Bone mineral density in chimpanzees,humans, and Japanese macaques

We performed a comparative study of bone mechanical properties in the radii of chimpanzees (Pan troglodytes), humans (Homo sapiens), and Japanese macaques (Macaca fuscata) using peripheral quantitative computed tomography. We investigated: (1)cortical bone area relative to the total periosteal area (PrA); (2) trabecular bone area relative to PrA; (3) cortical bone density; and (4) trabecular bone density. The cortical bone area index for chimpanzees was almost the same as that of Japanese macaques, whereas the equivalent value in humans was about the two-fifths that of the others. Values for the other three properties were constant among these three catarrhine species. Chimpanzees do not particularly resemble humans, but are more similar to digitigrade macaques in terms of bone properties. The constant trabecular bone area index and trabecular density value in these species may suggest that a certain amount of trabecular bone (20–30% of total bone area at the distal 4% level of the forearm) is necessary to achieve normal bone turnover. The physiological metabolism of bone, including cortical bone density, might be conserved in these catarrhines. Electronic Publication     

Insulin-Like Growth Factor 1, Glycation and Bone Fragility: Implications for Fracture Resistance of Bone

Despite our extensive knowledge of insulin-like growth factor 1 (IGF1) action on the growing skeleton, its role in skeletal homeostasis during aging and age-related development of certain diseases is still unclear. Advanced glycation end products (AGEs) derived from glucose are implicated in osteoporosis and a number of diabetic complications. We hypothesized that because in humans and rodents IGF1 stimulates uptake of glucose (a glycation substrate) from the bloodstream in a dose-dependent manner, the decline of IGF1 could be associated with the accumulation of glycation products and the decreasing resistance of bone to fracture. To test the aforementioned hypotheses, we used human tibial posterior cortex bone samples to perform biochemical (measurement of IGF1, fluorescent AGEs and pentosidine (PEN) contents) and mechanical tests (crack initiation and propagation using compact tension specimens). Our results for the first time show a significant, age-independent association between the levels of IGF1 and AGEs. Furthermore, AGEs (fAGEs, PEN) predict propensity of bone to fracture (initiation and propagation) independently of age in human cortical bone. Based on these results we propose a model of IGF1-based regulation of bone fracture. Because IGF1 level increases postnatally up to the juvenile developmental phase and decreases thereafter with aging, we propose that IGF1 may play a protective role in young skeleton and its age-related decline leads to bone fragility and an increased fracture risk. Our results may also have important implications for current understanding of osteoporosis- and diabetes-related bone fragility as well as in the development of new diagnostic tools to screen for fragile bones.     

Streptozotocin, Type I Diabetes Severity and Bone

As many as 50% of adults with type I (T1) diabetes exhibit bone loss and are at increased risk for fractures. Therapeutic development to prevent bone loss and/or restore lost bone in T1 diabetic patients requires knowledge of the molecular mechanisms accounting for the bone pathology. Because cell culture models alone cannot fully address the systemic/metabolic complexity of T1 diabetes, animal models are critical. A variety of models exist including spontaneous and pharmacologically induced T1 diabetic rodents. In this paper, we discuss the streptozotocin (STZ)-induced T1 diabetic mouse model and examine dose-dependent effects on disease severity and bone. Five daily injections of either 40 or 60 mg/kg STZ induce bone pathologies similar to spontaneously diabetic mouse and rat models and to human T1 diabetic bone pathology. Specifically, bone volume, mineral apposition rate, and osteocalcin serum and tibia messenger RNA levels are decreased. In contrast, bone marrow adiposity and aP2 expression are increased with either dose. However, high-dose STZ caused a more rapid elevation of blood glucose levels and a greater magnitude of change in body mass, fat pad mass, and bone gene expression (osteocalcin, aP2). An increase in cathepsin K and in the ratio of RANKL/OPG was noted in high-dose STZ mice, suggesting the possibility that severe diabetes could increase osteoclast activity, something not seen with lower doses. This may contribute to some of the disparity between existing studies regarding the role of osteoclasts in diabetic bone pathology. Examination of kidney and liver toxicity indicate that the high STZ dose causes some liver inflammation. In summary, the multiple low-dose STZ mouse model exhibits a similar bone phenotype to spontaneous models, has low toxicity, and serves as a useful tool for examining mechanisms of T1 diabetic bone loss.     

