Fluid shear stress in trabecular bone marrow due to low-magnitude high-frequency vibration

Low-magnitude high-frequency (LMHF) loading has recently received attention for its anabolic effect on bone. The mechanism of transmission of the anabolic signal is not fully understood, but evidence indicates that it is not dependent on bone matrix strain. One possible source of signaling is mechanostimulation of the cells in the bone marrow. We hypothesized that the magnitude of the fluid shear stress in the marrow during LMHF loading is in the mechanostimulatory range. As such, the goal of this study was to determine the range of shear stress in the marrow during LMHF vibration. The shear stress was estimated from computational models, and its dependence on bone density, architecture, permeability, marrow viscosity, vibration amplitude and vibration frequency were examined. Three-dimensional finite element models of five trabecular bone samples from different anatomic sites were constructed, and a sinusoidal velocity profile was applied to the models. In human bone models during axial vibration at an amplitude of 1 g, more than 75% of the marrow experienced shear stress greater than 0.5Pa. In comparison, in vitro studies indicate that fluid induced shear stress in the range of 0.5 to 2.0Pa is anabolic to a variety of cells in the marrow. Shear stress at the bone-marrow interface was as high as 5.0Pa. Thus, osteoblasts and bone lining cells that are thought to reside on the endosteal surfaces may experience very high shear stress during LMHF loading. However, a more complete understanding of the location of the various cell populations in the marrow is needed to quantify the effects on specific cell types. This study suggests the shear stress within bone marrow in real trabecular architecture during LMHF vibration could provide the mechanical signal to marrow cells that leads to bone anabolism.     

氧化钛纳米管对即刻种植骨结合影响的实验研究

目的:评价氧化钛纳米管对犬即刻种植骨结合效果的影响。方法:犬拔牙后即刻将光滑表面(对照组)和氧化钛纳米管表面(实验组)种植体植入拔牙窝内,于12周后处死取材,进行显微CT扫描、组织学染色分析以及生物力学检测。结果:扫描电镜显示经过阳极氧化后,钛表面形成了直径为30-80纳米的纳米管状结构;12周后,显微CT扫描结果提示实验组骨体积分数(BV/TV)、骨小梁数目(Tb.N)、骨小梁厚度(Tb.Th)均显著高于对照组,骨小梁间隙(Tb.Sp)显著低于对照组,差异具有统计学意义(P0.05)。术后12周,实验组与对照组骨结合率分别为49.35±11.76%、31.79±13.07%,最大拔出力分别为105.28±27.87N、79.23±20.46N,实验组均显著高于对照组,差异均具有统计学意义(P0.05)。结论:氧化钛纳米管表面有利于促进即刻种植后骨结合的效果。     

Antimicrobial and bone repair effects of boric acid in a rat model of dry socket (alveolar osteitis) following dental extraction

BackgroundAlveolitis occurs after dental extraction without blood clot formation, leading to an inflammatory process and bacterial contamination. Boric acid (BA) demonstrates anti-inflammatory, antimicrobial, and osteogenic properties. This study aims to evaluate the possible antimicrobial effects and bone repair of BA in a rat model of alveolitis (dry socket).Methods33 male Wistar rats were submitted to the extraction of the upper right incisor and dry socket induction. They were first divided into two groups: dry socket (n = 17) and dry socket + 0.75 % BA (n = 16). Samples for the microbiological analysis were collected immediately after dental extraction, at the detection of clinical alveolitis, 7, and 14 days after BA application. For microCT and histological analysis, samples from euthanized rats were used in 14 and 28 days after alveolitis detection.ResultsHigher bacterial counts were found in 4–5 days after alveolitis induction, compared to the baseline in both experimental groups, decreasing significantly after 7 and 14 days of treatment with BA (P < 0.05). The microCT evaluation displayed increased bone volume, bone volume fraction, trabecular thickness, and bone mineral density in a time-dependent manner, regardless of BA treatment. On the other hand, the number of trabeculae and total bone porosity decreased over the 28 days of the experiment in the dry-socket group and both groups, respectively (P < 0.05). Histological analysis did not differ on bone repair in both experimental groups.ConclusionThis was the first report investigating the effects of BA in a rat model of alveolitis regarding microbiological and bone repair aspects. The BA local application decreased the total aerobic and facultative bacteria counts and does not seem to benefit the bone repair after alveolitis development. This study paves the way for more studies involving alveolitis and different BA applications.     

