Antiresorptive agents enhance ossification of free flap reconstructions of the mandible: a radiological retrospective cohort study.

Background: The aim of this study was to investigate the effect of antiresorptive agents on the ossification of reconstructed mandibles by free bone grafts for the first time. Methods: A total of 38 reconstructions of the jaw were retrospectively evaluated for ossification between bone segments by two raters based on postoperative panoramic radiographs. The study group (n = 13) had segmental resection of the mandible and free bone flap reconstruction due to medication-related osteonecrosis of the jaw (MRONJ). The control group (noMRONJ, n = 25) comprised segmental mandibular resections and free bone flap reconstructions due to tumors, chronic osteomyelitis, or trauma without any radiation. Ossification time and influencing factors were evaluated. Results: Both duration of surgery (346 ± 90 min. vs. 498 ± 124 min.; p < 0.001) and hospitalization (8.7 ± 2.8 days vs. 13.4 ± 5.3 days, p = 0.006) were shorter in the MRONJ group compared to the noMRONJ group. Ossification after mandibular reconstruction was significantly faster in the MRONJ study group [224 days, interquartile range (IQR) 175-287] compared to the control group (288 days, IQR 194-445; p < 0.001). Moreover, good initial contact between the segments resulted in faster ossification (p < 0.001) in the MRONJ group. Ossification rate between original and grafted bone or between grafted bone segments only did not differ in both the study and control groups (MRONJ, p = 0.705 vs. control, p = 0.292). The type of antiresorptive agent did not show any significance for ossification. The rate of wound healing disturbances did also not differ between the study and control groups (p = 0.69). Conclusion: Advanced MRONJ (stage 3) can be resected and reconstructed safely with free microvascular bone flaps. Antiresorptive agents enhance the ossification of the bone segments. Optimal initial contact of the bone segments accelerates bone healing. Surgery and hospitalization are markedly shortened in this vulnerable group of MRONJ patients compared to oncologic patients.

Antiresorptive agent-related osteonecrosis of the jaw risk in cancer patients before bone-modifying agent therapy: A retrospective study of 511 patients.

INTRODUCTION: Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a serious adverse event associated with therapies for advanced cancer involving bone-modifying agents (BMAs). Although many studies have investigated the risk factors for ARONJ, none have provided sufficient clarifications. We aimed to determine whether there is a correlation between tooth extraction before BMA therapy and the development of ARONJ. PATIENTS AND METHODS: We included 511 patients who were admitted to our department before BMA therapy. The incidence of ARONJ and its risk factors was retrospectively evaluated, focusing on tooth extraction before BMA therapy and radiological findings of the extracted tooth. RESULTS: Of the 511 patients, 135 underwent tooth extraction before undergoing BMA therapy. ARONJ was observed in 17.7 % and 7.2 % of patients in the extraction and non-extraction groups, respectively (p = 0.0002). Regarding the findings of panoramic radiographs before tooth extraction, the incidence of periapical disease was significantly higher in the ARONJ group than that in the non-ARONJ group (50 % and 27 %, respectively, p = 0.034), and the proportion of bone sclerotic changes in the surrounding teeth was significantly higher in the ARONJ group (58.3 %) than in the non-ARONJ group (24.4 %) (p = 0.0004). CONCLUSION: The presence of a hopeless tooth that requires extraction prior to BMA therapy is a risk factor for MRONJ. However, extraction of such teeth should be considered, as this is known to decrease the risk of MRONJ development after BMA therapy initiation. Moreover, the radiological findings of periapical disease and bone sclerotic changes in the extracted teeth identified in this study can be used as novel predictive factors for ARONJ.

Histopathological findings affect quantitative values of single photon emission computed tomography in patients with antiresorptive agent-related osteonecrosis of the jaws.

Objectives: This study investigated the relationships between quantitative values calculated from bone single photon emission computed tomography/computed tomography (SPECT/CT) images and histopathological findings observed in surgical specimens from patients with antiresorptive agent-related osteonecrosis of the jaw (ARONJ); it sought to clarify histopathological factors that cause accumulation in bone SPECT/CT images of patients with ARONJ. Methods: This study included 81 pathological specimens of 21 lesions obtained from 18 patients with ARONJ who underwent SPECT/CT and jaw resection. The maximum standardized uptake value (SUVmax) of each volume of interest of the specimens was calculated using RAVAT® software. The ratio of the SUVmax to the mean value of SUVmax in temporal bone was termed rSUVmax. The rSUVmax and pathological findings (sequestration, degree of fibrosis, degree of trabecular bone destruction, degree of inflammatory cell infiltration, and vascularity) were compared using the Mann-Whitney U test and the Kruskal-Wallis test. Results: In univariate analysis with rSUVmax as the dependent variable, the pathological findings of sequestration (P=0.058), degree of fibrosis (P=0.810), degree of trabecular bone destruction (P=0.237), degree of inflammatory cell infiltration (P=0.120), and vascularity (P=0.111) showed no significant difference among the groups for each variable. Conclusions: We found no association between quantitative values in bone SPECT/CT and histological changes in ARONJ, probably because bone SPECT/CT has limited spatial resolution. Limitations of this study may include the imaging findings of a decrease in tracer accumulation because of an involucrum of necrosed bone, various histopathological findings in ARONJ, and failure to consider the effect of preoperative anti-inflammatory treatment.

Incidence of antiresorptive agent-related osteonecrosis of the jaw: A multicenter retrospective epidemiological study in Hyogo Prefecture, Japan.

Background/purpose: The incidence of medication-related osteonecrosis of the jaw is increasing worldwide, mostly due to the use of antiresorptive agents (ARAs) such as bisphosphonate (BP) and denosumab (Dmab). However, the proportion of BP-related osteonecrosis of the jaw (BRONJ) and Dmab-related osteonecrosis of the jaw (DRONJ) among all ARA-related osteonecrosis of the jaw (ARONJ) cases is not clear; this hinders appropriate treatment, recurrence-prevention planning, and avoidance of unnecessary Dmab withdrawal. Moreover, the causative drug administered at each disease stage remains unknown. Therefore, we conducted a retrospective study of patients with ARONJ who visited oral and maxillofacial surgery departments at hospitals in Hyogo Prefecture, Japan, over 3 years to classify and compare patient characteristics with those having BRONJ and DRONJ. We sought to identify the proportion of DRONJ in ARONJ. Materials and methods: After excluding stage 0 patients, 1021 patients were included (471 high-dose; 560 low-dose). ARA treatment for bone metastases of malignant tumors and multiple myeloma was considered high dose, while that for cancer treatment-induced bone loss and osteoporosis was low dose. Results: Low doses of BP and Dmab accounted for >50% patients; the results differed from those in other countries. DRONJ accounted for 58% and 35% of high-dose and low-dose cases, respectively. Stage 3 ARONJ cases comprised 92 (19.5%) low-dose BRONJ, 39 (20.1%) high-dose BRONJ, 24 (30%) low-dose DRONJ, and 68 (24.5%) high-dose DRONJ. Eighty-nine patients who received switch therapy were divided into BRONJ or DRONJ, but there was no difference in the ratio of each stage compared to the non-switch therapy. Conclusion: To the best of our knowledge, this is the first study to clarify the proportion of BRONJ and DRONJ cases, causative drug, and its doses by disease stages. DRONJ accounted for approximately 30% of the ARONJ, approximately 60% of which was due to high doses.

Cooperation between physicians and dentists for osteonecrosis of the jaw: a 2022 Japanese survey.

INTRODUCTION: A 2015 survey of the Japan Osteoporosis Society (JOS) on medication-related osteonecrosis of the jaw (MRONJ) revealed that cooperation between physicians and dentists was poor. Discontinuation of antiresorptive agents before tooth extraction was found to increase adverse events without preventing MRONJ. We compared this 2015 survey with a new survey conducted in 2022 to investigate cooperation between physicians and dentists for MRONJ. MATERIALS AND METHODS: A web-based structured questionnaire including 13 key queries was sent to 3813 physicians who were members of JOS, and 1227 (32.2%) responses were received. RESULTS: Of the 1227 respondents, 909 (74.1%) had complied with a discontinuation request from a dentist before tooth extraction, although 25.4% of medications were not related to the incidence of MRONJ. Of these, 177 respondents reported 252 adverse events including 10 (1.3%) cases of MRONJ. The prevalence of fractures increased from 4.8% in 2015 to 8.2% in 2022. The rates of respondents who requested oral health care by a dentist before antiresorptive agent therapy and reported cooperation between physicians and dentists were 72.7% and 42.4% in 2022 compared with 32.9% and 24.8% in 2015, respectively. The rates of cooperation among the 47 prefectures in Japan were significantly different, ranging from 10.0 to 83.3% (p = 0.02). CONCLUSION: This study confirmed increased cooperation between physicians and dentists for MRONJ in Japan. However, a more equal distribution of cooperation across Japan is necessary to optimally manage MRONJ. Discontinuation of antiresorptive agents is no longer necessary because fractures during discontinuation continue to increase in Japan.

