Total Bone Volume Research Articles

Failure strength of human vertebrae: Prediction using bone mineral density measured by DXA and bone volume by micro-CT

Significant relationships exist between areal bone mineral density (BMD) derived from dual energy X-ray absorptiometry (DXA) and bone strength. However, the predictive validity of BMD for osteoporotic vertebral fractures remains suboptimal. The diagnostic sensitivity of DXA in the lumbar spine may be improved by assessing BMD from lateral-projection scans, as these might better approximate the objective of measuring the trabecular-rich bone in the vertebral body, compared to the commonly-used posterior–anterior (PA) projections. Nowadays, X-ray micro-computed tomography (μCT) allows non-destructive three-dimensional structural characterization of entire bone segments at high resolution. In this study, human lumbar cadaver spines were examined ex situ by DXA in lateral and PA projections, as well as by μCT, with the aims (1) to investigate the ability of bone quantity measurements obtained by DXA in the lateral projection and in the PA projection, to predict variations in bone quantity measurements obtained by μCT, and (2) to assess their respective capabilities to predict whole vertebral body strength, determined experimentally.Human cadaver spines were scanned by DXA in PA projections and lateral projections. Bone mineral content (BMC) and BMD for L2 and L3 vertebrae were determined. The L2 and L3 vertebrae were then dissected and entirely scanned by μCT. Total bone volume (BVtot=cortical+trabecular), trabecular bone volume (BV), and trabecular bone volume fraction (BV/TV) were calculated over the entire vertebrae. The vertebral bodies were then mechanically tested to failure in compression, to determine ultimate load.The variables BVtot, BV, and BV/TV measured by μCT were better predicted by BMC and BMD measured by lateral-projection DXA, with higher R2 values and smaller standard errors of the estimate (R2=0.65–0.90, SEE=11%–18%), compared to PA-projection DXA (R2=0.33–0.53, SEE=22%–34%). The best predictors of ultimate load were BVtot and BV assessed by μCT (R2=0.88 and R2=0.81, respectively), and BMC and BMD from lateral-projection DXA (R2=0.82 and R2=0.70, respectively). Conversely, BMC and BMD from PA-projection DXA were lower predictors of ultimate load (R2=0.49 and R2=0.37, respectively).This ex vivo study highlights greater capabilities of lateral-projection DXA to predict variations in vertebral body bone quantity as measured by μCT, and to predict vertebral strength as assessed experimentally, compared to PA-projection DXA. This provides basis for further exploring the clinical application of lateral-projection DXA analysis.

Topical Application of Slow-Release Simvastatin as a Bone Substitute in Bone Defects in the Rat Tibia: A Pilot Study

PURPOSE It is hypothesized that local application of statins positively affects bone formation. The aim of this study was to evaluate the potential effect of topical slow-release simvastatin as a bone substitute on the healing of bone defects in rat tibia. MATERIALS AND METHODS Granules of slow-releasing hydroxypropyl methylcellulose, with or without simvastatin, were inserted into critical-size defects in the tibiae of 16 rats (8 in the study group, 8 in the control group). Bone static and dynamic histomorphometric variables were examined at 2, 4, 6, and 8 weeks postsurgery. RESULTS All indices examined in the study group indicated improved healing relative to the control group, although statistical significance was not demonstrated for all variables. In the static histomorphometric analysis, osteoid thickness and volume were significantly higher in the study group, but the fraction of trabecular surface covered with active osteoblasts, the fraction of trabecular surface covered with osteoid, and total calcified bone volume were not significantly higher in the experimental group. In the dynamic histomorphometric analysis, the mineral apposition rate, determined by time-repeated calcein labeling, was significantly higher in the study group than in the control group. Experimental time and dosage effects were observed for most bone values in the study group. CONCLUSION The findings indicate that topical application of simvastatin for the treatment of bone defects enhances the process of healing. Dosage and the methodology of administration require further calibration.

