Bone Mineral Density Distribution Research Articles

Association between bone mineral density distribution and various radiographic parameters in patients with advanced medial osteoarthritis of the knee

PurposePatients with severe osteoarthritis (OA) of the knee have changes in bone mineral density (BMD) of the distal femur and proximal tibia. Correlations between the medial-to-lateral BMD (M/L-BMD) ratio (which normalizes the potentially confounding effects of body size and sex on BMD) and radiographic parameters that indicate OA progression have not been adequately studied. The purpose of this study was to evaluate correlations between radiographic indicators of OA progression and femoral and tibial M/L-BMD ratios. MethodsA consecutive series of 182 knees in 156 patients with advanced medial knee OA who underwent total knee arthroplasty were included. We evaluated correlations between the femoral and tibial M/L-BMD ratios and various radiographic parameters, including tibiofemoral angle (TFA), mechanical axis angle (MAA), tibial coronal angle, tibiofemoral subluxation (%), load-bearing axis deviation at the tibial plateau (%), and medial and lateral laxity. ResultsUnivariate analyses using Spearman's correlation coefficient revealed significant positive correlations between femoral and tibial M/L-BMD ratios and both TFA and MAA and negative correlations with tibial coronal angle and load-bearing axis deviation. Multivariate analyses showed significant associations between TFA and the femoral M/L-BMD ratio (β = 0.434, p < 0.001) and between MAA and the tibial M/L-BMD ratio (β = 0.384, p < 0.001). ConclusionBMD distribution around the knee might be predictable with radiographic parameters such as the TFA for the femur and MAA for the tibia. The findings of this study provide in vivo data on the evaluation of preoperative femoral and tibial M/L-BMD ratios without dual-energy X-ray absorptiometry.

Biomechanical Study of Implant Treatment For Maxillas With Different Bone Quality

Purpose: The purpose of this study is to characterize the effects of the implant treatment on the distribution of the strain energy density in the maxillas using finite element analysis.Methods: Three-dimensional maxillary bone models of a male and a female patient were constructed using their CT-images. The distributions of Young’s modulus were estimated from their bone mineral density distributions. Total six implants were embedded into each of the maxillary models. Finite element analysis of the maxilla models was then performed in order to assess the concentrations of the strain energy density, especially in the vicinity of the embedded implants under the two different loading conditions.Results: In both models, strain energy density was concentrated especially around the right-molar implant, suggesting the outbreak of damage and subsequent absorption of bone tissue in this region. The female model with smaller size and lower bone density exhibited much higher localized concentration of the strain energy density than the male model. Therefore, a modified placement of the right-molar implant was then introduced into the female model and such high concentration was effectively reduced by using the inclined and longer implant.Conclusion: This kind of three-dimensional modeling can clinically be used to predict the optimal implant treatment for each of dental patients.

Correspondence between bone mineral density and intervertebral disc degeneration across age and sex.

While the decline of bone mineral density (BMD) in the aging spine is well established, the extent to which age influences BMD distribution within the vertebra is less clear. Measures of regional BMD (rBMD) may improve predictions of vertebral strength and suggest how vertebrae might adapt with intervertebral disc degeneration. Thus, we aimed to assess how rBMD values were associated with age, sex, and disc height loss (DHL). We measured rBMD in the L3 vertebra of 377 participants from the Framingham Heart Study (41-83years, 181 M/196 F). Integral (Int.BMD) and trabecular BMD (Tb.BMD) were measured from QCT images. rBMD ratios (anterior/posterior, superior/mid-transverse, inferior/mid-transverse, and central/outer) were calculated from the centrum. A radiologist assigned a DHL severity score to adjacent intervertebral discs (L2-L3 and L3-L4). Int.BMD and Tb.BMD were both associated with age, though the decrease across age was greater in women (Int.BMD, - 2.6mg/cm3 per year; Tb.BMD, - 2.6mg/cm3 per year) than men (Int.BMD, - 0.5mg/cm3 per year; Tb.BMD, - 1.2mg/cm3 per year). The central/outer (- 0.027/decade) and superior/mid-transverse (- 0.018/decade) rBMD ratios were negatively associated with age, with similar trends in men and women. Higher Int.BMD or Tb.BMD was associated with increased odds of DHL after adjusting for age and sex. Low central/outer ratio and high anterior/poster and superior/mid-transverse ratios were also associated with increased odds of DHL. Our results indicate that the distribution of bone within the L3 vertebra is different across age, but not between sexes, and is associated with disc degeneration.

