Evaluation of Preventive Role of Systemically Applied Erythropoietin after Tooth Extraction in a Bisphosphonate-Induced MRONJ Model

Background and Objectives: In this experimental study, the prophylactic effect of systemically administered erythropoietin (EPO) in medication-related osteonecrosis of the jaw (MRONJ) was evaluated. Materials and Methods: The osteonecrosis model was established using 36 Sprague Dawley rats. EPO was systemically applied before and/or after tooth extraction. Groups were formed based on the application time. All samples were evaluated histologically, histomorphometrically, and immunohistochemically. A statistically significant difference in new bone formation was observed between the groups (p Results: When new bone-formation rates were compared, no significant differences were observed between the control group and the EPO, ZA+PostEPO, and ZA+Pre-PostEPO groups (p = 1, 0.402, and 1, respectively); however, this rate was significantly lower in the ZA+PreEPO group (p = 0.021). No significant differences in new bone formation were observed between the ZA+PostEPO and ZA+PreEPO groups (p = 1); however, this rate was significantly higher in the ZA+Pre-PostEPO group (p = 0.009). The ZA+Pre-PostEPO group demonstrated significantly higher intensity level in VEGF protein expression than the other groups (p Conclusions: Administering EPO two weeks pre-extraction and continuing EPO treatment for three weeks post-extraction in ZA-treated rats optimized the inflammatory reaction, increased angiogenesis by inducing VEGF, and positively affected bone healing. Further studies are needed to determine the exact durations and doses

Preventive effect of doxycycline sponge against bisphosphonate-related osteonecrosis of the jaws: an animal study

The aim of this study is to investigate the effect of doxycycline collagen sponge on bisphosphonate-related osteonecrosis of the jaw (BRONJ) and the level of serum biomarkers as an indicator of osteonecrosis. Twenty-four rats were divided into four groups. Animals in the control group were injected with saline and animals in Groups I, II and III were injected with zoledronate three times a week for eight weeks. After eight weeks, the following procedures were performed in each group. In Group I: extraction of maxillary first molar, in Group II: extraction of maxillary first molar and mucoperiosteal coverage was performed and in Group III: extraction of maxillary first molar and mucoperiosteal coverage with doxycycline collagen sponges was performed. At the end of 16 weeks, all animals were sacrificed. Serum collagen type I C-telopeptide (CTx), tartrate-resistant acid phosphatase (TRACP 5b) and alkaline phosphatase (ALP) levels’ analysis, clinical examination, histological and histomorphometrical analysis were performed. As a result no significant difference in CTx, TRACP 5b and ALP levels was observed between groups. Complete mucosal healing was observed in all animals in the control group and 66.7% of animals in Group III. The necrotic bone area in Group III was significantly lower than the other groups (p < 0.01). Statistically significant difference was observed between groups in terms of detached osteoclast number (p < 0.01). In conclusion, local application of doxycycline could have a positive effect in reducing the risk of BRONJ in rats

Headache in idiopathic/genetic epilepsy: Cluster analysis in a large cohort

Objective The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features. Methods Patients aged 6-40 years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm. Results Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, >= 5 headache attacks, duration of headache >= 24 months, headaches lasting >= 1 h, and visual analog scale scores > 5 were grouped in one cluster, and subjects with juvenile myoclonic epilepsy (JME), myoclonic seizures, and generalized tonic-clonic seizures (GTCS) were clustered in this group (Cluster 1). Self-limited epilepsy with centrotemporal spikes and epilepsy with GTCS alone were clustered in Cluster 2 with the opposite characteristics. For children/adolescents, the same features as in adult Cluster 1 were clustered in a separate group, except for the presence of JME syndrome and GTCS alone as a seizure type. Focal seizures were clustered in another group with the opposite characteristics. In the entire group, the model revealed an additional cluster, including patients with the syndrome of GTCS alone (50.51%), with >= 5 attacks, headache lasting >4 h, and throbbing headache; 65.66% of patients had a family history of headache in this third cluster (n = 99). Significance Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies