Medication‐related osteonecrosis of the jaw: Surgical or non‐surgical treatment?

Medication‐related osteonecrosis of the jaw (MRONJ) is a severe side effect of antiresorptive (bisphosphonates and denosumab) and anti‐angiogenic therapy used in the management of oncologic and, less frequently, osteoporotic patients. While there is good international agreement on the diagnostic and staging criteria of MRONJ and the cessation of antiresorptive/anti‐angiogenic treatments, the gold standard of treatment is still controversial, in particular between non‐surgical and surgical approaches. The former usually includes antiseptic mouth rinse, cyclic antibiotic therapy, low‐level laser therapy and periodic dental checks; the latter consists of surgical necrotic bone removal. The purpose of this retrospective study was to describe the therapeutic approaches and outcomes of 131 lesions from 106 MRONJ patients treated at the Policlinic of Bari. Non‐surgical treatments were chosen for 24 lesions that occurred in 21 patients who, due to comorbidities and/or the impossibility of stopping oncologic therapies, could not undergo surgical treatment. As to the outcome, all the surgically treated lesions (107) showed complete healing, with the exception of 13.5% of the lesions, all of which were stage III, which did not completely heal but showed reduction to stage I. The 24 non‐surgically treated lesions never completely healed and, rather, generally remained stable. Only two cases exhibited a reduction in staging. Based on our observations, MRONJ occurring both in neoplastic and non‐neoplastic patients benefits more from a surgical treatment approach, whenever deemed possible, as non‐surgical treatments do not seem to allow complete healing of the lesions.     

Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate‐related osteonecrosis of the jaws: can they be utilized as risk markers?

Purpose: The purpose of this retrospective study was to examine the possibility of utilizing serum C‐terminal telopeptide cross‐link of type I collagen (s‐CTX) and serum osteocalcin (s‐OC) as risk markers for oral bisphosphonate‐related osteonecrosis of the jaws (BRONJ). Patients and methods: The s‐CTX values and the s‐OC values were measured from 23 patients (one male, 22 females) diagnosed with BRONJ using clinical and radiographic examinations. The two biochemical markers were evaluated during a regular checkup for osteoporosis management. For the control group of s‐CTX study, s‐CTX values were obtained from 61 independently recruited postmenopausal women who have been on bisphosphonate therapy for >6 months. The s‐CTX values of the ONJ group and the control group were compared. Because of retrospective nature of this study, the control group for s‐OC study could not be established. A single sample t‐test was performed for the s‐OC value from the ONJ group. Result: Twenty‐three ONJ patients had taken alendronate for osteoporosis treatment, and the s‐CTX testing results were low levels of 10–192 pg/ml (mean: 93.2±49.4 pg/ml). Mean of s‐CTX of the control (n=61) was 125±85.7 pg/ml. The duration of BP therapy ranged between 1 and 10 years (4.82±2.6). The s‐OC level was estimated between 0.2 and 5.4 ng/ml (1.91±1.51 ng/ml). The mean s‐CTX value of the control group was higher but without significance (P=0.12). The s‐OC values of the ONJ group were significantly lower than the lowest value of the reference range (P<0.001). Conclusion: As a result of the s‐CTX and s‐OC testings at the diagnosis of BRONJ, the values of the two markers were decreased. The decrease of the s‐OC values implies a problem during the bone‐formation process. Therefore, we can assume that in this patient group, invasive dental surgery contributes to an increase in the risk of BRONJ incidence. This result may imply that, during bisphosphonate therapy, simultaneous consideration of s‐CTX showing inhibition of bone resorption and s‐OC indicating the degree of bone formation might be a set of risk markers assessing risk prediction for BRONJ before invasive dental surgery. To cite this article:
Kwon Y‐D, Ohe J‐Y, Kim D‐Y, Chung D‐J, Park Y‐D. Retrospective study of two biochemical markers for the risk assessment of oral bisphosphonate‐related osteonecrosis of the jaws: can they be utilized as risk markers?
Clin. Oral Impl. Res. 22 , 2011; 100–105.
doi: 10.1111/j.1600‐0501.2010.01965.x     

Effectiveness of treatments for medication-related osteonecrosis of the jaw: A systematic review and meta-analysis

Background

The effectiveness of management strategies used for the treatment of medication-related osteonecrosis of the jaw (MRONJ) remains poorly understood. The authors evaluated systematically the effectiveness of the various treatment modalities used for MRONJ.