DXA Measured Distal Femur Bone Mineral Density in Patients After Total Knee Arthroplasty: Method Development and Reproducibility

Introduction: Total knee arthroplasty (TKA) is increasingly being performed. Distal femur periprosthetic fracture is a potentially catastrophic complication following TKA and existing data document substantial distal femur bone mineral density (BMD) loss following TKA. However, distal femur BMD is virtually never measured clinically as no consensus approach exists. This pilot study's purpose was to define regional BMD variation throughout the femur, suggest standard dual-energy X-ray absorptiometry (DXA) regions of interest (ROIs) and evaluate BMD reproducibility at these ROIs. Methods: Thirty volunteers 2–5 yr post TKA had both entire femurs imaged twice using a Lunar iDXA with subject repositioning between scans; the atypical femur fracture feature of enCORE software was utilized. To define femoral BMD distribution, custom 1 cm ROIs were stacked one atop the other starting at the intercondylar notch and continuing to the base of the lesser trochanter. Femur length was measured with the ruler tool to calculate distance at 5% increments. ROIs encompassing each 5% increment were utilized to measure BMD at each location. Descriptive statistics were used to determine mean BMD at each ROI and reproducibility at the 15%, 25%, 45%, 60%, and 80% ROIs. Results: The 5 and 10% ROIs included prosthetic and/or patella, causing high BMD values. Distal femur BMD was lowest at the 15% ROI and was higher (p < 0.05) at each more proximal ROI to 45%, then plateaued from 45% to 75%. BMD reproducibility at these regions was excellent; coefficient of variation (CV) from ∼1% to 3.5%. As periprosthetic fractures generally occur in the distal femur, we propose measuring femur BMD using ROIs placed at 15% and 25%. A 60% region could also be used as a highly cortical site. Conclusion: Existing DXA capabilities allow distal femur BMD measurement with good reproducibility. Further research using standardized ROIs to assess distal femur BMD loss after TKA, and interventions to mitigate this loss, is indicated.

BMD-based assessment of local porosity in human femoral cortical bone.

Cortical pores are determinants of the elastic properties and of the ultimate strength of bone tissue. An increase of the overall cortical porosity (Ct.Po) as well as the local coalescence of large pores cause an impairment of the mechanical competence of bone. Therefore, Ct.Po represents a relevant target for identifying patients with high fracture risk. However, given their small size, the in vivo imaging of cortical pores remains challenging. The advent of modern high-resolution peripheral quantitative computed tomography (HR-pQCT) triggered new methods for the clinical assessment of Ct.Po at the peripheral skeleton, either by pore segmentation or by exploiting local bone mineral density (BMD). In this work, we compared BMD-based Ct.Po estimates with high-resolution reference values measured by scanning acoustic microscopy. A calibration rule to estimate local Ct.Po from BMD as assessed by HR-pQCT was derived experimentally. Within areas of interest smaller than 0.5 mm2, our model was able to estimate the local Ct.Po with an error of 3.4%. The incorporation of the BMD inhomogeneity and of one parameter from the BMD distribution of the entire scan volume led to a relative reduction of the estimate error of 30%, if compared to an estimate based on the average BMD. When applied to the assessment of Ct.Po within entire cortical bone cross-sections, the proposed BMD-based method had better accuracy than measurements performed with a conventional threshold-based approach.

Sex differences in the spatial distribution of bone in relation to incident hip fracture: Findings from the AGES-Reykjavik study.