The Clinical Benefits of Antiresorptive Agents in Patients with Primary Breast Cancer Receiving Adjuvant Endocrine Therapy: A Systematic Review with Pairwise and Network Meta-analysis.

CONTEXT: Clinical trials have investigated the role of antiresorptive agents, including bisphosphonates and denosumab, in patients with primary breast cancer receiving adjuvant endocrine therapy, aiming for better bone protection and/or improving survival. OBJECTIVE: To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy. METHODS: We systematically reviewed and synthesized the clinical benefits and harms of antiresorptive agents in patients with early breast cancer receiving endocrine therapy by calculating the risk ratios (RRs). RESULTS: In the pooled meta-analysis, antiresorptive agents had significant clinical benefits on disease recurrence (RR 0.78, 95% CI 0.67-0.90) and locoregional recurrence (RR 0.69, 95% CI 0.49-0.95) in patients with breast cancer receiving endocrine therapy. Early use of antiresorptive agents has a beneficial effect on secondary endocrine therapy resistance instead of primary resistance. Safety analysis revealed that potential risk for osteonecrosis of the jaw (ONJ, RR 3.29, 95% CI 1.12-9.68) with antiresorptive agents; however, there is an insignificant difference in arthralgia. The subgroup analyses revealed that intervention with bisphosphonates might have profound clinical benefits, but also increased the occurrence of ONJ. A network meta-analysis further supported the clinical effects of early antiresorptive agent use compared with delayed use or placebo. CONCLUSION: Using antiresorptive agents early in patients with breast cancer receiving adjuvant endocrine therapy may provide additional benefits in risk reduction of recurrence, but there is a potential risk of ONJ.

Clinical risk factors for severity and prognosis of antiresorptive agent-related osteonecrosis of the jaw: a retrospective observational study.

INTRODUCTION: The incidence of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is rare, and its management has not yet been established. This study aimed to investigate the predictors for advanced stage and healing of ARONJ to establish an appropriate treatment strategy. MATERIALS AND METHODS: We retrospectively analyzed patients diagnosed with ARONJ at Kobe City Medical Center General Hospital between April 2014 and March 2020. Outcomes were defined as stage ≥ 2 ARONJ (primary) and healing of ARONJ (secondary). Multivariate logistic regression analysis was used to detect factors associated with the outcomes, and odds ratios (OR) and 95% confidence intervals (CI) were calculated. RESULTS: This study included 143 patients (stage ≥ 2 ARONJ, 51%; healing of ARONJ, 60%). Multivariate logistic regression analysis revealed that advanced age (per year) (OR 1.037; 95% CI 1.003-1.072; p = 0.028) and serum albumin (per g/dL) (OR 0.430; 95% CI 0.213-0.869; p = 0.018) were significantly associated with stage ≥ 2 ARONJ. Furthermore, multivariate logistic regression analysis revealed that cancer (yes) (OR 0.099; 95% CI 0.029-0.339; p < 0.001), conservative surgical treatment (yes) (OR 15.42; 95% CI 5.657-42.0; p < 0.001), C-reactive protein (per mg/dL) (OR 0.599; 95% CI 0.415-0.864; p < 0.001), and vitamin D analog (yes) (OR 0.167; 95% CI 0.034-0.827; p = 0.028) were factors associated with healing. CONCLUSION: Our findings suggest that age and hypoalbuminemia are associated with the severity of ARONJ, and cancer, high inflammation, and vitamin D analog may impair healing. In contrast, conservative surgical treatment can overcome the poor treatment outcomes associated with ARONJ.

