Does childhood chemotherapy affect mandibular bone structures in a lifetime?

BACKGROUND: Chemotherapy, one of the most important treatment modalities for treating childhood cancers, is a major cause of bone loss in patients and survivors. OBJECTIVES: This study aimed to evaluate mandibular bone structures in childhood cancer survivors (CCSs) by means of fractal dimension (FD) analysis and the Klemetti index (KI), and to compare them with regard to the control group. MATERIAL AND METHODS: In this retrospective study, the panoramic radiographs of 49 CCSs were included as the study group and the panoramic radiographs of 49 cancer-free volunteers were included as the control group. Based on the panoramic radiographs, FD and KI were determined. RESULTS: No significant differences were observed between the study and control groups in terms of mean FD values for regions of interest (ROIs) ROI_1, ROI_2 and ROI_3 (p = 0.750, p = 0.490 and p = 0.910, respectively). The mean FD values for ROI_1 for the study and control groups were 1.08 ±0.18 and 1.07 ±0.14, respectively. The mean FD values for ROI_2 for the study and control groups were 1.11 ±0.13 and 1.09 ±0.13, respectively. The mean FD values for ROI_3 for the study and control groups were 1.15 ±0.14 and 1.15 ±0.15, respectively. Statistically significant differences between the study and control groups were noted only in the distribution of the KI categories (p = 0.015). CONCLUSIONS: Childhood chemotherapy may affect mandibular bone structures during a lifetime. The Klemetti index should be considered a useful clinical diagnostic tool for the examination of mandibular bone structures.

Comparison of the Postoperative Effects of Local Antibiotic versus Systemic Antibiotic with the Use of Platelet-Rich Fibrin on Impacted Mandibular Third Molar Surgery: A Randomized Split-Mouth Study.

The surgery of the impacted mandibular third molar is the most frequent procedure in dentistry. The prescription of systemic antibiotics after the third molar extraction is widespread among dentists, but this is still argumentative. This study is aimed at evaluating the postoperative effects of local antibiotic mixed with platelet-rich fibrin (PRF) and a postoperative systemic antibiotic prescribed for mandibular third molar surgery. The study included 75 patients divided into a control and 4 test groups (n = 15). In the control group, only PRF was placed into the extracted socket, and no antibiotic was prescribed. In the first and third groups, PRF was applied to the socket; penicillin and clindamycin were prescribed as oral medications, respectively. In the second and fourth groups, only PRF combined with penicillin and clindamycin was applied into the socket, respectively. The outcome variables were pain, swelling, analgesic intake, and trismus. These variables were also assessed based on the first, second, third, and seventh days following the operation. Unpaired Student's t-test and Mann-Whitney U test were used for analysis. There were significant differences in the total VAS pain scores between the control and group 3 (p < 0.05), groups 1 and 2 (p < 0.01), and group 4 (p < 0.001) in ascending order. For analgesic intake, there was no significant difference for group 1 (p > 0.05). However, there were statistical differences between the control group and groups 2 and 3 (p < 0.01) and group 4 (p < 0.001). Trismus and swelling did not differ among the groups (p > 0.05). This study showed that the effects of local and systemic antibiotics with the use of PRF reduced postoperative outcomes. Moreover, local antibiotics with PRF may be a viable method to avoid the possible side effects of systemic antibiotics.

The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation.

BACKGROUND: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier "polybutylcyanoacrylate" (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. METHODOLOGY: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. RESULTS: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of -1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. CONCLUSION: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.

The Dual Effects of Reactive Oxygen Species on the Mandibular Alveolar Bone Formation in SOD1 Knockout Mice: Promotion or Inhibition.

