Bone Tissue Level Research Articles

Hungry Bone Syndrome after Parathyroidectomy for Primary Hyperthyroidism

Parathyroidectomy is the treatment of choice in patients with primary hyperparathyroidism (PHPT). This disease affects calcium metabolism at the level of bone tissue and renal tubules, resulting in hypercalcaemia, often asymptomatic, associated with hypophosphataemia and hypomagnesaemia. Sudden suppression of parathyroid hormone (PTH), caused by successful parathyroidectomy, in patients with preoperative high levels of PTH and hypercalcaemia from enhanced bone turnover, may induce severe postoperative hypocalcaemia that may lead to symptoms of tetany. This relatively uncommon condition is known as “hungry bone syndrome” (HBS), because it is believed to be due mainly to enhanced bone formation. Several risk factors have been advocated for HBS, and the syndrome is reported to be more likely to rise in subjects with severe preoperative bone disease. Other modifiable risk factors are preoperative vitamin D deficiency and high PTH and calcium levels. Treatment of HBS is basically the administration of high amounts of calcium immediately after the onset of postoperative hypocalcaemia. Supplements of active metabolites of vitamin D, as well as magnesium in depleted subjects are complementary in supporting bone remineralization. Oral supplementation may be requested for months after parathyroidectomy. Prevention is poorly documented, but it is reasonable to propose the correction of vitamin D deficit and the use of bisphosphonates aimed to lower PTH levels and bone resorption before parathyroidectomy.

Zinc as a nutritional approach to bone loss prevention in an ovariectomized rat model

In this study, we have investigated the role of zinc supplementation (a nutritional antioxidant) in an ovariectomized osteopenic rat model. Forty-eight female Wistar rats were assigned to four groups: control, zinc, ovariectomy (OVX), and OVX + zinc. Analysis was performed to compare the study groups on bone metabolism markers, bone antioxidant enzymes, and zinc and copper levels in serum and bone tissues. Electron microscopy was also performed to assess morphological changes. Estradiol levels decreased and tartarate-resistant acid phosphatase 5b levels increased in the OVX group. In the OVX + zinc group, these levels were regulated; however, estradiol levels were still significantly lower than those in controls. The OVX group showed significantly higher urinary excretion of hydroxyproline, which recovered upon zinc supplementation but was higher than normal levels. The activities of catalase and superoxide dismutase decreased in ovariectomized animals and up-regulated upon zinc supplementation. Zinc supplementation in the OVX group revoked reduced glutathione levels and elevated malondialdehyde levels. Reduction in zinc and copper levels was observed in the bone tissues and serum of the OVX group. Zinc administration restored these levels to normal. Electron microscopic studies revealed a looser structure and resorbed areas in ovariectomized rat cortical bone. Zinc administration restored bone tissue morphology. These findings suggest that changes in cortical bone attributed to estrogen deficiency are arrested by zinc supplementation, which can be a sustainable approach to improving bone health.

Quantitative Reconstruction of Weaning Ages in Archaeological Human Populations Using Bone Collagen Nitrogen Isotope Ratios and Approximate Bayesian Computation

BackgroundNitrogen isotope analysis of bone collagen has been used to reconstruct the breastfeeding practices of archaeological human populations. However, weaning ages have been estimated subjectively because of a lack of both information on subadult bone collagen turnover rates and appropriate analytical models.MethodologyTemporal changes in human subadult bone collagen turnover rates were estimated from data on tissue-level bone metabolism reported in previous studies. A model for reconstructing precise weaning ages was then developed using a framework of approximate Bayesian computation and incorporating the estimated turnover rates. The model is presented as a new open source R package, WARN (Weaning Age Reconstruction with Nitrogen isotope analysis), which computes the age at the start and end of weaning, 15N-enrichment through maternal to infant tissue, and value of collagen synthesized entirely from weaning foods with their posterior probabilities. The model was applied to 39 previously reported Holocene skeletal populations from around the world, and the results were compared with weaning ages observed in ethnographic studies.ConclusionsThere were no significant differences in the age at the end of weaning between the archaeological (2.80±1.32 years) and ethnographic populations. By comparing archaeological populations, it appears that weaning ages did not differ with the type of subsistence practiced (i.e., hunting–gathering or not). Most of -enrichment (2.44±0.90‰) was consistent with biologically valid values. The nitrogen isotope ratios of subadults after the weaning process were lower than those of adults in most of the archaeological populations (−0.48±0.61‰), and this depletion was greater in non-hunter–gatherer populations. Our results suggest that the breastfeeding period in humans had already been shortened by the early Holocene compared with those in extant great apes.

