ARTÍCULO CLÍNICO

 

Bisphosphonate-associated osteonecrosis of the jaw

Osteonecrosis de los maxilares asociada al empleo de bifosfonatos

 

 

J.L. del Castillo Pardo de Vera¹, J.A. García de Marcos¹, S. Arroyo Rodríguez², M. Galdeano Arenas¹, J. Calderón Polanco³

1 Especialista en Cirugía Oral y Maxilofacial.
2 Especialista en Cirugía Oral y Maxilofacial. Jefe de Sección.
3 Especialista en Cirugía Oral y Maxilofacial. Jefe de Servicio. Doctor en Medicina y Cirugía.
Servicio de Cirugía Oral y Maxilofacial. Complejo Hospitalario Universitario de Albacete, España

Correspondence

 

 

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ABSTRACT

Bisphosphonates constitute a group of inhibitors of bone resorption that are used for treating many disor-ders such as osteoporosis, Paget´s disease, multiple myeloma, malignant hypercalcemia and bone metas-tases associated with breast and prostate cancer. The main pharmacological effect of bisphosphonates is the inhibition of bone resorption, mediated by a decreased function of osteoclasts without interfering in bone formation and mineralization.
These drugs are used worldwide, with clear and clinically proven benefits. Several publications within the last three years consider osteonecrosis of the jaw to be associated with bisphosphonate therapy as a result of their extensive use.
It is important for patients to be informed of the risk of this complication, so that they have the oppor-tunity to assess the need for dental treatment before starting therapy. Preventive measures must be taken before, during, and after treatment with bisphosphonates. Surgical treatment should be reserved for those patients who are symptomatic. Further investigation is needed to completely elucidate this complication.

Key words: Bisphosphonates (BP); Osteonecrosis of the jaw; Zoledronic acid.

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RESUMEN

Los bifosfonatos constituyen un grupo de fármacos inhibidores de la resorción ósea, utilizados en el tratamiento de numerosas patologías como la osteoporosis, la enfermedad de Paget, el mieloma múltiple, la hipercalcemia maligna y las metástasis óseas asociadas al cáncer de mama o de próstata. El principal efecto farmacológico de los bifosfonatos es la inhibición de la resorción ósea, mediante una disminución de la actividad de los osteoclastos, sin intervenir en la formación y mineralización del hueso. Son fármacos utilizados a nivel mundial con unos claros beneficios contrastados clínicamente. Numerosas publicaciones durante los últimos tres años, y debido a su utilización masiva, consideran que la osteonecrosis de los maxilares está asociada al tratamiento con bifosfonatos.
Es importante que los pacientes sean informados del riesgo de presentarse esta complicación, para tener la oportunidad de someterse a procedimientos dentales previos al inicio del tratamiento. Las medidas preventivas deben realizarse antes, durante y después del tratamiento con bifosfonatos. El tratamiento quirúrgico debe reservarse para aquellos pacientes que presenten síntomas. Son necesarias nuevas investigaciones que clarifiquen esta complicación.

Palabras clave: Bifosfonatos (BF); Osteonecrosis; Ácido zoledrónico.

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Introduction

BPs constitute a group of drugs that inhibit the resorption of bone and their therapeutic relevance is con-tinually increasing. They have been used for reducing bone pain, malignant hypercalcemia and skeletal complications in patients with multiple myeloma or Paget´s disease, and for treating bone metastases as-sociated with breast or prostrate cancer.^1,2 The appearance of BPs has marked a before and after in the treatment of bone metastases from cancer.³ Most of the osteonecrosis cases described have arisen after patients have undergone some type of dental procedure, especially extractions. It was at the beginning of 2006 that osteonecrosis cases started to appear, which were largely spontaneous, after oral BP treatment for osteoporosis.¹

The structure of the BP nucleus is made up of two phosphate groups joined through a single carbon atom (P-CP). The action mechanism, its biological potency and its clinical efficiency depend on the presence or absence of a nitrogen molecule in its bioactive structure. Those that contain nitrogen in their molecule are stronger, and these include alendronate, zoledronic acid and pamidronate.

