Quantitative Computed Tomography Scans Research Articles

The effect of in situ/in vitro three-dimensional quantitative computed tomography image voxel size on the finite element model of human vertebral cancellous bone.

Quantitative computed tomography-based finite element modeling technique is a promising clinical tool for the prediction of bone strength. However, quantitative computed tomography-based finite element models were created from image datasets with different image voxel sizes. The aim of this study was to investigate whether there is an influence of image voxel size on the finite element models. In all 12 thoracolumbar vertebrae were scanned prior to autopsy (in situ) using two different quantitative computed tomography scan protocols, which resulted in image datasets with two different voxel sizes (0.29 × 0.29 × 1.3 mm(3) vs 0.18 × 0.18 × 0.6 mm(3)). Eight of them were scanned after autopsy (in vitro) and the datasets were reconstructed with two voxel sizes (0.32 × 0.32 × 0.6 mm(3) vs. 0.18 × 0.18 × 0.3 mm(3)). Finite element models with cuboid volume of interest extracted from the vertebral cancellous part were created and inhomogeneous bilinear bone properties were defined. Axial compression was simulated. No effect of voxel size was detected on the apparent bone mineral density for both the in situ and in vitro cases. However, the apparent modulus and yield strength showed significant differences in the two voxel size group pairs (in situ and in vitro). In conclusion, the image voxel size may have to be considered when the finite element voxel modeling technique is used in clinical applications.

Quantitative computed tomography-based finite element analysis predictions of femoral strength and stiffness depend on computed tomography settings

The aim of the present study was to compare proximal femur strength and stiffness obtained experimentally with estimations from Finite Element Analysis (FEA) models derived from Quantitative Computed Tomography (QCT) scans acquired at two different scanner settings. QCT/FEA models could potentially aid in diagnosis and treatment of osteoporosis but several drawbacks still limit their predictive ability. One potential reason is that the models are still sensitive to scanner settings which could lead to changes in assigned material properties, thus limiting their results accuracy and clinical effectiveness. To find the mechanical properties we fracture tested 44 proximal femora in a sideways fall-on-the-hip configuration. Before testing, we CT scanned all femora twice, first at high resolution scanner settings, and second at low resolution scanner settings and built 88 QCT/FEA models of femoral strength and stiffness. The femoral set neck bone mineral density, as measured by DXA, uniformly covered the range from osteoporotic to normal. This study showed that the femoral strength and stiffness values predicted from high and low resolution scans were significantly different (p<0.0001). Strength estimated from high resolution QCT scans was larger for osteoporotic, but smaller for normal and osteopenic femora when compared to low resolution scans. In addition, stiffness estimated from high resolution scans was consistently larger than stiffness obtained from low resolution scans over the entire femoral dataset. While QCT/FEA techniques hold promise for use in clinical settings we provided evidence that further improvements are required to increase robustness in their predictive power under different scanner settings and modeling assumptions.

Different Tools for the Assessment of Bone Mass among Egyptian Adults

BACKGROUND: Several tools such as, dual X-ray absorptiometry (DXA), quantitative computed tomography (QCT) and self-assessment tool (OST), are being used for diagnosis of osteoporosis. OBJECTIVE: to compare the sensitivity and specify detection rate of bone mineral density (BMD) changes for DXA versus QCT and OST among a sample of Egyptian adults of both sexes. SUBJECTS AND METHODS: This study is a cross sectional one, which included 62 Egyptians, aged 20-65 years. Each individual was assessed for BMD using DXA at femur and spine sites; QCT and OST which take into account body weight and age. Accordingly they were diagnosed as either osteoporotic/osteopenic or normal. RESULTS: The highest prevalence of osteopenia or osteoporosis was diagnosed among menopause women. DXA at femur has diagnosed more cases of osteoporosis (both osteopenic and osteoporotic) as compared to spine DXA or QCT, but OST is out of rang; as it failed to diagnose any case. CONCLUSION: DXA has been found to be more efficacious than QCT scan in the diagnosis of osteoporosis. DXA in femur is better than DXA-spine and QCT. Generally, DXA is the gold standard when assessing osteoporosis. Further studies are needed to modify the equation of OST and confirm its efficiency in Egyptians population.