Bone Allografts: Past, Present and Future

Bone allograft transplantation has been performed in humans for more than one hundred and twenty years. During the first one hundred years (1880–1980), the major problem in bone allograft transplantation was availability. Most of the bone grafts used during this time were autografts. Allografts were not available due to a lack of legislation protecting procurers and processers. In addition, surgical procedures requiring allografts were not being performed. During the next twenty years (1980–2000), as allografis began to be used, the major issue was safety. Diseases transmitted during this period included AIDS and hepatitis. Avoidance of disease transmission became paramount. Sensitive blood tests and extensive efforts by bone banks to develop ways to clean. bone and clear it of infectious agents helped provide safe transplants. With concerns of availability and safety receding, the major issue in the future (2000–? ) will be the efficacy of the transplant. How allograft bone remodels in the host, how it incorporates and heals to host bone and how it integrates with the host skeleton will be the most important concerns of bone bankers and tissue transplant surgeons. Future research efforts will be applied to bone allograft transplantation to ensure that bone transplants heal quickly and sufficiently to be able to function as part of the weight-bearing skeletal system.     

Stain Technology a Bone Stain for Osteoid Seams in Fresh, Unembedded, Mineralized Bone

Fresh, ground, mineralized bone sections 75-100 μ thick are stained 90 minutes or 48 hours in the Bone Stain, a preparation containing fast green FCF, orange G, basic fuchsin, and azure II. Surface stain is then removed by grinding under running water. Sections are washed in 0.1% zephiran chloride (benzalkonium chloride) or in 0.01% mild soap and again washed in tap water, followed with distilled water. Sections are next differentiated in 0.01% acetic acid in 95% methanol, dehydrated in 95% ethanol and 100% ethanol, cleared in alcohol:xylene 1:1, 1:4, 1:9 and 2 changes of xylol, and then mounted permanently in Eukitt's mounting media.

Osteoid seams stain either green to jade green or red to dark red, incompletely mineralized bone red or orange yellow, and the zone of demarcation light green. The walls of lacunae, canaliculae, feathered bone, procedural artifacts and periosteocyte lacunar low-density versions stain red.

The method helps in the differential diagnosis of certain metabolic bone diseases in human biopsy and autopsy material.     

Bone cell interactions through Eph/ephrin: Bone modeling,remodeling and associated diseases

Bones cannot properly form or be maintained without cell-cell interactions through ephrin ligands and Eph receptors. Cell culture analysis and evaluation of genetic mouse models and human diseases reveal various ephrins and Eph functions in the skeletal system. Migration, attachment and spreading of mesenchymal stem cells are regulated by ephrinB ligands and EphB receptors. ephrinB1 loss-of-function is associated with craniofrontonasal syndrome (CFNS) in humans and mice. In bone remodeling, ephrinB2 is postulated to act as a “coupling stimulator.” In that case, bidirectional signaling between osteoclastic ephrinB2 and osteoblastic EphB4 suppresses osteoclastic bone resorption and enhances osteoblastic bone formation, facilitating the transition between these two states. Parathyroid hormone (PTH) induces ephrinB2 in osteoblasts and enhances osteoblastic bone formation. In contrast to ephrinB2, ephrinA2 acts as a “coupling inhibitor,” since ephrinA2 reverse signaling into osteoclasts enhances osteoclastogenesis and EphA2 forward signaling into osteoblasts suppresses osteoblastic bone formation and mineralization. Furthermore, ephrins and Ephs likely modulate pathological conditions such as osteoarthritis, rheumatoid arthritis, multiple myeloma and osteosarcoma. This review focuses on ephrin/Eph-mediated cell-cell interactions in bone biology.     

