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Macrophages have established roles supporting bone formation. Despite their professional phagocytic nature, the role of macrophage phagocytosis in bone homeostasis is not well understood. Interestingly, apoptosis is a pivotal feature of cellular regulation and the primary fate of osteoblasts is apoptosis. Efferocytosis (phagocytosis of apoptotic cells) is a key physiologic process for the homeostasis of many tissues, and is associated with expression of osteoinductive factors. To test effects of macrophage depletion and compromised phagocytosis on bone, 16-week-old male C57BL/6J mice were treated with trabectedin-a chemotherapeutic with established anti-macrophage effects. Trabectedin treatment reduced F4/80+ and CD68+ macrophages in the bone marrow as assessed by flow cytometry, osteal macrophages near the bone surface, and macrophage viability in vitro. Trabectedin treatment significantly reduced marrow gene expression of key phagocytic factors (Mfge8, Mrc1), and macrophages from treated mice had a reduced ability to phagocytose apoptotic mimicry beads. Macrophages cultured in vitro and treated with trabectedin displayed reduced efferocytosis of apoptotic osteoblasts. Moreover, efferocytosis increased macrophage osteoinductive TGF-β production and this increase was inhibited by trabectedin. Long-term (6-week) treatment of 16-week-old C57BL/6J mice with trabectedin significantly reduced trabecular BV/TV and cortical BMD. Although trabectedin reduced osteoclast numbers in vitro, osteoclast surface in vivo was not altered. Trabectedin treatment reduced serum P1NP as well as MS/BS and BFR/BS, and inhibited mineralization and Runx2 gene expression of osteoblast cultures. Finally, intermittent PTH 1-34 (iPTH) treatment was administered in combination with trabectedin, and iPTH increased trabecular bone volume fraction (BV/TV) in trabectedin-treated mice. Collectively, the data support a model whereby trabectedin significantly reduces bone mass due to compromised macrophages and efferocytosis, but also due to direct effects on osteoblasts. This data has immediate clinical relevance in light of increasing use of trabectedin in oncology. © 2017 American Society for Bone and Mineral Research.

Bone fractures are associated with considerable morbidity and increased mortality. A major limitation to healing is lack of bone blood flow, which is impaired by physical disruption of intraskeletal and/or periosteal vasculature by the fracture. Thus, pharmacological interventions are needed to improve osseous blood flow, thereby accelerating bone fracture closure. Relaxin is secreted by the ovary and circulates in rodents and humans during pregnancy. Because relaxin might benefit bone fracture healing by stimulating angiogenesis, vasculogenesis (and potentially osteogenesis) through mobilization and activation of bone marrow progenitor cells, and by increasing blood flow via vasodilation, we investigated whether relaxin administration would accelerate closure of a calvarial defect in mice. Whether administered systemically by osmotic pump or locally by collagen scaffolds for ~2 week period after lesioning, relaxin did not accelerate bone healing. Despite implementing relaxin doses that reached plasma concentrations spanning the physiological to supraphysiological range, testing the closure of two different sizes of calvarial lesions, allowing for different intervals of time from instigation of cranial lesion to euthanasia, and investigating mice of different ages, we did not observe a significant benefit of relaxin in bone lesion healing. Nor did we observe stimulation of blood vessel formation in the bone lesion by the hormone. An incidental finding was that relaxin appeared to enhance trabecular bone growth in an uninjured control bone (femur). Although the results of this study were not supportive of a therapeutic benefit for relaxin on calvarial defect closure, future investigation is needed employing different animal species and experimental models of bone fracture.

Summary Regional anaesthesia has been shown to have several advantages over general anaesthesia in reducing the need for, and hence cost of, unscheduled outpatient visits or readmission to hospital. However, the benefit has not been evaluated in a direct comparison between day-care patients and inpatients. We randomly allocated 120 patients undergoing unilateral foot surgery to either inpatient (two-day postoperative stay) or day-care management under continuous regional anaesthesia, and compared the impact on unscheduled postoperative outpatient visits, readmissions to hospital and the associated costs. The operations were performed under popliteal sciatic nerve block. A perineural catheter was inserted before surgery and removed from all patients on the third postoperative day. We found no significant difference in the incidence of outpatient visits (3.3% day-care vs 5.0% inpatient, p = 0.640), readmissions (6.7% day-care vs 3.3% inpatient, p = 0.395) or complications between the two groups. Costs were also significantly lower in the day-care group (net difference €8011 (£6684; $10 986) per patient, p

Clinical and basic science studies have demonstrated the anti-inflammatory properties of local anaesthetics. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. Regional anaesthesia is associated in some retrospective clinical studies with reduced risk of metastasis and increased long-term survival. The potential beneficial effects of regional anaesthesia have been attributed mainly to the inhibition of the neuroendocrine stress response to surgery and to the reduction in the requirements of volatile anaesthetics and opioids. Because cancer is linked to inflammation and local anaesthetics have anti-inflammatory effects, these agents may participate in reducing the risk of metastasis, but their mechanism of action is unknown. We demonstrated in vitro that amide local anaesthetics attenuate tumour cell migration as well as signalling pathways enhancing tumour growth and metastasis. This has provided the first evidence of a molecular mechanism by which regional anaesthesia might inhibit or reduce cancer metastases.

OBJECTIVE The rice rat (Oryzomys palustris) develops periodontitis-like lesions when fed a diet rich in sucrose and casein (H-SC). We aimed to establish whether this model can accurately mimic the development of human periodontitis. MATERIALS AND METHODS For this purpose, 28-day-old rice rats (15/group) were assigned to standard (STD) or H-SC diets and sacrificed after 6, 12, and 18 weeks. Jaws were processed for morphometric, histometric, histologic, histomorphometric, and micro-CT analyses. RESULTS We found a progressive increase in horizontal alveolar bone loss (ABL) with age in maxillae of rats fed the STD diet as determined by morphometry. The H-SC diet exacerbated horizontal ABL at the palatal surface at 12 and 18 weeks. Furthermore, increased vertical ABL was detected in mandibles and maxillae of rats fed the H-SC diet for 12 and/or 18 weeks by histometry and micro-CT. Remarkably, the H-SC diet significantly increased bone remodeling at the interproximal alveolar bone of mandibles from rats fed for 6 weeks, but not in those fed for longer periods. CONCLUSIONS These findings indicate that the H-SC diet induced a transient increase in alveolar bone remodeling, which is followed by ABL characteristic of moderate periodontitis.

This paper presents a numerical validation of a thin-walled beam (TWB) finite element (FE) model of a realistic wind turbine rotor blade. Based on the theory originally developed by Librescu et al. and later extended to suit FE modelling by Phuong, Lee and others, this computationally efficient yet accurate numerical model is capable of capturing most of the features found in large blades including thin-walled hollow cross section with variable thickness along the section's contour, inner reinforcements, arbitrary material layup and non-linear anisotropic fibre-reinforced composites; the present application is, for the time being, restricted to linearity. This one-dimensional (1D) FE model allows retaining information of different regions of the blade's shell and therefore approximates the behaviour of more complex three-dimensional (3D) shell or solid FE models more accurately than typical 1D FE beam models. A 9.2 m rotor blade, previously reported in specialized literature, was chosen as a case study to validate the static and dynamic behaviour predicted by a TWB model against an industry-standard 3D shell model built in a commercial software tool. Given the geometric and material complexities involved, an excellent agreement was found for static deformation curves, as well as a good prediction of the lowest frequency modes in terms of resonance frequencies, mode shapes and frequency response functions; the highest (sixth) frequency mode shows only a fair agreement as expected for an FE model. It is concluded that despite its simplicity, a TWB FE model is sufficiently accurate to serve as a design tool for the recursive analyses required during design and optimization stages of wind turbines using only readily available computational tools

Oral Diseases (2010) 16, 674–685 Objectives: Tooth extraction has been identified as an important risk factor for bisphosphonate-induced osteonecrosis of the jaw. Therefore, the main goal of this study was to determine the effects of alendronate on healing of the extraction socket and on interdental alveolar bone after tooth extraction in rats. Materials and methods: Animals were injected subcutaneously with vehicle or alendronate for 3–4 weeks before the first mandibular molar was extracted and these treatments were continued during post-extraction periods of 10, 21, 35 and 70 days. Mandibles were processed to evaluate healing of the extraction socket and adjacent alveolar bone by assessing bone formation, bone resorption and vascularity by histomorphometric techniques. Results: Alendronate decreased new woven bone formation, blood vessel area, perimeter and number in the extraction socket at 10 days postextraction, but not at later time points. Furthermore, alendronate-treated rats had increased interdental alveolar bone volume and height only at 10 days postextraction. In addition, a 2.5-fold increase in the percentage of empty osteocyte lacunae was found in alveolar bone of alendronate-treated rats only at 10 days postextraction. Conclusions: Alendronate transiently decreases bone formation and vascularity in the extraction socket and delays the removal of interdental alveolar bone after tooth extraction in rats.