Effect of isolation of periosteum and dura on the healing of rabbit calvarial inlay bone grafts

Little is understood about the role of the recipient site in the revascularization and incorporation of autogenous inlay bone grafts in the craniofacial skeleton. Clinical experience demonstrates that secondary complex cranial vault reconstruction performed with scarred avascular dura or poor soft-tissue coverage may undergo significant resorption, thus compromising the aesthetic outcome. This study was designed to determine the effect of isolating autogenous orthotopic inlay calvarial bone grafts from the surrounding dura and/or periosteum on graft revascularization, healing, and volume maintenance in the adult rabbit. Adult rabbits were randomized into four groups (n = 10 per group); in each rabbit, the authors created a circular, 15-mm in diameter, full-thickness cranial defect followed by reconstruction with an autogenous calvarial bone graft, which was replaced orthotopically and held with microplate fixation. Silicone sheeting (0.5 mm thickness) was used to isolate the dura (group II), the periosteum (group II), or both dura and periosteum (group IV) from the graft interface. No silicone was placed in group I. Animals were killed 10 weeks postoperatively, and calvaria were harvested to assess graft surface area, morphology, quantitative histology, fluorochrome staining, and revascularization. Grafts isolated from both the dura and periosteum exhibited significant decreases in total bone (cortical and trabecular) surface area, blood vessel count, and interface healing compared with nonisolated control grafts. Isolation of either the dura or periosteum significantly (p < 0.05) decreased blood vessel count but had no significant effect on interface healing. Isolation of the dura alone was associated with a significant (p < 0.05) decrease in graft cross-sectional surface area and dural cortical thickness compared with nonisolated control grafts, but this effect was not observed when the periosteum alone was isolated. Quantitative histology performed 10 weeks after surgery indicated that graft isolation was associated with increased marrow fibrosis and necrosis compared with nonisolated controls; it also demonstrated evidence of increased activity in bone remodeling (osteoblast and osteocyte count, new trabecular bone, and surface resorption). Triple fluorochrome staining suggested increased bone turnover in the nonisolated grafts compared with isolated grafts at 1 and 5 weeks postoperatively. This study demonstrates that isolating a rabbit calvarial inlay autogenous bone graft from the dura and/or periosteum results in significantly (p < 0.05) decreased revascularization, interface healing, and cross-sectional areas of amount of mature bone compared with nonisolated control grafts 10 weeks after surgery. At this time point, histologic examination demonstrates a paradoxical increase in bone remodeling in isolated bone grafts compared with controls. It is possible that the inhibition of revascularization results in a delayed onset of the remodeling phase of graft incorporation. However, in the model studied, it is not known whether the quantitative histologic and morphometric parameters measured in these isolated grafts exhibit a "catch-up" phenomenon at time points beyond 10 weeks after surgery. The results of this study emphasize the importance of a healthy recipient site in the healing and incorporation of calvarial bone grafts but stress the need for further investigation at later time points.     

Yeast-Incorporated Gallium Promotes Fracture Healing by Increasing Callus Bony Area and Improving Trabecular Microstructure on Ovariectomized Osteopenic Rats

The purpose of this study was to analyze the impact of yeast-incorporated gallium on fracture healing in ovariectomized osteopenic rats. Forty Wistar female rats used were divided into three groups: sham-operated rats (SHAM), ovariectomized (OVX) rats, and ovx rats treated with yeast-bound gallium (YG). A standardized fracture-healing model with stable plate fixation was established for rat femoral. After 4-week stable fixation, animals were killed to prepare bones for Micro-CT, biomechanical testing, and histomorphometry. In addition, bone samples were obtained to evaluate the content of mineral substances in bones. Quantitative analysis of the bones from animals in the organic gallium group revealed significantly increased mineral contents compared to bones from OVX and SHAM groups. Micro-CT showed that treatment with yeast-incorporated gallium increased BV/TV and trabecular thickness and decreased trabecular separation in ovx animals. Histomorphometric evaluation demonstrated that YG increased callus area and callus bone formation. Yeast-bound gallium also improved the biomechanical properties of bone healing. In conclusion, this study suggests that yeast-incorporated gallium could promote fracture healing in ovariectomized rats.     

Pulsed Electromagnetic Field Versus Whole Body Vibration on Cartilage and Subchondral Trabecular Bone in Mice With Knee Osteoarthritis

Pulsed electromagnetic field (PEMF) and whole body vibration (WBV) interventions are expected to be important strategies for management of osteoarthritis (OA). The aim of the study was to investigate the comparative effectiveness of PEMF versus WBV on cartilage and subchondral trabecular bone in mice with knee OA (KOA) induced by surgical destabilization of the medial meniscus (DMM). Forty 12-week-old male C57/BL mice were randomly divided into four groups (n = 10): Control, OA, PEMF, and WBV. OA was induced (OA, PEMF, and WBV groups) by surgical DMM of right knee joint. Mice in PEMF group received 1 h/day PEMF exposure with 75 Hz, 1.6 mT for 4 weeks, and the WBV group was exposed to WBV for 20 min/day with 5 Hz, 4 mm, 0.3 g peak acceleration for 4 weeks. Micro-computed tomography (micro-CT), histology, and immunohistochemistry analyses were performed to evaluate the changes in cartilage and microstructure of trabecular bone. The bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) increased, and bone surface/bone volume (BS/BV) decreased by micro-CT analysis in PEMF and WBV groups. The Osteoarthritis Research Society International (OARSI) scores in PEMF and WBV groups were significantly lower than in the OA group. Immunohistochemical results showed that PEMF and WBV promoted expressions of Aggrecan, and inhibited expressions of IL-1β, ADAMTS4, and MMP13. Superior results are seen in PEMF group compared with WBV group. Both PEMF and WBV were effective, could delay cartilage degeneration and preserve subchondral trabecular bone microarchitecture, and PEMF was found to be superior to WBV. Bioelectromagnetics. 2020;41:298–307 © 2020 Bioelectromagnetics Society     

Intramembranous Bone Healing Process Subsequent to Tooth Extraction in Mice: Micro-Computed Tomography,Histomorphometric and Molecular Characterization

Bone tissue has a significant potential for healing, which involves a significant the interplay between bone and immune cells. While fracture healing represents a useful model to investigate endochondral bone healing, intramembranous bone healing models are yet to be developed and characterized. In this study, a micro-computed tomography, histomorphometric and molecular (RealTimePCRarray) characterization of post tooth-extraction alveolar bone healing was performed on C57Bl/6 WT mice. After the initial clot dominance (0h), the development of a provisional immature granulation tissue is evident (7d), characterized by marked cell proliferation, angiogenesis and inflammatory cells infiltration; associated with peaks of growth factors (BMP-2-4-7,TGFβ1,VEGFa), cytokines (TNFα, IL-10), chemokines & receptors (CXCL12, CCL25, CCR5, CXCR4), matrix (Col1a1-2, ITGA4, VTN, MMP1a) and MSCs (CD105, CD106, OCT4, NANOG, CD34, CD146) markers expression. Granulation tissue is sequentially replaced by more mature connective tissue (14d), characterized by inflammatory infiltrate reduction along the increased bone formation, marked expression of matrix remodeling enzymes (MMP-2-9), bone formation/maturation (RUNX2, ALP, DMP1, PHEX, SOST) markers, and chemokines & receptors associated with healing (CCL2, CCL17, CCR2). No evidences of cartilage cells or tissue were observed, strengthening the intramembranous nature of bone healing. Bone microarchitecture analysis supports the evolving healing, with total tissue and bone volumes as trabecular number and thickness showing a progressive increase over time. The extraction socket healing process is considered complete (21d) when the dental socket is filled by trabeculae bone with well-defined medullary canals; it being the expression of mature bone markers prevalent at this period. Our data confirms the intramembranous bone healing nature of the model used, revealing parallels between the gene expression profile and the histomorphometric events and the potential participation of MCSs and immune cells in the healing process, supporting the forthcoming application of the model for the better understanding of the bone healing process.     

