[Risk assessment of medication-related osteonecrosis of the jaw in general dental practice]. / A gyógyszer által indukált állcsontnecrosis-kockázat mértékének meghatározása az általános fogorvosi gyakorlatban.

Medication-related osteonecrosis of the jaw may appear as adverse effect in antiresorptive therapy. Its successful treatment is challenging. We aimed to gather the systemic and local factors playing a role in etiology, published after its recognition. Risk factors were collected from the PubMed database 1998-2018. The three main groups of risk patients are: patients starting, patients having antiresorptive therapy, osteonecrosis diagnosed patients. The dentist must recognize risk factors, determine appropriate treatment plan and frequency of check-ups. Oncological disease treated intravenously means the greatest risk. Further systemic risk factors are: supportive therapies, concomitant disease, way of life, individual factors. Local risk factors may be: dentoalveolar surgery, periapical and periodontal inflammation, ill-fitting denture, presence of some anatomical structures. The accumulation of risk factors determines the probability of the manifestation of osteonecrosis. The most favorable case is patient starting antiresorptive therapy with a dental status needing no treatment. Orv hetil. 2019; 160(7): 243-251.

The assessment of surgical and non-surgical treatment of stage II medication-related osteonecrosis of the jaw.

BACKGROUND: Non-surgical treatment has generally been recommended for stage II medication-related osteonecrosis of the jaw (MRONJ) in preference to surgery. However, non-surgical treatment is not empirically effective. The aim of this study was to evaluate whether surgical or non-surgical treatment leads to better outcomes for stage II MRONJ. MATERIAL AND METHODS: In this retrospective study, surgery was performed in a total of 28 patients while 24 patients underwent non-surgical treatment. The outcomes of both treatment approaches after 6 months were evaluated and statistically compared. In addition, risk factors for surgical and non-surgical treatments were assessed for each. RESULTS: Surgical treatment in 25 patients (89.3%) resulted in success, with failure in 3 patients (10.7%). Non-surgical treatment was successful for 8 patients (33.3%) and failed in 16 patients (66.7%). There was therefore a significant difference between surgical and non-surgical treatment outcomes (P<0.01). Regarding risk factors, in non-surgical treatment primary diseases, medications, and drug holiday had a significant effect on outcomes (P<0.01). Risk factors for surgical treatment could not be clarified. CONCLUSIONS: Surgical treatment is more effective than non-surgical treatment for stage II MRONJ, and drug holiday, primary disease, and medication constitute risk factors in non-surgical treatment.

Preventive Dental Treatment Workload/Costs to Mitigate Antiresorptive Bone Medication-related Osteonecrosis Risk.

PURPOSE: To determine the extent of dental disease and associated treatment costs designed to mitigate the risk of medication-related osteonecrosis of the jaws (MRONJ) among older, socially disadvantaged veterans prior to physician's administration of antiresorptive medication for osteoporosis or malignant bone disease. MATERIALS AND METHODS: This prospective study based on over seven years (2008-2015) of data describes the type and volume of disease, treatment, work-load measures, and costs using Veterans Affairs databases. RESULTS: One hundred fifty-two outpatients (94% male, mean age 69 ± 12 years) were referred by physicians for clinical/radiographic examination and treatment. Sixteen had a healthy dentition and 17 were completely edentulous with satisfactory prostheses. Three edentulous patients required prosthesis adjustment, 116 dentate individuals required restoration of carious teeth (mean 6.3 ± 5.7) and multiple quadrant (mean 3.1 ± 1.0) scaling/subgingival curettage. In the latter group, 75 required extractions (mean 6.0 teeth, range 1-23). Clinician's (dentist and dental assistant) costs for providing care and preventive education over the 7-year timespan came to almost $132,700. CONCLUSION: Older veterans requiring initiation of antiresorptive bone medication harbor extensive, untreated dental disease requiring immediate treatment. An appropriate physician-to-dentist referral network and provision of oral care and patient education prior to initiation of medication can potentially moderate the risk of jaw osteonecrosis.

Retrospective Audit: Does Prior Assessment by Oral and Maxillofacial Surgeons Reduce the Risk of Osteonecrosis of The Jaw in Patients Receiving Bone-Targeted Therapies for Metastatic Cancers to the Skeleton?--Part II.