Immunolocalization of Myostatin (GDF-8) Following Musculoskeletal Injury and the Effects of Exogenous Myostatin on Muscle and Bone Healing

The time course and cellular localization of myostatin expression following musculoskeletal injury are not well understood; therefore, the authors evaluated the temporal and spatial localization of myostatin during muscle and bone repair following deep penetrant injury in a mouse model. They then used hydrogel delivery of exogenous myostatin in the same injury model to determine the effects of myostatin exposure on muscle and bone healing. Results showed that a "pool" of intense myostatin staining was observed among injured skeletal muscle fibers 12-24 hr postsurgery and that myostatin was also expressed in the soft callus chondrocytes 4 days following osteotomy. Hydrogel delivery of 10 or 100 µg/ml recombinant myostatin decreased fracture callus cartilage area relative to total callus area in a dose-dependent manner by 41% and 80% (p<0.05), respectively, compared to vehicle treatment. Myostatin treatment also decreased fracture callus total bone volume by 30.6% and 38.8% (p<0.05), with the higher dose of recombinant myostatin yielding the greatest decrease in callus bone volume. Finally, exogenous myostatin treatment caused a significant dose-dependent increase in fibrous tissue formation in skeletal muscle. Together, these findings suggest that early pharmacological inhibition of myostatin is likely to improve the regenerative potential of both muscle and bone following deep penetrant musculoskeletal injury.

Protective effect of folic acid on cyclosporine-induced bone loss in rats

Hyperhomocysteinemia is seen in patients with decreased bone mineral density. Cyclosporine can cause alveolar bone loss and osteopenia. It is also associated with elevated serum homocysteine levels. We aimed to investigate the effect of cyclosporine on serum homocysteine level, bone volume, and bone density, and determine whether folic acid had a protective effect against bone loss. In an experimental study, 40 male Sprague-Dawley rats were randomly assigned to five groups and received dietary supplementation for 6 weeks with olive oil (Group A), cyclosporine (Group B), folic acid (Group C), and cyclosporine plus folic acid (Group D), or no supplementation (Group F, control). Serum homocysteine, calcium, alkaline phosphatase, total bone volume, periodontal ligament volume, and volume density of bone were compared between groups. Mean serum homocysteine level (10.84 ± 0.93 μmol/l) was significantly higher in group B (cyclosporine supplementation) compared with the other groups (P = 0.001). Mean total mandibular volume was 46.3 ± 13.6 mm(3) in rats treated with cyclosporine, 80.4 ± 15.70 mm(3) in rats treated with folic acid (P = 0.004), and 73.9 ± 21.3 mm(3) in rats treated with cyclosporine plus folic acid (P = 0.028). In our experimental model, cyclosporine increased serum homocysteine levels and decreased bone volume and density. Folic acid may have a preventive role against bone loss in rats treated with cyclosporine.

A mouse model for spondyloepiphyseal dysplasia congenita with secondary osteoarthritis due to a Col2a1 mutation

Progeny of mice treated with the mutagen N-ethyl-N-nitrosourea (ENU) revealed a mouse, designated Longpockets (Lpk), with short humeri, abnormal vertebrae, and disorganized growth plates, features consistent with spondyloepiphyseal dysplasia congenita (SEDC). The Lpk phenotype was inherited as an autosomal dominant trait. Lpk/+ mice were viable and fertile and Lpk/Lpk mice died perinatally. Lpk was mapped to chromosome 15 and mutational analysis of likely candidates from the interval revealed a Col2a1 missense Ser1386Pro mutation. Transient transfection of wild-type and Ser1386Pro mutant Col2a1 c-Myc constructs in COS-7 cells and CH8 chondrocytes demonstrated abnormal processing and endoplasmic reticulum retention of the mutant protein. Histology revealed growth plate disorganization in 14-day-old Lpk/+ mice and embryonic cartilage from Lpk/+ and Lpk/Lpk mice had reduced safranin-O and type-II collagen staining in the extracellular matrix. The wild-type and Lpk/+ embryos had vertical columns of proliferating chondrocytes, whereas those in Lpk/Lpk mice were perpendicular to the direction of bone growth. Electron microscopy of cartilage from 18.5 dpc wild-type, Lpk/+, and Lpk/Lpk embryos revealed fewer and less elaborate collagen fibrils in the mutants, with enlarged vacuoles in the endoplasmic reticulum that contained amorphous inclusions. Micro-computed tomography (CT) scans of 12-week-old Lpk/+ mice revealed them to have decreased bone mineral density, and total bone volume, with erosions and osteophytes at the joints. Thus, an ENU mouse model with a Ser1386Pro mutation of the Col2a1 C-propeptide domain that results in abnormal collagen processing and phenotypic features consistent with SEDC and secondary osteoarthritis has been established.