Multi-Scale Approach for the Evaluation of Bone Mineralization in Strontium Ranelate-Treated Diabetic Rats

Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics. Young male Wistar rats (half non-diabetic, half with streptozotocin/nicotinamide-induced diabetes) were either untreated or orally administered 625 mg/kg/day of SrR for 6 weeks. After sacrifice, femora from all animals were evaluated by a multi-scale approach (X-ray diffraction, Fourier transform infrared spectroscopy, inductively coupled plasma optical-emission spectrometry, static histomorphometry, pQCT, and mechanical testing) to determine chemical, crystalline, and biomechanical properties. Untreated diabetic animals (versus untreated non-diabetic) showed a decrease in femoral mineral carbonate content, in cortical thickness and BMC, in trabecular osteocyte density, in maximum load supported at rupture and at yield point, and in overall toughness at mid-shaft. Treatment of diabetic animals with SrR further affected several parameters of bone (some already impaired by diabetes): crystallinity index (indicating less mature apatite crystals); trabecular area, BMC, and vBMD; maximum load at yield point; and structural elastic rigidity. However, SrR was also able to prevent the diabetes-induced decreases in trabecular osteocyte density (completely) and in bone ultimate strength at rupture (partially). Our results indicate that SrR treatment can partially but significantly prevent some bone structural mechanical properties as previously affected by diabetes, but not others (which may even be worsened).     

Patterns in ontogeny of human trabecular bone from SunWatch Village in the Prehistoric Ohio Valley: general features of microarchitectural change

Although adult skeletal morphological variation is best understood within the framework of age-related processes, relatively little research has been directed towards the structure of and variation in trabecular bone during ontogeny. We report here new quantitative and structural data on trabecular bone microarchitecture in the proximal tibia during growth and development, as demonstrated in a subadult archaeological skeletal sample from the Late Prehistoric Ohio Valley. These data characterize the temporal sequence and variation in trabecular bone structure and structural parameters during ontogeny as related to the acquisition of normal functional activities and changing body mass. The skeletal sample from the Fort Ancient Period site of SunWatch Village is composed of 33 subadult and three young adult proximal tibiae. Nondestructive microCT scanning of the proximal metaphyseal and epiphyseal tibia captures the microarchitectural trabecular structure, allowing quantitative structural analyses measuring bone volume fraction, degree of anisotropy, trabecular thickness, and trabecular number. The microCT resolution effects on structural parameters were analyzed. Bone volume fraction and degree of anisotropy are highest at birth, decreasing to low values at 1 year of age, and then gradually increasing to the adult range around 6-8 years of age. Trabecular number is highest at birth and lowest at skeletal maturity; trabecular thickness is lowest at birth and highest at skeletal maturity. The results of this study highlight the dynamic sequential relationships between growth/development, general functional activities, and trabecular distribution and architecture, providing a reference for comparative studies.     

动态观察去卵巢骨质疏松大鼠股骨骨微结构的变化

目的:绝经后骨质疏松是好发于中老年女性人群中的骨代谢疾病,去卵巢骨质疏松大鼠模型是国内外通用的模拟绝经后骨质疏松发生的经典动物模型,本研究通过观察去卵巢骨质疏松大鼠股骨骨微结构的动态变化,为骨质疏松大鼠模型的临床应用提供理论参考依据。方法:将90只3月龄雌性SD大鼠按体重分层后随机分为基础组(10只)、假手术组(40只)和去卵巢组(40只)。分别在手术前(基础组)和后的3、6、12、24周,腹主动脉取血处死基础组以及假手术组和去卵巢组大鼠,每组各8-10只。每组中随机取6只大鼠,对其左股骨行micro-CT扫描及三维结构重建。选择股骨远端距生长板远端1 mm处,2.0 mm×3.5 mm,厚0.9 mm的骨组织为感兴趣区域,对感兴趣区域进行骨形态计量学分析。结果:与0周组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨vBMD、BV/TV和Tb.N显著降低,Tb.Sp和SMI显著升高,而Tb.Th无显著变化;与0周组比较,从假手术后3周开始一直到24周,假手术组所有检测指标均无显著变化。与同周龄假手术组比较,从去卵巢3周开始一直持续到24周,去卵巢组大鼠股骨Tb.N、BV/TV和vBMD显著降低,Tb.Sp显著升高,而Tb.Th没有显著变化。从去卵巢6周开始一直到24周,去卵巢组大鼠SMI显著增加。结论:3月龄大鼠股骨远端的骨微结构在去卵巢3周时就出现显著变化。提示,采用3月龄大鼠进行抗骨质疏松药物筛选时,去卵巢3周后就可以进行药物处理。     

