3D printing vs traditional workflow for the fabrication of mandibular implant overdentures: study protocol for a mixed-methods cross-over RCT.

BACKGROUND: Complete tooth loss is a significant global oral health issue, particularly impacting older individuals with lower socioeconomic status. Computer-assisted technologies enhance oral healthcare access by the elderly. Despite promising in vitro reports on digital denture materials, evidence from randomized clinical trials (RCTs) is lacking to verify their performance. This cross-over RCT will investigate whether 3D-printed implant-retained mandibular overdentures (IMO) are more satisfactory for edentulous seniors than those made through traditional methods. METHODS/DESIGN: We will recruit 26 completely edentulous participants (any sex/gender) based on the following eligibility criteria: age ≥ 60 years, no tooth extraction in the past 12 months, two implants in the lower jaw, and need for new dentures in both jaws. Each participant will receive two denture pairs, either manufactured by 3D printing or traditionally, to be worn in a random order. A timeline of 3 months with each denture pair will be considered for outcome assessment (total: 6 months). Patient satisfaction with dentures will be measured by the McGill Denture Satisfaction Questionnaire. We will evaluate other patient-reported outcomes (including oral health-related quality of life) as well as clinician-assessed quality and cost. At the end of the trial, participants will choose which denture pair they wish to keep and interviewed about their experiences with the 3D-printed IMO. The quantitative and qualitative data will be incorporated through an explanatory mixed-methods strategy. A final quantitative assessment will happen after 12 months with the preferred IMO to assess the long-term performance and maintenance needs. DISCUSSION: This mixed-methods RCT will explore patient experiences with 3D-printed IMOs, aiming to assess the potential for altering clinical practice and dental public health policies. Our results will inform policies by showing whether 3D printing offers comparable outcomes at lower costs, facilitating greater access to oral care for the elderly. TRIAL REGISTRATION: ClinicalTrials.gov, NCT06155630, Registered on 04 December 2023. https://classic. CLINICALTRIALS: gov/ct2/show/NCT06155630.

Fostering Digital Life Skills Through Social Media With Adolescents in 6 German States: Protocol for an Accessibility Study According to the RE-AIM Framework.

BACKGROUND: Social media is essential in the lives of adolescents, with 97% of US teenagers engaging daily. While it facilitates communication, learning, and identity development, it also poses risks like harmful content exposure and psychological distress, particularly for adolescents in their critical developmental stage. Teaching digital life skills innovatively counters these risks, adapting traditional competencies such as decision-making, problem-solving, creative and critical thinking, communication, interpersonal skills, self-awareness, empathy, and emotional and stress management to digital challenges. OBJECTIVE: This study evaluates the accessibility of the "leduin" program, a novel intervention designed to impart digital life skills through Instagram. The program aims to leverage social media's educational potential, focusing on effective strategies to engage adolescents. Emphasizing accessibility is crucial, as it determines the program's overall impact. METHODS: The leduin program, developed through intervention mapping, applies behavior change techniques via social media for 9th and 10th graders. It is a 14-week spaced learning curriculum with daily sessions <5 minutes. Emphasizing the "reach" aspect of the reach, effectiveness, adoption, implementation, and maintenance (RE-AIM) model, the recruitment targets diverse educational settings across 6 German states, aiming for inclusivity. Recruitment will involve schools, youth centers, and therapeutic facilities. The study seeks at least 128 participants, a calculated minimum to detect medium-sized effects in the quasi-experimental design and explore varying engagement levels and program responses. Data collection includes preintervention, postintervention, and 6-month follow-up surveys, using multilevel regression, latent growth models, and qualitative analysis to extensively assess reach and gain first insights on effectiveness, acceptance, implementation, and maintenance. The study aims to reveal key factors influencing program participation and interaction; a detailed analysis of engagement patterns will reveal the effectiveness of the recruitment strategies and barriers to participation. Additionally, initial indications of the program's impact on life skills, social media-related skills, health status, risk behaviors, and academic performance will be analyzed. RESULTS: Recruitment was planned from May 2023 until the beginning of the leduin program in October 2023. As of March 2024, we have recruited 283 participants. CONCLUSIONS: The leduin program stands as an innovative and essential initiative in adolescent health promotion, harnessing the power of social media to teach important digital life skills. This study highlights the critical role of accessibility in the success of social media interventions. Effective adolescent engagement strategies are imperative, as they dictate the overall impact of such interventions. The insights gained from this study will be instrumental in shaping future programs, laying groundwork for a subsequent, more comprehensive cluster-randomized controlled trial. The study's design acknowledges the limitations of the current quasi-experimental approach, including the anticipated sample size and the absence of a control group, and aims to provide a foundational understanding for future research in this field. TRIAL REGISTRATION: Deutsches Register Klinischer Studien DRKS00032308; https://drks.de/search/de/trial/DRKS00032308. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/51085.

When Cortical Bone Matrix Properties Are Indiscernible between Elderly Men with and without Type 2 Diabetes, Fracture Resistance Follows Suit.

Type 2 diabetes mellitus (T2DM) is a metabolic disease affecting bone tissue and leading to increased fracture risk in men and women, independent of bone mineral density (BMD). Thus, bone material quality (i.e., properties that contribute to bone toughness but are not attributed to bone mass or quantity) is suggested to contribute to higher fracture risk in diabetic patients and has been shown to be altered. Fracture toughness properties are assumed to decline with aging and age-related disease, while toughness of human T2DM bone is mostly determined from compression testing of trabecular bone. In this case-control study, we determined fracture resistance in T2DM cortical bone tissue from male individuals in combination with a multiscale approach to assess bone material quality indices. All cortical bone samples stem from male nonosteoporotic individuals and show no significant differences in microstructure in both groups, control and T2DM. Bone material quality analyses reveal that both control and T2DM groups exhibit no significant differences in bone matrix composition assessed with Raman spectroscopy, in BMD distribution determined with quantitative back-scattered electron imaging, and in nanoscale local biomechanical properties assessed via nanoindentation. Finally, notched three-point bending tests revealed that the fracture resistance (measured from the total, elastic, and plastic J-integral) does not significantly differ in T2DM and control group, when both groups exhibit no significant differences in bone microstructure and material quality. This supports recent studies suggesting that not all T2DM patients are affected by a higher fracture risk but that individual risk profiles contribute to fracture susceptibility, which should spur further research on improving bone material quality assessment in vivo and identifying risk factors that increase bone fragility in T2DM. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation.

Diabetes mellitus (DM) is an emerging metabolic disease, and the management of diabetic bone disease poses a serious challenge worldwide. Understanding the underlying mechanisms leading to high fracture risk in DM is hence of particular interest and urgently needed to allow for diagnosis and treatment optimization. In a case-control postmortem study, the whole 12th thoracic vertebra and cortical bone from the mid-diaphysis of the femur from male individuals with type 1 diabetes mellitus (T1DM) (n = 6; 61.3 ± 14.6 years), type 2 diabetes mellitus (T2DM) (n = 11; 74.3 ± 7.9 years), and nondiabetic controls (n = 18; 69.3 ± 11.5) were analyzed with clinical and ex situ imaging techniques to explore various bone quality indices. Cortical collagen fibril deformation was measured in a synchrotron setup to assess changes at the nanoscale during tensile testing until failure. In addition, matrix composition was analyzed including determination of cross-linking and non-crosslinking advanced glycation end-products like pentosidine and carboxymethyl-lysine. In T1DM, lower fibril deformation was accompanied by lower mineralization and more mature crystalline apatite. In T2DM, lower fibril deformation concurred with a lower elastic modulus and tendency to higher accumulation of non-crosslinking advanced glycation end-products. The observed lower collagen fibril deformation in diabetic bone may be linked to altered patterns mineral characteristics in T1DM and higher advanced glycation end-product accumulation in T2DM. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A quality improvement approach to develop an educational initiative for an age-friendly health system.

Authors describe a quality improvement approach to develop and pilot test educational materials with an aim to educate MinuteClinic providers in the provision of age-friendly care using the 4Ms Framework: What Matters, Medication, Mentation, Mobility. The team used surveys, focus groups and site visits to develop educational prototypes with Plan-Do-Study-Act iterative cycles to improve the education. Educational materials introduced providers to 4Ms assessment and evidence-based act on strategies for older adults in the convenient care setting. The education activities included an interactive orientation module comparing standard care to 4Ms care, 10 video vignettes with experts addressing gerontological topics, and 12 grand rounds presented monthly on topics applying the 4Ms with older adults. The information gained from the staff aided in the development and the iterative improvement of the materials. This article highlights the benefits of using a quality improvement approach in development of clinician education in provision of age-friendly care.

