Dental implications of osteogenesis imperfecta: treatment with IV bisphosphonate: report of a case

Osteogenesis imperfect (OI) is a group of genetically diverse connective tissue disorders. Bisphosphonates therapy to manage bone fragility, a now common medical therapy for OI, can increase the risk of bisphosphonate-associated osteonecrosis of the jaws. In this report, a 6 ? year child, who was receiving bisphosphonate therapy for OI, underwent full mouth dental rehabilitation in the operating room while under general anesthesia. The child had numerous teeth restored and multiple primary molar extractions. The patient, who received prophylactic antibiotics intraoperatively, demonstrated no clinical signs of bisphosphonate-associated osteonecrosis when seen at follow-up. Although bisphosphonate osteonecrosis is a possible sequel in children who receive multiple extractions, no clinical signs were manifested in our patient, who required multiple primary tooth extractions along with restorative treatment under general anesthesia. While no dental guidelines have been developed to manage OI children having been treated with bisphosphonates, consent for extractions should include the risk of bone necrosis and careful post-operative observation to monitor wound healing.     

Endodontic implications of bisphosphonate-associated osteonecrosis of the jaws: a report of three cases

Bisphosphonates are commonly used in medicine to maintain bone density in patients with certain nonneoplastic diseases or cancers. A serious adverse effect of bisphosphonates that has substantial dental significance is osteonecrosis that appears to uniquely affect the mandible and maxilla without occurring in other bones of the skeleton. Patients with bisphosphonate associated osteonecrosis of the jaws may present with pain and exposed necrotic bone. This has substantial clinical implications because surgical procedures (including extractions or endodontic surgical procedures) are contraindicated in the jaws of these patients and the presenting pain may mimic pain of odontogenic origin. This report describes three patients with bisphosphonate associated osteonecrosis and emphasizes the endodontic implications of managing these patients.     

Identification and treatment of bisphosphonate-associated actinomycotic osteonecrosis of the jaws

Osteonecrosis of the jaws (ONJ) is a condition characterized by necrotic exposed bone in the jaws of patients receiving intravenous or oral bisphosphonate therapy. A review of the medical and dental literature reveals that the pathoetiology of ONJ remains unknown and there is no established link that bisphosphonates are the primary cause of this bone pathology. However, there is clinical evidence that Actinomyces may play a critical role in the pathogenesis of bisphosphonate-associated ONJ. Identification and a prolonged course of oral antimicrobial therapy may lead to complete resolution of this actinomycotic osteonecrosis.     

Osteonecrosis of the maxilla in a patient with a history of bisphosphonate therapy

Bisphosphonates, which inhibit osteoclasts, alleviate many of the devastating consequences of metastatic bone disease. However, bisphosphonates may play a role in the development of osteonecrosis of the jaws. We report our experience in the management of a patient with a history of bisphosphonate therapy who presented with osteonecrosis of the jaws following dental extraction to make others, particularly the broader dental community, aware of this potential complication. We also review the pharmacologic properties of bisphosphonates and their possible role in the pathophysiology of osteonecrosis. Until more is known about the role of bisphosphonates in the development of osteonecrosis of the jaws, we recommend that measures be taken to prevent osteonecrosis in those at risk, including, when feasible, a dental consultation before initiating bisphosphonate therapy.     

Case series of 589 tooth extractions in patients under bisphosphonates therapy. Proposal of a clinical protocol supported by Nd: YAG low-level laser therapy