Bone density phenotypes in mice aneuploid for the Down syndrome critical region

Down syndrome (trisomy 21) is associated with reduced bone density in humans, but it is unclear whether this is due to specific effects of chromosome 21 genes or lifestyle factors. Mouse models with aneuploidy of segments of mouse chromosome 16 that are homologous to human chromosome 21 can be used to elucidate the mechanism by which Down syndrome phenotypes arise. Ts1Rhr and Ms1Rhr mice are trisomic and monosomic, respectively, for the hypothesized "Down syndrome critical region" containing approximately 33 genes. We assessed the skeletons of these mice from 3 to 16 weeks of age using dual X-ray absorptiometry. Ts1Rhr mice were unexpectedly similar to normal controls, showing that a larger region of trisomy is necessary to recapitulate the Down syndrome phenotype. Ms1Rhr mice, in contrast, showed decreases in weight, bone mineral content, bone mineral density, and bone area from weaning to adulthood. Regional bone density was also decreased in the femur, tibia, and lower lumbar spine. The microarchitecture of 3 week old Ms1Rhr femurs was then analyzed using µCT. Volumetric density, total tissue volume, bone volume, and bone fraction were all reduced in both cortical and trabecular bone. Ms1Rhr trabeculae were thinner and had decreased connectivity. A 31.5% reduction in the level of insulin-like growth factor I in the serum was found, and we hypothesize that this is responsible for the bone density phenotype. We discuss bone-related genes in the region and propose that humans with distal chromosome 21 deletions may exhibit reduced bone density.

Local delivery of FTY720 accelerates cranial allograft incorporation and bone formation

Endogenous stem cell recruitment to the site of skeletal injury is key to enhanced osseous remodeling and neovascularization. To this end, this study utilized a novel bone allograft coating of poly(lactic-co-glycolic acid) (PLAGA) to sustain the release of FTY720, a selective agonist for sphingosine 1-phosphate (S1P) receptors, from calvarial allografts. Uncoated allografts, vehicle-coated, low dose FTY720 in PLAGA (1:200 w:w) and high dose FTY720 in PLAGA (1:40) were implanted into critical size calvarial bone defects. The ability of local FTY720 delivery to promote angiogenesis, maximize osteoinductivity and improve allograft incorporation by recruitment of bone progenitor cells from surrounding soft tissues and microcirculation was evaluated. FTY720 bioactivity after encapsulation and release was confirmed with sphingosine kinase 2 assays. HPLC-MS quantified about 50% loaded FTY720 release of the total encapsulated drug (4.5μg) after 5days. Following 2weeks of defect healing, FTY720 delivery led to statistically significant increases in bone volumes compared to controls, with total bone volume increases for uncoated, coated, low FTY720 and high FTY720 of 5.98, 3.38, 7.2 and 8.9mm(3), respectively. The rate and extent of enhanced bone growth persisted through week 4 but, by week 8, increases in bone formation in FTY720 groups were no longer statistically significant. However, micro-computed tomography (microCT) of contrast enhanced vascular ingrowth (MICROFIL®) and histological analysis showed enhanced integration as well as directed bone growth in both high and low dose FTY720 groups compared to controls.