Additive effect of anti-citrullinated protein antibodies and rheumatoid factor on bone erosions in patients with RA

ObjectiveTo determine whether there is an additive effect of anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF) on the number and size of bone erosions in patients with rheumatoid arthritis...

Reproducibility of a peripheral quantitative computed tomography scan protocol to measure the material properties of the second metatarsal.

BackgroundPeripheral quantitative computed tomography (pQCT) is an established technology that allows for the measurement of the material properties of bone. Alterations to bone architecture are associated with an increased risk of fracture. Further pQCT research is necessary to identify regions of interest that are prone to fracture risk in people with chronic diseases. The second metatarsal is a common site for the development of insufficiency fractures, and as such the aim of this study was to assess the reproducibility of a novel scanning protocol of the second metatarsal using pQCT.MethodsEleven embalmed cadaveric leg specimens were scanned six times; three times with and without repositioning. Each foot was positioned on a custom-designed acrylic foot plate to permit unimpeded scans of the region of interest. Sixty-six scans were obtained at 15% (distal) and 50% (mid shaft) of the second metatarsal. Voxel size and scan speed were reduced to 0.40 mm and 25 mm.sec-1. The reference line was positioned at the most distal portion of the 2nd metatarsal. Repeated measurements of six key variables related to bone properties were subject to reproducibility testing. Data were log transformed and reproducibility of scans were assessed using intraclass correlation coefficients (ICC) and coefficients of variation (CV%).ResultsReproducibility of the measurements without repositioning were estimated as: trabecular area (ICC 0.95; CV% 2.4), trabecular density (ICC 0.98; CV% 3.0), Strength Strain Index (SSI) - distal (ICC 0.99; CV% 5.6), cortical area (ICC 1.0; CV% 1.5), cortical density (ICC 0.99; CV% 0.1), SSI – mid shaft (ICC 1.0; CV% 2.4). Reproducibility of the measurements after repositioning were estimated as: trabecular area (ICC 0.96; CV% 2.4), trabecular density (ICC 0.98; CV% 2.8), SSI - distal (ICC 1.0; CV% 3.5), cortical area (ICC 0.99; CV%2.4), cortical density (ICC 0.98; CV% 0.8), SSI – mid shaft (ICC 0.99; CV% 3.2).ConclusionsThe scanning protocol generated excellent reproducibility for key bone properties measured at the distal and mid-shaft regions of the 2nd metatarsal. This protocol extends the capabilities of pQCT to evaluate bone quality in people who may be at an increased risk of metatarsal insufficiency fractures.

Improving Reliability of pQCT-Derived Muscle Area and Density Measures Using a Watershed Algorithm for Muscle and Fat Segmentation

In peripheral quantitative computed tomography scans of the calf muscles, segmentation of muscles from subcutaneous fat is challenged by muscle fat infiltration. Threshold-based edge detection segmentation by manufacturer software fails when muscle boundaries are not smooth. This study compared the test-retest precision error for muscle-fat segmentation using the threshold-based edge detection method vs manual segmentation guided by the watershed algorithm. Three clinical populations were investigated: younger adults, older adults, and adults with spinal cord injury (SCI). The watershed segmentation method yielded lower precision error (1.18%–2.01%) and higher (p < 0.001) muscle density values (70.2 ± 9.2 mg/cm3) compared with threshold-based edge detection segmentation (1.77%–4.06% error, 67.4 ± 10.3 mg/cm3). This was particularly true for adults with SCI (precision error improved by 1.56% and 2.64% for muscle area and density, respectively). However, both methods still provided acceptable precision with error well under 5%. Bland-Altman analyses showed that the major discrepancies between the segmentation methods were found mostly among participants with SCI where more muscle fat infiltration was present. When examining a population where fatty infiltration into muscle is expected, the watershed algorithm is recommended for muscle density and area measurement to enable the detection of smaller change effect sizes.