Objective: Trauma during dental surgery is a predisposing factor for bisphosphonates (BP)-related osteonecrosis of the jaws (BRONJ). However, about 40% of cases of BRONJ are not related to dental invasive procedures, being probably associated to endodontic or periodontal infections. Extraction of non-treatable teeth is considered a reliable choice, to improve symptoms and to reduce the risk of BRONJ. Here we report our experience of tooth extractions in patients under oral or intravenous BP therapy. Study Design: Two-hundred and seventeen patients (38 males, 179 females; mean age 68.72 ± 11.26 years, range 30 to 83 years) under BP therapy received 589 tooth extractions at the Unit of Oral Medicine, Pathology and Laser-assisted Surgery of the University of Parma, Italy, between June 2006 and December 2010. Ninety five patients were under BP therapy for oncological disease (multiple myeloma (MM): 23; bone metastases (BM): 72) and 122 patients for non oncological diseases: 119 osteoporosis (OP), 2 rheumatoid arthritis (RA) and 1 Paget’s disease (PD). The mean duration of BP was of 35 months. Antibiotic treatment was administered three days before and 2 weeks after tooth extractions. Patients were additionally treated with low level laser therapy (LLLT) through Nd:YAG laser (1064 nm – power 1.25 W; frequency 15 Hz; fibre diameter: 320 ?m), 5 application of 1 minute each. Patients were evaluated 3 days and once a week for 2 months after the extractions and every time they received LLLT. Mean follow-up was 15 months (ranging from 4 to 31 months). Results: In a total of 589 extractions (285 mandibular, 304 maxillary) performed, a minimal bone exposure was observed in 5 cases, treated with Er:YAG laser vaporization and than healed. Conclusions: Our experience supports the hypothesis that the association of antibiotic treatment and LLLT can be effective in preventing ONJ after tooth extractions in patients under BPT. Key words:Nd:YAG laser, low level laser therapy, tooth extractions, bisphosphonates, jaws osteonecrosis.     

A Rational Approach to Dental Management of Patients on Bisphosphonates

There has been a lot of focus on osteonecrosis of the jaws associated with the usage of bisphosphonates both in dental and medical literature in recent years. However, the exact pathogenesis of bisphosphonate-related osteonecrosis of the jaws remains unclear. Against the background of emerging evidence of an evolving condition, it is not surprising that there is a lack of robust evidence-based recommendations on dental treatment of patients on bisphosphonates. This paper seeks to provide a rational approach to the dental management of patients on bisphosphonates based on current literature.     

Dental endosseous implants in patients on bisphosphonate therapy

About a decade ago, bisphosphonates were introduced as an alternative to hormone replacement therapies for osteoporosis and to treat osteolytic tumors. More recently, it has became evident that the bisphosphonates used intravenously such as pamidronate (Aredia; Novartis Pharmaceuticals Corp., East Hanover, NJ) and zoledronate (Zometa; Novartis Pharmaceuticals Corp.), in particular, could lead to painful refractory bone exposure (sometimes termed osteochemonecrosis or osteonecrosis) in the jaws. Patients with osteonecrosis of the jaws usually present after dental treatment with oral signs and symptoms of painful, exposed, and necrotic bone, primarily of the mandible and, to a lesser extent, the maxilla. Although the precipitating event that produces this complication may be spontaneous, there is little doubt that oral surgery and endosseous implants can be responsible. Exodontia is the main precipitant. The present postulated mechanism of osteonecrosis of the jaws is that prolonged use of bisphosphonates may suppress bone turnover to the point that the repair function of physiologic microdamage of bone is abolished. Such a mechanism could presumably interfere with the healing process after implant placement. Although, to our knowledge, there is no evidence that bone disorders are a contraindication to implants, there is evidence that bisphosphonate therapy is a contraindication. Where possible, extractions should be avoided, and it is best to avoid all elective oral surgery in patients on bisphosphonates, including endosseous implant placement, or the treatment should be performed well before commencing bisphosphonates. If surgery is essential on a patient taking bisphosphonate therapy, the patient must be counseled about the risks.     

Bisphosphonate osteonecrosis of the jaws; an increasing problem for the dental practitioner

Osteonecrosis of the jaws is an increasingly recognised complication of bisphosphonate therapy. Although this has generated a large amount of literature in the last few years, it is difficult to know how the complications associated with bisphosphonates are impacting on general dental practitioners (GDPs). Bisphosphonates are commonly prescribed in the management of osteoporosis, hypercalcemia and multiple myeloma. The risk of osteonecrosis in patients taking bisphosphonates is low but difficult to quantify. The risk associated with oral therapy is in the order of 0.01% although with parenteral therapy it may be as high as 10%. Associated factors in the development of osteonecrosis include poor dental health, odontogenic infection and invasive dental treatment. Guidelines on managing patients who are currently taking or have previously taken bisphosphonates have not yet been published in the UK. The management of patients relies on existing experience in managing patients with apparently similar conditions such as osteoradionecrosis. Most GDPs do not routinely make specific efforts to identify patients who have taken bisphosphonates, and as patients may be poor at providing such information voluntarily, it is likely that many patients are currently not identified when they attend general dental practice. The dental management of patients with a history of bisphosphonate treatment is based around prevention and minimally traumatic treatment. Failure to recognise these patients and manage them appropriately could contribute to the development of osteonecrosis, which can be very difficult to manage.     