Detection of fatigue microdamage in whole rat femora using contrast-enhanced micro-computed tomography

Microdamage in bone tissue is typically studied using destructive, two-dimensional histological techniques. Contrast-enhanced micro-computed tomography (micro-CT) was recently demonstrated to enable non-destructive, three-dimensional (3-D) detection of microdamage in machined cortical and trabecular bone specimens in vitro. However, the accumulation of microdamage in whole bones is influenced by variations in the magnitude and mode of loading due to the complex whole bone morphology. Therefore, the objective of this study was to detect the presence, spatial location, and accumulation of fatigue microdamage in whole rat femora in vitro using micro-CT with a BaSO4 contrast agent. Microdamage was detected and observed to accumulate at specific spatial locations within the cortex of femora loaded in cyclic three-point bending to a 5% or 10% reduction in secant modulus. The ratio of the segmented BaSO4 stain volume (SV) to the total volume (TV) of cortical bone was adopted as a measure of damage. The amount of microdamage measured by micro-CT (SV/TV) was significantly greater for both loaded groups compared to the control group (p<0.05), but the difference between loaded groups was not statistically significant. At least one distinct region of microdamage, as indicated by the segmented SV, was observed in 85% of loaded specimens. A specimen-specific finite element model confirmed elevated tensile principal strains localized in regions of tissue corresponding to the accumulated microdamage. These regions were not always located where one might expect a priori based upon Euler–Bernoulli beam theory, demonstrating the utility of contrast-enhanced micro-CT for non-destructive, 3-D detection of fatigue microdamage in whole bones in vitro.

Allometry in the distribution of material properties and geometry of the felid skull: Why larger species may need to change and how they may achieve it

Extant members of the cat family (Felidae) have been considered behaviourally and morphologically conservative, i.e., despite great differences in size, there is relatively little variation in either the shape of the felid skull and dentition across species, or in the way in which these structures are used to kill and dismember prey. Consequently felids have been considered an appropriate focus for a number of investigations into the influence of allometry on craniomandibular mechanics and morphology. However, although previous treatments have considered the role of shape, they have not investigated the influence of differences in the distribution of relatively stiff cortical and more compliant cancellous bone on performance. Here, using models that incorporate material properties for both cortical and cancellous bone, we apply three-dimensional (3D) finite element analysis (FEA) to models representing the skulls of seven extant felid species. Our objectives being to determine allometric trends regarding both overall geometry and the relative distributions of cortical and cancellous bone tissue. We also more comprehensively assess variation in the efficiency with which muscular force is converted to bite force and the capacity to resist associated stresses. Our results show that the cheetah ( Acinonyx jubatus) may be exceptional regarding both the efficiency with which muscular force is converted to bite force and the distribution of stress. We found a negative allometric trend between cortical bone volume and total skull bone volume, and positive allometry between the total skull bone volume and skull surface area. Results gained from mathematical modelling of beam analogies suggest that these trends reflect a need for larger species to respond to physical challenges associated with increased size, and, that changes in skull shape, bone composition, or a combination of both may be required to accommodate these challenges. With geometrical scaling stress increases by the same factor, and displacement by the same factor squared, but the ultimate failure stress of the material is invariant. We find that as species become larger, overall skull bone volume relative to surface area increases by adding a higher proportion of less dense and more compliant cancellous bone. This results in an increased cross-sectional area and second moment of inertia, which acts to reduce the overall stresses. An overall saving in mass is a likely additional consequence. Although we do find evidence that skull stiffness does diminish with size, we also argue that this is at least in part mitigated through the influence of these allometric trends. We further suggest that these trends and the explanations for them may be universal for vertebrates.

Acceleration of spinal fusion using COMP-angiopoietin 1 with allografting in a rat model