Quantitative Ultrasound Assessment of Cortical Bone Properties Beyond Bone Mineral Density

The development of quantitative ultrasound (QUS) technologies to measure bone is motivated by the need to overcome the limitations of X-ray based methods, measuring bone mineral density (BMD) which is the gold standard to date for the diagnosis of osteoporosis. Because it uses mechanical waves, the ultrasound modality is a particularly relevant means to probe bone mechanical resistance. The vast majority of QUS technologies commercialized to date merely aim to provide surrogate markers for BMD. During the past decade, innovative QUS approaches have emerged to assess bone beyond BMD. This may be achieved by (1) specifically assessing the cortical bone compartment, independently of trabecular bone, and (2) providing intrinsic bone properties such as cortical bone thickness and material properties. One specific motivation is to estimate intracortical porosity, a quantity reflected in material properties. This article aims at an overview of recent QUS developments to measure cortical bone properties. We also draw a picture of the current knowledge on bone material properties of interest for bone QUS. We discuss the potential of ultrasound to provide novel biomarkers of bone health through the assessment of material properties.     

Validation of Bone Conversion in Osteoconductive and Osteoinductive Bone Substitutes

Bone reconstruction can be performed with an autogeneic graft from various donor regions. Osteoconductive and osteoinductive bone substitutes originate from substances of diverse chemical and morphological types and can have a synthetic or a biological derivation. Alongside autogeneic bone transplants and allogenic and xenogeneic bone implants, alloplastic bone replacements of synthetic or semi-synthetic origin are being used for defect reconstruction. In an animal model in rabbits five bone substitutes and one autogeneic graft were surgically incorporated into identical bone defects (10times 10 mm in size) in six anatomically defined regions of the skull. With scintigraphic and histological methods, the metabolic dynamics of the bone is examined as it reacts to the transplantation of autogeneic bone or to implanted bone replacement material. The different autogeneic, xenogeneic and alloplastic bone replacement materials can be differentiated according to the functional quality of the new tissue and the dynamics of the bone conversion thus induced. In the comparison of mineralized, osteoconductive bone subsitutes (TCP, HA, calcium carbonate ceramics) with demineralized, osteoinductive implants (DBM new, DBM old) and autogeneic bone grafts, the bone inducing matrices show the largest quantity of new bone formation, making possible a volume-constant reconstruction. This revised version was published online in July 2006 with corrections to the Cover Date.     

Bone remodeling, energy metabolism, and the molecular clock

The adult skeleton is constantly renewed through bone remodeling. Four recent papers (Baldock et al., 2007; Lee et al., 2007; Lundberg et al., 2007; Sato et al., 2007) provide new insights into central and peripheral control of this remodeling sequence. Two of the studies add to our knowledge of the complex hypothalamic modulation of bone turnover mediated by NMU and NPY via the sympathetic nervous system, while the other two focus on the peripheral neural target, the osteoblast, and its regulation by neuropeptides and osteocalcin. These findings support a new paradigm concerning the regulation of bone remodeling and provide a foundation for novel approaches to preventing osteoporosis.     

Application of VEGFA and FGF-9 Enhances Angiogenesis,Osteogenesis and Bone Remodeling in Type 2 Diabetic Long Bone Regeneration

Although bone regeneration is typically a reliable process, type 2 diabetes is associated with impaired or delayed healing processes. In addition, angiogenesis, a crucial step in bone regeneration, is often altered in the diabetic state. In this study, different stages of bone regeneration were characterized in an unicortical bone defect model comparing transgenic type 2 diabetic (db^-/db^-) and wild type (WT) mice in vivo. We investigated angiogenesis, callus formation and bone remodeling at early, intermediate and late time points by means of histomorphometry as well as protein level analyses. In order to enhance bone regeneration, defects were locally treated with recombinant FGF-9 or VEGFA. Histomorphometry of aniline blue stained sections indicated that bone regeneration is significantly decreased in db^-/db^- as opposed to WT mice at intermediate (5 days post operation) and late stages (7 days post operation) of bone regeneration. Moreover, immunohistochemical analysis revealed significantly decreased levels of RUNX-2, PCNA, Osteocalcin and PECAM-1 in db^-/db^- defects. In addition, osteoclastogenesis is impaired in db^-/db^- indicating altered bone remodeling. These results indicate significant impairments in angiogenesis and osteogenesis in type 2 diabetic bones. Importantly, angiogenesis, osteogenesis and bone remodeling could be reconstituted by application of recombinant FGF-9 and, in part, by VEGFA application. In conclusion, our study demonstrates that type 2 diabetes affects angiogenesis, osteogenesis and subsequently bone remodeling, which in turn leads to decreased bone regeneration. These effects could be reversed by local application of FGF-9 and to a lesser degree VEGFA. These data could serve as a basis for future therapeutic applications aiming at improving bone regeneration in the type 2 diabetic patient population.     

