Higher Bone Density Research Articles

Modified enzymatic collagen digestion-mediated isolation of osteocytes

This study established a method for isolating large numbers of high-purity osteocytes from high-density bone. Bone fragments derived from mice tibia and femurs were alternately digested with type I collagenase and EDTA nine times, and the digested cells and bone chips (BC) were cultured, digested, and passaged when cells were fully grown. The types of cells obtained were identified by morphology, viable cell counts, alkaline phosphatase staining, and biochemical activity analyses, and specific osteocyte and osteoblast markers were evaluated by quantitative real-time polymerase chain reaction. Our results showed that among the cells obtained from the third digestion (fractions 7–9) of wild mice tibias and femurs and the remaining BCs, 85%–90% of the cells were osteocytes. Moreover, their morphology was approximately one-tenth to one-fifth the size of osteoblasts, star-shaped or polygonal, with a dendritic structure, negative for alkaline phosphatase staining, and showed a high expression of dmp1 and sclerostin. Ninety percent of the cells in fractions 1–3 were osteoblasts, and were fusiform or polygonal shape. The activity of osteoblast-specific alkaline phosphatase and mRNA expression were high in this fraction, while the expression of osteocyte-specific dmp1 and sclerostin was not detected. In the second portion (fractions 4–6), a large number were osteoblasts, mixed with a small number of osteocytes, and had high alkaline phosphatase activity and osteocyte mRNA levels, a specific level of the osteocyte marker dmp1, and no sclerostin was detected. Osteocytes in daβcatot mice were also successfully isolated by this method, and we found that Wnt signaling increased the proliferation of these osteocytes. The proposed method can be used to culture osteocytes and osteoblasts of high purity and can be used for isolation and culture of these two kinds of cells from high-density bone, which provides an avenue for the study of osteocyte function in vitro.

Efeito do posicionamento crestal do implante na estabilidade primária antes e após carga: um estudo in vitro

Abstract Introduction Primary stability is one of the goals of modern implant dentistry and if achieved, reduces treatment time for prosthetic rehabilitation and the number of interventions made in patients mouth. Several companies state as protocol for connical conection implants, a subcrestally positioning. Objective This in vitro study aimed to evaluate the effect of placing a conical connection implant equicrestally and subcrestally on static and loading condition in two types of bone density. Material and method A total of 200 bone cylinders were extracted from femur of pigs, standardized by means of x-rays and computerized microtomography scan (microCT) and separated in low and high density specimens. The implants were placed on the center of the bone cylinders and were evaluated before and after loading by means of microCT and histomorphometry. Result The results showed that placing the evaluated implant subcrestally provided better primary stability and performance on static and loading situations on low and high density bone. Conclusion Placing implant subcrestally improve primary stability outcomes under loading and static situations.

Dosimetric comparison of analytical anisotropic algorithm and the two dose reporting modes of Acuros XB dose calculation algorithmin volumetric modulated arc therapy of carcinoma lung and carcinoma prostate.