Finite element prediction with experimental validation of damage distribution in single trabeculae during three-point bending tests

There is growing evidence that information on trabecular microarchitecture can improve the assessment of fracture risk. One current strategy is to exploit finite element (FE) analysis applied to experimental data of mechanically loaded single trabecular bone tissue obtained from non-invasive imaging techniques for the investigation of the damage initiation and growth of bone tissue. FE analysis of this type of bone has mainly focused on linear and non-linear analysis to evaluate the bone's failure properties. However, there is a lack of experimentally validated FE damage models at trabecular bone tissue level allowing for the simulation of the progressive damage process (initiation and growth) till complete fracture. Such models are needed to perform enhanced prediction of the apparent failure mechanical properties needed to assess the fracture risk of bone organs. In the current study, we develop a FE model based on a continuum damage mechanics (CDM) approach to simulate the damage initiation and propagation of a single trabecula till complete facture in quasi-static regime. Three-point bending experiments were performed on single bovine trabeculae and compared to FE results. In order to validate the proposed FE mode, (i) the force displacement curve was compared to the experimental one and (ii) the damage distribution was correlated to the measured one obtained by digital image correlation based on stress whitening in bone, reported to be correlated to microdamage. A very good agreement was obtained between the FE and experimental results, indicating that the proposed damage investigation protocol based on FE analysis and testing is reliable to assess the damage behavior of bone tissue and that the current damage model is able to accurately simulate the damaging and fracturing process of single trabeculae under quasi static load.

Micro-CT finite element model and experimental validation of trabecular bone damage and fracture

Most micro-CT finite element modeling of human trabecular bone has focused on linear and non-linear analysis to evaluate bone failure properties. However, prediction of the apparent failure properties of trabecular bone specimens under compressive load, including the damage initiation and its progressive propagation until complete bone failure into consideration, is still lacking. In the present work, an isotropic micro-CT FE model at bone tissue level coupled to a damage law was developed in order to simulate the failure of human trabecular bone specimens under quasi-static compressive load and predict the apparent stress and strain. The element deletion technique was applied in order to simulate the progressive fracturing process of bone tissue. To prevent mesh-dependence that generally affects the damage propagation rate, regularization technique was applied in the current work. The model was validated with experimental results performed on twenty-three human trabecular specimens. In addition, a sensitivity analysis was performed to investigate the impact of the model factors' sensitivities on the predicted ultimate stress and strain of the trabecular specimens. It was found that the predicted failure properties agreed very well with the experimental ones.

Impact of Bone Quality and Implant Type on the Primary Stability: An Experimental Study Using Bovine Bone

The purpose of this in vitro study was to compare the primary stability and removal torque of bone level and tissue level implants in different bone qualities. Twenty tissue level and bone level implants (3.3 × 10 mm and 4.1 × 10 mm) were used for assessing the stability in type II and type IV bone. Forty bovine rib blocks were used in this study. The primary stability of the implant was measured by the resonance frequency using an Osstel device. The removal torque values (RTV) of the implants was assessed using a digital torque gauge instrument. The implant stability quotient (ISQ) values and the RTV showed a marginally higher stability with bone level implants as compared to tissue level implants. However, these differences were not statistically significant in both type of bone used (P > 0.05). On the other hand, compared to type IV, type II bone showed significant differences in the ISQ (P < 0.01) and RTV (P < 0.001) of bone level and tissue level implants. The study concluded that bone quality is an important factor in establishing primary stability than the implant dimension. Bone level and tissue level implants of same dimensions can be selected based on the esthetic demands since they showed similar mechanical properties.

RANKL is downregulated in bone cells by physical activity (treadmill and vibration stimulation training) in rat with glucocorticoid-induced osteoporosis.

