Bisphosphonate-induced osteonecrosis of the jaw in a rat model arises first after the bone has become exposed. No primary necrosis in unexposed bone

J Oral Pathol Med (2012) 41 : 494–499 Background: Bisphosphonate‐related osteonecrosis of the jaw was first described to start with sterile osteocyte death, similar to osteonecrosis in other parts of the skeleton. The typical chronic osteomyelitis was thought to develop when the dead bone was exposed to the oral cavity. An alternative explanation would be that the chronic osteomyelitis is a result of a bisphosphonate‐related inability of infected bony lesions to heal. We tested the hypothesis that primary osteocyte death is not necessary for the development of jaw osteonecrosis. Material and methods: Forty rats were randomly allocated to four groups of 10. All animals underwent unilateral molar extraction and received the following drug treatments: Group I, controls with no drug treatment; Group II, 200 μg/kg per day alendronate; Groups III and IV, 200 μg/kg per day alendronate and 1 mg/kg of dexamethasone. All rats were euthanized after 14 days. Presence of osteonecrosis was determined by clinical and histological observations for groups I–III. For group IV, osteocyte viability at the contralateral uninjured site was examined using lactate dehydrogenase histochemistry (LDH). Results: All animals in the alendronate plus dexamethasone groups developed large ONJ‐like lesions. Lactate dehydrogenase staining showed viable osteocytes in the contralateral jaw with no tooth extraction. No signs of osteonecosis were seen in the other groups. Conclusion: Bisphosphonates and dexamethasone caused no osteocyte death in uninjured bone, but large ONJ‐like lesions after tooth extraction. Osteonecrosis of the jaw appears to arise first after the bone has been exposed. Possibly, bisphosphonates hamper the necessary resorption of bone that has become altered because of infection.     

Coronary flow reserve, strain and strain rate imaging during pharmacological stress before and after percutaneous coronary intervention: comparison and correlation

Introduction: Coronary flow reserve (CFR) could apply reliable information about the coronary circulation, and strain (S) and strain rate imaging (SRI) are able to quantify the left ventricular myocardial performance. The aim of this study was to assess myocardial performance in relation to the function of the coronary circulation before and after successful percutaneous coronary intervention (PCI) of the left anterior descending artery. Material and Method: Fourteen patients (10 men, 4 women, mean age 53.2 ± 11.4 years) with severe left anterior descending stenosis who had a successful selective PCI were recruited into this study. CFR and myocardial deformity indices (S and SR) were recorded before and after percutaneous intervention, both at rest and during stress echo test. Results: CFR, S, and SR increased after intervention significantly. There was significant correlation between CFR ratio and poststress systolic strain (SS) ratio and early diastolic strain rate (ESR) ratio (P < 0.05 and r > 0.6). Also CFR improvement had significant relationship with changes of poststress Systolic SR and poststress Systolic S (P < 0.05 and r > 0.6). Based on regression analysis the amount of change in CFR was independently associated with change in SS during stress and systolic SR. Conclusion: PCI improves CFR (a marker of coronary perfusion), strain, and strain rate (markers of regional cardiac wall deformation). The independent association between CFR improvement and poststress systolic strain and strain rate means that SRI parameters can independently predict CFR changes after PCI. (Echocardiography 2011;28:570‐574)     

Serum Interleukine-6 Concentration,But Not Interleukine-18, is Associated with Head and Neck Squamous Cell Carcinoma Progression

Inflammation has been linked to various steps in tumorigenesis. Interleukin (IL)-6 and IL-18 are two inflammatory cytokines whose serum concentrations are elevated in several types of cancer, including head and neck squamous cell carcinoma (HNSCC) in some studies. This study was designed to analyze the serum concentrations of these cytokines in Iranian HNSCC patients. Serum IL-6 and IL-18 concentrations were assayed by ELISA commercial kits in 65 untreated patients and 20 healthy volunteers. Serum IL-6 concentration was significantly increased in patients compared to healthy individuals (p < 0.000). IL-6 concentration increased as the tumor stage progressed, and a significant difference appeared between stage IV vs. stage I/II/III (p = 0.03) disease. Although serum IL-18 concentration was higher in patients than in healthy individuals, the difference was not statistically significant (p = 0.06). Moreover, there was no association between serum IL-18 concentration and tumor stage (p = 0.47). A significant difference was observed in serum IL-18 concentration according to the gender with higher IL-18 concentration in male patients (p = 0.01). In conclusion, serum concentration of IL-6 might correlate with the stage of tumor progression in Iranian HNSCC patients. Further studies with larger numbers of patients are required to exclude the possible minor correlation of serum IL-18 concentration with tumor stage.     

Prevention of osteonecrosis of the jaw by mucoperiosteal coverage in a rat model

There is evidence for a link between the use of systemic bisphosphonates and osteonecrosis of the jaw (ONJ). This condition has the appearance of chronic osteomyelitis, and antibiotics prevent the development of ONJ in animal models. Clinically, ONJ can sometimes be treated successfully by mucoperiosteal coverage. If ONJ is indeed primarily caused by bacterial infection, immediate coverage of the extraction alveolus might reduce the risk of ONJ developing in risk patients. Therefore, we studied whether immediate mucoperiosteal coverage after tooth extraction could prevent the development of ONJ in a rat model. Thirty rats were randomly allocated to three groups (10 in each): (1) group I (controls): extraction, no drug treatment; (2) group II (non-coverage): extraction, dexamethasone plus alendronate; (3) group III (coverage): extraction, dexamethasone plus alendronate, plus coverage with a mucoperiosteal flap. Rats were examined for macroscopic ONJ-like wounds after 2 weeks. All animals in the non-coverage group developed large ONJ-like changes. The coverage and control groups showed an intact overlying mucosa in all rats. Findings were confirmed with histology. Bisphosphonates and dexamethasone caused ONJ-like lesions after tooth extraction in a rat model. This was prevented by immediate mucoperiosteal coverage. The risk of ONJ in patients using bisphosphonates might be reduced by mucoperiosteal coverage after tooth extraction.