Allografting has become widely available for the elimination of morbidity due to autogenous bone grafting procedures for spinal fusion. Enhancement of stable bone formation could facilitate this procedure. COMP-Ang1 is a recombinant chimeric protein of angiopoietin-1 that induces angiogenesis and vascular enlargement. We investigated the osteogenic potential of COMP-Ang1 for spinal fusion with allograft based on the enhancement of angiogenesis. Sixty Sprague-Dawley rats underwent bilateral posterior and posterolateral arthrodesis with allograft at L3-4 and L4-5. The animals were divided into three groups (n=20 each): (1) no treatment (sham group); (2) the bovine serum albumin-impregnated collagen sponge group (BSA group); 3) the COMP-Ang1-impregnated collagen sponge group (COMP-Ang1 group). Animals were sacrificed at six weeks for evaluation of spinal fusion using manual palpation, radiographs, and biomechanical and histomorphometric assessments. Total RNA was prepared from the fusion site and analyzed for osteogenic marker protein expression using RT-PCR analysis. The fusion rates determined by manual palpation were 38.9% in the sham group, 42.1% in the BSA group, and 89.5% in the COMP-Ang1 group. Optical density of fusion masses in the COMP-Ang1 group was significantly higher than those in the sham and BSA groups (p<0.001). Total bone volume was significantly higher in the COMP-Ang1 group than in the sham and BSA groups (p<0.001). The mechanical strength was significantly greater in the COMP-Ang1 group than in the sham and BSA groups (p<0.01). Histologically, the fusion site of the COMP-Ang1 group showed a larger number of reactive bones compared with those in the BSA and sham groups. Immunostaining of endothelial cells for factor VIII revealed that COMP-Ang1 group showed higher levels of vascularity in the fusion site. Runt-related transcription factor 2 and its target genes were significantly up-regulated in the COMP-Ang1 group. COMP-Ang1 induced radiologically and histologically demonstrable active osteogenesis by promoting angiogenesis in spinal fusions. It was concluded that COMP-Ang1 enhances spinal fusion and hence the strength of the fusion.

Quantitative assessment of trabecular bone micro-architecture of the wrist via 7 Tesla MRI: preliminary results.

The goal of this study was to determine the feasibility of performing quantitative 7 T magnetic resonance imaging (MRI) assessment of trabecular bone micro-architecture of the wrist, a common fracture site. The wrists of 4 healthy subjects (1 woman, 3 men, 28 ± 8.9 years) were scanned on a 7 T whole body MR scanner using a 3D fast low-angle shot (FLASH) sequence (TR/TE = 20/4.5 m s, 0.169 × 0.169 × 0.5 mm). Trabecular bone was segmented and divided into 4 or 8 angular subregions. Total bone volume (TBV), bone volume fraction (BVF), surface-curve ratio (SC), and erosion index (EI) were computed. Subjects were scanned twice to assess measurement reproducibility. Group mean subregional values for TBV, BVF, SC, and EI (8 subregion analysis) were as follows: 8489 ± 3686, 0.27 ± 0.045, 9.61 ± 6.52; and 1.43 ± 1.25. Within each individual, there was subregional variation in TBV, SC, and EI (>5%), but not BVF (<5%). Intersubject variation (≥12%) existed for all parameters. Within-subject coefficients of variation were ≤10%. This is the first study to perform quantitative 7T MRI assessment of trabecular bone micro-architecture of the wrist. This method could be utilized to study perturbations in bone structure in subjects with osteoporosis or other bone disorders.

Maxillary sinus augmentation with microstructured tricalcium phosphate ceramic in sheep

The objective of this study was to evaluate the biological performance of osteoinductive microstructured tricalcium phosphate (MSTCP) particles in maxillary sinus floor augmentation surgery in sheep. Sinus floor augmentation was performed in eight Swifter sheep. In each animal, the maxillary sinus floor was unilaterally augmented with MSTCP particles. Computed tomography (CT) imaging and histological analyses were performed after 12 weeks of implantation. Maxillofacial CT, histology, histomorphometrical analysis and sequential polychrome fluorescent labeling indicated that MSTCP particles provided a scaffold for cell ingrowth and bone formation. After a 12-week implantation period, the sinuses grafted with MSTCP showed an increased bone height of 6 mm and a mean total bone volume of 43%, with significant degradation of MSTCP particles. MSTCP particles represent a suitable bone substitute material for maxillary sinus floor augmentation surgery.