The aim of this study was to investigate bone tissue and plasma levels of RANKL and OPG in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity on the skeletal system by treadmill and vibration platform training. Osteoporosis is a disease characterised by low bone mass and structural deterioration of bone tissue leading to bone fragility. Vibration exercise is a new and effective measure to prevent muscular atrophy and osteoporosis. The animals were divided into 5 groups. 1: control rats; 2: rats with osteoporosis receiving prednisolone; 3: rats receiving prednisolone and treadmill training; 4: rats receiving prednisolone and vibration stimulation training; 5: rats receiving prednisolone, treadmill and vibration stimulation training. For bone evaluations we used whole-body scans, histology and histomorphometric analysis. RANKL and OPG expression was evaluated by immunohistochemistry and biochemical analysis. After treatment, our data demonstrated that RANKL expression was significantly increased in groups 2 and 3 and decreased in groups 4 and 5. Conversely, OPG expression was significantly decreased in groups 2 and 3 and increased in groups 4 and 5. In conclusion, our findings suggest that mechanical stimulation inhibits the activity of RANKL. This finding provides new insights into the occurrence and progression of osteoporosis.

Peri-implant Crestal Bone Preservation: Where do We Stand?

The purpose of this article is to throw light on various factors that can cause peri-implant bone loss and range of solutions that can prevent the postoperative stigma of marginal bone loss. In this article main focus is given on the four specific implant designs which have proven to be successful in maintaining the peri-implant bone level that includes Laser-Lok implant collar, platform switching at implant abutment junction, conical implant abutment interface and microthreading on implant neck. This article also presents three case reports treated by these modified nonconventional implant designs with 1 year follow-up. The added features in them found to play an imperative role in maintaining the peri-implant marginal bone and soft tissue level and thereby influence the success and survival rates of implant supported prosthesis.

The effects of physical activity (treadmill and vibration stimulation training) on RANKL and OPG expression in bone cells, in rats with glucorticoid-induced osteoporosis

The aim of this study was to investigate bone tissue and plasma levels of RANKL and OPG in rats with prednisolone-induced osteoporosis and to evaluate the outcomes of physical activity on the skeletal system by treadmill and vibration platform training. Osteoporosis is a disease characterised by low bone mass and structural deterioration of bone tissue leading to bone fragility. Vibration exercise is a new and effective measure to prevent muscular atrophy and osteoporosis. The animals were divided into 5 groups. 1: control rats; 2: rats with osteoporosis receiving prednisolone; 3: rats receiving prednisolone and treadmill training; 4: rats receiving prednisolone and vibration stimulation training; 5: rats receiving prednisolone, treadmill training and vibration stimulation training. Bone evaluations used whole-body scans, histology and histomorphometric analysis. RANKL and OPG expression was evaluated by immunohistochemistry and biochemical analysis. After treatment, our data demonstrated that RANKL expression was significantly increased in groups 2 and 3 and decreased in groups 4 and 5. Conversely, OPG expression was significantly decreased in groups 2 and 3 and increased in groups 4 and 5. In conclusion, our findings suggest that mechanical stimulation inhibits the activity of RANKL. This finding provides new insights into the occurrence and progression of osteoporosis.

Novel method to analyze post-yield mechanical properties at trabecular bone tissue level

Tissue level mechanics is a key factor to be investigated to improve the knowledge of how the overall trabecular structure reacts to loading and overloading. The aim of this study was to develop a new device for measuring the mechanical competence of single trabeculae in the post-yield region for both tensile and bending tests, characterized by high accuracy and precision, and to assess the effect of testing mode, donor age and material composition. A novel approach for measuring the displacement and deformation was developed (accuracy error of 0.3% and a precision of 2.7%). A total of 30 samples from two bovine femora of different ages (from <3-year-old and 14-year-old cows) were tested in tension or bending, while average material properties have been acquired by means of Raman spectroscopy. A group of trabeculae was tested in bending after treatment for collagen degradation. As a result, a complete set of post-yield properties has been reported. The results highlight significant differences between tensile and bending groups, with higher values for the bending test mode for yield strain, ultimate strain and post-yield work and lower for the elastic modulus. Significant higher values were found for the old donor (differences in the range of 30–60%) for elastic modulus, yield stress and ultimate stress as well as for material properties measured by Raman spectroscopy. We quantified that changes in materials properties induced by collagen degradation corresponded to a substantial decrease (up to 120% for post-yield work) of mechanical competence, both in the elastic and inelastic region.

Expression and significance of Kruppel-like factor 6 gene in osteosarcoma.