Predictive Value of Neutrophil-Lymphocyte Ratio as a Marker in Antiresorptive Agent-Related Osteonecrosis of the Jaw: A Retrospective Analysis.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ), a multifactorial disease, can drastically affect a patient's quality of life. Moreover, disease progression to severe acute inflammation can hinder treatment. Therefore, we aimed to investigate the diagnostic value of the neutrophil−lymphocyte ratio (NLR) and platelet−lymphocyte ratio (PLR) in predicting the risk of acute inflammation in patients with ARONJ. In total, 147 patients with ARONJ were enrolled between 1 January 2011 and 31 December 2019. They were divided into two groups according to their baseline NLR (high NLR vs. low NLR) or PLR (high PLR vs. low PLR) to analyze the relationship between NLR and PLR and the outcomes of acute inflammatory events. An optimal NLR cut-off value of 2.83 was identified for hospitalization for an inflammatory event. Logistic regression analysis showed that NLR > 2.83 was associated with an increased risk of hospitalization for an inflammatory event. A PLR cut-off value of 165.2 was identified for hospitalization for an inflammatory event. However, logistic regression analysis showed that PLR > 165.2 was not significantly associated with hospitalization for an inflammatory event. Our study findings suggest that the NLR has diagnostic value in predicting the risk of hospitalization for inflammatory events among patients with ARONJ.

Advances in Our Understanding of the Mechanism of Action of Drugs (including Traditional Chinese Medicines) for the Intervention and Treatment of Osteoporosis.

Osteoporosis (OP) is known as a silent disease in which the loss of bone mass and bone density does not cause obvious symptoms, resulting in insufficient treatment and preventive measures. The losses of bone mass and bone density become more severe over time and an only small percentage of patients are diagnosed when OP-related fractures occur. The high disability and mortality rates of OP-related fractures cause great psychological and physical damage and impose a heavy economic burden on individuals and society. Therefore, early intervention and treatment must be emphasized to achieve the overall goal of reducing the fracture risk. Anti-OP drugs are currently divided into three classes: antiresorptive agents, anabolic agents, and drugs with other mechanisms. In this review, research progress related to common anti-OP drugs in these three classes as well as targeted therapies is summarized to help researchers and clinicians understand their mechanisms of action and to promote pharmacological research and novel drug development.

Novel Cell Therapy Using Mesenchymal Stromal Cell Sheets for Medication-Related Osteonecrosis of the Jaw.

Despite medication-related osteonecrosis of the jaw (MRONJ) being first reported in 2003, the optimal treatment and prevention modalities for MRONJ are not clear. As a result, dentistry, oral surgery, and departments involved in the treatment of cancer and bone diseases are struggling with the management of MRONJ. Several cases of MRONJ cannot be managed by conventional treatment strategies recommended in various position papers. Therefore, studies have been conducted to investigate the efficacy of novel therapies for MRONJ. However, the optimal treatment is unknown. Several cell therapies including autologous cell transplantation have been reported for MRONJ. Although the efficacy of cell therapy for MRONJ has been demonstrated, large, statistically accurate clinical trials are lacking. We have been investigating the efficacy of MRONJ treatment using mesenchymal stromal cell (MSC) sheets since 2013 and confirmed its efficacy through various experiments, wherein MSC sheets were transplanted in model rats and beagle dogs with MRONJ-like lesions. Based on these results, we are planning to conduct a clinical trial of MRONJ therapy using periodontal ligament-derived MSC sheets.

Retrospective Analysis of Treatment Outcomes of Maxillary Sinusitis Associated with Medication-Related Osteonecrosis of the Jaw.

Although maxillary sinusitis often occurs in patients with medication-related osteonecrosis of the jaw (MRONJ) of the upper jaw, there have been few reports on the treatment and outcomes for maxillary sinusitis associated with maxillary MRONJ. This study aimed to retrospectively investigate the treatment outcomes of maxillary sinusitis in patients with MRONJ of the upper jaw. There were 34 patients diagnosed with maxillary MRONJ and sinusitis by preoperative computed tomography who underwent surgery in our institution between January 2011 and December 2019. Age, sex, primary disease, stage of MRONJ, class and administration period of an antiresorptive agent, corticosteroid administration, preoperative leukocyte count and serum albumin level, periosteal reaction, sinusitis grade, maxillary sinus surgical procedure, and treatment outcomes of MRONJ and sinusitis were examined. There were 7 male and 27 female patients (average age, 74.7 years). Complete healing of MRONJ was obtained in 29 of 34 patients (85.3%). Maxillary sinusitis resolved or improved in 21 patients (61.8%) but did not change or worsen in 13 patients (38.2%). We found that complete resection of necrotic bone with intraoperative irrigation of the maxillary sinus may provide good treatment outcomes for maxillary sinusitis associated with MRONJ, although our findings were not statistically significant owing to the small number of patients.