Can children be affected by bisphosphonate-related osteonecrosis of the jaw? A systematic review

Knowledge of bisphosphonate-related osteonecrosis of the jaw (BRONJ) is mostly based on adult cases, however bisphosphonates are also currently recommended for different paediatric diseases resulting in osteoporosis. The aim of this study was to review the literature on the risk of developing BRONJ in children and adolescents. The PubMed, LILACS, Web of Science, Scopus, and Cochrane databases were searched using the key words “bisphosphonates”, “osteonecrosis”, “jaw”, and “children”. Literature reviews, case reports, abstracts, theses, textbooks, and book chapters were excluded. Studies involving children and young adults (younger than 24 years of age) were included. A total of 56 publications were identified. After applying the eligibility criteria, only seven articles remained. Although no cases of osteonecrosis were identified, all studies had weaknesses such as a limited sample size or the absence of risk factors for the development of osteonecrosis. There is general consensus that this subject should be of concern and that further studies should be conducted before any definitive opinion is reached. It is believed that patients with secondary osteoporosis who use bisphosphonates continuously should be followed up during adulthood, since bone turnover decreases over the years.     

Systematic review of medication related osteonecrosis of the jaw (MRONJ) in patients undergoing only antiangiogenic drug therapy: surgery or conservative therapy?

Osteonecrosis of the jaw is a severe adverse condition affecting patients exposed to specific types of medications. Previous studies have highlighted that osteonecrosis of the jaw is triggered by invasive dental procedures and can be very challenging to manage, especially in patients with cancer. The primary aim of this review was to analyse all available evidence on the management (surgical and/or conservative) of medication related osteonecrosis of the jaws (MRONJ) in patients with a history of antiangiogenic drugs therapy and who had not been previously exposed to any antiresorptive drug treatments. A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until November 2020. Data were extracted from relevant papers and analysed according to the outcomes selected in this review. The search generated 28 studies eligible for the analysis. The total number of patients included in the analysis was 36. Sixteen patients were treated with anti-vascular endothelial growth factor drugs (anti-VEGF) while the remaining patients were administered a combination of antiangiogenic drugs. The most common MRONJ site was the mandible in 29 patients. MRONJ recurrence after treatment was only reported in six patients, the majority of which were treated conservatively. The data reviewed confirmed that an invasive procedure was the most common trigger of MRONJ with relatively high frequency of postoperative recurrence following treatment. However, due to the low quality of available research in the literature, it is difficult to draw a definitive conclusion on the validity of the presented treatment to manage patients affected by MRONJ associated with angiogenic therapy.     

Bisphosphonate-associated osteonecrosis of the jaw: what do we currently know? A survey of knowledge given in the recent literature

Increasing application of bisphosphonates for therapy of osteopathies has led to reports of the severe associated adverse effects of osteonecrosis of the jaw (ONJ). We reviewed recent literature to assess several aspects of bisphosphonate-associated ONJ, and to provide healthcare professionals with an overview of treatment and preventive options. Literature databases were searched using keywords. Information of 54 articles were discussed and completed by additional literature. High-risk factors were application of nitrogen-containing bisphosphonates, teeth extractions, and ill-fitting dentures. Treatment included non-surgical options and radical surgery. Success and failure were described for all treatment options; further studies investigating long-term recovery and recurrence are warranted. Paying attention to effective prevention of ONJ before, during, and after treatment is essential.     

What and where are the stem cells for Dentistry?

Disinfection of root canals followed by the replacement of the infected or inflamed pulp tissues by inert materials is the foundation for treating irreversible damaged dental pulps. The management of pathological conditions of the periodontium is mainly based solely upon infection control via the reestablishment of oral hygiene, scaling and root planing to control inflammation which stops progressive bone loss. As one may see, the clinical management of endodontic and periodontal diseases has not changed drastically despite the development of new materials, techniques and medicaments. Tissue engineering is a multi-disciplinary field focused on the development of materials, techniques and strategies to improve or replace damaged or lost biological functions and tissues. As the tissue engineering field progresses, “scaffolds”, “suggest pathways” and “stem cells” abandoned their role as technical words exclusively used by scientists and slowly assume a part in the language of students, educators, clinicians and patients. However the unfamiliarity with some of the concepts can lead to misinterpretations of the current status and overexcitement about future applications of stem cells for dental-related tissue regeneration. This paper will present a panorama and the future challenges on the path to use of stem cells for endodontic and periodontal tissue regeneration.     