The status of reactive oxygen species (ROS) correlates closely with the normal development of the oral and maxillofacial tissues. Oxidative stress caused by ROS accumulation not only affects the development of enamel and dentin but also causes pathological changes in periodontal tissues (periodontal ligament and alveolar bone) that surround the root of the tooth. Although previous studies have shown that ROS accumulation plays a pathologic role in some oral and maxillofacial tissues, the effects of ROS on alveolar bone development remain unclear. In this study, we focused on mandibular alveolar bone development of mice deficient in superoxide dismutase1 (SOD1). Analyses were performed using microcomputerized tomography (micro-CT), TRAP staining, immunohistochemical (IHC) staining, and enzyme-linked immunosorbent assay (ELISA). We found for the first time that slightly higher ROS in mandibular alveolar bone of SOD1(-/-) mice at early ages (2-4 months) caused a distinct enlargement in bone size and increased bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and expression of alkaline phosphatase (ALP), Runt-related transcription factor 2 (Runx2), and osteopontin (OPN). With ROS accumulation to oxidative stress level, increased trabecular bone separation (Tb.Sp) and decreased expression of ALP, Runx2, and OPN were found in SOD1(-/-) mice at 6 months. Additionally, dosing with N-acetylcysteine (NAC) effectively mitigated bone loss and normalized expression of ALP, Runx2, and OPN. These results indicate that redox imbalance caused by SOD1 deficiency has dual effects (promotion or inhibition) on mandibular alveolar bone development, which is closely related to the concentration of ROS and the stage of growth. We present a valuable model here for investigating the effects of ROS on mandibular alveolar bone formation and highlight important roles of ROS in regulating tissue development and pathological states, illustrating the complexity of the redox signal.

Mandibular metastases in neuroblastoma: Outcomes and dental sequelae.

BACKGROUND: Although metastatic involvement of bony sites including cranial bones is common in neuroblastoma (NB), mandibular metastases (MM) are uncommon, and specific outcomes have not been reported upon in the modern therapeutic era. METHODS: In this retrospective study, medical records on patients with MM from NB were reviewed. Statistical analysis was performed using the Kaplan-Meier method. RESULTS: Of 29 patients, nine (31%) had MM at diagnosis, whereas in 20 (69%) MM were first detected at NB relapse at a median time of 26 (6-89) months from diagnosis. Median maximal diameter of lesions was 3 (range 0.8-4.9) cm. MM were unilateral in 83% of patients, with ascending ramus (55%) and mandibular body (38%) being the two most common sites. All patients received systemic chemotherapy, and 26 (93%) patients received radiotherapy to MM. At a median follow-up of 37.3 (24.2-219.5) months, eight of nine patients with MM at diagnosis did not experience mandibular progressive disease. Eighteen of 20 patients with MM at relapse received therapeutic radiotherapy; objective responses were noted in 78%. Seventy-two percent (5/18) had not experienced relapse within the radiation field at a median of 12 (2-276) months postradiotherapy. Dental findings at follow-up after completion of NB therapy included hypodontia, hypocalcification of enamel, and trismus. Median 3-year overall survival in patients with relapsed MM was 51 ± 12% months from relapse. CONCLUSION: MM when detected at diagnosis is associated with a prognosis similar to that for other skeletal metastases of NB. Radiotherapy is effective for control of MM detected both at diagnosis and relapse. Significant dental abnormalities posttherapy warrant regular dental evaluations and appropriate intervention.

Effects of Drynaria Total Flavonoid on the Microstructure of the Mandible in Ovariectomized Rats.

BACKGROUND The aim of this study is to investigate the effects of Drynaria total flavonoids (DTF) on mandible microarchitecture, serum estrogen (E2), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in an ovariectomy-induced osteoporosis rat model. MATERIAL AND METHODS Thirty female Sprague-Dawley rats were divided into 5 groups (n=6 per group): sham surgery, ovariectomy (OVX), and low-dose, middle-dose, and high-dose DTF. Mandibular osteoporosis was induced by ovariectomy; an equal amount of ovary-sized fat tissue was removed from the sham group. The DTF-treated groups were given DTF gavage at different doses for 12 weeks; the sham and OVX groups were given saline. After the treatment phase, the effects of DTF on the microarchitecture of the mandible were evaluated by measuring bone density, maximum load, morphometric parameters, and histopathological alterations. Serum E2, OPG, and RANKL levels were measured. RESULTS The OVX group showed obvious osteoporosis in the mandible and decreased serum E2 levels and OPG/RANKL ratio. The low-dose group did not show significant improvement in mandibular microstructure. The middle-dose group showed significantly ameliorated osteoporosis. The high-dose group had further improvement in bone microstructures and increase of OPG/RANKL over the middle-dose group. Furthermore, ovariectomy significantly decreased serum E2, but DTF treatment failed to restore serum E2 levels. CONCLUSIONS Ovariectomy can cause significant bone loss in the rat mandible and a decrease in serum E2 and OPG/RANKL. DTF significantly improved the mandibular microstructure and restored OPG/RANKL balance, but it did not restore the decreased serum E2 concentration following ovariectomy.