3D Image Registration Marginally Improves the Precision of HR-pQCT Measurements Compared to Cross-Sectional-Area Registration in Adults With Osteogenesis Imperfecta.

Repositioning error in longitudinal high-resolution peripheral-quantitative computed tomography (HR-pQCT) imaging can lead to different bone volumes being assessed over time. To identify the same bone volumes at each time point, image registration is used. While cross-sectional area image registration corrects axial misalignment, 3D registration additionally corrects rotations. Other registration methods involving matched angle analysis (MA) or boundary transformations (3D-TB) can be used to limit interpolation error in 3D-registering micro-finite-element data. We investigated the effect of different image registration methods on short-term in vivo precision in adults with osteogenesis imperfecta, a collagen-related genetic disorder resulting in low bone mass, impaired quality, and increased fragility. The radii and tibiae of 29 participants were imaged twice on the same day with full repositioning. We compared the precision error of different image registration methods for density, microstructural, and micro-finite-element outcomes with data stratified based on anatomical site, motion status, and scanner generation. Regardless of the stratification, we found that image registration improved precision for total and trabecular bone mineral densities, trabecular and cortical bone mineral contents, area measurements, trabecular bone volume fraction, separation, and heterogeneity, as well as cortical thickness and perimeter. 3D registration marginally outperformed cross-sectional area registration for some outcomes, such as trabecular bone volume fraction and separation. Similarly, precision of micro-finite-element outcomes was improved after image registration, with 3D-TB and MA methods providing greatest improvements. Our regression model confirmed the beneficial effect of image registration on HR-pQCT precision errors, whereas motion had a detrimental effect on precision even after image registration. Collectively, our results indicate that 3D registration is recommended for longitudinal HR-pQCT imaging in adults with osteogenesis imperfecta. Since our precision errors are similar to those of healthy adults, these results can likely be extended to other populations, although future studies are needed to confirm this. © 2022 American Society for Bone and Mineral Research (ASBMR).

Potential Role of Perilacunar Remodeling in the Progression of Osteoporosis and Implications on Age-Related Decline in Fracture Resistance of Bone.

PURPOSE OF REVIEW: We took an interdisciplinary view to examine the potential contribution of perilacunar/canalicular remodeling to declines in bone fracture resistance related to age or progression of osteoporosis. RECENT FINDINGS: Perilacunar remodeling is most prominent as a result of lactation; recent advances further elucidate the molecular players involved and their effect on bone material properties. Of these, vitamin D and calcitonin could be active during aging or osteoporosis. Menopause-related hormonal changes or osteoporosis therapies affect bone material properties and mechanical behavior. However, investigations of lacunar size or osteocyte TRAP activity with age or osteoporosis do not provide clear evidence for or against perilacunar remodeling. While the occurrence and potential role of perilacunar remodeling in aging and osteoporosis progression are largely under-investigated, widespread changes in bone matrix composition in OVX models and following osteoporosis therapies imply osteocytic maintenance of bone matrix. Perilacunar remodeling-induced changes in bone porosity, bone matrix composition, and bone adaptation could have significant implications for bone fracture resistance.

Compressive Strength of Iliac Bone ECM Is Not Reduced in Osteogenesis Imperfecta and Increases With Mineralization.