Medication-Related Osteonecrosis of the Jaw in Dental Practice: A Retrospective Analysis of Data from the Milan Cohort.

A retrospective analysis was performed with the aim of understanding whether the risk factors showed in the literature for medication-related osteonecrosis of the jaws (MRONJ) in cancer patients are also relevant in osteoporotic patients taking antiresorptive drugs (ARDs). Data were retrospectively pooled from health records of patients on ARDs who requested a dental visit between January 2006 and April 2020 in the Dental Unit at Fondazione Ca' Granda IRCCS Ospedale Maggiore Policlinico, University of Milan. A total of 434 patients were included. The following variables were collected: sex, age, smoking habit, type of ARD, duration of treatment, route of administration, therapeutic indication, concurrent systemic therapies and pathologies. Statistical analysis confirmed the relevance of chemotherapy, smoking, and immunosuppressive drugs as risk factors. In addition, a higher frequency of MRONJ in osteoporotic patients was reported in our cohort in association with an immunodeficiency disorder of variable origin. In conclusion, the identification of individual risk-profile before dental treatments is crucial for prevention. Anamnesis should include main risk factors, such as immunosuppression, dental extractions, smoking, trauma, and poor dental health. Nevertheless, our suggestion for dental professionals is to conduct a complete medical history of patients who mention long-term per oral therapies with ARDs for osteoporosis. Osteoporotic, as well as cancer patients, may also benefit from periodic monitoring of the ARDs therapy in order to prevent MRONJ.

Nonexposed antiresorptive agent-related osteomyelitis of the jaw: a single-center cohort study.

INTRODUCTION: The nonexposed variant of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) presents with nonspecific clinical findings. The diagnosis of nonexposed ARONJ poses a critical challenge, and there is little evidence regarding its treatment and outcomes. This study aimed to examine the clinical outcomes in patients with nonexposed antiresorptive agent-related osteomyelitis of the jaw (AROMJ). The terms ARONJ and AROMJ were used separately in this study. MATERIALS AND METHODS: We enrolled patients with nonexposed AROMJ (osteomyelitis of the jaw without bone exposure associated with antiresorptive agents) with partial reference to an existing position paper on ARONJ. The initiating event of osteomyelitis was limited to periodontitis. Based on the findings of bone scintigraphy, panoramic radiography, computed tomography, and histopathological examination, we also used the hierarchical diagnostic criteria (HDC) for osteomyelitis of the jaw. RESULTS: There were 58 confirmed cases of nonexposed AROMJ based on the HDC. All patients had sufficient clinical findings to be diagnosed with nonexposed AROMJ as osteomyelitis underwent extraction with bone debridement. The healing rate was 93.1% (54/58). Univariable analysis showed a strong association between the healing status and malignant disease, while multivariable analysis showed no strong association between them. CONCLUSIONS: The present study had a relatively large sample size of patients with nonexposed AROMJ. The primary disease in patients with nonexposed AROMJ may not have a strong association with the healed status of the lesion. Based on its high healing rate, extraction with bone debridement in confirmed nonexposed AROMJ may prevent progression.

Evidence for the major contribution of remodeling-based bone formation in sclerostin-deficient mice.