In this case-cohort study, we used data-driven computational anatomy approaches to assess within and between sex spatial differences in proximal femoral bone characteristics in relation to incident hip fracture. One hundred male and 234 female incident hip fracture cases, and 1047 randomly selected noncase subcohort participants (562 female) were chosen from the population-based AGES-Reykjavik study (mean age of 77 years). The baseline -i.e. before hip fracture- hip quantitative computed tomography scans of these subjects were analyzed using voxel-based morphometry, tensor-based morphometry, and surface-based statistical parametric mapping to assess the spatial distribution of volumetric bone mineral density (vBMD), internal structure, and cortical bone properties (thickness, vBMD and trabecular vBMD adjacent to the endosteal surface) of the proximal femur, respectively, in relation to incident hip fracture. Results showed that in both men and women: 1) the superior aspect of the femoral neck and the trochanteric region (except for cortical bone thickness) were consistently identified as being associated with incident hip fracture, and 2) differences in bone properties between noncases and incident hip fracture cases followed similar trends, were located at compatible regions, and manifested heterogeneity in the spatial distribution of their magnitude with focal regions showing larger differences. With respect to sex differences, most of the regions with a significant interaction between fracture group and sex showed: 1) differences of greater magnitude in men between noncases and incident hip fracture cases with different spatial distributions for all bone properties with the exception of cortical bone thickness, and 2) that while most of these regions showed better bone quality in male cases than in female cases, female cases showed higher vBMD in the principal compressive group and higher endotrabecular vBMD at several regions including the anterior, posterior, and lateral aspects of the proximal femur. These findings indicate the value of these image analysis techniques by providing unique information about the specific patterns of bone deterioration associated with incident hip fracture and their sex differences, highlighting the importance of looking to men and women separately in the assessment of hip fracture risk.

Late stages of mineralization and their signature on the bone mineral density distribution

ABSTRACTPurpose: Experimental measurements of bone mineral density distributions (BMDDs) enable a determination of secondary mineralization kinetics in bone, but the maximum degree of mineralization and how this maximum is approached remain uncertain. We thus test computationally different hypotheses on late stages of bone mineralization by simulating BMDDs in low-turnover conditions. Materials and methods: An established computational model of the BMDD that accounts for mineralization and remodeling processes was extended to limit mineralization to various maximum calcium capacities of bone. Simulated BMDDs obtained by reducing turnover rate from the reference trabecular BMDD under different assumptions on late stage mineralization kinetics were compared with experimental BMDDs of low-turnover bone. Results: Simulations show that an abrupt stopping of mineralization near a maximum calcium capacity induces a pile-up of minerals in the BMDD statistics that is not observed experimentally. With a smooth decrease of mineralization rate, imposing low maximum calcium capacities helps to match peak location and width of simulated low-turnover BMDDs with peak location and width of experimental BMDDs, but results in a distinctive asymmetric peak shape. No tuning of turnover rate and maximum calcium capacity was able to explain the differences found in experimental BMDDs between trabecular bone (high turnover) and femoral cortical bone (low turnover). Conclusions: Secondary mineralization in human bone does not stop abruptly, but continues slowly up to a calcium content greater than 30 wt% Ca. The similar mineral heterogeneity seen in trabecular and femoral cortical bones at different peak locations was unexplained by the turnover differences tested.

Inter-site variability of the osteocyte lacunar network in the cortical bone underpins fracture susceptibility of the superolateral femoral neck.