Differences in leg bone geometry in young, old and very old women

Bone geometry is an important measure of bone strength and is known to be affected by weight-bearing and adult ageing. Engagement in weight-bearing activity decreases with age, thus in this study we compared bone geometry changes between weight-bearing (tibia) and non-weight-bearing (fibula) leg bones in three different age groups of women. Magnetic resonance images of the right leg were acquired in 9 young (20-27years), 7 old (61-69years) and 7 very old (71-80years) women. Total and cortical bone volumes and medullary cavity volumes (mm(3)) were calculated at proximal and distal sites for both bones. Tibial cortical bone volume was significantly less at the proximal site in old (17%) and very old (24%) groups versus young subjects. Cortical bone volume in the proximal fibula was also significantly reduced in the older groups (7 and 12%), but to a substantially lesser extent than in the tibia. In contrast, distal bone geometry appeared largely to be conserved in both tibia and fibula. Proximally, medullary cavity volume was greater in the older groups in the tibia but not the fibula. Distally, the only difference found in either bone was a significantly greater fibular medullary cavity in the very old group. These findings suggest weight-bearing bones in women are more susceptible than non-weight-bearing bones to age-related changes in bone geometry likely due to decreases in weight-bearing activities. Also, weight-bearing activity appears to provide a greater osteogenic stimulus at the distal portions of the leg bones.

In vivo performance of bilayer hydroxyapatite scaffolds for bone tissue regeneration in the rabbit radius

The objective of this study was to investigate the in vivo biomechanical performance of bone defects implanted with novel bilayer hydroxyapatite (HAp) scaffolds that mimic the cortical and cancellous organization of bone. The scaffolds maintained architectural continuity in a rabbit radius segmental defect model and were compared to an untreated defect group (negative control) and autologous bone grafts (positive control). Micro-CT evaluations indicated total bone and scaffold volume in the experimental group was significantly greater than the defect group but lesser than the autologous bone graft treatment. The flexural toughness of the scaffold and the autograft groups was significantly greater than the flexural toughness of the defect group. Interestingly, the absolute density of the bone mineral as well as calcium to phosphorus (Ca/P) ratio in that mineral for the scaffold and autograft contralateral bones was significantly higher than those for the defect contralaterals suggesting that the scaffolds contributed to calcium homeostasis. It was concluded from this study that new bone regenerated in the bilayer HAp scaffolds was comparable to the empty defects and while the HAp scaffolds provided significant increase in modulus when compared to empty defect and their flexural toughness was comparable to autografts after 8 weeks of implantation.

Irradiation induces bone injury by damaging bone marrow microenvironment for stem cells

Radiation therapy can result in bone injury with the development of fractures and often can lead to delayed and nonunion of bone. There is no prevention or treatment for irradiation-induced bone injury. We irradiated the distal half of the mouse left femur to study the mechanism of irradiation-induced bone injury and found that no mesenchymal stem cells (MSCs) were detected in irradiated distal femora or nonirradiated proximal femora. The MSCs in the circulation doubled at 1 week and increased fourfold after 4 wk of irradiation. The number of MSCs in the proximal femur quickly recovered, but no recovery was observed in the distal femur. The levels of free radicals were increased threefold at 1 wk and remained at this high level for 4 wk in distal femora, whereas the levels were increased at 1 wk and returned to the basal level at 4 wk in nonirradiated proximal femur. Free radicals diffuse ipsilaterally to the proximal femur through bone medullary canal. The blood vessels in the distal femora were destroyed in angiographic images, but not in the proximal femora. The osteoclasts and osteoblasts were decreased in the distal femora after irradiation, but no changes were observed in the proximal femora. The total bone volumes were not affected in proximal and distal femora. Our data indicate that irradiation produces free radicals that adversely affect the survival of MSCs in both distal and proximal femora. Irradiation injury to the vasculatures and the microenvironment affect the niches for stem cells during the recovery period.