Osteosarcoma is primary malignant tumour of bone. Kruppel-like factor 6 (KLF6) is a tumor suppressor gene frequently inactivated in a number of human cancers and a ubiquitously expressed zinc-finger transcription factor. The present study aimed to first explore the relationship between the expression level of the KLF6 gene in osteosarcoma and the occurrence of bone tumours. KLF6 mRNA and protein expression levels in osteosarcoma and normal bone tissue were assayed by real-time quantitative PCR and immunohistochemistry. KLF6 mRNA and protein expression levels in osteosarcoma cells and normal osteoblasts were detected by semi-quantitative reverse transcription PCR and Western blotting, respectively. Both the expression of KLF6 mRNA and protein in osteosarcoma cells and tissues were significantly lower than that in normal cells and tumour-adjacent tissues. KLF6 is a putative tumor suppressor gene involved in osteosarcoma which can be used as a new therapeutic target and an important marker for early diagnosis and postoperative monitoring.

Cone Beam Computed Tomographic Measurement of Maxillary Central Incisors to Determine Prevalence of Facial Alveolar Bone Width ≥2 mm

The initial thickness of maxillary bone has significant impact on the responding level of facial bone and soft tissue after extraction and immediate implant placement. A prevailing notion is that following implant placement in fresh extraction sites, at least 2 mm of facial bone is needed to prevent soft tissue recession, fenestration, and dehiscence. The purpose of this study was to use cone beam computed tomography (CBCT) to measure horizontal width of facial alveolar bone overlying healthy maxillary central incisors and to determine prevalence of bone thickness ≥2 mm. Tomographic data from 101 randomly selected patients were evaluated by two independent observers. Assessments were made of facial bone width at levels 1.0 to 10.0 mm apical to the bone crest. Healthy maxillary central incisors (n= 202) were measured from 101 patient scans. The percent of teeth with facial bone ≥2 mm at levels 1, 2, 3, 4, and 5 mm from the bone crest was 0, 1.5, 2.0, 3.0, and 2.5%, respectively. Overall mean thickness of the bone was 1.05 mm for right and left central incisors combined. The range of individual measurements for all levels was 0 to 5.1 mm. The occurrence of ≥ 2 mm thickness bone measurements increased with increasing depth. However, mean widths observed at levels 6 to 10 mm from the crest ranged only 1.0 to 1.3 mm because of apparent fenestration occurrence (0 mm bone) in approximately 12% of teeth. Overall, no significant differences in bone thickness were found between ethnic, gender, age, or scan groups. Using CBCT, occurrences of ≥2 mm maxillary facial alveolar bone were found on no more than 3% of root surfaces 1.0 to 5.0 mm apical to the bone crest in this sample of maxillary central incisors. The study evidenced prevalence of a thin facial alveolar bone (<2 mm) that may contribute to risk of facial bone fenestration, dehiscence, and soft tissue recession after immediate implant therapy.

Inhibition of WNT-B-catenin signalling promotes cartilage repair at injured growth plate in young rats

Growth plate cartilage is responsible for bone lengthening in children, and its injury is often repaired by bony tissue, which can cause limb length discrepancy and/or bone angulation deformities. While earlier studies on growth plate injury repair have identified inflammatory, mesenchymal infiltration, osteogenesis and remodelling repair responses, the molecular mechanisms involved in the bony repair remain unknown. Since the Wnt-β-catenin signalling pathway is known to play a crucial role in the osteogenic differentiation of mesenchymal progenitor cells, this study investigated the potential roles of Wnt-β-catenin signalling pathway in the bony repair of injured growth plate in rats. Suggestive of a role of Wnt/β-catenin signalling pathway in the early stage of the repair, our Affymetrix gene microarray analysis with RNA isolated from laser-capture microdissected injury site tissue identified an increase in β-catenin expression and yet a decrease in expression of Wnt signalling inhibitors sFRP1 & 4 at day 4 post-injury vs later time points. Compared to the vehicle control, treatment of the injured rats with the β-catenin inhibitor ICG-001 (oral gavage at 200 mg/kg/day for 8 days, commenced at day 2 post injury) enhanced collagen-2 gene expression (by qRT-PCR), increased proportion of cartilage tissue and decreased level of bone tissue (as measured by histological analysis) at the injury site by day 10 post- injury (n = 8, pb 0.001). Consistently, in vitro studies with bone marrow stromal cells from normal rats showed that β-catenin inhibitor ICG-001 at 25 mM suppressed osteogenic (by CFU-f-ALP assay) but enhanced chondrogenic (by pellet culture) differentiation. These results suggest that Wnt-β-catenin signalling promotes osteoblast differentiation and suppresses chondrogenic differentiation during bony repair of the injured growth plate, and intervention of this signalling could represent a potential approach in enhancing cartilage regeneration after growth plate injury. This article is part of a Special Issue entitled ECTS 2012. Disclosure of interest: None declared.