Osteogenesis imperfecta (OI) is an inheritable, genetic, and collagen-related disorder leading to an increase in bone fragility, but the origin of its "brittle behavior" is unclear. Because of its complex hierarchical structure, bone behaves differently at various length scales. This study aims to compare mechanical properties of human OI bone with healthy control bone at the extracellular matrix (ECM) level and to quantify the influence of the degree of mineralization. Degree of mineralization and mechanical properties were analyzed under dry conditions in 12 fixed and embedded transiliac crest biopsies (control n = 6, OI type I n = 3, OI type IV n = 2, and OI type III n = 1). Mean degree of mineralization was measured by microcomputed tomography at the biopsy level and the mineral-to-matrix ratio was assessed by Raman spectroscopy at the ECM level. Both methods revealed that the degree of mineralization is higher for OI bone compared with healthy control. Micropillar compression is a novel technique for quantifying post-yield properties of bone at the ECM level. Micropillars (d = 5 µm, h = 10 µm) were fabricated using focused ion beam milling and quasi-statically compressed to capture key post-yield properties such as ultimate strength. The qualitative inspection of the stress-strain curves showed that both OI and healthy control bone have a ductile response at the ECM level. The quantitative results showed that compressive strength is not reduced in OI bone and is increasing with OI severity. Nanoindentation measurements revealed that OI bone tends to have a higher Young's modulus, hardness, and dissipated energy compared with healthy bone. Micropillar strength and indentation modulus increased linearly and significantly (p < .0001) with mineral-to-matrix ratio. In conclusion, this study indicates that compressive mechanical properties of dry OI bone at the iliac crest are not inferior to healthy control at the ECM level and increase with mineralization. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Multisite longitudinal calibration of HR-pQCT scanners and precision in osteogenesis imperfecta.

BACKGROUND: For high-resolution peripheral quantitative computed tomography (HR-pQCT) to be used in longitudinal multi-center studies to assess disease and treatment effects, data must be aggregated across multiple timepoints and scanners. This requires an understanding of the factors contributing to scanner precision, and multi-scanner cross-calibration procedures, especially for clinical populations with severe phenotypes, like osteogenesis imperfecta (OI). METHODS: To address this, we first evaluated single- and multi-center short- and long-term precision errors of standard HR-pQCT parameters. Two imaging phantoms were circulated among 13 sites (7 XtremeCT and 6 XtremeCT2) and scanned in triplicate at 3 timepoints/site. Additionally, duplicate in vivo radial and tibial scans were acquired in 29 individuals with OI. Secondly, we investigated subject- and scanner-related factors that contribute to precision errors using regression analysis. Thirdly, we proposed a reference site selection criterion for multisite cross-calibration and demonstrated the external validity of phantom-based calibrations. RESULTS: Our results show excellent short-term single-site precision in both phantoms (CV % < 0.5%) and in density, microarchitecture and finite element parameters of OI participants (CV % = 0.75 to 1.2%). In vivo reproducibility significantly improved with (i) cross sectional area image registration versus no registration and (ii) scans with no motion artifacts. While reproducibility was similar across OI subtypes and anatomical sites, XtremeCT2 scanners achieved ~2.5% better precision than XtremeCT for trabecular parameters. Finally, we demonstrate that multisite longitudinal precision errors resulting from inconsistencies between scanners can be partially corrected through scanner cross-calibration. CONCLUSIONS: This study is the first to assess long-term reproducibility and cross-calibration in a study using first and second generation HR-pQCT scanners. The results presented in this context provide timely guidelines for future use of this powerful clinical imaging modality in multi-center longitudinal clinical trials.

Breaking new ground in mineralized tissue: Assessing tissue quality in clinical and laboratory studies.

Mineralized tissues, such as bone and teeth, have extraordinary mechanical properties of both strength and toughness. This mechanical behavior originates from deformation and fracture resistance mechanisms in their multi-scale structure. The term quality describes the matrix composition, multi-scale structure, remodeling dynamics, water content, and micro-damage accumulation in the tissue. Aging and disease result in changes in the tissue quality that may reduce strength and toughness and lead to elevated fracture risk. Therefore, the capability to measure the quality of mineralized tissues provides critical information on disease progression and mechanical integrity. Here, we provide an overview of clinical and laboratory-based techniques to assess the quality of mineralized tissues in health and disease. Current techniques used in clinical settings include radiography-based (radiographs, dual energy x-ray absorptiometry, EOS) and x-ray tomography-based methods (high resolution peripheral quantitative computed tomography, cone beam computed tomography). In the laboratory, tissue quality can be investigated in ex vivo samples with x-ray imaging (micro and nano-computed tomography, x-ray microscopy), electron microscopy (scanning/transmission electron imaging (SEM/STEM), backscattered scanning electron microscopy, Focused Ion Beam-SEM), light microscopy, spectroscopy (Raman spectroscopy and Fourier transform infrared spectroscopy) and assessment of mechanical behavior (mechanical testing, fracture mechanics and reference point indentation). It is important for clinicians and basic science researchers to be aware of the techniques available in different types of research. While x-ray imaging techniques translated to the clinic have provided exceptional advancements in patient care, the future challenge will be to incorporate high-resolution laboratory-based bone quality measurements into clinical settings to broaden the depth of information available to clinicians during diagnostics, treatment and management of mineralized tissue pathologies.