Osteonecrosis of the jaws in periodontal patients with a history of bisphosphonates treatment

BACKGROUND/AIM: Osteonecrosis of the jaws is being increasingly reported in patients with bone metastasis from a variety of solid tumours and disseminated multiple myeloma receiving intra-venous bisphosphonates. The signs and symptoms that may occur before the appearance of clinical evident osteonecrosis include changes in the health of periodontal tissues, non-healing mucosal ulcers, loose teeth and unexplained soft-tissue infection. A series of nine periodontally involving patients showing osteonecrosis of the jaws that appeared following the intra-venous use of bisphosphonates is reported. MATERIAL AND METHODS: Nine consecutive patients with osteonecrosis of the jaws were prospectically studied. Patients' past medical histories and the drugs that they had received for their malignant disease were systematically documented. Clinical, histopathological and radiographic features and proposal for treatment modalities of osteonecrosis are also reported. RESULTS: Of the nine patients (six women and three men) observed, all had osteonecrosis in the mandible; two had maxillary involvement as well. All nine patients had a history of extraction of periodontally hopeless teeth preceding the onset of osteonecrosis. In two patients, the lesions also appeared in edentulous areas spontaneously. All the patients had received intra-venous bisphosphonates as treatment for their disseminated haematological neoplasms or metastatic bone disease. The duration of bisphosphonate therapy at presentation ranged from 10 to 70 months (median: 33 months). CONCLUSIONS: Jaw osteonecrosis appears to be associated with the intra-venous use of bisphosphonates. Dental professionals should be aware of this potentially serious complication in periodontal patients receiving long-term treatment with bisphosphonates.     

Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy: strategies for prevention and early recognition

BACKGROUND: Bisphosphonates, inhibitors of osteoclasts, have been shown to alleviate many of the devastating consequences associated with metastatic bone disease. However, recent reports have shown that bisphosphonates may cause osteonecrosis of the jaws. Since the publication of these initial reports, the authors have treated several patients with osteonecrosis of the jaws who had a history of receiving bisphosphonate therapy. METHODS: The authors reviewed the medical records of patients who visited their clinic between September 2003 and December 2004 and who had osteonecrosis of the jaws and a history of having received bisphosphonate therapy but no irradiation to the head and neck. RESULTS: Eleven patients (four female and seven male) with a mean age of 69 years were included in this report. They had received bisphosphonate therapy for a mean duration of 34 months. Radiographic data showed loss of bone density at sites of osteonecrosis, and histologic examination demonstrated necrosis of bone without evidence of metastases. CONCLUSIONS AND CLINICAL IMPLICATIONS: Further research is required for better understanding of the role of bisphosphonates in the development of osteonecrosis of the jaws. Until more is known, the authors recommend that measures be taken to prevent osteonecrosis those at risk, including identifying patients with a history of having received bisphosphonate therapy before they undergo dental surgery. To help identify such patients, the authors propose the use of a screening questionnaire. When feasible, physicians should consult with their patients' general dentists or oral surgeons before patients begin bisphosphonate therapy.     

Osteonecrosis of jaws after bisphosphonates: an internet resource on the web for dentist

The purpose of this paper is to enumerate the Internet resources on the web available to the general dentist on bisphosphonate-associated osteonecrosis of jaws. The general dental practitioners have a key role to play in identifying patients at risk of developing bisphosphonate-associated osteonecrosis of the jaws. The problem is likely to become commonplace as the number of patients on bisphosphonate increases. The management of bisphosphonates osteonecrosis of the jaws presents a challenge to dentists as there is no effective treatment for this condition. The Internet may be a good vehicle where information can be shared and advisory disseminated.     

