Accelerated Development With Increased Bone Mass and Skeletal Response to Loading Suggest Receptor Activity Modifying Protein-3 as a Bone Anabolic Target

Knockout technologies provide insights into physiological roles of genes. Studies initiated into endocrinology of heteromeric G protein-coupled receptors included deletion of receptor activity modifying protein-3, an accessory protein that alters ligand selectivity of calcitonin and calcitonin-like receptors. Initially, deletion of Ramp3-/- appeared phenotypically silent, but it has emerged that mice have a high bone mass phenotype, and more subtle alterations to angiogenesis, amylin homeostasis, and a small proportion of the effects of adrenomedullin on cardiovascular and lymphatic systems. Here we explore in detail, effects of Ramp3-/- deletion on skeletal growth/development, bone mass and response of bone to mechanical loading mimicking exercise. Mouse pups lacking RAMP3 are healthy and viable, having accelerated development of the skeleton as assessed by degree of mineralisation of specific bones, and by microCT measurements. Specifically, we observed that neonates and young mice have increased bone volume and mineralisation in hindlimbs and vertebrae and increased thickness of bone trabeculae. These changes are associated with increased osteoblast numbers and bone apposition rate in Ramp3-/- mice, and increased cell proliferation in epiphyseal growth plates. Effects persist for some weeks after birth, but differences in gross bone mass between RAMP3 and WT mice lose significance in older animals although architectural differences persist. Responses of bones of 17-week old mice to mechanical loading that mimics effects of vigorous exercise is increased significantly in Ramp3-/- mice by 30% compared with WT control mice. Studies on cultured osteoblasts from Ramp3-/- mice indicate interactions between mRNA expression of RAMPs1 and 3, but not RAMP2 and 3. Our preliminary data shows that Ramp3-/- osteoblasts had increased expression β-catenin, a component of the canonical Wnt signalling pathway known to regulate skeletal homeostasis and mechanosensitivity. Given interactions of RAMPs with both calcitonin and calcitonin-like receptors to alter ligand selectivity, and with other GPCRs to change trafficking or ligand bias, it is not clear whether the bone phenotype of Ramp3-/- mice is due to alterations in signalling mediated by one or more GPCRS. However, as antagonists of RAMP-interacting receptors are growing in availability, there appears the likelihood that manipulation of the RAMP3 signalling system could provide anabolic effects therapeutically.

Difference in the Alveolar Bone Remodeling Between the Adolescents and Adults During Upper Incisor Retraction: a Retrospective Study

Background: The purpose of this study was to compare the difference of alveolar bone remodeling between the adolescents and adults in the maxillary incisor area during retraction. Methods: This retrospective study included 72 female patients who needed moderate anchorage to correct the bimaxillary protrusion. Subjects were further divided into the minor group (n=36, 11-16 years old) and adult group (n=36, 18-35 years old). Digital lateral cephalography and cone beam CT scanning were taken in each patient before (T0) and after treatment (T1). Cephalometry was conducted to assess incisor retraction, while alveolar bone thickness (ABT), alveolar bone distance (ABD, and alveolar bone area (ABA) were detected to assess changes in the alveolar bone. Results: No difference in the inclination of upper incisors was observed at both T0 and T1. Changes in the alveolar bone showed a similar tendency with bone apposition on the labial side and resorption on the palatal side. Less increase in the labial ABT (T1-T0) and more decrease in the palatal ABT (T1-T0) was found in the adult group, leading to less total ABT in the adult group. Higher reduction inn ABD (T1-T0) was found in the adult group. Moreover, more decrease in the ABA (T1-T0) was found in the adult group. Conclusion: When compared adolescents, adult patients have less alveolar bone support after orthodontic treatment, showing a through-the-bone remodeling pattern. Orthodontic should take the age into consideration to reduce the potential periodontal risks during treatment planning.

Bone apposition at the mandibular angles as a radiological sign of bruxism: a retrospective study

Background The main objective of this investigation was to determine on panoramic radiographs the prevalence of macroscopically visible alterations (bone apposition in combination with directional change) in the mandibular angle region in bruxism patients. Another aim was to describe and detect different morphological characteristics of the jaw angles. Methods Two hundred panoramic radiographs were studied: 100 images of adults with clinically diagnosed bruxism (73 women, 27 men, age range 21–83 years), 100 images of a comparison group consisting of adolescents (66 girls, 34 boys, age range 12–18 years). Results The morphological changes of the 400 jaw angles could be classified into four degrees. In the adult group, almost half of mandibular angles showed bone apposition. Conversely, the prevalence in the control group was zero. The localization of the appositions corresponds to the insertions of the masseter and medial pterygoid muscles at the mandibular angle. Conclusions The bone apposition at the mandibular angles should be interpreted as a functional adaptation to the long-term increased loads that occur during the contraction of the jaw closing muscles due to bruxism. Hence, radiologically diagnosed bone apposition may serve as an indication or confirmation of bruxism.