Volumetric Modulated Arc Therapy (VMAT) is an important modality for radical radiotherapy of all major treatment sites. This study aims to compare Analytical Anisotropic Algorithm (AAA) and the two dose-reporting modes of Acuros XB (AXB) algorithm -the dose to medium option (Dm) and the dose to water option (Dw) in Volumetric Modulated Arc Therapy (VMAT) of carcinoma lung and carcinoma prostate. We also compared the measured dose with Treatment Planning System calculated dose for AAA and the two dose reporting options of Acuros XB using Electronic Portal Imaging Device (EPID) and ArcCHECK phantom. Treatment plans of twenty patients each who have already undergone radiotherapy for cancer of lung and cancer of prostate were selected for the study. Three sets of VMAT plans were generated in Eclipse Treatment Planning System (TPS), one with AAA and two plans with Acuros-Dm and Acuros-Dw options. The Dose Volume Histograms (DVHs) were compared and analyzed for Planning Target Volume (PTV) and critical structures for all the plans. Verification plans were created for each plan and measured doses were compared with TPS calculated doses using EPID and ArcCHECK phantom for all the three algorithms. For lung plans, the mean dose to PTV in the AXB-Dw plans was higher by 1.7% and in the AXB-Dm plans by 0.66% when compared to AAA plans. For prostate plans, the mean dose to PTV in the AXB-Dw plans was higher by 3.0% and in the AXB-Dm plans by 1.6% when compared to AAA plans. There was no difference in the Conformity Index (CI) between AAA and AXB-Dm and between AAA and AXB-Dw plans for both sites. But the homogeneity worsened in AXB-Dw and AXB-Dm plans when compared to AAA plans for both sites. AXB-Dw calculated higher dose values for PTV and all the critical structures with significant differences with one or two exceptions. Point dose measurements in ArcCHECK phantom showed that AXB-Dm and AXB-Dw options showed very small deviations with measured dose distributions than AAA for both sites. Results of EPID QA also showed better pass rates for AXB-Dw and AXB-Dm than AAA for both sites when gamma analysis was done for 3%/3 mm and 2%/2 mm criteria. With reference to the results, it is always better to choose Acuros algorithm for dose calculations if it is available in the TPS. AXB-Dw plans showed very high dose values in the PTV when compared to AAA and AXB-Dm in both sites studied. Also, the volume of PTV receiving 107% dose was significantly high in AXB-Dw plans compared to AXB-Dm plans in sites involving high density bones. Considering the results of dosimetric comparison and QA measurements, it is always better to choose AXB-Dm algorithm for dose calculations for all treatment sites especially when high density bony structures and complex treatment techniques are involved. For patient specific QA purposes, choosing AXB-Dm or AXB-Dw does not make any significant difference between calculated and measured dose distributions.

Avoiding Glenoid Baseplate Fixation Failure by Altering Surgical Technique for Varying Bone Densities.

Background:Glenoid baseplate failure is one of the causes of revision and poor outcomes in reverse shoulder arthroplasty (RSA). The objective of this study was to determine whether alterations in surgical technique can improve time-zero fixation of the baseplate in varying bone densities. A secondary objective was to identify whether preoperative radiographic glenoid sclerosis width was associated with the implementation of these techniques.Methods:This study included a biomechanical analysis and a retrospective radiographic review. The biomechanical portion describes 2 alterations to the standard surgical technique (under-preparation [A1] or over-preparation [A2] of the central screw pilot hole) and determined their torque-compression relationship via bone-substitute blocks with varying densities. Patients who underwent the described technical alterations were identified from a registry database of primary RSAs performed between 2007 and 2020. These patients were matched to patients who underwent the standard surgical technique, and preoperative radiographs were compared. Interrater reliability testing was performed to determine reproducibility.Results:With respect to the biomechanical arm, the average compressive force of the baseplate in the low-density block model when using the standard technique was 112 N compared with 300 N for the A1 technique (p = 0.01). In the high-density bone model, the standard technique resulted in failure to seat the baseplate, or screw breakage. Performing the A2 technique, the baseplate was seated without failure, with an average compressive force of 450 N. In the clinical arm, retrospective intraoperative video review for use of the alternative techniques found 20 shoulders in the “low-density” cohort and 21 in the “high-density” cohort. There was a significant difference in the glenoid sclerosis thickness between the experimental and matched control groups in our “high-density” cohort (p = 0.0014). The interrater reliability coefficient was found to be 0.69 for the “low-density” glenoid sclerosis thickness measurement and 0.92 for the “high-density” measurement.Conclusions:In low- and high-density bone models, alterations in surgical technique significantly improved compression and improved the ability to successfully seat the glenoid baseplate. Preoperative radiographs can assist in indicating the alternative technique in the sclerotic glenoid.Clinical Relevance:Utilization of these techniques intraoperatively will improve time-zero fixation of the glenoid baseplate and potentially avoid failure of fixation.

A customizable anthropomorphic phantom for dosimetric verification of 3D-printed lung, tissue, and bone density materials.