The action mechanism has not been completely clarified but there is no doubt that the maximum ac-cumulation arises in the bone matrix, and especially in the osteoclasts, as the first effects of BP are their reduction. It is here that they are deposited during the first 24-48 hours and, as they are not metabolized, bone concentration is kept high for prolonged periods.³

Therapeutic indications

BPs make up a group of drugs that are specific inhibitors of osteoclastic activity that are widely used around the world. They are clearly beneficial for treating numerous pathologies affecting the bones and they have been clinically contrasted. BPs are able to control bone pain, fracture risk and halt the devel-opment of new bone metastases, with the help of analgesics and other therapeutic measures such as radiotherapy. ³ The principal indications for bisphosphonates are:

• They reduce bone pain and skeletal complications in patients with multiple myeloma.⁴

• They are able to diminish hypercalcemia, fractures and alleviate pain in bone metastases associated with breast or prostrate cancer in conjunction with the usual antineoplastic therapy.

• In cases of malignant hypercalcemia, reducing hypercalcemia and pain should be attempted in addition to preventing the development of osteolytic lesions and fractures.

• Paget´s disease.

• In cases of corticoid and postmenopausal osteoporosis an attempt should be made to prevent the ap-pearance of bone pain and pathologic fractures.

Bisphosphonates (BP)

The strongest and most used bisphosphonates are third generation, and the most employed are pamidro-nate (Aredia^®) and zoledronic acid (Zometa^®).⁵ Both are only administered systemically.

1. Alendronate. Fosamax^® produces an increase in bone mineral density which can be observed just 6 months after starting treatment. Alendronate, administered at a dose of 70 mg once a week, is a bisphosphonate that is indicated only for treating postmenopausal osteoporosis. Randomized clinical trials are currently demonstrating that the incidence of osteoporotic fractures is reduced, including fractures of the hip.

2. Pamidronate. This is one of the stronger bisphosphonates and it is used to diminish the pain pro-duced by bone metastases associated with breast cancer and multiple myeloma. It is only adminis-tered intravenously using a 60-90 mg dose in perfusion over two hours. It has been demonstrated that it reduces and delays the appearance of skeletal complications such as bone pain, pathological fractures and hypercalcemia.^6,7

3. Zoledronic acid. Zometa^® is 850 times stronger than pamidronate. Its concentration level in bone is much higher than in plasma and this descends slowly after six months. It is administered by in-travenous perfusion and, due to the risk of significant deterioration in renal function, the single dose should not exceed 4 mg and the duration of the infusion should not be less than 15 minutes. It is not recommended for patients that have serious renal damage nor should it be used during pregnancy. ^6,7

Action mechanism

The action mechanism of BPs depends on the presence or absence of a nitrogen molecule in its bioac-tive structure. Non-nitrogen containing BPs produce direct cellular toxicity on being metabolized intracel-lularly into toxic substances. The nitrogen-containing components on the other hand produce, by means of the inhibition of the specific metabolic pathways of the osteoclasts, the inactivation of these cells and their early apoptosis.^5,8

On a tissular level, BPs inhibit bone resorption and they reduce bone turnover. The degree of distur-bance in bone formation is related with its effects on bone turnover, which is closely associated with bone formation. At a cellular level they act on osteoclasts and they can affect their function by means of re-cruitment inhibition, reduction of the mean life span, and by disrupting osteoclastic activity on bone surfaces. ^3,9 At a molecular level, it has been postulated that they could modulate the function of the osteo-clasts by interacting with a cell receptor or with an intracellular enzyme. At an experimental level it has been observed that they can inhibit angiogenesis and the suppression of endothelial cells, which results in avascular necrosis. In addition, a reduction has been observed in the vascular growth factor of patients treated with zoledronic acid.^10-12

Secondary effects of BPS

BPs are generally well-tolerated drugs if their administration is carried out correctly. The most common adverse reactions in orally taken treatment, relate to problems of a digestive type: gastric ulcers, gastroin-testinal disturbances or esophagitis. When the treatment is carried out intravenously there may be in addi-tion: pseudo-flue syndrome (fever, shivering, arthralgias, myalgias, bone pain), fatigue, phlebitis, anemia, weakness, edemas or dyspnea.⁶ A less frequent complication, but one that is potentially more serious, concerns renal function in the form of renal failure or acute tubular necrosis that can appear in cases in which the administration of BP is carried out quickly. Over recent years there has been an increase in published cases of bone necrosis located in the jaws of patients undergoing BP treatment for pathologies such as multiple myeloma, malignant hypercalcemia and bone metastases associated with breast or pros-trate cancer (Table 1).¹³

