|Year : 2022 | Volume
| Issue : 3 | Page : 261-268
Implications of endodontic treatment in chemo-osteonecrosis of the maxillary jaw due to bisphosphonates. An updated review
Elena Bermudez-Bejarano, Aline Savariz Martins, Alberto Sierra Lorenzo, Ana Boquete Castro, Alejandro Peña López
Universidad Católica San Antonio de Murcia, Murcia, Spain
|Date of Submission||22-Dec-2021|
|Date of Decision||14-Feb-2022|
|Date of Acceptance||15-Feb-2022|
|Date of Web Publication||1-Sep-2022|
Dr. Ana Boquete Castro
C Italia 35, Bajo, 04009, Almería
Source of Support: None, Conflict of Interest: None
Introduction: Chemo-osteonecrosis of the jaw can be caused by the pharmacodynamics of bisphosphonates and periapical-pulp physiopathology. Therefore, the objective of this study was to carry out a bibliographic review on endodontic treatment and chemo-osteonecrosis of the jaw and its recommendations.
Materials and Methods: An electronic systematic review has been prepared in the PubMed and manual verification from 2005 to 2020, according to the 2020 Prism Guidelines and using inclusion and exclusion criteria, under the terms: “Bisphosphonate AND root canal therapy” and “Bisphosphonate associated osteonecrosis of the jaw AND endodontics.”
Results: The 22 selected articles were divided into two differentiated blocks. The first one includes endodontic treatment in patients with bisphosphonate therapy and its relationship with maxillary chemo-osteonecrosis. The second includes recommendations to be followed in patients on bisphosphonate and root canal therapy.
Conclusions: Patients who were administered intravenous or intraoral bisphosphonates for more than 4 years with associated risk factors are more predisposed to chemo-osteonecrosis of the jaw. Endodontics is safe compared to other traumatic procedures.
Keywords: Bisphosphonates, bisphosphonate-related osteonecrosis of the jaw, endodontic treatment, review, root canal therapy
|How to cite this article:|
Bermudez-Bejarano E, Martins AS, Lorenzo AS, Castro AB, López AP. Implications of endodontic treatment in chemo-osteonecrosis of the maxillary jaw due to bisphosphonates. An updated review. Saudi Endod J 2022;12:261-8
|How to cite this URL:|
Bermudez-Bejarano E, Martins AS, Lorenzo AS, Castro AB, López AP. Implications of endodontic treatment in chemo-osteonecrosis of the maxillary jaw due to bisphosphonates. An updated review. Saudi Endod J [serial online] 2022 [cited 2022 Oct 5];12:261-8. Available from: https://www.saudiendodj.com/text.asp?2022/12/3/261/354830
| Introduction|| |
Bisphosphonates are suitable for metabolic bone diseases and malignant hypercalcemia. They are known as the stable analogous of inorganic pyrophosphates. They are classified according to the route of administration (oral or intravenous) and whether they have a nitrogen atom in their side chain (nitrogenous or not). Intravenous administration of bisphosphonates and nitrogenous bisphosphonates has the greatest side effects, including bisphosphonate-related osteonecrosis of the jaw (BRONJ).,
Due to its mechanism of action, Marx, warned of a new complication, bisphosphonate-related maxillary chemo-osteonecrosis, in 2003. This pathology is an exposure of bone tissue located in the arches (maxillary, mandibular, or both) that persists for more than 6–8 weeks, associated with bisphosphonate therapy and in the absence of previous radiotherapy., Although the etiology of this pathology has not been fully elucidated, there are two hypotheses that could explain its appearance. The first is related to the pharmacodynamics of the drug itself and the second to the risk factors that trigger it.