Low magnitude and high frequency mechanical loading prevents decreased bone formation responses of 2T3 preosteoblasts

Bone loss due to osteoporosis or disuse such as in paraplegia or microgravity is a significant health problem. As a treatment for osteoporosis, brief exposure of intact animals or humans to low magnitude and high frequency (LMHF) mechanical loading has been shown to normalize and prevent bone loss. However, the underlying molecular changes and the target cells by which LMHF mechanical loading alleviate bone loss are not known. Here, we hypothesized that direct application of LMHF mechanical loading to osteoblasts alters their cell responses, preventing decreased bone formation induced by disuse or microgravity conditions. To test our hypothesis, preosteoblast 2T3 cells were exposed to a disuse condition using the random positioning machine (RPM) and intervened with an LMHF mechanical load (0.1–0.4 g at 30 Hz for 10–60 min/day). Exposure of 2T3 cells to the RPM decreased bone formation responses as determined by alkaline phosphatase (ALP) activity and mineralization even in the presence of a submaximal dose of BMP4 (20 ng/ml). However, LMHF mechanical loading prevented the RPM‐induced decrease in ALP activity and mineralization. Mineralization induced by LMHF mechanical loading was enhanced by treatment with bone morphogenic protein 4 (BMP4) and blocked by the BMP antagonist noggin, suggesting a role for BMPs in this response. In addition, LMHF mechanical loading rescued the RPM‐induced decrease in gene expression of ALP, runx2, osteomodulin, parathyroid hormone receptor 1, and osteoglycin. These findings suggest that preosteoblasts may directly respond to LMHF mechanical loading to induce differentiation responses. The mechanosensitive genes identified here provide potential targets for pharmaceutical treatments that may be used in combination with low level mechanical loading to better treat osteoporosis or disuse‐induced bone loss. J. Cell. Biochem. 106: 306–316, 2009. © 2009 Wiley‐Liss, Inc.     

Estimation of an early meaningful time point of bone parameter changes in application to an osteoporotic rat model with in vivo microcomputed tomography measurements

The commonly used preclinical animal model of postmenopausal osteoporosis is the mature ovariectomized rat, whereby cessation of ovarian oestrogen production consequently results in bone volume reduction. The study aim was to precisely define the time course of structural changes resulting from ovariectomy and thereby reduce the time animals have to be treated to judge the effects of osteoporosis treatment. For this purpose, we assessed architectural changes by microcomputed tomography (μCT) during 10 weeks following ovariectomy or sham surgery at two-week intervals. Moreover, the trabecular microarchitecture of the lumbar vertebrae was assessed after necropsy. Besides this, serum biomarkers of bone turnover were determined. These data were in a new approach additionally correlated to femur mRNA expression profiles. We selected the osteoblast marker genes osteocalcin and type I collagen as well as the two osteoclast marker genes cathepsin k and tartrate-resistant acid phosphatase 5. The gene expression analysis suggested an activation of osteoblasts as well as octeoclasts. The significantly induced serum levels of osteocalcin and collagen degradation fragments also revealed this higher rate of bone turnover. Our results indicate that as soon as four weeks after ovariectomy the bone volume fraction exhibited a decline of 30% and 50% of the connectivity density. In addition, significant decreases of trabecular number and thickness as well as of the bone volume fraction were only observed in vertebrae of ovariectomized animals. Interestingly, changes of trabecular morphology were also found in the sham animals as a consequence of senescence.     