Osteonekrose der Kiefer unter Bisphosphonat-Langzeittherapie

For several decades bisphosphonates have been used to reduce skeletal related events in patients with both osteoporosis or bone metastases. Under long term application, besides the known therapy side effects, a new clinical picture has been described within the last few years. This is osteonecrosis of the jaws, which is characterized by its difficulty in treatment. Besides exposed jaw bone, the start of the disease usually lacks any symptoms. The typical clinical symptoms then are foetor ex ore, swelling, exsudation, loosening of teeth, pain or paresthesia. Later oro-antral/nasal or oro-cutaneous fistula can develop. The X-ray shows persisting tooth sockets after extractions and later cloudy radio-lucency, sequestra or fractures. The patient exposed to bisphosphonate can be grouped according to the risk for osteonecrosis: high risk patients with intravenous bisphosphonate therapy and additional chemo-, radiation or corticoid therapy – predominantly patients with a malignant underlying disease and bone metastases low risk patients with an oral bisphosphonate therapy without additional chemo-, radiation or corticoid therapy – preferably patients with non-corticoid-induced osteoporosis Before starting a bisphosphonate therapy possible causes of infection should be treated and risk of injuries to the mucosa should be reduced according to the individual risk profile. This is supplemented by information of the patient about the risk of necrosis and the possibilities for prevention. Regular dental recall under bisphophonate therapy is emphasised for early recognition of possible problems. Prophylaxis is recommended for the prevention of periodontal infection combined with a follow up of removable denture for possible ulcera. Generally, conservative treatment measures are preferred to surgical ones. Inevitable operations are carried out non- traumatically using broad spectrum antibiotic prophylaxis until the day of suture removal (not before day 10). Long term follow up examinations are recommended. Patients with dental implants inserted before a bisphophonate therapy should be subject to intensive recall examinations. For patients undergoing or following a bisphosphonate therapy the indication for dental implants should be as strict as for patients following head and neck radiation therapy. In the present for patients with osteonecrosis, even after healing, dental implants are regarded as contra-indication. Therapy of the necrosis often requires general anaesthesia, hospitalisation, naso-gastral feeding tube and intravenous, systemic antiinfective treatment. The necrosis is removed completely and a tension free wound closure with vascularised tissue is intended. A literature review shows the metabolic effect of biphosphonates, the known pathogenesis of the bisphosphonate-induced jaw necrosis. It is essential to develop interdisciplinary communication, aiming at a joint care for this group of concerned patients and involving not only those medical disciplines, which order and use bisphosphonates, but especially dentists and maxillofacial surgeons.     

Bisphosphonate associated osteonecrosis of the jaws--the role of the dentist in prevention and early diagnosis

During the past few years numerous cases of osteonecrosis of the jaws in patients receiving bisphosphonate therapy were published in the literature. In most cases, the osteonecrosis was diagnosed following dento-alveolar surgery, especially following extraction of teeth. To date, no efficient therapy is available and most efforts are geared towards prevention. The propose of the present review is to inform the Israeli dental community about osteonecrosis of the jaws in patients receiving bisphosphonate therapy and to suggest strategies for prevention.     

Bisphosphonates and their clinical implications in endodontic therapy

This review gives an overview of the factors that may play a role in the development of osteonecrosis of the jaw in patients treated with bisphosphonates (BPs) and undergoing nonsurgical endodontic treatment as well as some recommendations for its prevention. BPs are a widely prescribed group of drugs for diverse bone diseases. The occasional but devastating adverse effect of these drugs has been described as bisphosphonate‐related osteonecrosis of the jaw (BRONJ). As this condition is debilitating and difficult to treat, all efforts should be made to prevent its occurence in patients at risk. The main triggering event is considered to be dental extraction. Even though nonsurgical endodontic treatment appears to be a relatively safe procedure, care remains essential. After an overview of this class of drugs, the clinical presentation, epidemiology and pathogenesis of BRONJ, as well as the possible risk factors associated with its development after nonsurgical endodontic treatment will be described. Finally, several strategies will be proposed for the prevention of BRONJ during nonsurgical endodontic treatment.     

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.     