3D printed composite scaffolds with dual small molecule delivery for mandibular bone regeneration.

Functional reconstruction of craniomaxillofacial defects is challenging, especially for the patients who suffer from traumatic injury, cranioplasty, and oncologic surgery. Three-dimensional (3D) printing/bioprinting technologies provide a promising tool to fabricate bone tissue engineering constructs with complex architectures and bioactive components. In this study, we implemented multi-material 3D printing to fabricate 3D printed PCL/hydrogel composite scaffolds loaded with dual bioactive small molecules (i.e. resveratrol and strontium ranelate). The incorporated small molecules are expected to target several types of bone cells. We systematically studied the scaffold morphologies and small molecule release profiles. We then investigated the effects of the released small molecules from the drug loaded scaffolds on the behavior and differentiation of mesenchymal stem cells (MSCs), monocyte-derived osteoclasts, and endothelial cells. The 3D printed scaffolds, with and without small molecules, were further implanted into a rat model with a critical-sized mandibular bone defect. We found that the bone scaffolds containing the dual small molecules had combinational advantages in enhancing angiogenesis and inhibiting osteoclast activities, and they synergistically promoted MSC osteogenic differentiation. The dual drug loaded scaffolds also significantly promoted in vivo mandibular bone formation after 8 week implantation. This work presents a 3D printing strategy to fabricate engineered bone constructs, which can likely be used as off-the-shelf products to promote craniomaxillofacial regeneration.

Effect of α2­macroglobulin in the early stage of jaw osteoradionecrosis.

Advanced osteoradionecrosis (ORN) is one of the most serious complications in patients with head and neck cancer, resulting in poor prognosis. Numerous studies have therefore focused on the pathogenesis and interventions of ORN early stage. The present study aimed to investigate whether α2­macroglobulin (α2M) could prevent early­stage jaw osteoradionecrosis caused by radiotherapy (RT). Following local injection of α2M, a single dose of 30 Gy was delivered to rats for pathological exploration. For 28 days, the irradiated mandible and soft tissues were examined for potential changes. Furthermore, primary human bone marrow mesenchymal stem cells pretreated with α2M followed by 8 Gy irradiation (IR) were also used. Tartrate­resistant acid phosphatase assay, terminal uridine deoxynucleotidyl nick end labeling assay and immunohistochemical staining were performed on irradiated mandibular bone, tongue or buccal mucosa tissues from rats. Cell proliferation was assessed by evaluating the cell morphology by microscopy and by using the cell counting kit­8. Fluorescence staining, flow cytometry and western blotting were conducted to detect the reactive oxygen species level, cell apoptosis and protein expression of superoxide dismutase 2 (SOD2), heme oxygenase­1 (HO­1) and phosphorylated Akt following irradiation. The results demonstrated that α2M attenuated physical inflammation, osteoclasts number and fat vacuole accumulation in mandibular bone marrow and bone marrow cell apoptosis following IR in vivo. Furthermore, α2M pretreatment suppressed the expression of 8­hydroxy­2'­deoxyguanosine in mandibular bone and tongue paraffin embedded sections, which is a marker of oxidative damage, and increased SOD2 expression in mucosa and tongue paraffin embedded sections. The present study demonstrated the efficient regulation of antioxidative enzymes, including SOD2 and heme oxygenase­1, and reduction in oxidative damage by α2M. In addition, in vitro results confirmed that α2M may protect cells from apoptosis and suppress reactive oxygen species accumulation. Overall, the present study demonstrated that α2M treatment may exert some radioprotective effects in early­stage ORN via antioxidant mechanisms, and may therefore be considered as a potential alternative molecule in clinical prophylactic treatments.

Bisphophonate alterations of the jaw bones in individuals with multiple myeloma.