Bone resorption and bone remodelling in juvenile carp, Cyprinus carpio L.

The present study considers the important role of bone resorption for bone growth in general, and aims to clarify if and how bone resorption contributes to the skeletal development of carp, Cyprinus carpio L., a teleost species with ‘normal’ osteocyte‐containing (cellular) bone. To ensure the identification of osteoclasts and sites of bone resorption independently from the morphology of the bony cells, bones were studied by histological procedures, and by demonstration of the enzymes which serve as osteoclast markers, viz. tartrate resistant acid phosphatase (TRAP), ATPase and a vacuolar proton pump. Two types of bone‐resorbing cells were observed in juvenile carp: (1) multinucleated giant cells displaying morphological and biochemical attributes which are known from mammalian osteoclasts; and (b) flat cells which lack a visible ruffled border and for which identification requires the performance of enzyme histochemical procedures. Bone resorption performed by osteoclasts mainly occurs at endosteal bone surfaces. To a lesser extent, bone resorption also takes place at periosteal bone surfaces, but without an apparent connection to bone growth. The latter observation, and the occurrence of bone remodelling, suggest that the endoskeleton of juvenile carp might be involved in mineral metabolism. Morphological differences and biochemical similarities to bone resorption in teleosts with acellular bone are discussed.     

Bone mass, bone strength, and their relationship in developing CD-1 mice

Optimizing nutrition during development may provide effective prevention strategies to protect against osteoporosis during later life. Because the mouse model is commonly used to test nutritional interventions on bone health, the overall objective of this study was to determine how bone develops during the first 4 months of life by assessing bone mass (bone mineral content (BMC) and bone mineral density (BMD)) and biomechanical strength properties such as peak load in male and female CD-1 mice. Bone outcomes were assessed at 1 month intervals from 1 to 4 months of age. Femur and spine BMC and BMD at 3 months were similar to 4 months, indicating that the accumulation of bone mass occurs primarily during the first 3 months of life. In contrast, the timing of changes in peak load, a measure of bone strength, varied by skeletal site. Regression analyses demonstrated that femur BMC is a significant predictor of femur peak load at the femur midpoint and neck. The study findings suggest that nutritional interventions aimed at optimizing peak bone mass to prevent osteoporosis may be most effective during pubertal growth.     

微波高温灭活及自体髂骨异体骨粒复合骨水泥修复 治疗长骨骨巨细胞瘤骨缺损

目的:探讨微波高温灭活及自体髂骨、异体骨粒复合骨水泥修复骨巨细胞瘤病灶刮除后骨缺损的临床应用效果。方法:应用原位分离插入式微波天线高温灭活技术,自体髂骨、异体骨粒复合骨水泥修复21例长骨骨巨细胞瘤术后骨缺损,从手术技术、肿瘤复发情况、肢体关节功能等方面全面综合评价此方法临床应用效果。结果:21例患者均获得骨性愈合,无骨折及内固定断裂发生,2例复发,复发率9.8%;肢体关节功能优18例(85.7%)、良3例(14.3%)、中差0例。结论:微波高温能彻底杀灭肿瘤组织降低复发率,自体髂骨保证与近关节软骨下骨愈合,异体骨粒复合骨水泥能良好充填残余瘤腔、且具有良好的生物力学性能,以防发生关节软骨面塌陷。     

Arthritis Induces Early Bone High Turnover,Structural Degradation and Mechanical Weakness