Relating micromechanical properties and mineral densities in severely suppressed bone turnover patients, osteoporotic patients, and normal subjects

Mineralization of bone, from the tissue level to whole bones, is associated with mechanical properties. The relationship between bone tissue mineralization and micromechanical properties may be affected by age, disease, and drug treatment. Patients with severely suppressed bone turnover (SSBT) suffered atypical fractures while on bisphosphonate treatment. The role of tissue level mineralization in predicting material level properties of SSBT bone may be different from that of other osteoporotic patients and of normal subjects. The aim of this study was to compare the relationships between mineralization and micromechanical properties of bone biopsies from patients with SSBT, bisphosphonate-naive osteoporotic patients with typical vertebral fracture, and normal young and age-matched subjects. We used nanoindentation and quantitative backscattered electron microscopy to characterize the elastic modulus, contact hardness, plastic deformation resistance, and tissue mineralization of the biopsies at site-matched locations within each biopsy. The linear mineralization–mechanical property relationships were different among the groups with respect to the intercepts for only cortical bone tissue but not the slopes for cortical and trabecular bone tissues. For a given mineral density, there was a trend of greater plastic deformation resistance in SSBT cortical bone compared to young normal bone. Similarly, there was a trend of greater plastic deformation resistance in osteoporotic trabecular bone compared to young normal bone for a given mineral density. The age-matched normal group had higher elastic modulus and a trend of higher contact hardness compared to the young normal group for a given mineral density. However, the mechanical property–mineralization relationships within an individual were weak, and only 21 of 53 biopsies that were analyzed had at least one significant association between mineralization and a mechanical property measurement for either cortical or trabecular bone tissues. The average properties of microstructural regions (deep and superficial remodeling packets in trabecular bone; osteonal and interstitial regions in cortical bone) were consistent with mineral accumulation with tissue age, with the exception of the SSBT group. SSBT trabecular bone deep packets had higher hardness and plastic deformation resistance than superficial packets, but mineralization levels and tissue modulus were not different between packet types. We conclude that relationships between mineral and mechanical properties were different between fracture and normal groups and between young and old normal groups, and that atypical fracture may be associated with changed microstructural material properties and tissue level mineralization compared to osteoporotic patients with vertebral fracture and normal subjects. We hypothesize that tissue level bone quality may be an important determinant in fracture risk, such that tissue mineral density may predict different material properties in different patient groups.

Vitamin D and bone health

Current data demonstrate that vitamin D deficiency contributes to the aetiology of at least two metabolic bone diseases, osteomalacia and osteoporosis. Osteomalacia, or rickets in children, results from a delay in mineralization and can be resolved by normalization of plasma calcium and phosphate homeostasis independently of vitamin D activity. The well characterized endocrine pathway of vitamin D metabolism and activities is solely responsible for vitamin D regulating plasma calcium and phosphate homeostasis and therefore for protecting against osteomalacia. In contrast a large body of clinical data indicate that an adequate vitamin D status as represented by the serum 25-hydroxyvitamin D concentration protects against osteoporosis by improving bone mineral density and reducing the risk of fracture. Interestingly adequate serum 1,25-dihydroxyvitamin D concentrations do not reduce the risk of fracture. In vitro human bone cell cultures and animal model studies indicate that 25-hydroxyvitamin D can be metabolised to 1,25-dihydroxyvitamin D by each of the major bone cells to activate VDR and modulate gene expression to reduce osteoblast proliferation and stimulate osteoblast and osteoclast maturation. These effects are associated with increased mineralization and decreased mineral resorption. Dietary calcium interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on bone through the endocrine system or an anabolic action through a bone tissue autocrine or paracrine system.