Influence of 3D QCT scan protocol on the QCT-based finite element models of human vertebral cancellous bone

Quantitative computed tomography (QCT)-based finite element (FE) models provide a better prediction of vertebral strength than dual-energy X-ray absorptiometry. However, FE models are often created from datasets acquired at different CT scan protocols and it is unclear whether this influences the FE results. The aim of this paper was to investigate whether there was an effect of the CT scan protocol on the FE models. 12 human thoracolumbar vertebrae were scanned on top of a calcium hydroxyapatite calibration phantom using a standard QCT scan protocol – 120kV, 100mAs (PA); and a low dose protocol – 90kV, 150mAs (PB). FE cancellous models with cuboid volume of interest and inhomogeneous nonlinear bone properties were created. Axial compression was simulated. The apparent BMD, modulus and yield strength showed significant differences between the two scan protocols. The apparent BMD, the modulus and yield strength between the two groups were highly linearly correlated. This paper indicated that the FE models created from image datasets acquired at different X-ray tube voltage settings would give significantly different results and this effect could be possibly corrected using a linear correction approach.

Metaphyseal Screw Augmentation of the LISS-PLT Plate With Polymethylmethacrylate Improves Angular Stability in Osteoporotic Proximal Third Tibial Fractures

The incidence of osteoporotic proximal tibial fractures has increased during the last 2 decades. A promising approach in osteoporotic fracture fixation is polymethylmethacrylate-based cement augmentation of implants to gain better implant purchase in the bone. This study investigates the biomechanical benefits of screw augmentation in less invasive stabilization system-proximal lateral tibial (LISS-PLT) plates in cadaveric extraarticular comminuted proximal tibial fractures (OTA-41-A3.3). Standardized extraarticular proximal tibial fractures were stabilized with the LISS-PLT plate in 6 paired osteoporotic cadaveric tibiae. Bone mineral density was measured with high-resolution, quantitative computed tomography scans to identify bone quality. In the augmented group, the 5 proximal screws of the LISS-PLT plate were augmented with 1 mL of bone cement each, whereas the contralateral tibia was instrumented conventionally as the control. Cyclic axial loading was applied to each specimen with a starting load of 150 N, using a ramp of 0.05 N per cycle to 10-mm axial displacement. Varus displacement was identified from anterior-posterior radiographs. Bone mineral density showed no significant difference between the 2 groups (P = 0.47). The nonaugmented group reached 9417 load cycles (SD 753) until failure, compared with 14,792 load cycles (SD 2088) in the augmented group (P = 0.002). In the early-onset failure (deformation at 8250 load cycles), varus displacement was significantly smaller in the augmented group (0.46 degrees, SD 0.6) than in the nonaugmented group (3.23 degrees, SD 1.7) (P = 0.01). This biomechanical study showed that cement augmentation of the LISS-PLT plate screws in osteoporotic proximal extraarticular tibial fractures significantly lowers the propensity toward screw migration and secondary varus displacement.

Major depressive disorder and bone mass in adolescents and young adults.