Bisphosphonates,vitamin D,parathyroid hormone,and osteonecrosis of the jaw. Could there be a missing link?

It is estimated that over 190 million bisphosphonates have been prescribed worldwide. But this drug can produce adverse effects, of which osteonecrosis of the jaw and severe hypocalcemia are the most serious. It is evident that bisphosphonate administration affects multiple and diverse biochemical mediators related to bone metabolism. This review of literature investigates four basic parameters in patients treated with bisphosphonates - parathyroid hormone (PTH), bisphosphonates, vitamin D, calcium, and jaw osteonecrosis - which are fundamental for assessing bone metabolism and so the efficacy and correct use of the drug. The imbalances generated by vitamin D and calcium deficiencies, together with their multiple systemic repercussions, have been widely researched but the outcomes of these imbalances in relation to bisphosphonate administration are not well known, and some research has indicated that they may be associated with osteonecrosis of the jaw (ONJ). The present review set out to explain the functioning of bone metabolism, the importance of different chemical mediators, the imbalances produced by incorrect use of this drug, in order to forewarn against the possible relation of these parameters with ONJ, whose physiopathology remains unknown. Medical and dental clinics should keep detailed anamneses of the use of vitamin D and calcium supplements, as it is of vital importance to maintain their correct levels in blood, given that these are related to ONJ as well as other adverse effects; this procedure is also necessary in order to ensure the correct use of the drug. Key words:Bisphosphonate-related osteonecrosis of the jaw, vitamin D, parathyroid hor     

Differences between auto-fluorescence and tetracycline-fluorescence in medication-related osteonecrosis of the jaw—a preclinical proof of concept study in the mini-pig

Clinical Oral Investigations - Fluorescence-guided bone surgery is a well-established technique in the treatment of medication-related osteonecrosis of the jaw. No histopathological evidence for...     

Does self‐weighting of items enhance the performance of an oral health‐related quality of life questionnaire?

OBJECTIVES: To determine if self-weighting of the items in an oral health-related quality of life questionnaire improves its psychometric properties. METHODS: The Surgical Orthodontic Outcome Questionnaire (SOOQ) was designed to assess the oral health-related quality of life of individuals before and after corrective surgery. Each of its 33 'items' consists of two questions: a question concerning the frequency with which a given functional or psychosocial problem had been experienced and a 'weighting' question which asked about how much the individual was bothered by that problem. The questionnaire was completed by three groups of individuals: (i) pretreatment; (ii) immediate (i.e. 2-6 months) postsurgery and (iii) postsurgery (i.e. more than 2 years after surgery). Unweighted scale scores were obtained by summing the response codes to the frequency question and weighted scores by summing the products of the frequency and bother questions. These scores were calculated for the full questionnaire and a short form consisting of 15 items. The discriminative and correlational construct validity of these scores was compared along with internal consistency reliability. The sensitivity to change and longitudinal construct validity of unweighted and weighted scores was assessed in a simulated evaluative study in which pretreatment and postsurgery subjects were paired. RESULTS: For both the long and short forms of the questionnaire, unweighted and weighted scores discriminated between the groups enrolled in the study. Correlations with a general health rating were similar, as were Cronbach's alpha values and test-retest reliabilities. The simulated evaluative study suggested no differences in sensitivity to change or longitudinal construct validity. When subscale scores were examined, there was a suggestion that weighting improved their reliability. CONCLUSIONS: Self-weighting of items did not substantially improve the performance of the SOOQ. Domain weights should be developed and tested to determine if they have an effect on its properties.     

Patients’ quality of life improves after surgical intervention of stage III medication-related osteonecrosis of the jaw

Oral and Maxillofacial Surgery - The treatment of advanced stages of medication-related osteonecrosis of the jaw (MRONJ) remains challenging. In order to improve decision making concerning the...