A three-scale finite element investigation into the effects of tissue mineralisation and lamellar organisation in human cortical and trabecular bone

Bone is an exceptional material that is lightweight for efficient movement but also exhibits excellent strength and stiffness imparted by a composite material of organic proteins and mineral crystals that are intricately organised on many scales. Experimental and computational studies have sought to understand the role of bone composition and organisation in regulating the biomechanical behaviour of bone. However, due to the complex hierarchical arrangement of the constituent materials, the reported experimental values for the elastic modulus of trabecular and cortical tissue have conflicted greatly. Furthermore, finite element studies of bone have largely made the simplifying assumption that material behaviour was homogeneous or that tissue variability only occurred at the microscale, based on grey values from micro-CT scans. Thus, it remains that the precise role of nanoscale tissue constituents and microscale tissue organisation is not fully understood and more importantly that these have never been incorporated together to predict bone fracture or implant outcome in a multiscale finite element framework. In this paper, a three-scale finite element homogenisation scheme is presented which enables the prediction of homogenised effective properties of tissue level bone from its fundamental nanoscale constituents of hydroxyapatite mineral crystals and organic collagen proteins. Two independent homogenisation steps are performed on representative volume elements which describe the local morphological arrangement of both the nanostructural and microstructural levels. This three-scale homogenisation scheme predicts differences in the tissue level properties of bone as a function of mineral volume fraction, mineral aspect ratio and lamellar orientation. These parameters were chosen to lie within normal tissue ranges derived from experimental studies, and it was found that the predicted stiffness properties at the lamellar level correlate well with experimental nanoindentation results from cortical and trabecular bone. Furthermore, these studies show variations in mineral volume fraction, mineral crystal size and lamellar orientation could be responsible for previous discrepancies in experimental reports of tissue moduli. We propose that this novel multiscale modelling approach can provide a more accurate description of bone tissue properties in continuum/organ level finite element models by incorporating information regarding tissue structure and composition from advanced imaging techniques. This approach could thereby provide a preclinical tool to predict bone mechanics following prosthetic implantation or bone fracture during disease.

Generation of mineral density distribution maps from subject-specific models of mandibles - a preliminary study

Determination of the mineral content of bone and its distribution by computed tomography (CT) enables one to define the insertion points for prosthetic devices, or determine the degree of healing in cases of fracture or surgical intervention. The use of subject-specific models allows mapping of the spatial structure and the mineral content of the bone graphically and quantitatively. Subject-specific models and mineral density maps from pig jaws were developed using segmentation, transcription tools and finite element analysis software. This study considered six frozen heads from pigs aged 10-12 months, and phantom solutions of K(2) HPO(4) . The predicted bone mass of each jaw was compared with its respective ash mass after incineration. The tridimensional maps show highest density values at the molar cusp and within the symphysis. The average percentage error relative to the mineral density maps was -18.4%. The radiation dose was reduced by a factor of eight from the recommended maximum without compromising the precision of the models. The computed tridimensional mineral density maps illustrate, numerically and graphically, the spatial distribution of the density field within the mandibular bone. These maps could facilitate the location of insertion points or determine the evolution of the mineralization level of a patient's bone tissue.

Bovine Viral Diarrhea Virus Cyclically Impairs Long Bone Trabecular Modeling in Experimental Persistently Infected Fetuses

Persistent infection (PI) with bovine viral diarrhea virus (BVDV) has been associated with osteopetrosis and other long bone lesions, most commonly characterized as transverse zones of unmodeled metaphyseal trabeculae in fetuses and calves. This study was undertaken to characterize the morphogenesis of fetal long bone lesions. Forty-six BVDV-naïve pregnant Hereford heifers of approximately 18 months of age were inoculated with noncytopathic BVDV type 2 containing media or media alone on day 75 of gestation to produce PI and control fetuses, respectively, which were collected via cesarean section on days 82, 89, 97, 192, and 245 of gestation. Radiographic and histomorphometric abnormalities were first detected on day 192, at which age PI fetal long bone metaphyses contained focal densities (4 of 7 fetuses) and multiple alternating transverse radiodense bands (3 of 7 fetuses). Day 245 fetuses were similarly affected. Histomorphometric analysis of proximal tibial metaphyses from day 192 fetuses revealed transverse zones with increased calcified cartilage core (Cg.V/BV, %) and trabecular bone (BV/TV, %) volumes in regions corresponding to radiodense bands (P < .05). Numbers of tartrate resistant acid phosphatase positive osteoclasts (N.Oc/BS, #/mm(2)) and bone perimeter occupied (Oc.S/BS, %) were both decreased (P < .05). Mineralizing surface (MS/BS, %), a measure of tissue level bone formation activity, was reduced in PI fetuses (P < .05). It is concluded that PI with BVDV induces cyclic abnormal trabecular modeling, which is secondary to reduced numbers of osteoclasts. The factors responsible for these temporal changes are unknown but may be related to the time required for osteoclast differentiation from precursor cells.