Bone adaptation: Safety factors and load predictability in shaping skeletal form.

Much is known about skeletal adaptation in relation to the mechanical functions that bones serve. This includes how bone adapts to mechanical loading during an individual's lifetime as well as over evolutionary time. Although controlled loading in animal models allows us to observe short-term bone adaptation (epigenetic mechanobiology), examining an assemblage of extant vertebrate bones or a group of fossils' bony structures can reveal the combined effects of long-term trends in loading history and the effects of natural selection. In this survey we examine adaptations that take place over both time scales and highlight a few of the extraordinary insights first published by John Currey. First, we provide a historical perspective on bone adaptation control mechanisms, followed by a discussion of safety factors in bone. We then summarize examples of structural- and material-level adaptations and mechanotransduction, and analyze the relationship between these structural- and material-level adaptations observed in situations where loading modes are either predictable or unpredictable. We argue that load predictability is a major consideration for bone adaptation broadly across an evolutionary timescale, but that its importance can also be seen during ontogenetic growth trajectories, which are subject to natural selection as well. Furthermore, we suggest that bones with highly predictable load patterns demonstrate more precise design with lower safety factors, while bones that experience less predictable loads or those that are less capable of repair and adaptation are designed with a higher safety factor. Finally, exposure to rare loading events with high potential costs of failure leads to design of structures with very high safety factor compared to everyday loading experience. Understanding bone adaptations at the structural and material levels, which take place over an individual's lifetime or over evolutionary time has numerous applications in translational and clinical research to understand and treat musculoskeletal diseases, as well as to permit the furthering of human extraterrestrial exploration in environments with altered gravity.

On the Origins of Fracture Toughness in Advanced Teleosts: How the Swordfish Sword's Bone Structure and Composition Allow for Slashing under Water to Kill or Stun Prey.

The osseous sword of a swordfish (Xiphias gladius) is specialized to incapacitate prey with stunning blows. Considering the sword's growth and maturation pattern, aging from the sword's base to the tip, while missing a mechanosensitive osteocytic network, an in-depth understanding of its mechanical properties and bone quality is lacking. Microstructural, compositional, and nanomechanical characteristics of the bone along the sword are investigated to reveal structural mechanisms accounting for its exceptional mechanical competence. The degree of mineralization, homogeneity, and particle size increase from the base toward the tip, reflecting aging along its length. Fracture experiments reveal that crack-growth toughness vastly decreases at the highly and homogeneously mineralized tip, suggesting the importance of aging effects. Initiation toughness, however, is unchanged suggesting that aging effects on this hierarchical level are counteracted by constant mineral/fibril interaction. In conclusion, the sword of the swordfish provides an excellent model reflecting base-to-tip-wise aging of bone, as indicated by increasing mineralization and decreasing crack-growth toughness toward the tip. The hierarchical, structural, and compositional changes along the sword reflect peculiar prerequisites needed for resisting high mechanical loads. Further studies on advanced teleosts bone tissue may help to unravel structure-function relationships of heavily loaded skeletons lacking mechanosensing cells.

Mechanical Competence and Bone Quality Develop During Skeletal Growth.