Enhancement of Bone Morphogenetic Protein-2-Induced Ectopic Bone Formation by Transforming Growth Factor-β1

Bone morphogenetic proteins (BMPs) possess osteoinductive activities and are useful for clinical treatments, including bone regeneration. We found that transforming growth factor (TGF)-β1 strongly enhances the osteoinductive activity of BMP-2. Collagen sponges containing 5 μg of BMP-2 were implanted into mouse muscle tissues, after which lump-like masses appeared and grew until day 7. Subsequently, calcification occurred in the lump-like masses by day 14. Addition of 50 ng of TGF-β1 to the BMP-2-containing sponges markedly accelerated the growth of the lump-like masses and resulted in a fivefold increase in total bone volume as compared with BMP-2 alone. The number of osteoblasts in ectopic bone tissues at 14 days after implantation induced by BMP-2+TGF-β1 was twofold greater than that with BMP-2 alone, whereas the number of osteoclasts was decreased by half. On the other hand, TGF-β1 accelerated the differentiation of both osteoblasts and osteoclasts in the early stage (2-7 days after implantation) of ectopic bone formation. We also implanted collagen sponges into bone defects surgically created in mouse calvaria. Sponges containing 2.5 μg of BMP-2 and 25 ng of TGF-β1 caused complete filling of the defects with orthotopic bone, whereas those containing 2.5 μg of BMP-2 alone caused only partial filling. These results suggest that TGF-β1 enhances BMP-2-induced ectopic bone formation by accelerating the growth of lump-like masses, and regulates osteoblast and osteoclast generation. Our findings may contribute to the development of a new treatment method for skeletal disorders.

Contrast-enhanced micro-computed tomography of fatigue microdamage accumulation in human cortical bone

Conventional methods used to image and quantify microdamage accumulation in bone are limited to histological sections, which are inherently invasive, destructive, two-dimensional, and tedious. These limitations inhibit investigation of microdamage accumulation with respect to volumetric spatial variation in mechanical loading, bone mineral density, and microarchitecture. Therefore, the objective of this study was to investigate non-destructive, three-dimensional (3-D) detection of microdamage accumulation in human cortical bone using contrast-enhanced micro-computed tomography (micro-CT), and to validate micro-CT measurements against conventional histological methods. Unloaded controls and specimens loaded in cyclic uniaxial tension to a 5% and 10% reduction in secant modulus were labeled with a precipitated BaSO 4 stain for micro-CT and basic fuchsin for histomorphometry. Linear microcracks were similarly labeled by BaSO 4 and basic fuchsin as shown by backscattered electron microscopy and light microscopy, respectively. The higher X-ray attenuation of BaSO 4 relative to the bone extracellular matrix provided enhanced contrast for the detection of damage that was otherwise not able to be detected by micro-CT prior to staining. Therefore, contrast-enhanced micro-CT was able to nondestructively detect the presence, 3-D spatial location, and accumulation of fatigue microdamage in human cortical bone specimens in vitro. Microdamage accumulation was quantified on segmented micro-CT reconstructions as the ratio of BaSO 4 stain volume (SV) to total bone volume (BV). The amount of microdamage measured by both micro-CT (SV/BV) and histomorphometry (Cr.N, Cr.Dn, Cr.S.Dn) progressively increased from unloaded controls to specimens loaded to a 5% and 10% reduction in secant modulus ( p < 0.001). Group means for micro-CT measurements of damage accumulation were strongly correlated to those using histomorphometry ( p < 0.05), validating the new methods. Limitations of the new methods in the present study included that the precipitated BaSO 4 stain was non-specific and non-biocompatible, and that micro-CT measurements exhibited greater variability compared to conventional histology. Nonetheless, contrast-enhanced micro-CT enabled non-destructive imaging and 3-D spatial information, which are not possible using conventional histological methods.