The osteocytic lacunar network is considered to be an integral player in the regulation of bone homeostasis, and reduction in osteocytes is associated with reduced bone strength. Here, we analyzed site-specific patterns in osteocyte characteristics and matrix composition in the cortical compartment of the femoral neck to reveal the structural basis of its fragility. Cross-sections of the human femoral neck - one of the most common fracture sites - were acquired from 12 female cadavers (age 34-86 years) and analyzed with backscattered scanning electron microscopy and high-resolution micro-computed tomography (μ-CT). The 2D/3D density and size of the osteocyte lacunae as well as bone mineral density distribution (BMDD) were measured in two regions subject to different biomechanical loads in vivo: the inferomedial (medial) region (habitually highly loaded in compression) and the superolateral (lateral) region (lower habitual loading intensity). Using quantitative polarized light microscopy, collagen fiber orientation was quantified in these two regions, accordingly. In 2D measurements, the inferomedial region displayed lower mineralization heterogeneity, 19% higher osteocyte lacunar density (p = 0.005), but equal lacunar size compared to the superolateral region. 3D measurements confirmed a significantly higher osteocyte lacunar density in the inferomedial region (p = 0.015). Osteocyte lacunar density decreased in aged individuals, and inter-site differences were reduced. Site-specific osteocyte characteristics were not accompanied by changes in collagen fiber orientation. Since osteocyte characteristics may provide valuable insights into bone mechanical competence, the variations in osteocyte properties might reflect the increased fracture susceptibility of the superolateral neck.

Mutations That Alter the Carboxy-Terminal-Propeptide Cleavage Site of the Chains of Type I Procollagen Are Associated With a Unique Osteogenesis Imperfecta Phenotype

Osteogenesis imperfecta (OI) is a genetic bone disorder characterized by fractures, low bone mass, and skeletal fragility. It most commonly arises from dominantly inherited mutations in the genes COL1A1 and COL1A2 that encode the chains of type I collagen. A number of recent reports have suggested that mutations affecting the carboxyl-terminal propeptide cleavage site in the products of either COL1A1 or COL1A2 give rise to a form of OI characterized by unusually dense bones. We have assembled clinical, biochemical, and molecular data from 29 individuals from 8 families with 7 different mutations affecting the C-propeptide cleavage site. The phenotype was generally mild: The median height was ∼33th centile. Eighty percent of subjects had their first fracture by the age of 10 years, and one-third had a femoral or tibial fracture by the age of 25 years. Fractures continued into adulthood, though rates varied considerably. Healing was normal and rarely resulted in long bone deformity. One-third of subjects older than 15 years had scoliosis. The teeth and hearing were normal in most, and blue sclerae were not observed. Other features noted included fibro-osseous dysplasia of the mandible and Achilles tendon calcification. The mean spinal bone mineral density Z-score was +2.9 (SD 2.1) compared with -2.2 (0.7) in subjects with COL1A1 haploinsufficiency mutations. Bone mineral density distribution, assessed by quantitative backscattered electron imaging in bone showed higher levels of mineralization than found in any other disorder. Bone histology showed high trabecular volume and increased cortical thickness, with hyperosteoidosis and delayed mineralization. In vitro studies with cultured skin fibroblasts suggested that these mutations interfere with processing of the chain in which the sequence alteration occurs, but the C-propeptide is eventually cleaved (and detectable in blood), suggesting there are alternative sites of cleavage. The precise mechanism of the bony pathology is not yet clear. © 2018 American Society for Bone and Mineral Research.

Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome

According to reports from small-sized case series, adults with Down syndrome (DS) appear to have lower bone mineral density (BMD) than the general population. The objective of our study was to further characterize the bone mass acquisition curve in an adult DS population. This is a retrospective study of 297 adults with DS from the Adult Down Syndrome Outpatient Clinic of a tertiary care hospital in Madrid, Spain, who underwent a bone densitometry (Hologic QDR-4500W), for clinical purposes between January 2010 and June 2015. The mean age of our sample population was 34 yr (±10.9); 51% were women. Bone mass peak was reached earlier and was lower than the general population (around 20–25 yr), with almost parallel curves. The mean BMD was 0.715 ± 0.12 g/cm2 in femoral neck (FN) and 0.872 ± 0.11 g/cm2 in lumbar spine (LS). According to FN scores, 52% of the subjects were classified as osteopenic and 18% as osteoporotic. According to LS scores, frequencies were 54% and 25%, respectively. BMD was considered inadequate for the age (Z-score < −2 standard deviation) in 18% of the subjects at FN and 40% at LS. BMD at LS was significantly lower in males than in females (52% vs 38%, p < 0.001). Male DS subjects had a 2.58-fold (95% confidence interval: 1.57–4.25) higher risk of developing reduced BMD at LS than females. Persons with DS reach the bone mass peak earlier and this bone mass is lower than the general population. Among subjects with DS, male gender is a risk factor for developing low BMD, especially at LS.