Pharmacodynamics and mechanism of action of bisphosphonates
Bisphosphonates present special predilection for bone (inhibit normal bone homeostasis). The arches, due to their high rate of bone turnover have a greater predisposition to the appearance of maxillary chemo-osteonecrosis. In addition, these drugs suppress angiogenesis and osteonecrosis is considered an interruption of vascular supply. For all these reasons, bisphosphonates provoke a modulatory and dysfunctional effect on the immune system, develop an environment more prone to delay healing and correct tissue healing, as well as favoring maxillary chemo-osteonecrosis.,,
Triggering risk factors
Local factors such as infection/inflammation, oral surgery, prosthetic or mucosal trauma, ulcers, periodontal disease, poor oral hygiene; systemic and demographic factors such as endocrine disorders (obesity, diabetes), tobacco, alcohol, age, race, among other genetic factors (Cytochrome P450, nucleotide polymorphisms (single nucleotide polymorphism). The duration, dose, type, and potency of bisphosphonates are also taken into account.,
In 2009, the American Association of Oral and Maxillofacial Surgeons published a consensus advocating that in patients undergoing therapy with intravenous bisphosphonates and nonrestorable teeth, the most conservative and least traumatic therapy possible should be performed instead of tooth extraction, thus reducing the possibility of spreading infection and inflammation to the periapical tissues., Invasive dental procedures (exodontia, dental implants, or periodontal surgery) are more frequently related to the appearance of BRONJ, without forgetting that infection, periodontal or endodontic, can also contribute to its development.
Consequently, the aim of the present work was to prepare a literature review with studies that include endodontic treatment in patients on bisphosphonate therapy and the possible relationship with maxillary chemo-osteonecrosis due to bisphosphonates, in order to establish recommendations on the management of patients on bisphosphonate therapy who are going to undergo root canal therapy.
| Materials and Methods|| |
The question formulated to conduct the present literature review was the following: Are patients on bisphosphonate therapy, after root canal therapy and compared to patients, not on bisphosphonate therapy, more likely to develop maxillary chemo-osteonecrosis?
Data base and search strategy
An electronic search was performed according to the 2020 Prism Guidelines, from 2005 to 2020 in the PubMed database and manual verification, under the terms: “Bisphosphonate AND root canal therapy” and “Bisphosphonate associated osteonecrosis of the jaw AND endodontics.” Initially, 70 articles were identified, of which 22 were selected according to the following inclusion and exclusion criteria.
Screening and selection
Academic publications in English, no more than 15 years old, prospective studies, retrospective studies, and case series, which are performed on human patients who have developed maxillary chemo-osteonecrosis due to bisphosphonates and root canal therapy is found among the dental treatments performed.
Articles that do not meet the aforementioned criteria, articles not related to the topic to be investigated, articles without abstracts or with anonymous authors, letters to the editor, expert opinions, and doctoral theses or duplicates.
| Results|| |
The 22 articles selected according to the 2020 Prism Guidelines [Figure 1] for this review have been classified into two distinct blocks. The first with the nine articles that include endodontic treatment in patients on bisphosphonate therapy and the possible association with maxillary chemo-osteonecrosis, and the second with the recommendations to be followed in this group of patients.
|Figure 1: The 22 articles selected according to the 2020 Prism Guidelines for this review. *Consider, if feasible to do so, reporting the number of records identified from each database or register searched (rather than the total number across all databases/registers). **If automation tools were used, indicate how many records were excluded by a human and how many were excluded by automation tools.|
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Maxillary chemo-osteonecrosis in patients with root canal treatment
After collecting the studies that met the proposed eligibility criteria, a table was drawn up in which the nine selected articles were arranged chronologically in ascending order and the three most frequently found parameters in local risk factors and systemic-demographic risk factors related to BRONJ, as well as the precipitating factors of endodontic therapy associated with BRONJ, were recorded [Table 1].
|Table 1: Endodontic therapy in patients undergoing treatment with bisphosphonates|
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In 2005, Marx conducted the first investigation of the association between BRONJ and endodontic therapy. After 1 year of follow-up, authors found 119 BRONJ, 81 in the mandible, 33 in the maxilla and 5 occurred in both jaws, with 13.4% endodontics and 28.6% dental abscesses being some of the local risk factors. Apical radiolucency and ineffective filling of the obturation were pointed out as possible precipitating factors of chemo-osteonecrosis.
In the same year, Sarathy et al. and Katz found that patients who developed BRONJ in both arches also presented local risk factors such as endodontics, endodontic surgery, exodontics, endodontics and periodontal surgery. Katz mentions biopulpectomy treatments (root canal treatment of teeth with vital pulp) and the use of epinephrine anesthesia as possible precipitating factors of endodontic treatment associated with BRONJ.