Alveolar bone changes after molar protraction in young adults with missing mandibular second premolars or first molars

ABSTRACT Objectives To assess the changes in alveolar bone of the mandibular second molars following molar protraction and investigate the factors associated with the alveolar bone changes. Materials and Methods Cone-beam computed tomography of 29 patients (mean age 22.0 ± 4.2 years) who had missing mandibular premolars or first molars and underwent molar protraction were reviewed. Alveolar bone level was measured as the distance from the cementoenamel junction at six points, buccal, lingual, mesiobuccal (MB), mesiolingual (ML), distobuccal (DB), and distolingual (DL), of the second molars at pretreatment (T0) and after molar protraction (T1). Factors associated with alveolar bone changes at the distal and mesial of the second molars were assessed. Results Mean alveolar bone changes ranged from −1.2 mm (bone apposition) to 0.8 mm (bone resorption). The presence of a third molar impaction at T0 (P < .001), third molar angulation at T0 (P < .001), and Nolla's stage of third molar at T0 (P = .005) were significantly associated with alveolar bone level changes distal to the second molars. Treatment duration (P = .028) was significantly associated with alveolar bone level changes mesial to the second molar. Conclusions Patients with impacted third molars, third molars at an earlier stage of development, and mesially angulated third molars at pretreatment may have less alveolar bone resorption distal to the second molars following protraction. Patients with increased treatment time may have reduced alveolar bone resorption mesial to the second molars.

Biomechanics in dental implants

Achieving primary stability in dental implants is crucial factor for accomplishing successful osteointegration with bone. Micro-motions higher than the threshold of 50 to 100 μm can lead to formation of fibrous tissue at the bone-to-implant interface. Therefore, osteointegration may be vitiated due to insufficient primary stability. Osseointegration is defined as a direct and functional connection between the implant biomaterial and the surrounding bone tissue. Osseointegration development requires an initial rigid implant fixation into the bone at the time of surgery and a secondary stage of new bone apposition directly onto the implant surface. Dental implants function to transfer the load to the surrounding biological tissues. Due to the absence of a periodontal ligament, its firm anchorage to bone, various forces acting on it and the presence of prosthetic components, they share a complex biomechanical relationship. The longevity of these osseointegrated implants depend on optimizing these complex interactions. Hence, the knowledge of forces acting on implant, design considerations of implant and bone mechanics is essential to fabricate an optimized implant supported prosthesis.

Argon Bioactivation of Implants Installed Simultaneously to Maxillary Sinus Lifting without Graft. An Experimental Study in Rabbits

Background: The treatment of the surface of titanium implants with argon plasma improved its hydrophilicity and cell adhesion, resulting in higher bone apposition on implant and graft surfaces. The spontaneous perforation over time of the sinus mucosa after sinus augmentation has been documented in experimental studies at both implants and graft particles. The aim of the present study was to evaluate the influence of plasma argon treatment of the implant surface on bone apposition and on the rate of sinus mucosa perforations. Methods: A sinus lifting procedure was performed bilaterally in sixteen rabbits, and implants, either treated with argon plasma or left without treatment (control), were placed simultaneously without grafts. After 8 weeks, histological analyses were carried out. Results: A collapse of the sinus mucosa was observed at all implants. Twenty-four out of thirty-two implants presented sinus mucosa perforations at the apex. Several perforations were also found at the threads. Thinned mucosa sites (width < 40 µm) were found around almost all implants. About 2.6–2.9 mm of the apical regions of the implant did not present signs of osseointegration and about 1.3 mm were exposed to the sinus cavity. No statistically significant differences were found between plasma and control sites. Conclusions: In conclusion, the sinus mucosa was damaged and perforated by direct contact with treated and non-treated implant surfaces. The treatment of the implant surface with argon plasma did not affect the outcomes.