OBJECTIVES: To verify quantitative differences of the mandibular cortical and trabecular bone between patients with multiple myeloma (MM) under bisphosphonate (BP) therapy and a control group never exposed to BP. METHODS: Clinical and demographic characteristics were collected through medical records and interviews. Mandibular cortical thickness (MCT) and fractal dimension (FD) were measured on cone beam computed tomography (CBCT) images, on the molar region, in both groups. Additionally, FD was measured on periapical digital intraoral radiography and results were compared to CBCT measurements. RESULTS: There were 33 patients with MM under BP therapy and 28 controls, with no significant differences in gender and age between groups. Pamidronate was used by all MM patients, either associated or not to other types of BP. The median MCT was higher in MM group exposed to BP (5.20 mm) than in controls (3.50 mm, p < 0.001). There were no significant differences in the median FD between patients in the MM group and controls, on CBCT (0.95 vs 0.90, p = 0.814) and periapical digital intraoral radiography (0.98 vs 0.96, p = 0.963), respectively, even when more than one type of BP was used. CONCLUSIONS: The MCT represents an useful tool in the detection of bone dimensional changes caused by BP, in patients with MM. Additional studies are necessary to improve the knowledge on the quantitative evaluation of trabecular jaw bone, in individuals with MM, under BP therapy.

Effects of different pre-operative doses of dexamethasone on alveolar repair in rats.

Dexamethasone has been widly used in oral and maxillofacial surgery for controlling of postoperative surgical inflammation. Despite its clinical effectiveness, several studies have demonstrated the negative impact of this drug on the healing of soft and hard tissues. This study aimed to assess the effects of different pre-operative doses of dexamethasone on alveolar repair. Sixty rats were divided into four groups of 15 animals each. Single pre-operative doses of dexamethasone equivalent to human doses of 4 mg (Group 4 mg), 8 mg (Group 8 mg), and 12 mg (Group 12 mg), calculated by allometric dose extrapolation, were administered; and rats in the Control Group were injected with saline solution. The animals were anesthetized, and their left mandibular first molars (M1) were removed. After three, seven, and 40 days, 5 animals from each group were euthanized, and bone samples of M1 alveolus were collected for radipgraphic, histomorphological and histometric evaluation of the early and late phases of alveolar healing. At three days, Group 12 mg presented reduced radiographic density, percentage of collagen, and connective matrix compared with the Control Group. At 7 days, the percentage of bone was increased in the Control Group compared to Groups 8 mg and 12 mg (P < 0.05). It can be concluded that a single pre-operative dose of 12 mg of dexamethasone affected the early stages of alveolar repair in rats.

Evaluation of mandibular morphometry in the bisphosphonate users / Evaluación de la morfometría mandibular en los usuarios de bifosfonatos

This study aimed to evaluate the effects of bisphosphonates on the mandibular bone. Bisphosphonates are drugs which are commonly used in the treatment of many diseases related to bone metabolism such as osteoporosis, breast cancer capable of bone metastasis, prostate and lung cancer and bone cancer such as multiple myeloma. Our study group consisted of a total of 100 panoramic radiographs which were obtained from the examinations of 50 individuals using bisphosphonate and 50 individuals in the control group who applied for routine dental examination to the Department of Oral and Maxillofacial Radiology of Akdeniz University Dentistry Faculty between years 2015 and 2016.The calculations of the mandibular cortical thickness (MCT), mandibular cortical index (MCI), panoramic mandibular index (PMI), condylar angle (CA), gonial angle (GA), antegonial angle (AGA), antegonial depth (AGD) and antegonial index (AGI) were made for each patient. It was found that both left and the right MCT and only the left PMI were affected by age. Only the left AGA and both the left and right MCT and AGD were affected by gender. The left and right AGI measurements of the patients using bisphosphonates were statistically lower than those of the individuals in the control group. Our results suggested that bisphosphonates had various effects on the jaw bones. However, further comprehensive studies need to be made to evaluate the longterm effect of bisphosphonates on bone metabolism.

