UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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).
UNASSIGNED: 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.

BACKGROUND: 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.
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).
CONCLUSIONS: 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.

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.
To summarize the clinical effects of antiresorptive agents in patients with early breast cancer receiving endocrine therapy.
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).
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.
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.

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.

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.

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.

BACKGROUND: 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.
CONCLUSIONS: 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.

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.
OBJECTIVE: 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.

UNASSIGNED: To assess the knowledge of dentists regarding medication-related osteonecrosis of the jaw (MRONJ).
UNASSIGNED: In this cross-sectional study, 74 dentists from governmental hospitals in Riyadh (Dental University Hospital in King Saud University, Military Hospital, National Guard Hospital), Jeddah (King Abdulaziz University Hospital, Ministry of Health Hospital), and the Eastern region of Saudi Arabia (Ministry of Health Hospitals in Dammam and Al-Ahsa) completed a two-part questionnaire. The first part gathered demographic data, such as sex and specialty. The second part included questions about bisphosphonate drugs and their indications; the identification of patients at risk of MRONJ; other medications associated with jaw necrosis; as well as the definition of MRONJ and its clinical features, risk factors, and preventive methods.
UNASSIGNED: Of the participating dentists, 60.8% knew about MRONJ, but only 35.1% were able to define it correctly. Most (79.7%) had never encountered MRONJ patients. Only 18.9% knew of the relationship between the risk of MRONJ in osteoporotic patients and long-term (>4 years) use of oral bisphosphonates or intravenous zoledronate, while 68.9% were unaware, and others answered incorrectly. Most participants did not know of MRONJ-predisposing medications, and 59.5% cited radiotherapy as the cause. Most participants identified dentoalveolar surgery as a major local factor, and the mandible as a common anatomic location.
UNASSIGNED: Dentists at the surveyed institutions had poor knowledge of MRONJ, although their knowledge of preventive measures was good. There is an urgent need for the optimization of educational programs pertaining to MRONJ, and its related dental management considerations.
UNASSIGNED: Dentists in the surveyed institutions in Kingdom of Saudi Arabia have poor knowledge of MRONJ management; thus, greater effort should be taken to educate undergraduate and postgraduate students regarding this pathology.

OBJECTIVE: The main aim is to identify, by means of different imaging modalities, the early bone changes in patients \"at risk\" and in stage 0 MRONJ.
METHODS: A search of the literature was performed on PubMed, Embase, Web of Science, and Cochrane Library databases, until June 9, 2020. No language or year restrictions were applied. Screening of the articles, data collection, and qualitative analysis was done. The Newcastle-Ottawa Scale (NOS) was used for observational studies, and the Systematic Review Centre for Laboratory Animal Experimentation\'s (SYRCLE) risk of bias tool for the animal studies.
RESULTS: A total of 1188 articles were found, from which 47 were considered eligible, whereas 42 were suitable for the qualitative analysis. They correspond to 39 human studies and 8 animal studies. Radiographic findings such as bone sclerosis, osteolytic areas, thickening of lamina dura, persisting alveolar socket, periapical radiolucency, thicker mandibular cortex, widening of the periodontal ligament space, periodontal bone loss, and enhancement of the mandibular canal were identified as early bone changes due to antiresorptive therapy. All those findings were also reported later in Stage 0 patients.
CONCLUSIONS: The main limitations of these results are the lack of prospective data and comparisons groups; therefore, careful interpretation should be made. It is a fact that radiographic findings are present in antiresorptive-treated patients, but the precise timepoint of occurrence, their relation to the posology, and potential risk to develop MRONJ are not clear.
CONCLUSIONS: The importance of a baseline radiographic diagnosis for antiresorptive-treated patients.