Bone remodelling patterns around orthodontic mini-implants migrating in bone: an experimental study in rat vertebrae

Summary Background Orthodontic implant migration has been clinically observed in presence of continuous loading forces. Recent studies indicate that osteocytes play a crucial role in this phenomenon. Objectives Aim of this study was to investigate local osteocytic gene expression, protein expression, and bone micro-structure in peri-implant regions of pressure and tension. Material and methods The present work reports a complementary analysis to a previous micro-computed tomography study. Two customized mini-implants were placed in one caudal rat vertebra and connected by a nickel–titanium contraction spring generating different forces (i.e. 0, 0.5, 1.0, and 1.5 N). Either at 2 or 8 weeks, the vertebrae were harvested and utilized for 1. osteocytic gene expression using laser capture micro-dissection on frozen sections coupled with qPCR, 2. haematoxylin–eosin staining for qualitative and quantitative analyses, 3. immunofluorescence staining and analysis, and 4. bone-to-implant contact on undecalcified samples. Results At the two time points for all the performed analyses no significant differences were observed with respect to the applied force magnitudes and cell harvesting localization. However, descriptive histological analysis revealed remarkable bone remodelling at 2 weeks of loading. At 8 weeks the implants were osseointegrated and, especially in 1.0 and 1.5 N groups, newly formed bone presented a characteristic load bearing architecture with trabecula oriented in the direction of the loading. Conclusions The present study confirmed that stress-induced bone remodelling is the biological mechanism of orthodontic implant migration. Bone apposition was found at ‘tension’ and ‘pressure’ sites thus limiting implant migration over time.

Longitudinal assessment of salivary vitamin D binding protein during orthodontic tooth movement

Background Vitamin D is critical for bone physiology. In this study, we quantified Vitamin D Binding Protein (VitDBP) levels in saliva as a measure of Vitamin D during orthodontic tooth movement. Methods In this longitudinal study, saliva samples were collected from 73 orthodontic patients for 4 timepoints for the first six months of orthodontic treatment, along with dental casts at the beginning and the end of the study period. The saliva was measured for VitDBP as a biological marker for bone apposition and clinical tooth movement. We used the absolute change in Little's Irregularity Index as a quantitative measure for alignment. In addition, we measured the levels of alkaline phosphatase (ALP) in saliva as a marker of bone turnover. Results Both low (< 2.75 ng/ml) and high (> 6.48 ng/ml) VitDBP levels were associated with reduced tooth movement. Significant (p < 0.05) seasonal changes in VitDBP using a two-season year model were found with lower levels observed in the summer (Apr–Sept) than in the winter (Oct–Mar). Conclusions Clinically significant orthodontic tooth movement is associated with an optimal range of VitDBP in saliva. Normal levels of VitDBP correlated with more orthodontic tooth movement, suggesting a "normal" range of salivary content of VitDBP. Given the strong trend that is independent of the confounding factors (ex. age, race or gender), the predictive value or salivary VitDBP for tooth movement should be studied in larger cohorts in future studies.

Bone Apposition at the Mandibular Angles as a Radiological Sign of Bruxism: a Retrospective Study

Background: The main objective of this investigation was to determine on panoramic radiographs the prevalence of macroscopically visible alterations (bone apposition in combination with directional change) in the mandibular angle region in bruxism patients. Another aim was to describe and detect different morphological characteristics of the jaw angles. Methods: Two hundred panoramic radiographs were studied: 100 images of adults with clinically diagnosed bruxism (73 women, 27 men, age range: 21 to 83 years), 100 images of a comparison group consisting of adolescents (66 girls, 34 boys, age range: 12 to 18 years). Results: The morphological changes of the 400 jaw angles could be classified into four degrees. In the adult group, almost half of mandibular angles showed bone apposition. Conversely, the prevalence in the control group was zero. The localization of the appositions corresponds to the insertions of the masseter and medial pterygoid muscles at the mandibular angle. Conclusions: The bone apposition at the mandibular angles should be interpreted as a functional adaptation to the long-term increased loads that occur during the contraction of the jaw closing muscles due to bruxism. Hence, radiologically diagnosed bone apposition may serve as an indication or confirmation of bruxism.

Bee Bread Can Alleviate Lipid Abnormalities and Impaired Bone Morphology in Obese Zucker Diabetic Rats

This study examined for the first time whether bee bread (BB, consisting of monofloral rape bee pollen) could alleviate lipid derangements and reduced bone quality in Zucker diabetic fatty (ZDF) rats, which are considered an appropriate animal model for type 2 diabetes mellitus (T2DM) investigation. Adult ZDF rats were segregated into four groups: lean non-diabetic rats (L group), obese diabetic rats untreated (C group), and those treated with the BB at two doses (500 and 700 mg/kg body weight, respectively, B1 and B2 groups) for 10 weeks. Significantly reduced levels of total cholesterol and triglyceride were recorded in the B2 group versus the C group. In both BB-treated groups, significantly increased relative volume of trabecular bone and trabecular thickness, enhanced density of secondary osteons, accelerated periosteal bone apposition, and improved blood flow were observed. A positive effect of higher dose of BB on femoral weight and cortical bone thickness was also demonstrated. Our results suggest a promising potential of BB to ameliorate T2DM-related complications associated with lipid and bone damages.