Osteonecrosis of the jaw

Osteonecrosis of the jaw in patients undergoing treatment with these drugs appears to be caused by the combination of a vascular supply deficit and a remodeling and bone regeneration deficit.² The jaw has a greater blood supply compared with other bone structures and faster bone remodeling due to daily me-chanical stimulation produced by the teeth in the jaw during mastication, two circumstances that increase the action of BPs on these bones.⁹ Another factor that favors osteonecrosis in this location is the fact that the arteries of the mandible are terminal arteries. These circumstances, together with the frequent pres-ence of dental pathologies, and odontological therapy that is physically aggressive for the bone, explain the greater risk of necrosis of the jaws, and the fact that they are only separated from the mouth by a fine layer of mucosa increases the risk of additional infection of necrotic bone.¹³

The area with osteoporosis can remain asymptomatic for weeks or months and it can appear as an area of the mandible or maxilla with bone exposure which progresses to sequestered bone (Fig. 1). When local defenses are weakened because of infection, trauma or surgery, microorganisms may invade the affected bone, with further infection of the area leading to necrosis. This is exacerbated by vascular com-promise that entails the inhibition of angiogenesis because of the BPs. The patients report considerable pain associated with localized swelling and purulent secretions. ⁹

In 2006 the American Dental Association (ADA) as well as the American Association of Oral and Maxillofacial Surgeons (AAOMS) published a series of recommendations for dental practice and a posi-tion paper on the management of osteonecrosis for patients undergoing bisphosphonate therapy.¹ A patient can be included in this group if the following three premises are met:

• Current or previous treatment with a BP.
• Exposed bone in the maxillofacial region that has persisted for more than eight weeks.
• No history of radiation therapy to the jaw.

It has been estimated that the incidence rate of osteonecrosis in patients taking intravenous BPs varies between 0.8 and 12%. In the case of oral therapy, the pharmaceutical company Merck published that the possible cases of patients taking Alendronate (the most prescribed bisphosphonate) was approximately 170 cases on a worldwide level, most of these in a spontaneous fashion; the incidence rate was calculated as around 0.7% of every 100.000 people per year of exposure to the drug.¹

Risk factors for developing osteonecrosis

A. Factors related with the drug

• BP strength: zoledronic acid (Zometa^®) is currently one of the most used systemic BPs and it is 850 times stronger than pamidronate, which is the strongest of those taken orally.
• Duration: very prolonged treatment appears to be associated with an increase in the risk of osteone-crosis.^20,21

B. Local factors

• Oral surgery: extractions, periapical surgery, periodontal surgery and the placement of dental implants.^1,2
• Anatomic factors: palatal and/or lingual torus. The necrosis tends to appear most commonly in the mandible rather than the maxilla (2:1) especially in bone areas that are more prominent.
• Oral pathology: trauma, inflammatory or infectious conditions affecting the teeth and/or mouth.

C. Demographic and systemic factors

• Age: with multiple myeloma cases taking BP the risk increases by 9% each decade.
• Race: more com mon in Caucasians.
• Type of oncological process: greater risk in cases of multiple myeloma followed by breast cancer.
• Osteopenia/osteoporosis associated with oncological processes.
• Systemic factors: corticoid therapy, diabetes, tobacco, alcohol, bad oral hygiene, periodontal disease, radiotherapy to the head and neck, coagulation therapy and concomitant chemotherapy.

 

Material and methods

Twelve cases are presented of patients with osteonecrosis of the jaw who were undergoing BP treat-ment for various pathologies. They were treated by the department of Oral and Maxillofacial Surgery of the University Hospital of Albacete between March and October 2006. All these patients were referred by the department of Medical Oncology and Internal Medicine for an evaluation of their jaw lesions. The mean age of the patients was 65, and the age range was between 49 and 77. There were 4 males and 8 females who were undergoing treatment with different BPs (alendronate, pamidronate and zoledronic acid) for the following pathologies: 4 patients had metastases from breast cancer, 3 had metastases from prostrate cancer, 4 had multiple myeloma and 1 was receiving treatment for osteoporosis.

In all cases the symptomatology consisted in pain and inflammation together with bone exposure; 9 patients had suppuration and two had active cutaneous fistulas. In 58.3% this affected the mandible ex-clusively, 25% the maxilla and in 16.6% both. With regard to causative factors, 66.6% of cases had pre-viously had extractions in the same area with the bone exposure. Most patients had received chemotherapy (83.3%), radiotherapy (16.6%) or corticoid therapy (33.3%), either alone or combined. The OPT and CAT scan images showed an exposed area of bone that was mottled or lytic (Figs. 2 and 3).

