Ioannis Melakopoulos

Osteonecrosis of the Jaw in Cancer After Treatment With Bisphosphonates: Incidence and Risk Factors

PURPOSE Osteonecrosis of the jaw (ONJ) has been associated recently with the use of pamidronate and zoledronic acid. We studied the incidence, characteristics, and risk factors for the development of ONJ among patients treated with bisphosphonates for bone metastases. PATIENTS AND METHODS ONJ was assessed prospectively since July 2003. The first bisphosphonate treatment among patients with ONJ was administered in 1997. Two hundred fifty-two patients who received bisphosphonates since January 1997 were included in this analysis. RESULTS Seventeen patients (6.7%) developed ONJ: 11 of 111 (9.9%) with multiple myeloma, two of 70 (2.9%) with breast cancer, three of 46 (6.5%) with prostate cancer, and one of 25 (4%) with other neoplasms (P = .289). The median number of treatment cycles and time of exposure to bisphosphonates were 35 infusions and 39.3 months for patients with ONJ compared with 15 infusions (P < .001) and 19 months (P = .001), respectively, for patients with no ONJ. The incidence of ONJ increased with time to exposure from 1.5% among patients treated for 4 to 12 months to 7.7% for treatment of 37 to 48 months. The cumulative hazard was significantly higher with zoledronic acid compared with pamidronate alone or pamidronate and zoledronic acid sequentially (P < .001). All but two patients with ONJ had a history of dental procedures within the last year or use of dentures. CONCLUSION The use of bisphosphonates seems to be associated with the development of ONJ. Length of exposure seems to be the most important risk factor for this complication. The type of bisphosphonate may play a role and previous dental procedures may be a precipitating factor.

Reduction of osteonecrosis of the jaw (ONJ) after implementation of preventive measures in patients with multiple myeloma treated with zoledronic acid

BACKGROUND Osteonecrosis of the jaw (ONJ) is a well-described complication of bisphosphonates use in patients with multiple myeloma (MM). We investigated whether the occurrence of ONJ decreased after the implementation of preventive measures in 128 patients with MM who received zoledronic acid. PATIENTS AND METHODS Patients with MM who received zoledronic acid were included in this analysis. Patients with a previous use of other bisphosphonates were excluded; patients were stratified into group A (n=38) and group B (n=90) if treatment was started before or after the implementation of preventive measures. RESULTS One hundred and twenty-eight patients were included in this analysis. Sixteen patients (12.5%) developed ONJ--group A: 8 (26.3%), group B: 2 (6.7%) (P=0.002). The incidence rate (IR) was 0.671/100 person-months for group A and 0.230/100 person-months for group B [IR ratio 2.92, P=0.029, 95% confidence interval 1.06-8.03]. No patient in group B developed stage III ONJ. CONCLUSION In conclusion, the risk of developing ONJ after treatment of zoledronic acid is reduced (but not deleted) by the implementation of preventive measures.

Conservative Treatment of Bisphosphonate-Related Osteonecrosis of the Jaw in Multiple Myeloma Patients

The use of intravenous bisphosphonates (pamidronate or zoledronic acid) is the cornerstone for the management of multiple myeloma-(MM-) related bone disease. However, osteonecrosis of the jaw (ONJ) is a rare, but sometimes difficult to manage, adverse effect of bisphosphonates therapy. A retrospective review of all MM patients who were treated with bisphosphonates in our department, from 2003 to 2013, and developed ONJ was performed. According to inclusion criteria, 38 patients were studied. All these patients were treated as conservatively as possible according to the American Association of Oral and Maxillofacial Surgeons criteria. Patients were managed with observation, oral antibacterial mouth rinse with chlorhexidine, oral antibiotics, pain control with analgesics, nonsurgical sequestrectomy with or without simultaneous administration of antibiotics, or major surgery with or without antibiotics. Healing of the lesions was achieved in 23 (60%) patients who were treated with conservative measures; the median time to healing was 12 months (95% CI: 4–21). The number of bisphosphonates infusions influenced the time to healing: the median time to healing for patients who received <16 infusions was 7 months and for those with >16 infusions was it 14 months (P = 0.017). We conclude that a primarily nonsurgical approach appears to be a successful management strategy for bisphosphonate-related ONJ.