To design and manufacture a customized thoracic phantom slab utilizing the 3D printing process, also known as additive manufacturing, consisting of different tissue density materials. Here, we demonstrate the 3D-printed phantom's clinical feasibility for imaging and dosimetric verification of volumetric modulated arc radiotherapy (VMAT) plans for lung and spine stereotactic ablative body radiotherapy (SABR) through end-to-end dosimetric verification. A customizable anthropomorphic phantom slab was designed using the CT dataset of a commercial phantom (adult female ATOM dosimetry phantom, CIRS Inc.). Material extrusion 3D printing was utilized to manufacture the phantom slab consisting of acrylonitrile butadiene styrene material for the lung and the associated lesion, polylactic acid (PLA) material for soft tissue and spinal cord, and both PLA and iron-reinforced PLA materials for bone. CT images were acquired for both the commercial phantom and 3D-printed phantom for HU comparison. VMAT plans were generated for spine and lung SABR scenarios and were delivered as per departmental SABR protocols using a Varian TrueBeam STx linear accelerator. End-to-end dosimetry was implemented with radiochromic films, analyzed with gamma criteria of 5% dose difference, and a distance-to-agreement of 1mm, at a 10% low-dose threshold by comparing with calculated dose using the Acuros algorithm of the Eclipse treatment planning system (v15.6). 3D-printed phantom inserts were observed to produce HU ranging from -750 to 2100. The 3D-printed phantom slab was observed to achieve a similar range of HU from the commercial phantom including a mean HU of -760 for lung tissue, a mean HU of 50 for soft tissue, and a mean HU of 220 and 630 for low- and high-density bone, respectively. Film dosimetry results show 2D-gamma passing rates for lung SABR (internal and superior) and spine SABR (inferior and superior) over 98% and 90%, respectively. The end-to-end testing of VMAT plans for spine and lung SABR suggests the clinical feasibility of the 3D-printed phantom, consisting of different tissue density materials that emulate lung, soft tissue, and bone in kV imaging and megavoltage photon dosimetry. Further investigation of the proposed 3D printing techniques for manufacturability and reproducibility will enable the development of clinical 3D-printed phantoms in radiotherapy.

Optimizing Lumbar Pedicle Screw Trajectory Utilizing a 3D-Printed Drill Guide to Ensure Placement of Pedicle Screws Into Higher Density Bone May Improve Pedicle Screw Pullout Resistance

Lower preoperative Hounsfield Unit (HU) values of vertebral body are associated with pedicle screw (PS) loosening after implantation with traditional trans-pedicular trajectory. However, the relationship between trajectory HU value and PS fixation quality remains unknown. This study aimed to investigate if 3-dimensionally (3D)-printed guider directed accurate implantationof pedicle screw could increase the anti-pulling properties of screws. 3D models of cadaveric spines were reconstructed by using computed tomography image and PS trajectories were designed for both sides of vertebra. The designed trajectories were divided into high HU group and low HU group. PS implantation with 3D-printed screw guide can be in complementary shape with target vertebra. Throughout 3D finite element analysis and biomechanical tests, the pull-out strength of screws in high or low trajectoryHU groups were compared. The HU value was 132 ± 13 (mean ± standard deviation) in low HU group and 189 ± 17 in high HU group. The distance between planned trajectories and actual trajectories was 1.69 ± 0.4 mm. Biomechanical tests showed that in the high trajectory HU group the pull-out strength of screws was 750.41 ± 80.65 N; compared with 655.83 ± 74.31 N in the low trajectory HU group, the difference was statistically significant. When simulated with the finite element method, the pull-out strength of low HU trajectory pedicle screws was lower than that of high HU trajectory pedicle screws. Preoperative computer-assisted trajectory design using a 3D-printed screw guide may direct more accurate implantation with optimal implantation trajectory, and may provide a new way to improve pedicle screw fixation.