Depression has been associated with reduced bone mass in adults, but the mechanisms remain unclear. In addition, little is known about the association between depression and bone health during growth and development. To address this knowledge gap, we examined bone density and structure in 222 adolescents and young adults (69% females, mean ± SD age: 19.0 ± 1.5 years), enrolled within 1 month of starting a selective serotonin reuptake inhibitor (SSRI) or unmedicated. Psychiatric functioning was assessed with self-report and researcher-administered instruments, including the Longitudinal Interval Follow-up Evaluation for Adolescents (A-LIFE). Anthropometric and laboratory measures included dual-energy x-ray absorptiometry and peripheral quantitative computed tomography scans. Linear multivariable regression analysis tested the association between depression and bone mass, after accounting for relevant confounders. The presence of current depression was associated with a significant reduction in age-sex-height-race-specific bone mineral density (BMD) and content (BMC) of total body less head and lumbar spine. The findings varied by assessment method with self-report scales, capturing symptom severity over the prior week or two, yielding the weakest associations. Depression was also associated with reduced cortical thickness and a trend for increased endosteal circumference. In contrast, generalized anxiety disorder was not associated with bone deficits. In sum, depressive illness is associated with significantly lower bone mass in youths. Future investigations must examine whether bone recovery is possible following depression remission or whether remedial interventions are warranted to optimize bone mass in order to minimize the long-term risk of osteoporosis.

The Influence of Proximal Anchors on the Risk of Proximal Junctional Fracture in the Osteoporotic Spine

Biomechanical comparison of the risk of proximal junctional fracture (PJF) after multilevel spinal instrumentation using pedicle screws or transverse process hooks on the top of a pedicle screw construct. To compare the loads leading to PJF when using pedicle screws or transverse process hooks at the proximal level after multilevel spinal instrumentation using pedicle screws. With stronger spinal fixation techniques, there is increased risk of PJF, especially in the osteoporotic spine. The use of transverse process hooks over pedicle screws at the proximal level of multilevel pedicle screw constructs has been proposed to decrease the incidence of PJF. However, there is no biomechanical study evaluating this concept. Twenty-four segments of 4 vertebrae from 6 human cadaveric spines were evaluated after instrumentation of the distal 3 vertebrae using pedicle screws, except at the top of the construct where either pedicle screws (AP group) or transverse process hooks (PTPH group) were placed. The proximal vertebra was left uninstrumented. Quantitative computed tomography scan was used before instrumentation in order to assess the bone density for each specimen. Cyclic compression loading between 50 and 1000 N at 1 Hz was applied to each of 24 instrumented spinal segments until obtaining a PJF. Bone density was similar between the AP and PTPH groups. A PJF occurred in 22 of 24 tested specimens. The number of cycles required to produce the PJF ranged between 2 and 1002. The number of cycles required to produce the PJF was similar between the AP construct group (median: 3; interquartile range: 3-7) and the PTPH construct group (median: 4; interquartile range: 3-5). The current study failed to observe a significant impact of using transverse process hooks over pedicle screws on top of multilevel pedicle screw construct to decrease the risk of PJF.

Kyphosis and paraspinal muscle composition in older men: a cross-sectional study for the osteoporotic fractures in men (MrOS) research group

BackgroundThe prevalence of hyperkyphosis is increased in older men; however, risk factors other than age and vertebral fractures are not well established. We previously reported that poor paraspinal muscle composition contributes to more severe kyphosis in a cohort of both older men and women.MethodsTo specifically evaluate this association in older men, we conducted a cross-sectional study to evaluate the association of paraspinal muscle composition and degree of thoracic kyphosis in an analytic cohort of 475 randomly selected participants from the Osteoporotic Fractures in Men (MrOS) study with baseline abdominal quantitative computed tomography (QCT) scans and plain thoracic radiographs. Baseline abdominal QCT scans were used to obtain abdominal body composition measurements of paraspinal muscle and adipose tissue distribution. Supine lateral spine radiographs were used to measure Cobb angle of kyphosis. We examined the linear association of muscle volume, fat volume and kyphosis using loess plots. Multivariate linear models were used to investigate the association between muscle and kyphosis using total muscle volume, as well as individual components of the total muscle volume, including adipose and muscle compartments alone, controlling for age, height, vertebral fractures, and total hip bone mineral density (BMD). We examined these associations among those with no prevalent vertebral fracture and those with BMI < 30 kg/m2.ResultsAmong men in the analytic cohort, means (SD) were 74 (SD = 5.9) years for age, and 37.5 (SD = 11.9) degrees for Cobb angle of kyphosis. Men in the lowest tertile of total paraspinal muscle volume had greater mean Cobb angle than men in the highest tertile, although test of linear trend across tertiles did not reach statistical significance. Neither lower paraspinal skeletal muscle volume (p-trend = 0.08), or IMAT (p-trend = 0.96) was associated with greater kyphosis. Results were similar among those with no prevalent vertebral fractures. However, among men with BMI < 30 kg/m2, those in the lowest tertile of paraspinal muscle volume had greater adjusted mean kyphosis (40.0, 95% CI: 37.8 – 42.1) compared to the highest tertile (36.3, 95% CI: 34.2 – 38.4).ConclusionsThese results suggest that differences in body composition may potentially influence kyphosis.