Metastatic breast carcinoma in the mandible presenting as a periodontal abscess: a case report

IntroductionTumors can metastasize to the oral cavity and affect the jaws, soft tissue and salivary glands. Oral cavity metastases are considered rare and represent approximately 1% of all oral malignancies. Because of their rarity and atypical clinical and radiographic appearance, metastatic lesions are considered a diagnostic challenge. The purpose of this report is to present a rare case of a metastatic breast carcinoma mimicking a periodontal abscess in the mandible.Case presentationA 55-year-old Caucasian woman was referred to our clinic for evaluation of bisphosphonate-induced jaw osteonecrosis. She had undergone modified radical mastectomy with axillary lymph node dissection for invasive ductal carcinoma of the left breast. Her clinical examination showed diffuse swelling and a periodontal pocket of 6 mm exhibiting suppuration in the posterior right mandible. Moreover, paresthesia of the lower right lip and chin was noted. There were no significant radiographic findings other than alveolar bone loss due to her periodontal disease. Although the lesion resembled a periodontal abscess, metastatic carcinoma of the breast was suspected on the basis of the patients medical history. The area was biopsied, and histological analysis confirmed the final diagnosis of metastatic breast carcinoma.ConclusionThe general dentist or dental specialist should maintain a high level of suspicion while evaluating patients with a history of cancer. Paresthesias of the lower lip and the chin should be considered ominous signs of metastatic disease. This case highlights the importance of the value of a detailed medical history and thorough clinical examination for the early detection of metastatic tumors in the oral cavity.

Genetic factors related with early onset of osteonecrosis of the jaw in patients with multiple myeloma under zoledronic acid therapy

Abstract Specific genetic polymorphisms (SNPs) have been correlated with the development of bisphosphonate-related osteonecrosis of the jaw (BRONJ) in small series. We screened 140 myeloma patients (36 patients with and 104 without BRONJ) for the presence of previously identified SNPs in PPARG and CYP2C8 genes. All the patients received exclusively zolendronic acid (ZA) therapy and were followed prospectively for BRONJ. SNPs in both genes were associated with a higher risk of development of early BRONJ, occurring within less than 2 years of ZA therapy (59% vs. 16%, p = .022 for PPARG and 29% vs. 7%, p = .07 for CYP2C8) and a shorter time to develop BRONJ (59% versus 12%, p = .011 for PPARG and 29% versus 0% at 2 years, p = .037 for CYP2C8), independently of indices of poor oral hygiene. Thus, although preliminary, our data indicate that the presence of SNPs in PPARG and CYP2C8 genes may be associated with increased risk of early BRONJ.

Reactive Fibrous Hyperplasia of Peri-implant Mucosa

I mplant-related reactive lesions of the oral mucosa are uncommon, compared with tooth-related ones. Although their pathogenesis is undetermined, local irritating factors such as dental plaque, tartar, and trauma are thought to be involved. Most implant-related reactive lesions reported up to date are pyogenic granulomas (PG) and peripheral giant cell granulomas (PGCG), but 1 case each of hemangioma and parulis-like soft tissue tumor were also reported. The aim of this paper is to describe a case of a fibrous hyperplasia that developed around 2 healing caps and discuss its possible pathogenesis, differential diagnosis, and treatment. To the best of our knowledge, there is no report of implantrelated fibrous hyperplasia in the literature.

A Parulis-Like Soft Tissue Tumor in Relation With a Dental Implant: Case Report

R eactive lesions of peri-implant mucosa seem to be rare, judging from the number of published reports, and most of them represent pyogenic granulomas (PGs) or peripheral giant cell granulomas (PGCGs). Factors such as dental plaque accumulation due to inadequate oral hygiene, traumatic factors, and anatomic drawbacks are common etiologic factors for those lesions. We report a case of tumor on the covering mucosa of a dental implant consistent with parulis and discuss its possible pathogenesis, differential diagnosis, and management.

Solitary Peripheral Osteoma of the Hard Palate : Case report and literature review

Osteomas are benign slow-growing osteogenic lesions of unknown aetiology which can be central, peripheral or extraskeletal. Peripheral osteomas of the maxilla are very uncommon. We report a 72-year-old female patient who presented to the Department of Oral & Maxillofacial Surgery, Dental School of Athens, Athens, Greece, in 2015 with swelling of the palate following a tooth extraction. Clinical and radiographical features were indicative of a solitary peripheral osteoma of the hard palate. An excisional biopsy and histological examination of the lesion confirmed the diagnosis. No complications occurred during the postoperative period and there was no evidence of recurrence at a one-year follow-up.