Men who receive bone-targeted therapy for metastatic prostate cancer are at increased risk of osteonecrosis of the jaw (ONJ). Development of ONJ has been associated with the administration of bone-targeted therapies in association with other risk factors. ONJ can be distressing for a patient because it can cause pain, risk of jaw fracture, body image disturbance, difficultly eating, and difficulty maintaining good oral hygiene. The aim of this article is to report results of an audit of prior assessment by oral and maxillofacial surgeons (OMFS) before initiation of bone-targeted therapies and whether it may reduce the risk of ONJ in patients receiving bone-targeted therapies for advanced cancers.

Intricate Assessment and Evaluation of Dental Implants in Patients on Bisphosphonate Therapy: A Retrospective Analysis.

BACKGROUND: Osteonecrosis is one of the prevalent side effects of bisphosphonate (BP) therapy in oral cancer patients. In case of patients with various oncologic lesions, standard guidelines contraindicate the use of dental implants if the patients are on BP therapy. Literature also quotes studies that emphasize on the safety of dental implants in patients on BP therapy. Hence, this study aimed to retrospectively evaluate the clinical outcome of dental implants in patients on BP therapy. MATERIALS AND METHODS: In this retrospective analysis, a total of 140 dental implants in 112 patients were included. Inclusion criteria included only those patients who were on or had history of BP therapy. Calculation of implant failure and survival rate was done. RESULTS: Ten cases of implant failure occurred, giving a success rate of above 92%, which was comparable to the results found in previous studies in patients who were not on BP therapy. CONCLUSION: No significant risk of implant failure is seen in patients on BP therapy compared with other patients.

Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

Non-exposed bisphosphonate-related osteonecrosis of the jaw: a critical assessment of current definition, staging, and treatment guidelines.

Non-exposed bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a newly reported complication arising from bisphosphonate therapy that presents with atypical symptoms and no apparent mucosal fenestration or exposure of necrotic bone. The clinical observation of the presence of necrotic bone underneath normal epithelial coverage was not conclusive for the diagnosis of BRONJ based on current guidelines established by the American Association of Oral and Maxillofacial Surgeons (AAOMS) and the American Society for Bone and Mineral Research (ASBMR), which specify the presence of clinically exposed necrotic bone for more than 8 weeks. Hence, the purpose of this review is to critically assess the current guidelines for diagnosis and management of BRONJ and propose a modified staging system and treatment guidelines to properly address the non-exposed variant of BRONJ lesions.

Osteonecrosis of the jaw in older osteoporosis patients treated with intravenous bisphosphonates.

BACKGROUND: Intravenous bisphosphonate therapy has been linked to osteo-necrosis of the jaw among patients with cancer. Some patients with osteoporosis also receive intravenous bisphosphonates, although at lower total doses than those with cancer. OBJECTIVE: To examine the risk for jaw osteonecrosis among a population-based cohort of older adults receiving intravenous bisphosphonates for the treatment of osteoporosis. METHODS: Using a 5% national sample of Medicare beneficiaries, we identified 2296 patients treated with intravenous infusions of bisphosphonates for osteoporosis and other metabolic bone diseases between January 1, 2000, and December 31, 2007. We matched this cohort to 6865 bisphosphonate nonusers, at a 1:3 ratio, on age, race, sex, type of bone disease, and risk factors for osteonecrosis of the jaw. Patients were followed until December 31, 2007. The jaw toxicity outcomes included operations on the facial bones or jaw and diagnosis of inflammatory conditions of the jaw. RESULTS: The absolute risk at 3 years for any jaw toxicity was 0.70 events per 100 patients using bisphosphonates and 0.30 events per 100 patients not using such drugs (2-sided log rank test, p = 0.08). In multivariable survival analyses (Cox proportional hazards regression) adjusting for potential confounders, intravenous bisphosphonate use was not significantly associated with diagnoses or procedures suggestive of osteonecrosis of the jaw (p = 0.24). CONCLUSIONS: Patients with osteoporosis who are treated with intravenous bisphosphonates do not appear to have a statistically significant increase in the incidence of osteonecrosis of the jaw over 3 years compared with those who do not receive such treatment. Future studies will further contribute to our understanding of the bisphosphonate risk profile, thereby allowing patients and physicians to more rigorously assess the risk-benefit ratio of this treatment across different clinical scenarios.