Bone fracture risk is influenced by bone quality, which encompasses bone's composition as well as its multiscale organization and architecture. Aging and disease deteriorate bone quality, leading to reduced mechanical properties and higher fracture incidence. Largely unexplored is how bone quality and mechanical competence progress during longitudinal bone growth. Human femoral cortical bone was acquired from fetal (n = 1), infantile (n = 3), and 2- to 14-year-old cases (n = 4) at the mid-diaphysis. Bone quality was assessed in terms of bone structure, osteocyte characteristics, mineralization, and collagen orientation. The mechanical properties were investigated by measuring tensile deformation at multiple length scales via synchrotron X-ray diffraction. We find dramatic differences in mechanical resistance with age. Specifically, cortical bone in 2- to 14-year-old cases exhibits a 160% greater stiffness and 83% higher strength than fetal/infantile cases. The higher mechanical resistance of the 2- to 14-year-old cases is associated with advantageous bone quality, specifically higher bone volume fraction, better micronscale organization (woven versus lamellar), and higher mean mineralization compared with fetal/infantile cases. Our study reveals that bone quality is superior after remodeling/modeling processes convert the primary woven bone structure to lamellar bone. In this cohort of female children, the microstructural differences at the femoral diaphysis were apparent between the 1- to 2-year-old cases. Indeed, the lamellar bone in 2- to 14-year-old cases had a superior structural organization (collagen and osteocyte characteristics) and composition for resisting deformation and fracture than fetal/infantile bone. Mechanistically, the changes in bone quality during longitudinal bone growth lead to higher fracture resistance because collagen fibrils are better aligned to resist tensile forces, while elevated mean mineralization reinforces the collagen scaffold. Thus, our results reveal inherent weaknesses of the fetal/infantile skeleton signifying its inferior bone quality. These results have implications for pediatric fracture risk, as bone produced at ossification centers during children's longitudinal bone growth could display similarly weak points. © 2019 American Society for Bone and Mineral Research.

Identification, recovery, and impact of ghost fishing gear in the Mullica River-Great Bay Estuary (New Jersey, USA): Stakeholder-driven restoration for smaller-scale systems.

The impact of ghost fishing in large coastal ecosystems has generated considerable interest. In smaller, understudied systems with fewer stakeholders, derelict fishing gear (DFGs) may have impacts similar to these larger systems at the same relative scale. Four years of side scan sonar surveys in the Mullica River-Great Bay Estuary (New Jersey, USA) supported the recovery of 1776 DFGs off-season by commercial partners. Locations with high densities of recovered DFGs (>200 DFGs/km2) occupied intersections of recreational vessel traffic and commercial crabbing activity. Condition and depth-in-sediment of recovered DFGs was used to evaluate true bycatch (terrapins, whelks, blue crabs) versus species utilizing degraded gear as habitat (juvenile tautog, oyster toadfish). Critically, gear recovered in-season with low cost sonars (an additional 225 DFGs) prevented the accumulation of new DFGs which likely generate the highest percentages of bycatch. Removal of DFGs in this system led to significant ecological (reduced bycatch), economic (>$61,000 in direct pay, reused gear), and anticipated future benefits (increased harvest).

Simulating the Role of the Parent: Promoting Family-Centered Nursing Care.

Parents of hospitalized children need support to diminish their own fear and anxiety and provide safe and loving care for the child. Baccalaureate nursing students, who are rarely parents themselves, often find it difficult to understand the needs of parents. An innovative simulation strategy was created to enhance students' understanding of the parent's role and its effect on family-centered care. This article describes the development of pediatric simulation experiences that actively incorporate the role of a parent. Portraying the parent during the simulation increases students' ability to be empathetic while providing safe family-centered care.

Mechanically stimulated ATP release from murine bone cells is regulated by a balance of injury and repair.

Bone cells sense and actively adapt to physical perturbations to prevent critical damage. ATP release is among the earliest cellular responses to mechanical stimulation. Mechanical stimulation of a single murine osteoblast led to the release of 70 ± 24 amole ATP, which stimulated calcium responses in neighboring cells. Osteoblasts contained ATP-rich vesicles that were released upon mechanical stimulation. Surprisingly, interventions that promoted vesicular release reduced ATP release, while inhibitors of vesicular release potentiated ATP release. Searching for an alternative ATP release route, we found that mechanical stresses induced reversible cell membrane injury in vitro and in vivo. Ca2+/PLC/PKC-dependent vesicular exocytosis facilitated membrane repair, thereby minimizing cell injury and reducing ATP release. Priming cellular repair machinery prior to mechanical stimulation reduced subsequent membrane injury and ATP release, linking cellular mechanosensitivity to prior mechanical exposure. Thus, our findings position ATP release as an integrated readout of membrane injury and repair.

Inter-site variability of the osteocyte lacunar network in the cortical bone underpins fracture susceptibility of the superolateral femoral neck.