여자대학생의 전공에 따른 신체조성 및 신체부위별 골밀도 비교 연구

The following conclusions were obtained by analyzing the body composition and bone density by body part according to the major of female college students, and analyzing body composition and bone density by part according to the type of physical activity.<BR> In this study, female college students were classified according to physical education, dance, and general majors, and as a result of frightening the difference between skeletal muscle mass and lean mass were significantly higher than those of general majors, and there was no significant difference. In addition, as a result of verifying the difference in bone density for each group, the leg bone density was significantly higher in physical education and dance majors than in general majors, and in pelvic, BMD, and T-score, the physical education majors were significantly higher than in general majors.<BR> According to the above results, physical education majors and dance majors have continued to engage in large amounts of intense physical activity through steady exercise and dance movements, confirming high skeletal muscle mass, fat mass, and normal bone density levels.

Physical, Chemical, and Mechanical Evaluation of Irradiated Xeno-Sheep Bony Implantation by Low-Level Laser Therapy of Long Bones Fractures in Rabbits.

Bone grafts/implantation is widely used in veterinary medicine. The present study aimed to evaluate the physical, chemical, and mechanical prosperities of irradiated xeno-sheepbony implantation(X-SBI) by low-level laser therapy (LLLT) implanted in the induced empty defect of the femoral bones in rabbits. A total of 10 adult rabbits were used to create a 1cm length of the femoral gab surgically; thereafter, the empty space was filled with X-SBI and internally fixed by intramedullary pinning with two femoral fragments. The operated rabbits were assigned to the un-irradiated control group 1 which was left without laser irradiation, and irradiated group (group 2) which was irradiated on a daily basis by a continuous diode laser, a single dose at four points at the lateral aspect of the X-SBI for 5 min at a period of 72 intervals for 14th days post-operation with a dosage of 850 nm, 148.4 J/cm2. The parameters which were used for the evaluation of results after 3rd-month post-operation were physical, chemical, and mechanical examinations. The physical examination revealed high bone density and hardness at the sites of X-SBI of the irradiated group, as compared to the un-irradiated animals. Moreover, the chemical analysis demonstrated an increment in the level of bone calcium and phosphorus elements, as well as a decrease in the level of magnesium, potassium, and sodium in the irradiated group, as compared to the un-irradiated group. The mechanical and fracture tolerance results demonstrated a gradually high resistance level of fracture tolerance of irradiated animals, as compared to un-irradiated rabbits. It can be concluded that the irradiated X-SBI by LLLT could be used strongly and successfully to fill the empty space in the femoral bone, supporting body weight better and faster than the control group, with no complications or body rejection.

Trabecular bone density distribution in the scapula of patients undergoing reverse shoulder arthroplasty.

BackgroundTo improve implant survival after reverse shoulder arthroplasty (RSA), surgeons need to maximize screw fixation. However, bone density variation and distribution within the scapula are not well understood as they relate to RSA. The three columns of bone in the scapula surrounding the glenoid fossa are the lateral border, the base of the coracoid process, and the spine of the scapula. In our previous study by Daalder et al on cadaveric specimens, the coracoid column was significantly less dense than the lateral border and spine. This study’s objective was to verify whether these results are consistent with computer tomography (CT) scan information from patients undergoing RSA.MethodsTwo-dimensional axial CT images from twelve patients were segmented, and a three-dimensional digital model of the scapula was subsequently created using Mimics 17.0 Materialise Software (Leuven, Belgium). Hounsfield unit (HU) values representing cortical bone were filtered out to determine the distributions of trabecular bone density. An analysis of variance with post hoc Bonferroni tests determined the differences in bone density between the columns of bone in the scapula.ResultsThe coracoid superolateral (270 ± 45.6 HU) to the suprascapular notch was significantly less dense than the inferior (356 ± 63.6 HU, P = .03, ds = 1.54) and anterosuperior portion of the lateral border (353 ± 68.9 HU, P = .04, ds = 1.42) and the posterior (368 ± 70 HU, P = .007, ds = 1.65) and anterior spine (370 ± 78.9 HU, P = .006, ds = 1.54).Discussion/ConclusionThe higher-density bone in the spine and lateral border compared with the coracoid region may provide better bone purchase for screws when fixing the glenoid baseplate in RSA. This is in agreement with our previous study and indicates that the previous cadaveric results are applicable to clinical CT scan data. When these studies are taken together, they provide robust evidence for clinical applications, including having surgeons aim screws for higher-density regions to increase screw fixation, which may decrease micromotion and improve implant longevity.