Delving into disability in Crohn's disease: Dysregulation of molecular pathways may explain skeletal muscle loss in Crohn's disease

Background/aimsIn Crohn's disease (CD), skeletal muscle mass and function are reduced compared to healthy controls, potentially resulting in disability. Mechanisms contributing to muscle impairment, and thus potential therapeutic targets, are poorly understood. This study aimed to measure and compare skeletal muscle size and molecular targets involved in skeletal muscle growth, in CD subjects and healthy controls. MethodsCD (n=27) and healthy (n=22) subjects were recruited from the IBD outpatient clinic and via local advertisement respectively. Demographics and clinical data were collected via survey and interview. Quadriceps muscle cross-sectional area was measured using peripheral quantitative CT scanning. Levels of muscle hypertrophy and atrophy signalling targets using quantitative PCR and western blotting were measured in muscle biopsies. ResultsMuscle size was 14% lower (p=0.055) and a 54% lower phosphorylated:total (p:t) Akt ratio was measured in the muscle samples (p<0.05), indicating an attenuated muscle hypertrophy pathway in CD compared with controls. In those with CD, a lower p:t Akt ratio (<0.97) was associated with lower serum vitamin D3, lower physical activity indices (49 vs 64mmol/L, 1.7 vs 2.2×106 accelerometer counts respectively, each p<0.05) and a trend towards lower serum ferritin levels (128 vs 322mg/L, p=0.07), compared with CD subjects with normal/high p:t Akt ratios. ConclusionThe reduced muscle mass in CD may be explained, in part, by impaired activation of muscle protein synthesis pathways, notably the IGF1–Akt pathway. Normal vitamin D levels and regular exercise may be protective in CD against this trend, though confirmatory longitudinal studies are needed.

Moderate exercise during pregnancy in Wistar rats alters bone and body composition of the adult offspring in a sex-dependent manner.

Exercise during pregnancy may have long-lasting effects on offspring health. Musculoskeletal growth and development, metabolism, and later-life disease risk can all be impacted by the maternal environment during pregnancy. The skeleton influences glucose handling through the actions of the bone-derived hormone osteocalcin. The purpose of this study was to test the effects of moderate maternal exercise during pregnancy on the bone and body composition of the offspring in adult life, and to investigate the role of osteocalcin in these effects. Groups of pregnant Wistar rats either performed bipedal standing exercise to obtain food/water throughout gestation but not lactation, or were fed conventionally. Litters were reduced to 8/dam and pups were raised to maturity under control conditions. Whole body dual-energy x-ray absorptiometry, and ex vivo peripheral quantitative computed tomography scans of the right tibia were performed. At study termination blood and tissue samples were collected. Serum concentrations of fully and undercarboxylated osteocalcin were measured, and the relative expression levels of osteocalcin, insulin receptor, Forkhead box transcription factor O1, and osteotesticular protein tyrosine phosphatase mRNA were quantified. Body mass did not differ between the offspring of exercised and control dams, but the male offspring of exercised dams had a greater % fat and lower % lean than controls (p=0.001 and p=0.0008, respectively). At the mid-tibial diaphysis, offspring of exercised dams had a lower volumetric bone mineral density than controls (p=0.01) and in the male offspring of exercised dams the bone: muscle relationship was fundamentally altered. Serum concentrations of undercarboxylated osteocalcin were significantly greater in the male offspring of exercised dams than in controls (p=0.02); however, the relative expression of the measured genes did not differ between groups. These results suggest that moderate exercise during pregnancy can result in lasting changes to the musculoskeletal system and adiposity in offspring, in a sex-specific manner.