BackgroundWe have previously found in the chronic SKG mouse model of arthritis that long standing (5 and 8 months) inflammation directly leads to high collagen bone turnover, disorganization of the collagen network, disturbed bone microstructure and degradation of bone biomechanical properties. The main goal of the present work was to study the effects of the first days of the inflammatory process on the microarchitecture and mechanical properties of bone.MethodsTwenty eight Wistar adjuvant-induced arthritis (AIA) rats were monitored during 22 days after disease induction for the inflammatory score, ankle perimeter and body weight. Healthy non-arthritic rats were used as controls for compar-ison. After 22 days of disease progression rats were sacrificed and bone samples were collected for histomorphometrical, energy dispersive X-ray spectroscopical analysis and 3-point bending. Blood samples were also collected for bone turnover markers.ResultsAIA rats had an increased bone turnover (as inferred from increased P1NP and CTX1, p = 0.0010 and p = 0.0002, respectively) and this was paralleled by a decreased mineral content (calcium p = 0.0046 and phos-phorus p = 0.0046). Histomorphometry showed a lower trabecular thickness (p = 0.0002) and bone volume (p = 0.0003) and higher trabecular sepa-ration (p = 0.0009) in the arthritic group as compared with controls. In addition, bone mechanical tests showed evidence of fragility as depicted by diminished values of yield stress and ultimate fracture point (p = 0.0061 and p = 0.0279, re-spectively) in the arthritic group.ConclusionsWe have shown in an AIA rat model that arthritis induc-es early bone high turnover, structural degradation, mineral loss and mechanical weak-ness.     

Bone Morphogenetic Proteins

Bone Morphogenetic Protein (BMP) refers to an activity derived from bone that induces the formation of cartilage and bone in vivo. This activity leads to a series of developmental processes including chemotaxis, proliferation, and differentiation, which result in the transient formation of cartilage and the production of living bone tissue, complete with hematopoietic marrow. The determination of the factor or factors responsible for this activity has clear significance both for our understanding of bone biology and for the clinical application of cartilage and bone replacement. Several newly discovered factors, BMP-1, BMP-2 (BMP-2A), BMP-3 (osteogenin), BMP-4 (BMP-2B), BMP-5, BMP-6, BMP-7, and osteoinductive factor (OIF) have been implicated in the BMP process. BMP-2 through BMP-7 are all in the TGF-β superfamily of molecules, and are closely related to two factors (Vg1 and dpp) which are involved in a variety of developmental processes during embryogenesis. A recently discovered factor, OIF, exhibits BMP activity only in the presence of TGF-β. BMP-2, expressed as a recombinant protein, is the only molecule described to date that has been shown to clearly induce by itself the entire cartilage and bone formation process seen with bone-derived BMP. Evidence is accumulating that the BMP effect is a result of the combined actions of a set of BMP-2-like molecules. Definitive examination of the activities of the other factors will require expression of the recombinant proteins and testing of these in vivo alone and in combinations.     

丁香油酚在牙槽骨组织中的骨保护作用评价

绝经后雌激素缺乏会引起牙槽骨质流失、重塑和炎症。丁香油酚是一种酚类化合物,在牙科应用广泛并具有抗炎特性。在本研究中,以卵巢切除的大鼠为模型,服用不同剂量丁香油酚(2mg·kg-1·d-1和4mg·kg-1·d-1)12周(卵巢切除组),研究丁香油酚在牙槽骨组织中的骨保护作用。使用ELISA法检测血清中骨代谢标记物和促炎细胞因子,使用高分辨率微型计算机断层摄影术(CT)扫描牙槽骨形态,并进行骨组织学分析(H&E染色)。研究结果表明,丁香油酚不会增加卵巢切除大鼠体重和延缓子宫萎缩。由丁香油酚处理的卵巢切除大鼠的骨代谢标志物和炎性细胞因子含量显著提高,特别是高剂量组。丁香油酚的处理显著减弱了牙槽骨的形态测量变化,改善了牙槽吸收功能和牙龈渗透。卵巢切除大鼠的牙槽骨由于丁香油酚处理得到改善,炎性细胞因子表达降低。本研究初步结论表明,丁香油酚可以防止卵巢切除动物实验性诱导的牙槽骨损失,具有抗炎作用,对牙槽骨组织具有保护作用。     

Bone structural parameters, dosimetry, and relative radiation risk in the beagle skeleton