 

Results

In all cases antibiotic therapy and chlorhexidine rinses were started. After following the lesions, only minimally aggressive therapy was carried out in those cases that were more recalcitrant to conservative therapy: in one patient curettage of the extraction socket was carried out, in 5 patients debridement was carried out just of the necrotic areas that had been exposed and that were rubbing, and in just one case was resection of the sequestered bone carried out (Tables 2 and 3). All the procedures were carried out with oral antibiotics, amoxicillin in conjunction with clavulanic acid, except for one patient who was allergic to betalactams, who was given clindamycin.

In all cases the painful symptoms were controlled together with the purulent secretion, but bone expo-sure remained. The patients continued with oral rinses with chlorhexidine at 0.12%. There was no in-crease in the exposed area in any of the cases and only the usual painkillers were given to control the dis-comfort in the oral cavity.

Preventative measures before starting bp therapy

As soon as the specialist decides on BP therapy, the patient should be referred to a dentist or maxillofacial surgeon for an extensive examination of the oral cavity and of the state of the teeth. Starting the treatment should be delayed, if the general condition of the patient allows this, until all the surgical procedures of the mouth and teeth have been carried out.³

The examination should include a complete clinical and radiological examination with panoramic and/or periapical radiographs. The dental treatment should be aimed at avoiding the appearance of possi-ble infections and any invasive dental procedures in the short or medium term should be prevented. Any extractions of teeth in bad condition should be included, periodontal surgery, root canal treatment, restorative caries treatment, cleaning and correct adjustment of prostheses. All the supporting areas of the dental prostheses should be thoroughly checked, complete as well as partial prostheses, in order to pre-vent trauma to the mucosa.^1,2,13

Placing osteointegrated implants in these patients should be avoided, as the risk of osteonecrosis aris-ing in the area of the implant is high.⁷ The current situation should be discussed with the patient, together with the risks, benefits and alternative therapies. The check-ups after placement should be more frequent than usual, in order to detect any periimplantitis promptly.^1,13

Unerupted, embedded teeth that are completely covered by bone or gums should not be extracted, but those that are in contact with the oral cavity should be. All interventions should be carried out at least one month before starting treatment. The patient should attend dental check-ups and any symptoms of pain, inflammation or any areas with bone exposure should be reported straight away.² The administration of prophylactic antibiotics before non-invasive odontogenic procedures is not in-dicated, but it is recommended for invasive or surgical dental procedures. The antibiotic of choice is peni-cillin. In cases of penicillin allergy, combinations of erythromycin with metronidazole or quinolones with metronidazole are recommended. ^1,22

There are very few cases of spontaneous osteonecrosis in intravenous therapy cases and most arise as a result of complications after dentoalveolar surgery (Fig. 4). The start of the treatment should be de-layed, providing the general health of the patient permits this, until these procedures have been finished.

Therapeutic protocols

Asymptomatic patients with intravenous bps

Oncologists should refer patients undergoing treatment with intravenous BPs to a dentist or maxillofacial surgeon for an exhaustive examination of the oral cavity. Bone exposure will be looked for in the most common sites and radiology tests will be carried out in order to detect any evidence of osteolysis, osteo-sclerosis, or an increase in the periodontal or furcation space. The best attitude is to maintain good oral hygiene and to keep teeth in good condition. ² The following recommendations should be used for all patients:

• Teeth with caries that cannot be restored should not be extracted. The crown should be opened and root canal treatment carried out.^4,13

• Teeth that move slightly should be secured with an acrylic splint.

• With more mobile teeth and/or a periapical cyst or a periodontal abscess there is a greater risk of developing necrosis, and the tooth should receive root canal therapy with antibiotic treatment.

• All prostheses should be checked, and the areas with excessive pressure or that are rubbing should be reduced and adjusted periodically.⁴

• All surgical procedures that involve the bone such as the extraction of embedded wisdom teeth, tori removal, periodontal surgery or the placement of osteointegrated implants should be avoided.

• These patients should be given the same dose of antibiotics as those not undergoing BP treatment.

Asymptomatic oral bp patients

There is less risk of developing osteonecrosis in the jaw if patients are receiving BPs orally. Oral surgery interventions are not contraindicated in these patients, but they should be informed of the risk of developing osteonecrosis after taking, and as a result of, BPs.⁷ This risk increases when the treatment is prolonged over years. It has been suggested that, depending on the patient’s condition, interrupting the administration of BPs for two or three months before and after a dental or oral surgery, can reduce the risk of osteonecrosis.^1,2 Chlorhexidine rinses are recommended for the first two months after surgery.