Modeling and simulation of bone mineral density in Japanese osteoporosis patients treated with zoledronic acid using tartrate-resistant acid phosphatase 5b, a bone resorption marker

SummaryAnnual intravenous administration of zoledronic acid is used in the treatment of osteoporosis. A mathematical model was developed to predict bone mineral density up to 2 years after two annual doses of zoledronic acid from the early values of a bone resorption marker in osteoporosis patients.IntroductionThe measurement of bone mineral density (BMD) has been used as a surrogate marker instead of the observation of incident fractures to detect the efficacy of treatment. However, this method requires a long time to obtain significant changes. On the other hand, bone resorption markers respond to bone resorption inhibitors within a few weeks. Therefore, the aim of this study was to develop a mathematical model predicting long-term BMD after two annual doses of zoledronic acid (ZOL) using the early response of a bone resorption marker in osteoporosis patients.MethodsThe model was constructed using 3410 tartrate-resistant acid phosphatase 5b (TRACP-5b) serum concentrations and 1146 lumbar spine (L2-L4) BMD values from 306 patients with primary osteoporosis. A mathematical model was developed to describe the time-dependent profiles of TRACP-5b and BMD.ResultsThe percentage changes from baseline of the BMD (%BMD) at up to 2 years were predicted from patients’ baseline BMD and baseline and 12-week TRACP-5b values by the model obtained. The simulated 90% prediction interval almost covered the observed %BMD distribution at each time point, and the predictions were comparable to the observed %BMD.ConclusionsThis is the first model to predict BMD for up to 2 years following two annual doses of ZOL using patients’ background characteristics and the early response of TRACP-5b. This model allows us to inform patients at the initial stage of ZOL treatment of their predicted response to treatment.

Graphene Oxide Laser Printing for Controlled STEM Cells Differentiation and Antibacterial Effects

Graphene and Graphene oxide (GO) are capable of inducing stem cells differentiation into bone tissue with variable efficacy depending on reductive state of the material. Thus, controlling the oxidative state of the GO it is possible, in principle, to modulate the osteogenic process and the bone mineral density distribution. In this study, we laser-printed GO surfaces in order to obtain both a local photo/thermal GO reduction and the formation of nano-wrinkles along precise geometric pattern. Calvarial-derived Mesenchimal Stem cells (CMSC) were isolated in primary culture from skull calvarial fragments and their behaviour was characterized on GO patterns. Initially, after cells adhesion on the surface, stem cells migrated and accumulated on the reduced/wrinkled surface. When the local density of the stem cells on the reduced stripes was high, cells started to proliferate and occupy the oxidized/flat area. The designed surfaces morphology guided stem cell orientation and the reduction accelerated differentiation. Furthermore, the reduced nano-wrinkles greatly inhibited the growth of S. aureus. We propose a promising laser-printing technology for tissue engineering and regenerative medicine, based on graphene to enhance cell growth and differentiation in a controlled way. We show that by adjusting the laser emission is possible to finely tune the GO reduction and shape substrate landscape to spatially control bone regeneration and microbial infection. This strategy can offer a revolution in present and future trends of medicine and surgery.

Analysis of effect of 1α-hydroxyvitamin D3 on benign paroxysmal positional vertigo and risk factors.