43 The Importance of Intraosseous Placement Location on Infusion Rates and Infusion Pressures in a High Bone Density Humerus and Sternum Cadaveric Swine (Sus Scrofa) Model

Intraosseous (IO) access is an emergent bridge to central venous access for the critically ill and injured. To effectively infuse fluids or blood products intraosseously, infusion flow rates must be sufficient to sustain life but at pressures that are low enough to avoid complications. However, published reports indicate that up to 30% of landmark-based IO catheter placements are suboptimal, which can result in low infusion flow rates at elevated infusion pressures. What was needed was a randomized prospective cadaveric study to determine infusion flow rates, mean pressures, and peak pressures based on IO catheter tip placements.

374 User Characteristics of Six Intraosseous Devices in a High Bone Density Humerus and Sternum Cadaveric Swine (Sus Scrofa) Model

Intraosseous (IO) infusion, the pressurized injection of fluids into bone through a catheter, is a life-preserving resuscitative technique for treating critical care patients and trauma patients with severe hemorrhage. To be effective as a bridge to central venous access, IO infusion flow rates must be sufficient to sustain life but at pressures low enough to avoid complications. However, little is known regarding end user characteristics of available battery-powered and manual IO devices. User characteristics are important, because to be efficient and effective, an IO device should optimally have a minimal set-up (placement) time and be perceived as easy and comfortable to use, resistant to bending and displacement, effective and trustworthy in meeting the demands of rapid resuscitation, and cause minimal hand fatigue. The present study was specifically designed to fill this important gap in the literature. Three experienced emergency medicine residents each inserted a variety of commercially available 15-gauge IO catheters in cadaveric swine (Sus scrofa) proximal humeri and sternums with bone density similar to adult humans (1.0-1.1 gm/cm2) in a randomized prospective experimental design, and then infused 500 cc of isotonic crystalloid using push-pull technique with a 60cc syringe. Devices included the battery-powered EZ-IO Rapid Infuser and the manual Jamshidi IO, Persys NIO, SAM Manual IO, Tactical Advanced Lifesaving IO Needle (TALON), and PYNG FASTR devices (30 trials per device, 10 per user). Pressures were measured using an in-line manometer. Subjective user characteristics were assessed across eight Likert-type items, which were analyzed individually and as a composite score. Objective and user ratings data were analyzed using ANOVA and nonparametric statistics at p<.05. Infusion flow rates, mean pressures, and peak pressures were generally similar across devices and locations, save that the TALON in the sternum conferred roughly 50% higher flow rates at 30% lower mean pressures and 15% lower peak pressures than other devices in sternum or humerus (each p<.0001). The EZ-IO demonstrated the fastest set-up times and the highest composite user ratings (Figure 1), including highest ratings for each of the eight survey items (p<.0001). The TALON conferred intermediate set-up times and next-highest user ratings overall. The Jamshidi had the longest set-up times, the slowest infusion rates, and relatively low user ratings. IO access devices differ in construction, method of application, effectiveness, and user characteristics. The commonly used battery-powered EZ-IO had the fastest set-up times and the highest user ratings. While the present study was limited by the utilization of a cadaveric swine model rather than an in vivo model, findings suggest the possibility that the TALON, which performed well in objective assessments and user ratings, may be worth considering as a manual backup to the battery-operated EZ-IO Rapid Infuser. Combined, these results highlight the importance of studying the end user characteristics of IO infusion devices towards preserving the lives of critically ill or injured patients requiring rapid fluid or blood product resuscitation.