A Meta-Analysis of Histomorphometric Results and Graft Healing Time of Various Biomaterials Compared to Autologous Bone Used as Sinus Floor Augmentation Material in Humans

To date, no studies have been published in which histomorphometric data from a large group of patients comparing various biomaterials for sinus floor augmentation procedures were evaluated. A meta-analysis of the English literature from January 1993 till April 2009 was carried out. Out of 147 titles, according to our criteria, 64 articles were selected for analysis describing the use of autologous bone and their alternatives, such as allogenic, xenogenic, and alloplastic materials. On the basis of autologous bone grafting, a reference value for total bone volume (TBV) of 63% was found. Particulation of the bone graft resulted in a general reduction of −18% in TBV. Delayed implant placement reduced the TBV with −7%. Overall TBV was 8% or 6% higher if a biopsy was, respectively, taken before 4.5 months or after 9.0 months after initial sinus augmentation surgery. Allogenic, xenogenic, alloplastic, or combinations of graft materials all resulted in a significant lower amount of TBV compared to autologous bone grafting ranging from −7% to −26%. Inventorying the effect of "biopsy time" for autologous bone, the TBV was significantly higher before 4.5 and after 9.0 months of healing time compared to period in between. Surprisingly, no significant differences in TBV with respect to "biopsy time" for bone substitutes were found. On the basis of the aspect of TBV autologous bone still has to be considered to be the gold standard in sinus augmentation surgery. However, the consequence of the TBV for implant survival is still unraveled yet.

Influence of vertical trabeculae on the compressive strength of the human vertebra

Vertebral strength, a key etiologic factor of osteoporotic fracture, may be affected by the relative amount of vertically oriented trabeculae. To better understand this issue, we performed experimental compression testing, high-resolution micro–computed tomography (µCT), and micro–finite-element analysis on 16 elderly human thoracic ninth (T9) whole vertebral bodies (ages 77.5 ± 10.1 years). Individual trabeculae segmentation of the µCT images was used to classify the trabeculae by their orientation. We found that the bone volume fraction (BV/TV) of just the vertical trabeculae accounted for substantially more of the observed variation in measured vertebral strength than did the bone volume fraction of all trabeculae (r2 = 0.83 versus 0.59, p < .005). The bone volume fraction of the oblique or horizontal trabeculae was not associated with vertebral strength. Finite-element analysis indicated that removal of the cortical shell did not appreciably alter these trends; it also revealed that the major load paths occur through parallel columns of vertically oriented bone. Taken together, these findings suggest that variation in vertebral strength across individuals is due primarily to variations in the bone volume fraction of vertical trabeculae. The vertical tissue fraction, a new bone quality parameter that we introduced to reflect these findings, was both a significant predictor of vertebral strength alone (r2 = 0.81) and after accounting for variations in total bone volume fraction in multiple regression (total R2 = 0.93). We conclude that the vertical tissue fraction is a potentially powerful microarchitectural determinant of vertebral strength. © 2011 American Society for Bone and Mineral Research.

Sinus Floor Augmentation Surgery Using Autologous Bone Grafts from Various Donor Sites: A Meta-Analysis of the Total Bone Volume

To date, no studies have been published that evaluated histomorphometric data from a large number of patients while comparing different sites and methods of autologous bone grafting in sinus floor augmentation procedures. A meta-analysis of the English literature from January 1995 till April 2009 was carried out. PubMed search engine and the following journals were explored: Clinical Oral Implant Research, International Journal of Oral and Maxillofacial Implants, International Journal of Periodontics and Restorative Dentistry, and the Journal of Periodontology. Out of 147 titles, according to our criteria, 25 articles were left for analysis. The majority were prospective controlled studies (21) and 2 randomized clinical trials, 1 pilot study and 1 case series. A reference value of 47% for total bone volume (TBV) was found while using iliac bone grafting as a standard. Use of intraoral bone grafts increases the TBV, with 11% for chin bone and 14% for bone grafted from other intraoral sites. Particulation of the bone graft has a negative effect on the TBV of 18%. Surprisingly, no correlation between TBV and the time of graft healing was found. Histological section thickness seemed to be a significant variable, as every micron increase of section thickness leads to an increase of 0.4% of TBV. Bone grafting from the iliac crest resulted in a significantly lower TBV compared with intraoral bone grafting. However, due to the limited availability of intraoral bone to be harvested, iliac grafts still have to be considered the gold standard in augmenting the severely atrophic maxilla.