Este estudio tuvo como objetivo evaluar los efectos de los bifosfonatos en el hueso mandibular. Los bifosfonatos son medicamentos que se usan comúnmente en el tratamiento de muchas enfermedades relacionadas con el metabolismo óseo, como la osteoporosis, el cáncer de mama, metástasis óseas, cáncer de próstata y pulmón y el cáncer de hueso como el mieloma múltiple. Nuestro grupo de estudio consistió en un total de 100 radiografías panorámicas que se obtuvieron de los exámenes de 50 individuos que utilizaron bisfosfonato y 50 individuos en el grupo de control que solicitaron un examen dental de rutina al Departamento de Radiología Oral y Maxilofacial de la Facultad de Odontología de la Universidad de Akdeniz, entre los años 2015 y 2016. En cada paciente se realizaron los cálculos del grosor cortical mandibular (GCM), índice cortical mandibular (ICM), índice mandibular panorámico (IMP), ángulo condilar (AC), ángulo gonial (AG), ángulo antegonial (AAG), profundidad antegonial ( PAG) y el índice antegonial (IAG). Se encontró que tanto el GCM izquierdo como el derecho y solo el IMP izquierdo estaban afectados por la edad. Solo el AAG izquierdo y el GCM izquierdo y derecho y el AGD fueron afectados de acuerdo al sexo. Las mediciones de IAG izquierdo y derecho de los pacientes que utilizan bifosfonatos fueron estadísticamente más bajas que las de los individuos en el grupo de control. Nuestros resultados sugirieron que los bifosfonatos tienen varios efectos en los huesos de la mandíbula. Sin embargo, es necesario realizar estudios más exhaustivos para evaluar el efecto a largo plazo de los bifosfonatos en el metabolismo óseo.

Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid.

Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.

Induction of maxillary and mandibular squamous epithelial cell proliferation in mink (Neovison vison) by ß-naphthoflavone.

A jaw lesion reported in mink exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and TCDD-like chemicals is considered a potential indicator of exposure to these chemicals. Many of the effects of TCDD-like chemicals are induced through interaction with the aryl hydrocarbon receptor. The present study indicates that mink dosed with ß-naphthoflavone, which is an aryl hydrocarbon receptor ligand but not a TCDD-like chemical, also develop the lesion. Environ Toxicol Chem 2019;38:460-463. © 2018 SETAC.

The effect of the new hemostatic agent Ostene on bone healing: an experimental study in rabbits

Introduction: Ostene is a water-soluble wax-like alkylene oxide copolymer preparation for use as a mechanical hemostatic agent. this study aims to evaluate the effects of Ostene on bone healing. materials and methods: twenty albino rabbits were divided into four groups according to post-treatment follow-up (24 hr, 3 days, 7 days, 14 days) with five rabbits in each group. each rabbit in all groups was treated with two study materials (Ostene and Gelfoam). three holes were made in the mandibular bone of each rabbit using 5mm surgical bur; two holes were made on right side: one for testing Ostene and another for Gelfoam. a third hole, on the left side of mandible, was not treated, and was used as a control. finally, the incision was closed. the specimens were collected at different days post-treatment and examined by histopathology. result and discussion: this study showed that there is a significant difference (p-value≤ 0.05) between the Ostene group and the other groups (Gelfoam and control). at 24 hr post intervention, there is a significant difference in osteoblast cell formation (p-value=0.03), and osteoclast cell formation (p-value=0.05). new blood vessel formation, osteoblast and osteoclast cell formation for Ostene group at 3 days post-intervention were also significantly different (p-values = 0.05, 0.03, 0.04, respectively). at 7 days post-intervention p-values were 0.05 for osteoblast formation and 0.04 for osteoclast formation, respectively. after 14 days of healing p-value for osteoblast cell formation in the Ostene group was 0.05 and 0.04 for osteoclast cell formation. conclusions: the bone hemostatic agent Ostene is an effective at enhancing osteogenesis by initiating proliferation of osteoblast and osteoclast cells.

Three-Dimensional Analysis of the Correlation Between Soft Tissue and Bone of the Lower Face Using Three-Dimensional Facial Laser Scan.