Bone formation by osteoblasts is achieved through remodeling-based bone formation (RBBF) and modeling-based bone formation (MBBF). The former is when bone formation occurs after osteoclastic bone resorption to maintain bone mass and calcium homeostasis. The latter is when new bone matrices are added on the quiescent bone surfaces. Administration of anti-sclerostin neutralizing antibody promotes MBBF in ovariectomized rats and postmenopausal women. However, it remains to be elucidated which mode of bone formation mainly occurs in Sost-deficient mice under physiological conditions. Here, we show that two-thirds of bone formation involves RBBF in 12-week-old Sost-deficient mice (C57BL/6 background). Micro-computed tomography and histomorphometric analyses showed that the trabecular bone mass in Sost-KO mice was higher than that in Sost+/- mice. In contrast, the osteoclast number remained unchanged in Sost-KO mice, but the bone resorption marker TRAP5b in serum was slightly higher in those mice. Treatment with anti-RANKL antibody increased the trabecular bone mass of Sost+/- or Sost-KO mice. Bone formation markers such as osteoid surfaces, the mineral apposition rate, and bone formation rate were almost completely suppressed in Sost+/- mice treated with anti-RANKL antibody compared with vehicle-treated Sost+/- mice. In Sost-KO mice, treatment with anti-RANKL antibody suppressed those parameters by more than half. These findings indicate that RBBF accounts for most of the bone formation in Sost+/- mice, whereas approximately two-thirds of bone formation is estimated to be remodeling-based in 12-week-old Sost-deficient mice. Furthermore, anti-RANKL antibody may be useful for detecting MBBF on trabecular bone.

The impact of acute fracture on interpretation of bone turnover marker measurements for patients starting anti-resorptive therapies.

INTRODUCTION: Bone turnover markers (BTM) are used in evaluating patients' response to anti-resorptive agents (ARA). Fracture and its healing process, however, can influence the measurements, which might make their interpretation difficult in patients with a recent fracture. We aimed to evaluate the effect of oral ARA on changes in BTM levels in patients with a recent distal radius fracture (DRF). METHODS: In 143 women who had a new DRF and then received oral ARA including selective estrogen receptor modulator (SERM, n = 101), and bisphosphonate (n = 42), we measured serum cross-linked C-telopeptides of type I collagen (CTXI) and osteocalcin, at baseline and six months, as well as lumbar and total hip bone mineral density (BMD) at baseline and one year after fracture. We determined the predictive value of BTM at six months in determining one-year responses in BMD. RESULTS: Both BTM levels decreased significantly at six months, with the average decrease of 27 ± 63% for CTX-I and 11% ± 37% for osteocalcin. The percent changes of BTM at six months were independent predictors of the BMD change. Cutoff points of 50.0% CTX-I decrease and 23.5% for osteocalcin decrease had the highest sensitivities and specificities for detecting BMD responders for bisphosphonate users, but cutoffs could not be found for SERM users. CONCLUSION: Although a fresh fracture can influence BTM, ARA therapy significantly reduced their levels and their percent change at six months could predict BMD improvement at one year. However, adjusted cutoff points can be necessary to increase sensitivity for detecting patients responsive to ARA treatment after a new DRF.

[A Case Report of Kampo Medicine Improving the Symptoms of Antiresorptive Agent-related Osteonecrosis of the Jaw (ARONJ)].

A 56-year-old woman visited an oral surgery clinic in October X with sudden pain in the left mandible. She was diagnosed with left mandibular osteomyelitis based on head computed tomography examination findings. The pain did not reduce even with amoxicillin and loxoprofen sodium hydrate. The patient was then referred to our clinic for treatment. Hainosankyuto (7.5 g/d), loxoprofen sodium hydrate (180 mg/d), and mecobalamin (1500 µg/d) alleviated the pain. However, numbness and tingling pain in the left part of the chin increased. Pregabalin 50 mg/d was then prescribed and then increased from 50 to 100 mg/d. The patient was diagnosed with antiresorptive agent-related osteonecrosis of the jaw (ARONJ). As the pain was exacerbated by discontinuation of the hainosankyuto, it was used continuously. The patient experienced no pain, even after discontinuing the mecobalamin and pregabalin. Platycodon root in hainosankyuto promotes drainage. The patient did not show any significant swelling because she took hainosankyuto during the early stages of inflammation. In addition, the pain resolved even when only hainosankyuto was used, possibly due to the analgesic effect of platycodon root, glycyrrhiza root, and peony root. Hainosankyuto may be an effective adjunctive treatment for patients with ARONJ whose pain is difficult to control with general treatment.

Effect of morphological findings in computed tomography on the quantitative values in single-photon emission computed tomography for patients with antiresorptive agent-related osteonecrosis of the jaw: a cross-sectional study.