The purpose of this study was to investigate the curative effect of 1α-hydroxyvitamin D3 on the benign paroxysmal positional vertigo (BPPV). Fifty BPPV patients diagnosed in the ENT Department of Anzhen Hospital from October 2015 to December 2016 were randomly selected as the treatment group, and treated with 0.25 µg 1α-hydroxyvitamin D3 once per day, in addition to the routine diagnosis and treatment. Moreover, 50 BPPV patients in the same period were selected as the control group, and received the routine diagnosis and treatment. The detection results of bone mineral density (BMD) t-value, vitamin D3 and bone metabolic markers before and after treatment were compared, and statistical analysis was performed on the results. There were no differences in the general data between treatment group and control group. There were no statistically significant differences in the BMD and age distribution of males and females between treatment group and control group (P>0.05). The BMD of male BPPV patients in each age group in the treatment group was significantly increased after treatment, and the difference was statistically significant (P<0.05). Although the BMD of male BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The BMD of female BPPV patients in each age group in treatment group was increased after treatment, and the difference was statistically significant (P<0.05). Similarly, although the BMD of female BPPV patients in each age group in control group was somewhat increased after treatment, the difference was not statistically significant (P>0.05). The average BMD of female BPPV patients in each age group was significantly lower than that of male patients, and the difference was statistically significant (P<0.05) (Table II). The BMD t-value of patients in treatment group showed a decreasing trend with the increase of age (Fig. 1). The levels of 25-hydroxyvitamin D3 and bone metabolic markers in treatment group were significantly improved compared with those before treatment (P<0.05). Multivariate Logistic regression analysis was performed to identify whether the treatment of BPPV was effective or not as a dependent variable, and six items, including the sex (female), hypertension, diabetes mellitus, age (>50 years), 25-hydroxyvitamin D3 and osteopenia/osteoporosis, as the independent variables, and the results suggested that the level of 25-hydroxyvitamin D3 and osteopenia/osteoporosis are the clinical features of whether the BPPV treatment is effective (P<0.05). The results showed that the treatment of BPPV with 1α-hydroxyvitamin D3 can effectively improve the symptoms of patients, and the level of vitamin D3 and the occurrence of osteopenia/osteoporosis are the clinical indexes of whether the BPPV treatment is effective.

The influence of osteoporotic bone structures of the pelvic-hip complex on stress distribution under impact load.

The aim of this study was to determine the effect of bone mineral density (BMD) on the stress distribution in pelvic-hip complex (PHC) model which included bone structures and soft tissues. Bone mass changes in osteoporosis and osteopenia were considered in this analysis. In addition, the relations between force direction and stress distribution causing PHC fractures were determined. This paper presents the development and validation of a detailed 3D finite element model with high anatomical fidelity of the PHC and BMD changes in trabecular and cortical bones, modelled based on CT scans. 10 kN loading was induced on a model consisting of 8 ligaments, the pelvis, sacrum, femur in front and side directions. For validation, the results of this model were compared to physiological stress in standing position and previous results with high-energy crashes under side impact load. Analysis of side-impact indicated the influence of BMD on femoral neck fractures, acetabular cartilage and sacroiliac joint delaminations. Front-impact analysis revealed the inferior pubic ramus, femoral neck fractures and soft tissue injuries, i.e., acetabular cartilage and symphysis pubis in osteoporosis and osteopenia. The elaborated PHC model enables effective prediction of pelvis injuries in high-energy trauma, according to Young-Burgess classification, and the determination of the influence of BMD reduction on pelvis trauma depending on force direction. The correlation between BMD and stress distribution causing varying injuries was determined.

Reduction and shaping of graphene-oxide by laser-printing for controlled bone tissue regeneration and bacterial killing

Graphene and graphene oxide (GO) are capable of inducing stem cells differentiation into bone tissue with variable efficacy depending on reductive state of the material. Thus, modulation of osteogenic process and of bone mineral density distribution is theoretically possible by controlling the GO oxidative state. In this study, we laser-printed GO surfaces in order to obtain both a local photo-thermal GO reduction and the formation of nano-wrinkles along precise geometric pattern. Initially, after cells adhered on the surface, stem cells migrated and accumulated on the reduced and wrinkled surface. When the local density of the stem cells on the reduced stripes was high, cells started to proliferate and occupy the oxidized/flat area. The designed surfaces morphology guided stem cell orientation and the reduction accelerated differentiation. Furthermore the reduced sharp nano-wrinkles were able to enhance the GO antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), a common cause of prosthetic joints infections. This strategy can offer a revolution in present and future trends of scaffolds design for regenerative medicine.

