prolonged follow-up period to detect any development of BRONJ associated with DIs.

Bisphosphonate-related osteonecrosis of the jaws: a single-center study of 101 patients.

PURPOSE: Osteonecrosis of the jaw (ONJ) is a devastating side effect of long-term bisphosphonate (BP) use. We present the largest case series from a single department. MATERIALS AND METHODS: This case series included 101 ONJ patients. Data on demographics, medical background, type and duration of BP use, possible triggering events, mode of therapy, and outcome were recorded. RESULTS: ONJ was associated with intravenous BPs in 85 patients and with oral BPs in 16 patients. It was diagnosed after 48, 27, and 67 months of pamidronate, zoledronic acid, and alendronate use, respectively. Long-term antibiotics and minimal surgical procedures resulted in complete or partial healing in 18% and 52% of the patients, respectively; 30% had no response. There was no association between ONJ and diabetes, steroid and antiangiogenic treatment, or underlying periodontal disease. Diagnostic biopsies aggravated lesions without being informative about pathogenesis. A conservative regimen is our treatment of choice. CONCLUSION: Solutions for decreasing morbidity and poor outcome of ONJ remain elusive.