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.

Complications of multiple myeloma therapy, part 2: risk reduction and management of venous thromboembolism, osteonecrosis of the jaw, renal complications, and anemia.

Venous thromboembolism (VTE), osteonecrosis of the jaw, renal failure, and anemia are all common complications of multiple myeloma therapy. Many of these adverse events have been documented only in the past 5 to 10 years, in conjunction with the introduction of a series of the newer therapies thalidomide, bortezomib, and lenalidomide. This article discusses these complications in detail and provides strategies for health care providers to best prevent, identify, and manage them. Preventive measures, such as VTE prophylaxis and appropriate dental hygiene, as well as patient education, dose adjustments, limited duration of drug treatment, and consideration of therapies that are associated with less burdensome adverse-event profiles, can contribute to substantially improved outcomes and quality of life.

A pilot case-control study on the alveolar bone density measurement in risk assessment for bisphosphonate-related osteonecrosis of the jaw.

UNLABELLED: Alveolar bone mineral density (BMD) measured by radiography standardized by aluminum step wedge pasted on the film and digitized by a computer system was significantly higher around osteonecrosis lesions than in control cases in a pilot case-control study. High alveolar bone density appears useful as a local risk factor for bisphosphonate-related osteonecrosis of the jaw (BRONJ). INTRODUCTION: In an attempt to find a reliable test method predicting the occurrence of BRONJ in addition to various risk factors suggested, an increase of alveolar bone density near the necrotic lesions was found by computerized radiogrammetry using dental films pasted with an aluminum step wedge (Bone Right, Dentalgraphic.Com Company, Himeji) in six cases of BRONJ. METHODS: The bone mineral density surrounding the osteonecrosis lesions showed distinctly higher density in BRONJ cases compared with age-matched controls. In one subject on bisphosphonate treatment in whom two extractions were simultaneously carried out, BRONJ occurred only at the location with extremely high alveolar bone density, but not at the other site with normal density. CONCLUSION: This method may be useful in detecting a rise of alveolar BMD frequently occurring near the necrotic lesion in subjects with impending risk for BRONJ.

Oral bisphosphonates as a cause of bisphosphonate-related osteonecrosis of the jaws: clinical findings, assessment of risks, and preventive strategies.

PURPOSE: Oral bisphosphonates are known to have potentially profound effects on oral health. A review of the evidence supporting answers to key clinical questions is necessary to assist surgeons in the care of their patients who are receiving oral bisphosphonates. MATERIALS AND METHODS: The literature is reviewed to address several questions, ie, what is the risk of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in my patient on oral bisphosphonates? Why are so few cases of BRONJ attributable to oral bisphosphonate use? What is the importance of cofactors in the development of osteonecrosis? How major a clinical problem is BRONJ, typically, in the oral bisphosphonate patient? What dental procedures are associated with a risk of BRONJ? Are other findings apart from BRONJ of importance in the oral bisphosphonate patient? Are there proven strategies to prevent BRONJ in the oral bisphosphonate patient? Should my patient discontinue the use of oral bisphosphonates temporarily or permanently? RESULTS: A review of the evidence offers information that will help in clinical decision-making. In general, the risk of BRONJ is between 1 in 10,000 and 1 in 100,000, but may increase to 1 in 300 after dental extraction. The great majority of BRONJ cases will likely remain in the intravenous population. Cofactors have not been firmly established, although smoking, steroid use, anemia, hypoxemia, diabetes, infection, and immune deficiency may be important. Rarely does BRONJ in the oral bisphosphonate patient appear to progress beyond stage 2, and many cases reverse with discontinuation of oral medication. Extraction is the only dental procedure shown to increase the risk of BRONJ. Dental implant therapy should be used with caution in the oral bisphosphonate patient. The benefits and risks of oral bisphosphonate use must be weighed individually and in consultation with the prescribing physician, before determining the need for temporary or permanent cessation of medication. CONCLUSION: Emerging evidence supports clinical decisions in favor of the oral and maxillofacial surgery patient taking oral bisphosphonates.

Dental extractions and bisphosphonates: the assessment, consent and management, a proposed algorithm.