Decrease in Local Volumetric Bone Mineral Density in Osteoarthritic Joints Is Associated with the Increase in Cartilage Damage: A Peripheral Quantitative CT Study

Osteoarthritis (OA) is the most common type of arthritis and a major cause of disability in the adult population. It affects both cartilage and subchondral bone in the joints. There has been some progress in understanding the changes in subchondral bone with progression of osteoarthritis. However, local changes in subchondral bone such as microstructure or volumetric bone mineral density in connection with the defect in cartilage are relatively unexplored. To develop an effective treatment for progression of OA, it is important to understand how the physical environment provided by the subchondral bone affects the overlying cartilage. In this study we examined the volumetric bone mineral density (vBMD) distribution in the osteoarthritic joint tissues obtained from total hip replacement surgeries due to osteoarthritis, using peripheral quantitative CT (pQCT). It was found that there is a significant decrease in volumetric bone mineral density, which co-localises with the damage in the overlying cartilage. This was not limited to the subchondral bone immediately adjacent to the cartilage defect but continued in the layers below. Bone resorption and cyst formation in the OA tissues were also detected. We observed that the bone surrounding subchondral bone cysts exhibited much higher volumetric bone mineral density than that of the surrounding bones. PQCT was able to detect significant changes in vBMD between OA and non-OA samples, as well as between areas of different cartilage degeneration, which points to its potential as a technique for detection of early OA.

Explicit expressions for the estimation of the elastic constants of lamellar bone as a function of the volumetric mineral content using a multi-scale approach

In this work, explicit expressions to estimate all the transversely isotropic elastic constants of lamellar bone as a function of the volumetric bone mineral density (BMD) are provided. The methodology presented is based on the direct homogenization procedure using the finite element method, the continuum approach based on the Hill bounds, the least-square method and the mean field technique. Firstly, a detailed description of the volumetric content of the different components of bone is provided. The parameters defined in this step are related to the volumetric BMD considering that bone mineralization process occurs at the smallest scale length of the bone tissue. Then, a thorough description provides the details of the numerical models and the assumptions adopted to estimate the elastic behaviour of the forward scale lengths. The results highlight the noticeable influence of the BMD on the elastic modulus of lamellar bone. Power law regressions fit the Young's moduli, shear stiffness moduli and Poisson ratios. In addition, the explicit expressions obtained are applied to the estimation of the elastic constants of cortical bone. At this scale length, a representative unit cell of cortical bone is analysed including the fibril orientation pattern given by Wagermaier et al. (Biointerphases 1:1-5, 2006) and the BMD distributions observed by Granke et al. (PLoS One 8:e58043, 2012) for the osteon. Results confirm that fibril orientation arrangement governs the anisotropic behaviour of cortical bone instead of the BMD distribution. The novel explicit expressions obtained in this work can be used for improving the accuracy of bone fracture risk assessment.

The Canadian HIV and aging cohort study - determinants of increased risk of cardio-vascular diseases in HIV-infected individuals: rationale and study protocol

BackgroundWith potent antiretroviral drugs, HIV infection is becoming a chronic disease. Emergence of comorbidities, particularly cardiovascular disease (CVD) has become a leading concern for patients living with the infection. We hypothesized that the chronic and persistent inflammation and immune activation associated with HIV disease leads to accelerated aging, characterized by CVD. This will translate into higher incidence rates of CVD in HIV infected participants, when compared to HIV negative participants, after adjustment for traditional CVD risk factors. When characterized further using cardiovascular imaging, biomarkers, immunological and genetic profiles, CVD associated with HIV will show different characteristics compared to CVD in HIV-negative individuals.Methods/designThe Canadian HIV and Aging cohort is a prospective, controlled cohort study funded by the Canadian Institutes of Health Research. It will recruit patients living with HIV who are aged 40 years or older or have lived with HIV for 15 years or more. A control population, frequency matched for age, sex, and smoking status, will be recruited from the general population. Patients will attend study visits at baseline, year 1, 2, 5 and 8. At each study visit, data on complete medical and pharmaceutical history will be captured, along with anthropometric measures, a complete physical examination, routine blood tests and electrocardiogram. Consenting participants will also contribute blood samples to a research biobank. The primary outcome is incidence of a composite of: myocardial infarction, coronary revascularization, stroke, hospitalization for angina or congestive heart failure, revascularization or amputation for peripheral artery disease, or cardiovascular death. Preplanned secondary outcomes are all-cause mortality, incidence of the metabolic syndrome, incidence of type 2 diabetes, incidence of renal failure, incidence of abnormal bone mineral density and body fat distribution. Patients participating to the cohort will be eligible to be enrolled in four pre-planned sub-studies of cardiovascular imaging, glucose metabolism, immunological and genetic risk profile.DiscussionThe Canadian HIV and Aging Cohort will provide insights on pathophysiological pathways leading to premature CVD for patients living with HIV.