The Efficacy and Safety of Acupuncture for Treating Osteoporotic Vertebral Compression Fracture- (OVCF-) Induced Pain: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

Background Osteoporotic vertebral compression fractures (OVCFs) are common health issues in the elderly that cause chronic pain in over one-third of patients. This study was sought to evaluate the efficacy and safety of acupuncture for alleviating pain caused by OVCFs. Methods We performed a search of 8 electronic databases for publications from the inception to 30th March 2021. Eligible studies were randomized clinical trials (RCTs) that evaluated the effect of acupuncture for the treatment of OVCFs. Two investigators evaluated literature quality and extracted data independently. RevMan V.5.4.1 was used for data analyses, with pooled risk estimates presented as mean difference (MD) or relative risk (RR) along with corresponding 95% confidence intervals (CIs), as appropriate. Results Fourteen RCTs involving 1,130 patients were included in this meta-analysis. Compared with the control group, acupuncture showed a greater benefit on pain reduction caused by OVCFs (1 week: MD = −1.26, 95% CI: (−1.82,−0.70); 1 month: MD = −1.63, 95% CI: (−1.82,−1.43); 6 months: MD = −1.13, 95% CI: (−1.55, −0.70)). Acupuncture treatment was also associated with fewer adverse events, lower ODI index, and higher bone density than the control group (safety: (RR: 0.30, 95% CI: 0.12–0.75); ODI: MD = −3.19, 95% CI: (−5.20, −1.19); bone density: MD = 0.15, 95% CI: (0.05, 0.26)). The GRADE quality of these results was assessed as low or very low. Conclusions Compared with the control treatment, acupuncture was more effective and safer in relieving the pain caused by OVCF and made a greater improvement on patient's ODI score and bone density. Given the low level of our study evidence, future high-quality studies are needed to verify our study findings.

Stress on the posteromedial region of the proximal tibia increased over time after anterior cruciate ligament injury.

Anterior cruciate ligament (ACL) injury induces anterior and rotatory instability of the knee. However, the effect of this instability on the stress distribution in the knee joint in living participants is not clear. The aim of this study was to compare the distribution pattern of subchondral bone density across the proximal tibia in the knees with and without ACL injury, and to investigate the correlation between the distribution patterns of the subchondral bone density and the duration of ACL-deficiency. Radiographic and computed tomography (CT) data pertaining to 20 patients with unilateral ACL injury without combined injury (ACL-deficient group) and 19 nontraumatic subjects (control group) were collected retrospectively. Subchondral bone density of the proximal tibia was assessed using CT-osteoabsorptiometry. Both the medial and lateral compartments of the proximal tibia were divided into three subregions of equal width in the sagittal direction. The percentage of high subchondral bone density areas (HDA%) in each subregion was quantitatively analyzed. HDA% of the posteromedial region was significantly higher in the ACL-deficient group (mean: 21.6%) than in the control group (14.7%) (p = 0.002). In contrast, HDA% of the anteromedial region was significantly lower in the ACL-deficient group (9.4%) than in the control group (15.3%) (p = 0.048). The logarithm of the time elapsed from ACL injury to CT examination showed a significant correlation with HDA% in the posteromedial region (p = 0.032). Subchondral bone density in the posteromedial region significantly increased after ACL injury and correlated with the duration of ACL-deficiency in semi-log manner in meniscus intact knees. The increase in stress on the posteromedial region after ACL injury, which induces a change in the subchondral bone density, justifies early ACL reconstruction after ACL injury.

Gut microbiome depletion and repetitive mild traumatic brain injury differentially modify bone development in male and female adolescent rats

Dysregulation of the gut microbiome has been shown to disrupt both bone formation and bone resorption in several preclinical and clinical models. However, the role of microbiome in adolescent bone development remains poorly understood. This effect of disrupted bone development may be more pronounced during adolescence, when bone development is vulnerable to environmental stimuli and external insults (e.g., antibiotic treatment and traumatic brain injury), as this is a critical window of development. Therefore, in this study, we sought to investigate the effect of repetitive mild traumatic brain injury (RmTBI) and gut microbiome depletion by antibiotic treatment on femur length and bone density in male and female adolescent Sprague Dawley rats. Rats were randomly assigned to receive standard or antibiotic autoclaved drinking water and to receive sham or RmTBIs injuries. Using micro-computed tomography (μCT), we found sexually dimorphic changes in adolescent bone development in response to microbiome depletion and RmTBI. Specifically, gut microbiome depletion stunted femur growth in males and altered cross sectional bone area (CSA), bone area fraction, and the bone volume of low and mid density bone in the distal metaphyseal region of the femur. Conversely, RmTBI and antibiotic treatment individually disrupted bone growth, bone area fraction, and bone volume of high-density bone within the distal metaphyseal region of the femur in females, but not when combined. Therefore, findings from this study indicate that gut microbiome and RmTBI may alter bone development in a sex-dependent manner during adolescence.