OBJECTIVE: Quantitative analyses of gamma-ray accumulation in single-photon emission computed tomography (SPECT), and the evaluation of antiresorptive agent-related osteonecrosis of the jaw (ARONJ) have been reported recently. However, the relationship between the quantitative parameters calculated from SPECT and the detailed morphological changes observed in computed tomography (CT) remains unclear. This study aimed to investigate patients' characteristics and morphological changes observed on CT, and their effects on the quantitative values in SPECT. METHODS: From April 2017 to March 2019, patients diagnosed with ARONJ at our hospital were enrolled. The data obtained before September 2017 were reviewed retrospectively, and other data were collected prospectively. CT scans were evaluated for internal texture, sequestrum formation, periosteal reaction, cortical perforation, bone expansion, and pathological fracture. For quantitative assessment, the ratio of the maximum standardized uptake value (SUV) to the mean SUV in the temporal bone (rSUVmax) was calculated from SPECT images. The factors affecting rSUVmax were investigated by multiple regression analysis. The statistical significance level was set at α = 0.05. RESULTS: Overall, 55 lesions of 42 patients (median age and interquartile range, 75 [67-80 years], 27 female) were evaluated. Male sex (p = 0.007) and bilateral location (p < 0.0001) were selected as variables in the multivariate analysis. Adjusted coefficient of determination R2 was 0.59 (p < 0.0001). CONCLUSION: Sex and horizontal progression of the disease may affect individually calibrated SUVs in SPECT for patients with ARONJ.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis.

BACKGROUND: The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. OBJECTIVES: The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. METHODS: PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran Q χ2 test and I2 statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). RESULTS: The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35-0.53; and p < 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74-0.96; and p = 0.009 and RR = 0.75; 95% CI = 0.58-0.97; and p = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00-1.02; and p = 0.23). CONCLUSIONS: Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

Odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw with facial subcutaneous abscess formation: A retrospective clinical study of difficult-to-diagnose cases.

OBJECTIVE: The objective of this study was to analyze difficult-to-diagnose cases of odontogenic infection and antiresorptive agent-related osteonecrosis of the jaw (ARONJ) with facial subcutaneous abscesses by otolaryngologists. METHODS: The study was conducted in the department of otolaryngology of a university hospital. Seven patients exhibiting odontogenic infection and ARONJ with facial subcutaneous abscesses diagnosed at the department of otolaryngology in our hospital from January 2008 to December 2018 were included in the study. We investigated the following information obtained from the patients: clinical department for initial treatment, sex, age, offending tooth, causative disease, site of the fistula, symptoms, methods of diagnoses, and therapy. RESULTS: Odontogenic infection with facial subcutaneous abscess formation can occur in individuals in a wide range of age groups; however, the pathological manifestations of ARONJ are often observed in older women, frequently at the chin and accompanied by nodules and pain in the adjacent teeth. Computed tomography and orthopantomography are useful for diagnosis and are especially indicated for patients under long-term follow-up or with frequent recurrences. Magnetic resonance imaging, cytodiagnosis, and histological analysis might be necessary to exclude the possibility of tumors. Management of such facial subcutaneous abscesses comprises dental treatment and infection control, and f surgical removal of the abscess is usually not required. Treatments such as sequestrectomy and sitafloxacin administration are useful for patients with ARONJ. CONCLUSION: Our results demonstrated that for patients with facial subcutaneous abscesses, involvement of odontogenic infection and ARONJ should be considered.

A Case of Antiresorptive Agent-Related Osteonecrosis of the Jaw Successfully Treated with Hochuekkito / 日本東洋医学雑誌

We herein report a case of 91-year-old woman with antiresorptive agent-related osteonecrosis of the jaw (ARONJ) developed during treatment for osteoporosis with intravenous ibandronate. Although she was treated with several antibiotics and had an incision for the drainage of a pus discharge at a dental clinic for two months after the onset of ARONJ, the discharge persisted. We then added hochuekkito to her treatment, which resulted in a gradual decreased in pus discharge and decrease in wound size and the wound resolved after approximately one month. ARONJ is considered a refractory disease, however, it was successfully treated with hochuekkito in this patient. ARONJ is also a rare condition and to our knowledge, this is considered to be the first case of ARONJ, which has been successfully treated with Kampo medicine.