Bisphosphonate-associated osteonecrosis of the jaws (BONJ) is recognised as a significant complication related to the use of bisphosphonates and currently is gaining importance due to the increasingly widespread use of these medications. Patients are placed into low or high risk groups of developing BONJ depending on the systemic condition for which they have received bisphosphonates. Numerically, the largest group worldwide is patients receiving bisphosphonates for osteoporosis and these generally fall into the low risk group for BONJ. The high risk group, while numerically smaller, is composed of those patients receiving bisphosphonates in the management of malignancy affecting the skeleton, either primary or secondary (metastatic disease). A number of additional systemic and local risk factors are proposed, which have the effect of increasing the risk of BONJ following an extraction. These risk factors may have the effect of moving a low risk categorised patient into a medium, or perhaps more realistically an unknown risk category. An example of a systemic risk factor is the concurrent use of corticosteroids and a local risk factor is mandibular molar extraction. The purpose of this paper is to define and validate an algorithm to guide clinicians in the area of patient information, consent and management for patients currently taking or having previously taken bisphosphonates who require dental extractions.

Review of osteoporosis pharmacotherapy for geriatric patients.

BACKGROUND: Fractures are a significant problem in geriatric patients, and understanding the evidence for benefit and possible harm of osteoporosis treatments is critical to appropriate management of this patient population. OBJECTIVE: The purpose of this article was to review the evidence and treatment considerations related to use of the approved osteoporosis treatments in the United States across the continuum of ages in the geriatric population. METHODS: MEDLINE and the Web of Science were searched to find English-language articles published from 2000 through July 2009. Search terms included: practice guideline, osteoporosis, calcium, vitamin D, pharmacoeconomics, ethnicity, and treatment. The generic names of each of the osteoporosis treatments approved in the United States were searched to find relevant clinical trials and randomized controlled trials (RCTs). Pivotal trials that included fracture data or focused specifically on elderly patients (> or = 60 years of age) were selected. Bibliographies in the identified articles were searched for additional articles, and the prescribing information for each of the approved treatments was reviewed. RESULTS: Many osteoporosis studies have a mean patient age >60 years, but data for older patients are limited. Subanalyses of older patient groups have found risedronate to be beneficial for vertebral fractures in patients aged 70 to 79 years (absolute risk reduction [ARR], 8.4%; P < 0.001) and teriparatide to be beneficial for both vertebral (ARR, 6.4%; P < 0.05) and new nonvertebral fragility fractures (ARR, 9.9%; P < 0.05) in women aged > or = 75 years. However, no RCTs of geriatric patients who were either nonambulatory or had multiple comorbidities were identified in the literature. CONCLUSIONS: Evidence indicates that the osteoporosis treatments currently available in the United States are beneficial for treating osteoporosis in geriatric patients. However, data are limited for the oldest patients (> or = 80 years) and those with significant comorbidities. Because of the limited availability of data for geriatric patients with significant comorbidities, the properties of the various agents, including efficacy, tolerability, and potential contraindications, should be considered carefully for each geriatric patient.

Risks and benefits of bisphosphonates.

Bone is the most common site for metastasis in cancer and is of particular clinical importance in breast and prostate cancers due to the prevalence of these diseases. Bone metastases result in considerable morbidity and complex demands on health care resources, affecting quality of life and independence over years rather than months. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma as well as a wide range of solid tumours affecting bone by 30-50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain. The use of bisphosphonates in early cancer is also increasingly important to prevent the adverse effects of cancer treatments on bone health. These include ovarian suppression and the use of aromatase inhibitors in breast cancer patients and androgen deprivation therapy in those with prostate cancer. Bisphosphonate strategies, similar to those used to treat postmenopausal osteoporosis, have suggested that bisphosphonates are a safe and effective treatment for the prevention of treatment-induced bone loss. When compared to other cancer therapies, the frequency and severity of adverse events related to bisphosphonate therapy are generally mild and infrequent; thus, the benefits of treatment with any bisphosphonate almost always outweigh the risks. However, renal dysfunction may occasionally occur and over recent years, a new entity, bisphosphonate-associated osteonecrosis of the jaw (ONJ), has been described. The incidence, clinical importance and prevention strategies to minimise the impact of this problem on patients requiring bisphosphonates is discussed.