Kaptan et al. studied two women aged 62–64 years, with 4 years duration of bisphosphonate therapy for breast cancer, for 1 year in 2013. Each patient developed a BRONJ lesion for implantological and endodontic reasons. Their development, with respect to endodontics, could also be related to biopulpectomy and clamp placement.
Alsalleeh in 2016, advocates nonsurgical endodontic treatment followed by coronal amputation and root hemisection, to prevent the development of osteonecrosis. However, prevention of apical periodontitis was unpredictable.
Guidelines, management, and recommendations
Thorough check-ups are recommended, in order to control cavities, subsequent infections, and periodontal status, and focus on motivation in oral hygiene, as well as conservative therapy, periodontal and/or endodontic therapy, if necessary. In these comprehensive check-ups, a careful dental examination is recommended, with its corresponding clinical and radiological follow-up and patient education on BRONJ symptomatology, with prevention being the key to success.,,
Depending on the stage of endodontic treatment, the following parameters should be taken into account: Before, during, and after root canal therapy.
Prior to root canal therapy
- Provide a thorough diagnosis of the case. Take a complete medical history, with special attention to the underlying pathologies, associated pharmacotherapy, bisphosphonate used (type, route, duration, dose and potency), local risk factors and systemic-demographic risk factors
- Upon receipt of all the patient's medical and dental data, in the case of those needing endodontic therapy, an informed consent should be provided to the patient after explaining the risks and benefits of the treatment, whether surgical or not
- Evaluation and justification of antibiotic prophylaxis due to the pharmacodynamics of bisphosphonates, the patient's own underlying pathology, and local and systemic-demographic risk factors that promote BRONJ. According to the European Society of Endodontics statement on the use of antibiotics in endodontics; patients on therapy with intravenous bisphosphonates who are going to perform a bone invasive procedure, such as endodontic surgery should take 2 g of Amoxicillin 1 h before treatment and for those allergic to Penicillin, Clindamycin 600 mgr 1 h before.
During root canal therapy
- Decrease the bacterial load present in the oral cavity with chlorhexidine mouth rinses before treatment.
- It is preferable to not use anesthesia with vasoconstrictor due to the antiangiogenic effect of bisphosphonates.
- During instrumentation and obturation of the canals, avoid over-instrumentation, over-extension, and over-obturation of the canals to avoid irritation or cytotoxicity of the surrounding tissues and thus reduce the extrusion of microorganisms during instrumentation, thus avoiding patency., The quality of endodontic therapy will be a fundamental part of the treatment, with a greater risk of BRONJ being found in teeth with radiographic failure in canal therapy or those with inadequate obturation of the canal system.
- In patients undergoing therapy with intravenous bisphosphonates and with extensive cavities, endodontic treatment and coronal resection would be chosen to avoid future infections, as it is a procedure designed to reduce the need for surgical procedures such as exodontia of carious teeth.,,,
- To assess the risks and benefits of endodontic surgery, knowing that dentoalveolar surgery favors the development of BRONJ.
After root canal therapy
- Cases should be reviewed with clinical and radiologic follow-up and make subsequent evaluations.
| Discussion|| |
There are studies in the literature confirming the relationship between endodontic treatment and BRONJ. The justification for this association could be related to the fact that in the generation of pulpo-periapical pathophysiology, three recognized factors in the genesis of BRONJ converge: Infection, inflammation and invasion by bacterial biofilm. Actinomyces stands out from this bacterial biofilm, and is also related to refractory periapical lesions in endodontic treatment. If this is added to the pharmacodynamics and mechanism of action of bisphosphonates, the location of dental treatment, the risk factors mentioned above and the patient's own underlying pathology, this could increase the chance of their appearance.
The causes of bisphosphonate therapy are due to malignant hypercalcemia such as multiple myeloma, breast cancer, and prostate cancer, and metabolic bone diseases such as osteoporosis., Based on the articles described in the literature, the use of bisphosphonates for more than 1 year predominates in women over 60 years of age who use in conjunction with intravenous bisphosphonates, or use intravenous and intraoral bisphosphonates simultaneously.,,, This higher incidence may be related to underlying diseases such as breast cancer.