Cadmium Is More Toxic on Volume Bone Mineral Density than Tissue Bone Mineral Density

It has been showed that Cd induces low areal bone mineral density, but we do not know the effect of Cd on cubic bone density. This study was aimed to investigate the effects of Cd on volumetric bone mineral density (VBMD) and tissue bone mineral density (TBMD) in male rats. Twenty-four Sprague-Dawley male rats were randomly divided into four groups that were given cadmium chloride by subcutaneous injection at doses of 0, 0.1, 0.5, and 1.5?mg/kg body weight for 8?weeks, respectively. Then, microcomputed tomography scanning was performed on the proximal tibia, and region of interest was reconstructed using microview software. The VBMD, bone volume fraction of rats treated with 1.5?mg Cd/kg, were significantly decreased compared to control (p?相似文献   

The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice

Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 g peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (−81%) and bone formation (−80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.KEY WORDS: Whole-body vibration, LMHFV, Fracture healing, Oestrogen receptor signalling, Wnt signalling     

Quantification of subchondral bone changes in a murine osteoarthritis model using micro-CT

In the past few years there has been a considerable interest in the role of bone in osteoarthritis. Despite the increasing evidence of the involvement of bone in osteoarthritis, it remains very difficult to attribute the cause or effect of changes in subchondral bone to the process of osteoarthritis. Although osteoarthritis in mice provides a useful model to study changes in the subchondral bone, detailed quantification of these changes is lacking. Therefore, the goal of this study was to quantify subchondral bone changes in a murine osteoarthritis model by use of micro-computed tomography (micro-CT). We induced osteoarthritis-like characteristics in the knee joints of mice using collagenase injections, and after four weeks we calculated various 3D morphometric parameters in the epiphysis of the proximal tibia. The collagenase injections caused cartilage damage, visible in histological sections, particularly on the medial tibial plateau. Micro-CT analysis revealed that the thickness of the subchondral bone plate was decreased both at the lateral and the medial side. The trabecular compartment demonstrated a small but significant reduction in bone volume fraction compared to the contralateral control joints. Trabeculae in the collagenase-injected joints were thinner but their shape remained rod-like. Furthermore, the connectivity between trabeculae was reduced and the trabecular spacing was increased. In conclusion, four weeks after induction of osteoarthritis in the murine knee subtle but significant changes in subchondral bone architecture could be detected and quantified in 3D with micro-CT analysis.     

Analysis of microstructural and mechanical alterations of trabecular bone in a simulated three-dimensional remodeling process

Bone remodeling is a complex dynamic process, which modulates both bone mass and bone microstructure. In addition to bone mass, bone microstructure is an important contributor to bone quality in osteoporosis and fragility fractures. However, the quantitative knowledge of evolution of three-dimensional (3D) trabecular microstructure in adaptation to the external forces is currently limited. In this study, a new 3D simulation method of remodeling of human trabecular bone was developed to quantitatively study the dynamic evolution of bone mass and trabecular microstructure in response to different external loading conditions. The morphological features of trabecular plate and rod, such as thickness and number density in different orientations were monitored during the remodeling process using a novel imaging analysis technique, namely Individual Trabecula Segmentation (ITS). We showed that the volume fraction and microstructures of trabecular bone including, trabecular type and orientation, were determined by the applied mechanical load. Particularly, the morphological parameters of trabecular plates were more sensitive to the applied load, indicating that they played the major role in the mechanical properties of the trabecular bone. Reducing the applied load caused severe microstructural deteriorations of trabecular bone, such as trabecular plate perforation, rod breakage, and a conversion from plates to rods.     

Establishment of an Animal Model of Bisphosphonate-Related Osteonecrosis of the Jaws in Spontaneously Diabetic Torii Rats

Background

We evaluated the side effects of bisphosphonate (BP) on tooth extraction socket healing in spontaneously diabetic Torii (SDT) rats, an established model of non-obese type 2 diabetes mellitus, to develop an animal model of BP-related osteonecrosis of the jaws (BRONJ).