Ossification of Non-vascularized Free-Fibula Graft for Mandibular Reconstruction after Resection of Ameloblastoma: Review of Literature and Presentation of 2 cases

Introduction: Ameloblastoma is a benign neoplasm of odontogenic epithelial origin occurring more commonly in the mandibular posterior region and rarely in the maxilla. About 50-60% of ameloblastomas occur in the mandibular ramus area, while only 10% is seen in mandibular anterior region. Ameloblastomas are slow growing, locally invasive, rarely malignant tumours affecting the jaw. Mostly commonly seen in the 4th-6th decade of life affecting males more commonly than females. The resection of the mandibular segment without adequate reconstruction leads to functional as well as esthetic loss. Case Report: Here we describe two case reports of ameloblastoma with segmental resection and reconstruction using fibula graft. Discussion &amp; Review of Literature: Avascular fibula graft with its high bone density, ease of access to harvest, and tendency to show less resorption helps to achieve satisfactory esthetic contour and function in reconstruction of segmental defects of mandible Conclusion: This article describes two case reports of ameloblastoma with segmental resection and reconstruction using fibula graft along with review of literature.

Oxytocin and Bone: Review and Perspectives.

Recent data demonstrate the anabolic effect of oxytocin on bone. Bone cells express oxytocin receptors. Oxytocin promotes osteoblasts differentiation and function, leading to an increased bone formation with no effect on bone resorption and an improvement of bone microarchitecture. Oxytocin is synthetized by osteoblasts, and this synthesis is stimulated by estrogen. Animal studies demonstrate a direct action of oxytocin on bone, as the systemic administration of oxytocin prevents and reverses the bone loss induced by estrogen deficiency. Although oxytocin is involved in bone formation in both sexes during development, oxytocin treatment has no effect on male osteoporosis, underlining the importance of estrogen that amplifies its local autocrine and paracrine secretion. There are few human data showing a decrease in the oxytocin serum level in anorexia nervosa independently of estrogen and in amenorrheic women associated with impaired bone microarchitecture; in post-menopausal women a higher oxytocin serum level is associated with higher bone density, but not in osteoporotic men. Oxytocin displays many effects that may be beneficial in the management of osteoporosis, cardiovascular diseases, cognitive disorders, breast cancer, diabetes and body fat gain, all age-related diseases affecting elderly women, opening exciting therapeutic perspectives, although the issue is to find a single route, dosage and schedule able to reach all these targets.

HEAT GENERATION DURING IMPLANT PLACEMENT IN HIGH-DENSITY BONE: EFFECT OF DIFFERENT DRILLING TECHNIQUES

ABSTRACT Introduction: A precise drilling-sequence-protocol is essential for long-term dental implant success in high bone density (mandibular cortical bone of D1-quality). Cone beam computed tomography (CBCT) radiographic imaging and CBCT-based construction of surgical guides have been substantial for diagnosis and treatment planning. Objectives: The study aimed to measure the effect of different guided drilling techniques on the amount of heat generated during implant placement in high density. Materials and Methods: Twenty-four osteotomies for implant placement, divided equally into three groups, to test the effect of the three drilling techniques Undersized Drilling (UD), Undersized Drilling + Ridge Spreader size 4 (UD+RS4) and Undersized Drilling + counter sink size 4 (UD+CS4) techniques. Heat generation was assessed using K-type thermocouple. Drilling and thermocouple canals were guided by the surgical template. Bone assessment, virtual planning of the implants and surgical guide construction were based on radiographic CBCT-imaging and software-based processing. Insertion torque values (ITVs) were recorded from readings of a geared motor. Results: The thermocouple results showed the least significant difference at 10 mm depth. At 5mm depth, a significant decrease in the temperature difference of the UD+RS4 group and UD+CS4 group compared to UD group was observed. At 1mm depth, there was a significant difference between the UD group and the two other groups. The UD group showed the maximum peak ITV. Conclusion: the results suggest possible advantages when self-tapping implants are inserted into high density cortical bone of D1-quality by a countersink drill since it provides lesser temperature increase at insertion.

Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report

BackgroundInfantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing.Case presentationWe present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO.ConclusionsTo date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

Exploring the B cell microenvironment in von-Hippel Lindau (Vhl) Dmp1-specific knockout mice

Abstract Osteoblasts (OBs) and osteocytes (OCYs) have been shown to support B cell development. The von-Hippel Lindau protein (VHL) regulates hypoxia-inducible factor degradation and is involved in responses to low oxygen environments. We utilized Dmp1-Cre;Vhl conditional knockout mice (cKO), in which Vhl is deleted in OBs and OCYs. The cKO display dysregulated bone growth, high bone density, smaller bone marrow (BM) cavity volume, and overall decrease in BM cellularity compared to wild-type (WT) mice. B cell progenitors were significantly increased in frequency and numbers whereas Hardy Fractions B, C, D, E and F were significantly decreased in the cKO BM. cKO Fraction B-C cells showed an increase in apoptosis and decreased proliferation. Reciprocal BM chimeras showed significant reduction in Fractions B-C and later Fractions in the WT→cKO, while B cell development was normal in the cKO→WT chimeras, indicating a cell-extrinsic effect of Vhl on B cells within the cKO BM microenvironment. We hypothesize that B cell development is not supported due to reduction of key niche cells such as stromal cells, OBs, mesenchymal stem cells and decreased production of key cytokines. In preliminary studies, we found that CXCL12 and SCF, key cytokines for B cell development, were reduced in the cKO BM serum. We have begun longitudinal studies using intravital and ex vivo imaging of the cKO BM to identify temporally dependent changes in oxygenation, blood vessel type, structure, permeability, and location of stromal cells. Ex vivo long bone imaging of cKO BM in 6-month-old mice revealed an increase in blood vessel diameter compared to WT. These studies will reveal details and novel molecular mechanisms by which Vhl in Dmp1 expressing cells may serve as a B cell niche.

Phenotypic and genotypic spectrum of CTSK variants in a cohort of twenty-five Indian patients with pycnodysostosis

BackgroundPycnodysostosis is an autosomal recessive skeletal dysplasia with easily recognizable clinical features and marked molecular heterogeneity. In this study, we explored the clinical and molecular spectrum of 25 Indian patients with pycnodysostosis from 20 families. MethodsClinical information was collected on a predesigned clinical proforma. Sanger method was employed to sequence all the exons and exon/intron boundaries of the CTSK gene. Novel variants were systematically assessed by prediction softwares and protein modelling. The pathogenicity of variant was established based on ACMG-AMP criteria. An attempt was also made to establish a genotype-phenotype correlation and devise a diagnostic scoring system based on clinical and radiological findings. ResultsConsanguinity and positive family history were present in 65% (13/20) and 45% (9/20) of the families respectively. Short stature and fractures were the predominant presenting complaints and was evident in 96% (24/25) and 32% (8/25) of affected individuals respectively. Gestalt facial phenotype and acro-osteolysis were present in 76% (19/25) and 82.6% (19/23) of the individuals respectively. Hepatosplenomegaly was present in 15% (3/20) of the individuals with one of them having severe anaemia. Causative sequence variations were identified in all of them. A total of 19 variants were identified from 20 families amongst which 10 were novel. Homozygous variants were identified in 90% (18/20) families. Amongst the novel variants, there was a considerable proportion (40%) of frameshift variants (4/10). No significant genotype-phenotype correlation was noted. Scoring based on clinical and radiological findings led to the proposal that a minimum of 2 scores in each category is required in addition to high bone density to diagnose pycnodysostosis with certainty. ConclusionThis study delineated the genotypic and phenotypic characterisation of Indian patients with pycnodysostosis with identification of 10 novel variants. We also attempted to develop a clinically useful diagnostic scoring system which requires further validation.