A variety of morphometric and histomorphometric parameters such as the mass of bone and marrow, bone surface areas, percentage of bone volume, percentage of the surface that is trabecular, and percentage of surfaces that are forming and resting are calculated for all major parts of the beagle skeleton. The total bone surface of the beagle is estimated at 2.9 m2 with 53.7% of the surface area being associated with trabecular bone. There are about 4.5 x 10(9) bone-lining cells and about 1 x 10(9) osteoblasts. From the fractional retention in each part of the skeleton, the initial surface concentration of 239Pu after a single injection of 592 Bq/kg body wt (0.016 microCi/kg) on resting surfaces and at sites of bone formation is calculated for various values of the affinity ratios of trabecular/cortical and forming/resting surfaces. These estimated concentrations then yield dose rates as well as cumulative and collective doses to bone-lining cells and osteoblasts in the different parts of the skeleton. On the assumption that the relative risk of tumor induction is proportional to the collective dose to either bone-lining cells or osteoblasts, the frequency of tumor occurrence is calculated and compared to observed frequencies. Both hypotheses yield approximate agreement with experimental data for different ratios of trabecular/cortical radiation sensitivity, although the differences between some bones are statistically significant.     

The Association between Metabolic Syndrome,Bone Mineral Density,Hip Bone Geometry and Fracture Risk: The Rotterdam Study

The association between metabolic syndrome (MS) and bone health remains unclear. We aimed to study the association between MS and hip bone geometry (HBG), femoral neck bone mineral density (FN-BMD), and the risk of osteoporosis and incident fractures. Data of 2040 women and 1510 men participants in the third visit (1997–1999) of the Rotterdam Study (RSI-3), a prospective population based cohort, were available (mean follow-up 6.7 years). MS was defined according to the recent harmonized definition. HBG parameters were measured at the third round visit whereas FN-BMD was assessed at the third round and 5 years later. Incident fractures were identified from medical registry data. After correcting for age, body mass index (BMI), lifestyle factors and medication use, individuals with MS had lower bone width (β = -0.054, P = 0.003), lower cortical buckling ratio (β = -0.81, P = 0.003) and lower odds of having osteoporosis (odds ratio =0.56, P = 0.007) in women but not in men. Similarly, MS was associated with higher FN-BMD only in women (β = 0.028, P=0.001). In the analyses of MS components, the glucose component (unrelated to diabetes status) was positively associated with FN-BMD in both genders (β = 0.016, P = 0.01 for women and β = 0.022, P = 0.004 for men). In men, waist circumference was inversely associated with FN-BMD (β = -0.03, P = 0.004). No association was observed with fracture risk in either sex. In conclusion, women with MS had higher FN-BMD independent of BMI. The glucose component of MS was associated with high FN-BMD in both genders, highlighting the need to preserve glycemic control to prevent skeletal complications.     

黑龙江齐齐哈尔洪河遗址出土的骨器

骨器研究是近年来动物考古学研究的重要课题之一,自1930年梁思永发现昂昂溪遗址的骨质工具以来,骨器正在成为学界研究嫩江流域史前经济形态的重要依据。2013、2014、2015和2017年黑龙江省文物考古研究所对洪河遗址进行了全面发掘,主要遗存归属于新石器时代晚期和青铜时代,除陶器、石制品和青铜器等,还出土了大量骨器,器类丰富,更有多种以往未曾见过的器类。本文通过对该遗址四个年度出土的343件骨制品进行全面介绍和梳理,分析该遗址骨器制作的工艺水平和生产变化,为进一步探讨该遗址乃至嫩江流域史前的生业模式提供重要线索。     

Bone graft survival in expanded skin

The effect of tissue expansion on iliac bone graft (onlay) survival was studied on the skulls of 35 New Zealand white rabbits. Wet bone weights at the time of grafting and at sacrifice in control animals (group I) were compared to three experimental groups. Histologic sections of the developing and resolving pseudosheath and skin envelope were performed. A self-inflating 5-mil-thick silicone expander was used for soft-tissue expansion over the rabbit snout. Bone grafts were subsequently placed in this site. Elliptical snout excision without expansion (group II) demonstrated no statistically significant difference in bone graft survival when compared to controls (group I) (p = 0.350). Full tissue expansion followed by immediate bone grafting (group III) within the pseudosheath cavity likewise demonstrated no statistically significant difference in bone graft survival when compared to controls (group I) (p = 0.500); however, when full tissue expansion was followed by delayed (2 weeks) bone grafting to allow for resolution of the giant cell inflammatory reaction of the pseudosheath (group IV), a statistically significant increased bone graft survival was achieved (p less than 0.001). The study demonstrates that the increased vascularity in the pseudosheath and in the expanded soft-tissue envelope significantly increased bone graft survival only when bone grafting was delayed.