Materials and Methods

Male Sprague-Dawley (SD) rats and SDT rats were randomly assigned to the zoledronic acid (ZOL)-treated groups (SD/ZOL or SDT/ZOL) or to the control groups (SD/control or SDT/control). Rats in the SD/ZOL or SDT/ZOL groups received an intravenous bolus injection of ZOL (35 μg/kg) every 2 weeks. Each group consisted of 6 rats each. Twenty-one weeks after ZOL treatment began, the left maxillary molars were extracted. The rats were euthanized at 2, 4, or 8 weeks after tooth extraction, and the total maxillae were harvested for histological and histochemical studies.

Results

In the oral cavity, bone exposure persisted at the tooth extraction site in all rats of the SDT/ZOL group until 8 weeks after tooth extraction. In contrast, there was no bone exposure in SD/control or SDT/control groups, and only 1 of 6 rats in the SD/ZOL group showed bone exposure. Histologically, necrotic bone areas with empty lacunae, microbial colonies, and less invasion by inflammatory cells were observed. The number of tartrate-resistant acid phosphatase-positive osteoclasts was lower in the SDT/ZOL group than in the SD/control group. The mineral apposition rate was significantly lower in the SDT/ZOL group compared with the SD/control group.

Conclusions

This study demonstrated the development of BRONJ-like lesions in rats and suggested that low bone turnover with less inflammatory cell infiltration plays an important role in the development of BRONJ.     

Calcium metabolism and bone mineralization in female rats fed diets marginally sufficient in calcium: effects of increased dietary calcium intake

Experiments were carried out to determine the ability of female rats with poorly mineralized skeletons to increase bone mineralization in response to increased dietary Ca consumption. We specifically addressed this question with regard to two different periods of the life cycle: the period of sexual maturation (6–9 weeks of age), and in animals that had attained adult rates of skeletal mineralization (100 days of age). We found that at both stages, increased dietary Ca consumption resulted in increased trabecular bone volume and total bone Ca. In the younger animals, it was found that dietary history influenced the disposition of bone mineral. Animals that were initially Ca-deprived exhibited increased trabecular bone and decreased cortical thickness compared to animals continuously fed 0.5% Ca. Ovariectomy of mature animals reduced but did not eliminate the response to increased Ca intake.     

Effects of freeze–thaw and micro-computed tomography irradiation on structure–property relations of porcine trabecular bone

We study the effects of freeze–thaw and irradiation on structure–property relations of trabecular bone. We measure the porosity, apparent density, mineral content, trabecular orientation, trabecular thickness, fractal dimension, surface area, and connectivity of trabecular bone using micro-computed tomography (micro-CT) and relate them to Young?s modulus and ultimate strength measured by uniaxial compression testing. The analysis is done on six-month porcine trabecular bone from femoral heads. The effects of freeze–thaw are studied by using bones from three different groups: fresh bone and bones frozen for one and five years. We find that the porosity and apparent density have most dominant influence on the elastic modulus and strength of fresh bone. Also, five years of freezing lowers both Young?s modulus and ultimate strength of trabecular bone. Additionally, the effects of radiation are investigated by comparing Young?s modulus before and after micro-CT exposure. We find that the micro-CT irradiation has a negligible effect on the Young?s modulus of trabecular bone. These findings provide insights on the effects of tissue preservation and imaging on properties of trabecular bone.     

PRP 与CPC 应用于拔牙后种植位点保存的实验研究

目的:探讨磷酸钙骨水泥(CPC)与富血小板血浆(PRP)混合物应用于拔牙后种植位点保存的可行性。方法:拔除6只犬下颌双侧第三切牙与一侧第一切牙,并于每只犬的3个拔牙窝颊舌侧骨壁分别制造2 mm×2 mm×3 mm缺损,随机在两个牙槽窝内分别植入CPC或CPC与PRP的混合物,第三个不加处置作对照,在术后4、8、12周各处死两只动物,行大体、X线、显微镜观察,比较各组的新骨生成情况。结果:术后4周时CPC/PRP混合物组骨形成早于其他组,8、12周时CPC/PRP混合物组新骨生成明显优于CPC组和对照组。结论:CPC混合PRP可促牙槽窝新骨生成并能保证成骨的高度和颊舌向宽度,从而为后期种植义齿修复提供了必要的条件。