Hard and Soft Tissue Changes After Crestal and Subcrestal Immediate Implant Placement

The purpose of this study is to assess the influence of the placement level of implants with a laser-microtextured collar design on the outcomes of crestal bone and soft tissue levels. In addition, we assessed the vertical and horizontal defect fill and identified factors that influenced clinical outcomes of immediate implant placement. Twenty-four patients, each with a hopeless tooth (anterior or premolar region), were recruited to receive dental implants. Patients were randomly assigned to have the implant placed at the palatal crest or 1 mm subcrestally. Clinical parameters including the keratinized gingival (KG) width, KG thickness, horizontal defect depth (HDD), facial and interproximal marginal bone levels (MBLs), facial threads exposed, tissue-implant horizontal distance, gingival index (GI), and plaque index (PI) were assessed at baseline and 4 months after surgery. In addition, soft tissue profile measurements including the papilla index, papilla height (PH), and gingival level (GL) were assessed after crown placement at 6 and 12 months post-surgery. The overall 4-month implant success rate was 95.8% (one implant failed). A total of 20 of 24 patients completed the study. At baseline, there were no significant differences between crestal and subcrestal groups in all clinical parameters except for the facial MBL (P = 0.035). At 4 months, the subcrestal group had significantly more tissue thickness gain (keratinized tissue) than the crestal group compared to baseline. Other clinical parameters (papilla index, PH, GL, PI, and GI) showed no significant differences between groups at any time. A facial plate thickness ≤1.5 mm and HDD ≥2 mm were strongly correlated with the facial marginal bone loss. A facial plate thickness ≤2 mm and HDD ≥3 were strongly correlated with horizontal dimensional changes. The use of immediate implants was a predictable surgical approach (96% survival rate), and the level of placement did not influence horizontal and vertical bone and soft tissue changes. This study suggests that a thick facial plate, small gaps, and premolar sites were more favorable for successful implant clinical outcomes in immediate implant placement.

Deriving tissue density and elastic modulus from microCT bone scans

Tissue level density and elastic modulus are intrinsic properties that can be used to quantify bone material and analyses incorporating those quantities have been used to evaluate bone on a macroscopic scale. Micro-computed tomography (microCT) technology has been used to construct tissue level finite element models to simulate macroscopic fracture strength, however, a single method for assigning voxel-specific tissue density and elastic modulus based on those data has not been universally accepted. One method prevalent in the literature utilizes an empirical relationship that derives tissue stiffness as a function of bone calcium content weight fraction. To derive calcium content weight fraction from microCT scans, a measure of tissue density is required and a constant value is traditionally used. However, experimental data suggest a non-trivial amount of tissue heterogeneity suggesting a constant tissue density may not be appropriate. A theoretical derivation for determining the relationship between voxel-specific tissue density and microCT scan data (i.e., microCT derived tissue mineral density (TMD), mgHA/cm(3)) and bone constituent properties is proposed. Constant model parameters used in the derivation include the density of water, ash, and organics (i.e., bone constituents) and the volume fraction of the organics constituent. The effect of incorporating the theoretically derived tissue density (instead of a constant value) in determining voxel-specific elastic modulus resulted in a maximum observed increase of 12GPa (5.9GPa versus 17.9GPa, for the constant value and derived tissue density formulations, respectively) for a measured TMD of 1.02gHA/cm(3). Average and bounding quantities for the four constant model parameters were defined from the literature and the influence of those values on the derived tissue density and elastic modulus relationships were also evaluated. The theoretical relationships of tissue density and elastic modulus, with the average constant model parameters applied, were consistent with previously published empirical relationships derived from experimental data. Tissue density as a function of microCT TMD was formulated as a linear relationship and the density of water and ash was shown to solely influence the proportionality (i.e., slope) between those values. The density of water and organics (i.e., collagen) and the volume fraction of the organics constituent were shown to influence the constant offset (intercept) between tissue density and TMD with no influence from ash density. Incorporating tissue density heterogeneity into the derivation of elastic modulus resulted in a significant increase in predicted modulus (for microCT TMD ranges observed for healthy tissue) as compared to when a constant tissue density was used. The presented approach provides a novel method for deriving tissue-level bone material properties and quantifies the effect of assuming tissue homogeneity when calculating elastic modulus (when using a prevalent method in the literature) from microCT scan data.