• Oral BP for less than three years and with no risk factors: all the dental, surgical or periodontal procedures can be carried out without interrupting the treatment.

• Oral BP for less than three years and with risk factors: if there are systemic risk factors and if the general condition of the patient allows it, the interruption of the treatment for at least two or three weeks should be evaluated before any type of intervention. This should not be restarted until bone in a satisfactory condition has been confirmed.

• Oral BP for more than three years with/or without systemic risk factors: if the general health of the patient permits it, interrupting the treatment for at least 2 or 3 months should be evaluated before any type of intervention.

Patients with established osteonecrosis induced by BPS

The treatment that has been established for osteonecrosis attempts to diminish or eliminate the sensa-tion of pain, to control the inflammation and/or infection of bone and soft tissue and to control the pro-gression of bone necrosis. This is a complication that is difficult to manage. Generally in most patients it is triggered by an action by the odontologist, dentist, or maxillofacial surgeon.²¹ Most of the attempts at controlling or diminishing the necrotic bone areas by means of curettage, drilling or local flaps of soft tissue, tend to be ineffective. They should be carried out only when the pain is refractory to the remaining non-surgical treatments. ^7,11 Surgical debridement sometimes does not achieve a vascularized surgical margin, as all the jaw is under the influence of the drug. According to Ruggiero, achieving a surgical re-section with viable bone margins is extremely difficult, although not impossible. Analgesics will be ad-ministered for treating the pain.^1,2,5,21

The exposed necrotic bone that rubs and causes inflammation of the gums, oral or lingual mucosa should be put in order, in spite of the risk of increasing bone exposure. The fragments of sequestered bone should be removed, without touching the adjacent bone. Most of the procedures tend to lead to an in-crease in the area of necrotic bone exposed or the appearance of new areas. As a result of all these reasons, aggressive surgical or dental treatment in the oral cavity should be delayed or avoided as much as possible.²³ If a surgical intervention in the oral cavity is undergone, prophylactic antibiotic treatment can be started 1 or 2 days before. The administration of antibiotics, in a continued or intermittent form, can be beneficial in some established osteonecrosis cases. Taking samples in order to carry out a culture and ad-ministering a specific antibiotic is recommended. Most of the germs that have been isolated are sensitive to beta-lactamase and therefore the antibiotic of choice is amoxicillin, alone or in conjunction with clavu-lanic acid at a dose of 500 mg three times a day and rinses with chlorhexidine at 0.12%. Metronidazole at a dose of 250 mg three times a day can in addition be used for more stubborn cases. Clindamycin can be used (300 mg three times a day) or Azitromycin (250 mg once a day) for allergic patients. Antibiotic treatment should be maintained for two weeks. According to Marx combining antibiotics and limited debridement is the best treatment option for exposed necrotic areas.² Treatment with hyperbaric oxygen, which for osteoradionecrosis or osteomyelitis cases gives such good results, has not shown itself to be efficient for treating necrosisinduced BPs.^24,25

 

Discussion

Over recent years a new complication has been described as part of the treatment for various patholo-gies (multiple myeloma, breast and prostrate cancer metastases, osteoporosis, malignant hypercalcemia, Paget´s disease...), osteonecrosis of the jaw. In all these cases, the only factor in common was the use of BPs, and especially Pamidronate and Zoledronic acid. As from the year 2003 various series of cases have been published in the literature suggesting that there could be a possible relationship between BPs and the appearance of osteonecrosis of the jaw.

In 2003 Wang and cols. published 3 cases of osteonecrosis of alveolar bone in patients undergoing chemotherapy in conjunction with BPs (Pamidronate) because of bone metastases from breast cancer. Two of these patients had bone necrosis after an extraction in the same area. In all cases the presence of bone necrosis was demonstrated and the possibility of a metastatic lesion was ruled out. At first the osteonecrosis was attributed to the use of chemotherapy, but later it was suspected that BPs were involved.²⁶

Marx and cols. published a series of 36 patients who had received BP treatment intravenously (Pamidronate and Zoledronic acid) and who developed a necrotic lesion in the maxilla.¹² In most cases ex-tractions had been carried out, but in nearly 30% this had been spontaneous. It was observed that the lesions were like radionecrosis lesions.