BACKGROUND: The osteocytic lacunar network is considered to be an integral player in the regulation of bone homeostasis, and reduction in osteocytes is associated with reduced bone strength. Here, we analyzed site-specific patterns in osteocyte characteristics and matrix composition in the cortical compartment of the femoral neck to reveal the structural basis of its fragility. METHODS: Cross-sections of the human femoral neck - one of the most common fracture sites - were acquired from 12 female cadavers (age 34-86 years) and analyzed with backscattered scanning electron microscopy and high-resolution micro-computed tomography (µ-CT). The 2D/3D density and size of the osteocyte lacunae as well as bone mineral density distribution (BMDD) were measured in two regions subject to different biomechanical loads in vivo: the inferomedial (medial) region (habitually highly loaded in compression) and the superolateral (lateral) region (lower habitual loading intensity). Using quantitative polarized light microscopy, collagen fiber orientation was quantified in these two regions, accordingly. RESULTS: In 2D measurements, the inferomedial region displayed lower mineralization heterogeneity, 19% higher osteocyte lacunar density (p = 0.005), but equal lacunar size compared to the superolateral region. 3D measurements confirmed a significantly higher osteocyte lacunar density in the inferomedial region (p = 0.015). Osteocyte lacunar density decreased in aged individuals, and inter-site differences were reduced. Site-specific osteocyte characteristics were not accompanied by changes in collagen fiber orientation. CONCLUSIONS: Since osteocyte characteristics may provide valuable insights into bone mechanical competence, the variations in osteocyte properties might reflect the increased fracture susceptibility of the superolateral neck.

Sclerostin Neutralizing Antibody Treatment Enhances Bone Formation but Does Not Rescue Mechanically Induced Delayed Healing.

During bone healing, tissue formation processes are governed by mechanical strain. Sost/sclerostin, a key Wnt signaling inhibitor and mechano-sensitive pathway, is downregulated in response to mechanical loading. Sclerostin neutralizing antibody (SclAb) increases bone formation. Nevertheless, it remains unclear whether sclerostin inhibition can rescue bone healing in situations of mechanical instability, which otherwise delay healing. We investigated SclAb's influence on tissue formation in a mouse femoral osteotomy, stabilized with rigid or semirigid external fixation. The different fixations allowed different magnitudes of interfragmentary movement during weight bearing, thereby influencing healing outcome. SclAb or vehicle (veh) was administeredand bone healing was assessed at multiple time points up to day 21 postoperatively by in vivo micro-computed tomography, histomorphometry, biomechanical testing, immunohistochemistry, and gene expression. Our results show that SclAb treatment caused a greater bone volume than veh. However, SclAb could not overcome the characteristic delayed healing of semirigid fixation. Indeed, semirigid fixation resulted in delayed healing with a prolonged endochondral ossification phase characterized by increased cartilage, lower bone volume fraction, and less bony bridging across the osteotomy gap than rigid fixation. In a control setting, SclAb negatively affected later stages of healing under rigid fixation, evidenced by the high degree of endosteal bridging at 21 days in the rigid-SclAb group compared with rigid-veh, indicating delayed fracture callus remodeling and bone marrow reconstitution. Under rigid fixation, Sost and sclerostin expression at the gene and protein level, respectively, were increased in SclAb compared with veh-treated bones, suggesting a negative feedback mechanism. Our results suggest that SclAb could be used to enhance overall bone mass but should be carefully considered in bone healing. SclAb may help to increase bone formation early in the healing process but not during advanced stages of fracture callus remodeling and not to overcome delayed healing in semirigid fixation. © 2018 American Society for Bone and Mineral Research.

Promoting Interprofessional Collaborative Practice Through Simulation.

A 12-week program was developed to educate nursing, medicine, and physician assistant faculty on the principles and best practices of simulation. The goal was to facilitate team building and collaborative practice through the implementation of an interprofessional (IP) simulation experience for students. Workshops focused on IP communication involving seminar-based instruction, discussion, and the progressive development of an IP simulation based on a National League for Nursing Advancing Care Excellence for Seniors scenario. During the final session, students participated in the simulation while faculty evaluated and revised the scenario to best meet the needs of students from the three disciplines.