The systemic-demographic factors found were radiotherapy, chemotherapy, smoking, corticosteroids, diabetes, and dexamethasone.,, BRONJ lesions are more frequent in the mandible and are linked to local risk factors, the most common being dentoalveolar surgery (exodontia and implants), periodontal disease, prosthesis, spontaneous cause and endodontics.
The review by Moinzadeh et al. mentions that some groups of patients are at special risk, including those treated with intravenous or oral bisphosphonates for more than 3 years who present systemic diseases such as diabetes or corticosteroid therapy, among others. This would support the idea of Sarathy et al. that there are other variables that could have an influence on the development of BRONJ, not only the fact that they are under treatment with bisphosphonates. In the two clinical cases presented by the authors, the individuals were men over 70 years of age with diabetes mellitus and were being treated with multiple drugs with significant effects on calcium metabolism and/or angiogenesis, so with so many variables it would be difficult to conclude a cause-effect relationship, although it seems reasonable that some associations could exist between these drugs and the disease.
The possible precipitating factors of endodontic treatment associated with BRONJ, in some studies were not reviewed, but in others biopulpectomy, necropulpectomy (root canal treatment of pulpless teeth), anesthesia with vasoconstrictor (epinephrine), placement of clamps, periapical radiolucency, acute apical abscess or inadequate filling in the obturation,, are mentioned. Therefore, endodontic treatment should be carried out under aseptic and atraumatic conditions as possible, and should be as atraumatic as possible due to the accumulation of the drug, not only in the bone cells but also in the cells of the oral epithelium. Furthermore; there may be a certain toxicity of the drugs, so damage to the surrounding soft tissues and bone tissues should be avoided.,,
Kaptan et al. recognized that endodontic treatment may not be the cause of BRONJ. The trigger being pulpal or periodontal inflammation/infection, as well as the spontaneous cause since dentoalveolar bone pain is the early symptom of stage zero BRONJ. For this reason, endodontic treatment or retreatment should be considered as an alternative to surgical endodontic treatment or extraction.
After endodontic treatment, the healing of the periapical will depend on the duration, dose, type, and potency of the bisphosphonate. For this reason, with intraoral bisphosphonates there do not seem to be significant differences when compared to patients without bisphosphonate treatment. An example of this is the results of the retrospective study by Hsiao et al. of periapical lesions in 34 teeth in 28 patients treated with oral bisphosphonates, and 38 teeth in 30 patients as a control sample, who were not on bisphosphonate therapy. The study found a strong relationship between duration of bisphosphonate therapy and reduction of periapical pathology. The proportion of unhealed or incompletely healed lesions in patients receiving zolendronic acid for more than 1 year was higher than those receiving bisphosphonates for <1 year. However, further studies would be needed to draw more enlightening conclusions.
Since 2005 there have been published case series correlating previous root canal treatment and the development of BRONJ, however, they do not have a large sample of participants and a clear directionality.,,,, However, in patients with bisphosphonate therapy, endodontic treatment should follow a series of guidelines and recommendations to avoid endodontic failure and the development of BRONJ. These are succinctly: Preventive measures (fluoride and 0.12% chlorhexidine) to reduce the bacterial load and biofilm, reduction of trauma to the periodontal-apical tissues by measuring the working length, instrumentation and obturation. In addition, it is important to minimize marginal, periodontal and surrounding bone tissue trauma when placing the rubber dam, which is one of the risk factors for BRONJ. Similarly, the present systematic review presents some limitations to be taken into account: More homogeneous samples are needed, as well as a greater number of investigations that relate the existing link between root canal therapy and maxillary chemo-osteonecrosis due to bisphosphonates, due to the fact that there are confounding factors such as local and systemic-demographic risk factors.
| Conclusions|| |
Patients on intravenous bisphosphonate therapy or with intraoral bisphosphonate administration for more than 4 years have associated risk factors: Precipitating factors, local factors, systemic-demographic factors and the patient's own underlying pathology increase the predisposition to develop maxillary chemo-osteonecrosis.
Endodontic treatment is considered the safest procedure in comparison to others that involve greater trauma to the tissues.
It is recommended to follow a series of guidelines before, during, and after endodontic treatment in patients undergoing bisphosphonate therapy.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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