Migliorati and cols. described a group of 5 patients with intraoral bone necrosis who were undergoing treatment with intravenous BPs. Three of the patients had previously had extractions but they were not able to detect locally what precipitated the necrosis in the other two patients.²⁵

The clinical trials before the commercialization and use of these drugs did not detect secondary effects and, given the increase in the publications on necrosis of the jaw on a world scale, in 2004 the company Novartis together with the FDA (Food and Drug Administration) made an announcement warning of the possible effects of BPs and modifying the recommendations for the use of Zometa^® and Aredia^®.

According to Marx and Ruggiero the appearance of osteonecrosis in the jaw is due to the greater blood supply and faster bone remodeling in the jaw due to the mechanical stimulation produced by the teeth.^2,7,12,21 The risk of osteonecrosis increases with surgical and dental procedures that, together with bad oral hygiene, increase the risk of additional infection of this necrotic bone, as there is exposure to oral flora. This results in considerable pain, swelling, purulent suppuration and bone exposure.

Some authors such as Dimitrakopoulos and cols. are of the opinion that the administration of BPs should be interrupted, providing the condition of the patient permits this, and that this, combined with debridement of the necrotic bone and antibiotherapy, could be suitable treatment for established osteone-crosis.³ Unfortunately, it has not been demonstrated whether interrupting the treatment of patients that have been undergoing BP treatment for years diminishes the risk of developing osteonecrosis.³

In August 2006, the American Dental Association (ADA) published a series of recommendations for dental practice in patients undergoing bisphosphonate therapy and for those with osteonecrosis (BON-bisphosphonate-associated osteonecrosis of the jaw). Similarly, and in order to have a treatment protocol, the American Association of Oral and Maxillofacial Surgeons (AAOMS) published in 2006 a consensus guide for the management of osteonecrosis cases of the jaw in patients undergoing treatment with bisphosphonate (BRON-bisphosphonate-related osteonecrosis of the jaw).¹ The objectives of these expert groups can be summed up using the following points:

• The risks and benefits of bisphosphonate treatment should be evaluated together with the possibil-ity of osteonecrosis appearing.

• Osteonecrosis cases of the jaw should be diagnosed in patients with a history of bisphosphonate therapy.

• Advice should be given on prevention and treatment of patients with bisphosphonate-induced os-teonecrosis.

The incidence of patients who develop osteonecrosis and who are receiving BPs is uncertain today, but what is particularly serious is that the number of cases being detected is multiplying. The possible role of BPs in triggering the development of avascular bone necrosis appears to be caused by a lack of vascu-lar supply and an antiangiogenic effect. To date, the influence of variables such as treatment duration, administration method, dose received and many other risk factors contributing to the development of lesions, is unknown. Providing more information through experimental studies and control cases is neces-sary in order to establish definitively the causal relationship between BPs and osteonecrosis of the jaw.

 

Conclusions

Bisphosphonates are drugs that are widely used on a worldwide scale with clear benefits that have been clinically proven. They result in a quality of life improvement for oncological patients with bone metastases and to a reduction in the incidence of bone fractures in women with postmenopausal osteoporosis.

Intravenous bisphosphonate therapy appears to be a determining factor in the appearance of osteone-crosis of the jaw in oncological patients. Thus, the recent publication of an ever-greater number of os-teonecrosis in patients undergoing oral bisphosphonate therapy should alert us.

What triggers bone exposure is generally surgical action taken by oral and maxillofacial surgeons, odontologists or dentists. Osteonecrosis is an entity that is difficult to manage and treat, as these patients tend to have a reduced quality of life because of their oncological condition. Correct oral hygiene, periodic revisions and conservative or minimally aggressive treatment, are the best recommendations for managing this condition.

A causal relationship has still to be demonstrated between necrosis and the use of BPs. There are no data available that would confirm if, by suspending BP therapy, the risk of osteonecrosis of the jaw is reduced in patients requiring dental treatment. New investigation is therefore needed in order to clarify the etiology behind this disorder, to reduce the incidence rate and to provide definitive treatment once these lesions appear.

 

 

Correspondence:
José Luis del Castillo Pardo de Vera
Complejo Hospitalario Universitario de Albacete, España
c/ Hermanos Falcó, 37
02006 Albacete, España
Email: delcastillo6@hotmail.com

Recibido: 15.02.07
Aceptado: 06.03.07

 

 

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