BACKGROUND: The prime aims of this study were to establish cephalometric linear and angular normative values of the lower face using a three-dimensional (3D) analysis in Korean individuals, and validate whether the linear and angular measurements using 3D laser scanner are comparable with measurements using 3D computed tomography (CT). METHODS: In this study, 40 Korean individuals aged between 18 and 60 years were enrolled. Using 3D CT scan and 3D laser scanner, linear and angular values of the lower face were measured and recorded. Statistical analysis was carried out to verify the concordance and correlation between two 3D imaging modalities. RESULTS: The 40 samples consisted of 11 women with a mean age of 40.8 ±â€Š14.5 years and 29 men with a mean age of 29.7 ±â€Š15.0 years. The results demonstrated the difference between sex and the tendency of asymmetry on both sides. Among different methods of measuring angular values, the gonial angle (GA) between tragion' (Tr')-gonion' (Go')-menton' (Me') from 3D laser scanning and between articulate-gonion-menton from CT scan demonstrated a good concordance and a high correlation. CONCLUSIONS: The GA measured between Tr'-Go'-Me' using a 3D facial laser scan was comparable with values from 3D CT scan. The reference points and the GA, which we assessed here for 3D laser scanning, can be a reliable alternative method evaluating mandibular angles for assessing patients and surgical planning in plastic and orthognathic surgery.

Systemic melatonin application increases bone formation in mandibular distraction osteogenesis.

This study aimed to investigate the effects of different doses of systemic melatonin application on new bone formation during mandibular distraction osteogenesis (DO) in rats. Mandibular DO was performed on 30 adult female Sprague-Dawley rats, which were randomly divided into three groups: control group (CNT), melatonin dose 1 (MLT-D1), and melatonin dose 2 (MLT-D2). A five-day latent waiting period and a ten-day distraction phase followed the surgery. After the surgery, rats from the MLT-D1 and MLT-D2 groups received 25 and 50 mg/kg melatonin, respectively, at 7, 14, 21, 28, and 35 days. The animals were euthanised 28 days after distraction, i.e. at 43 days after surgery. Histological and histomorphometric analyses revealed that the distracted bone area was completely filled with new bone formation in all three groups. The MLT-D2 group exhibited the most new bone formation, followed by MLT-D1 and CNT. The melatonin groups had more osteoclasts than the CNT (p < 0.05). The number of osteoblasts was higher in the melatonin groups than in the CNT group, and the MLT-D2 had more osteoclasts than the MLT-D1 group (p < 0.05). Finally, the osteopontin (OPN) and vascular endothelial growth factor (VEGF) levels were higher in the melatonin groups than in the CNT group, and the MLT-D2 had higher OPN and VEGF levels than the MLT-D1 (p < 0.05). This study suggests that systemic melatonin application could increase new bone formation in DO.

Histological and immunohistochemical evaluation of mandibular bone tissue regeneration.

The purpose of the study was to perform an immunohistochemical and histological evaluation of samples taken from different bone regeneration procedures in atrophic human mandible. 30 patients (15 men and 15 women, age range of 35-60 years), non-smokers, with good general and oral health were recruited in this study and divided into three groups. The first group included patients who were treated with blood Concentration Growth Factors (bCGF), the second group included patients who were treated with a mixture of bCGF and autologous bone, while the third group of patients was treated with bCGF and tricalcium phosphate/hydroxyapatite (TCP-HA). Six months after the regenerative procedures, all patients undergone implant surgery, and a bone biopsy was carried out in the site of implant insertion. Each sample was histologically and immunohistochemically examined. Histological evaluation showed a complete bone formation for group II, partial ossification for group I, and moderate ossification for group III. Immunohistochemical analysis demonstrated a statistically significant difference between the three groups, and the best clinical result was obtained with a mixture of bCGF and autologous bone.

Cathepsin K inhibitor causes changes in crystallinity and crystal structure of newly-formed mandibular bone in rats.

Cathepsin K inhibitors are new drugs with the potential for the treatment of osteoporosis because they sustain bony remodelling better than bone resorption inhibitors such as bisphosphonates. The treatment of osteoporosis with inhibitors of bony resorption is associated with osteonecrosis of the jaw, as the deterioration in bony quality that they induce is thought to be one of its causes. The quality of bone is delineated by structural and material characteristics (which include the degree and quality of mineralisation, and depends on the content of proteoglycan and the structural integrity of the bony collagen).1,2 Animal and clinical studies have shown that cathepsin K inhibitors improve the mineral density and structural characteristics of bone, but their effect on the rest remains unknown. We therefore hypothesised that these inhibitors will affect the material characteristics of newly-formed mandibular bone. To verify our hypothesis, we used Raman microspectroscopy to examine such bone in rats that were given a cathepsin K inhibitor, and found unusual crystallinity and an increased substitution of carbonate (CO32-) in its crystal structure.