A NEW METHOD TO DETERMINE VOLUMETRIC BONE MINERAL DENSITY FROM BI-PLANAR DUAL ENERGY RADIOGRAPHS USING A FINITE ELEMENT MODEL: AN EX-VIVO STUDY

Finite element models (FEMs) derived from QCT-scans were developed to evaluate vertebral strength but QCT scanners limitations are restrictive for routine osteoporotic diagnosis. A new approach considers using bi-planar dual energy (BP2E) X-rays absorptiometry to build vertebral FEM. The purpose was to propose a FEM based on BP2E absorptiometry and to compare the vertebral strength predicted from this model to a QCT-based FEM. About 46 vertebrae were QCT scanned and imaged with BP2E X-rays. Subject-specific vertebral geometry and bone material properties were obtained from both medical imaging techniques to build FEM for each vertebra. Vertebral body volumetric bone mineral density (vBMD) distribution and vertebral strength prediction from the BP2E-based FEM and the QCT-based FEM were compared. A statistical error of 7[Formula: see text]mg/cm3 with a RMSE of 9.6% and a [Formula: see text] of 0.83 were found in the vBMD distribution differences between the BP2E-based and qCT-based FEM. The average vertebral strength was 3321[Formula: see text][Formula: see text] and 3768[Formula: see text][Formula: see text] for the qCT-based and BP2E-based FEM, respectively, with a RMSE of 641[Formula: see text]N and [Formula: see text] of 0.92. This method was developed to estimate vBMD distribution in lumbar vertebrae from a pair of 2D-BMD images and demonstrated to be accurate to personalize the mechanical properties in vitro.

Method and Instrumented Fixture for Femoral Fracture Testing in a Sideways Fall-on-the-Hip Position.

Mechanical testing of femora brings valuable insights into understanding the contribution of clinically-measureable variables such as bone mineral density distribution and geometry on the femoral mechanical properties. Currently, there is no standard protocol for mechanical testing of such geometrically complex bones to measure strength, and stiffness. To address this gap we have developed a protocol to test cadaveric femora to fracture and to measure their biomechanical parameters. This protocol describes a set of adaptable fixtures to accommodate the various load magnitudes and directions accounting for possible bone orientations in a fall on the hip configuration, test speed, bone size, and left leg-right leg variations. The femora were prepared for testing by cleaning, cutting, scanning, and potting the distal end and greater trochanter contact surfaces in poly(methyl methacrylate) (PMMA) as presented in a different protocol. The prepared specimens were placed in the testing fixture in a position mimicking a sideways fall on the hip and loaded to fracture. During testing, two load cells measured vertical forces applied to the femoral head and greater trochanter, a six-axis load cell measured forces and moments at the distal femoral shaft, and a displacement sensor measured differential displacement between the femoral head and trochanter contact supports. High speed video cameras were used to synchronously record the sequence of fracture events during testing. The reduction of this data allowed us to characterize the strength, stiffness, and fracture energy for nearly 200 osteoporotic, osteopenic, and normal cadaveric femora for further development of engineering-based diagnostic tools for osteoporosis research.