New therapeutic protocol in the treatment of avascular necrosis of the jaws

Osteonecrosis of the jaws is being increasingly reported in patients with bone metastasis from a variety of solid tumors and disseminated multiple myeloma receiving intravenous bisphosphonates. Agreement exists that these drugs can initiate vascular endothelial cell damage and accelerate disturbances in the microcirculation of the jaws, possibly resulting in thrombosis of nutrient-end arteries. The role of bisphosphonates in cancer patients with previously treated jaws has yet to be elucidated. The signs and symptoms that may occur before the appearance of evident osteonecrosis include changes in the health of periodontal tissues, nonhealing mucosal ulcers, loose teeth and unexplained soft tissue infection. A series of 30 periodontally involved patients showing osteonecrosis of the jaws that appeared following the intravenous use of bisphosphonates is reported.Clinical management of the avascular necrosis of the jaws in patients treated with bisphosphonates presents several problems. An analysis of the international medical literature shows that surgical treatment of the necrotic jaws in patients treated with bisphosphonates has proven to be ineffective in stopping the pathological process. The use of hyperbaric oxygen and antibiotics are not effective, either. The authors have developed a new protocol for the management of these lesions. Compared with other therapeutic choices, this protocol has introduced the use of ozone therapy as therapeutic support.     

Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper

BACKGROUND: This position paper addresses the prevention of bisphosphonate-associated osteonecrosis (BON) and the management of care of patients with cancer and/or osteoporosis who are receiving bisphosphonates and who have BON or are at risk of developing it. METHODS: The authors reviewed the literature available on this newly described oral complication. Information of interest included bisphosphonates, the medications associated with this oral complication; the patient population at risk of developing BON and the diseases being treated with this class of medications; the clinical presentation of the oral lesions; guidelines for managing the care of patients who develop BON; the prevention of this complication based on current knowledge; and recommendations for routine dental treatment of patients receiving bisphosphonates. RESULTS: There is strong evidence that bisphosphonate therapy is the common link in patients with BON. The pathobiological mechanism leading to BON may have to do with the inhibition of bone remodeling and decreased intraosseous blood flow caused by bisphosphonates. People at risk include patients with multiple myeloma and patients with cancer metastatic to bone who are receiving intravenous bisphosphonates, as well as patients taking bisphosphonates for osteoporosis. The risk of developing complications appears to increase with time of use of the medication. There are no guidelines based on evidence, and the clinical management of the oral complication is based on expert opinion. CONCLUSION: Prevention of BON is the best approach to management of this complication. Existing protocols to manage the care of patients who will receive radiation therapy or chemotherapy may be used until specific guidelines for BON are developed.     

Clinical aspects and management of bisphosphonates-associated osteonecrosis of the jaws

OBJECTIVE: An increasing incidence of osteonecrosis of the jaws (ONJ) in patients treated with intravenous bisphosphonates has been reported in the literature. The aim of this study was to evaluate the clinical aspects, diagnostic investigations, and management of ONJ associated with bisphosphonates in a series of 12 patients. METHOD: Our patients included 1 asymptomatic and 11 symptomatic subjects. For the symptomatic patients, the osteonecrosis was diagnosed through histological investigations of exposed bone that showed avascular and necrotic tissue with inflammatory infiltrate. The patients were complaining of swelling, fever, and bone exposure involving the jaws. The asymptomatic patient presented as an occasional finding during a routine dental examination and the necrosis was confirmed on the basis of imaging investigations. Radiographic, scintigraphic, and microbiological examinations were carried out for all patients. Treatment included antibiotics, minor surgical interventions, and hyperbaric oxygen therapy. RESULTS: The radiological investigations revealed osteolytic areas and the scintigraphy demonstrated increased bone metabolism. The microbiological analysis showed pathogenic micro-organisms in the majority of patients. Therapy was useful in obtaining short-term symptomatic relief. CONCLUSIONS: Histological, radiological, nuclear medicine, and microbiological investigations are important diagnostic tools for patients with bisphosphonates-associated osteonecrosis of the jaws. However, a long-term follow-up is necessary if we are to better understand the treatment outcome.     

Osteonecrosis of the jaws: a secondary effect of bisphosphonates

When treated with intravenous bisphosphonates to prevent bone resorption, 4-10% of the patients may develop osteonecrosis of the jaws a side effect. The osteonecrosis is usually preceded by an invasive dental procedure such as the removal of a tooth. Treatment of the osteonecrosis should be conservative using aseptic mouth rinses, oral antibiotics and small debridement. It seems advisable to have a dental check-up before starting using intravenous bisphosphonates, since a potential dental infections can be treated before the bone healing capacity is reduced by the bisphosphonates.