Differing effects of denosumab and alendronate on cortical and trabecular bone

Vertebral fractures and trabecular bone loss are hallmarks of osteoporosis. However, 80% of fractures are non-vertebral and 70% of all bone loss is cortical and is produced by intracortical remodeling. The resulting cortical porosity increases bone fragility exponentially. Denosumab, a fully human anti-RANKL antibody, reduces the rate of bone remodeling more than alendronate. The aim of this study was to quantify the effects of denosumab and alendronate on cortical and trabecular bone. Postmenopausal women, mean age 61years (range 50 to 70), were randomized double blind to placebo (n=82), alendronate 70mg weekly (n=82), or denosumab 60mg every 6months (n=83) for 12months. Porosity of the compact-appearing cortex (CC), outer and inner cortical transitional zones (OTZ, ITZ), and trabecular bone volume/total volume (BV/TV) of distal radius were quantified in vivo from high-resolution peripheral quantitative computed tomography scans. Denosumab reduced remodeling more rapidly and completely than alendronate, reduced porosity of the three cortical regions at 6months, more so by 12months relative to baseline and controls, and 1.5- to 2-fold more so than alendronate. The respective changes at 12months were [mean (95% CI)]; CC: −1.26% (−1.61, −0.91) versus −0.48% (−0.96, 0.00), p=0.012; OTZ: −1.97% (−2.37, −1.56) versus −0.81% (−1.45, −0.17), p=0.003; and ITZ: −1.17% (−1.38, −0.97) versus −0.78% (−1.04, −0.52), p=0.021. Alendronate reduced porosity of the three cortical regions at 6months relative to baseline and controls but further decreased porosity of only the ITZ at 12months. By 12months, CC porosity was no different than baseline or controls, OTZ porosity was reduced only relative to baseline, not controls, while ITZ porosity was reduced relative to baseline and 6months, but not controls. Each treatment increased trabecular BV/TV volume similarly: 0.25% (0.19, 0.30) versus 0.19% (0.13, 0.30), p=0.208. The greater reduction in cortical porosity by denosumab may be due to greater inhibition of intracortical remodeling. Head to head studies are needed to determine whether differences in porosity result in differing fracture outcomes.

β-1 Adrenergic Agonist Mitigates Unloading-Induced Bone Loss by Maintaining Formation

Recent data indicate a direct relationship between the sympathetic nervous system and bone metabolism. The purpose of this study was to evaluate the effects of a beta-1 adrenergic (Adrb1) agonist, dobutamine (DOB), on disuse-induced changes in bone integrity during 28 d of hindlimb unloading (HU). Male Sprague-Dawley rats, age 6 months, were assigned to either a normal cage activity (CC) or HU (n = 24/group). Animals were given one daily bolus dose (4 mg·kg body weight a day) of DOB (n = 12) or an equal volume of saline (VEH, n = 12). In vivo peripheral quantitative computed tomography scans revealed a 9% loss in proximal tibia metaphysis (PTM) volumetric bone mineral density (vBMD) over 28 d of disuse. DOB administration during HU significantly attenuated reductions in PTM vBMD and inhibited reductions in mid-diaphysis tibia cross-sectional moment of inertia. A significant decline in PTM bone formation rate in the HU-VEH group (-56% vs CC-VEH) was completely abolished in the HU-DOB group. Significant reductions in strength of the femoral shaft and neck in the HU-VEH group (14% and 15%, respectively) were prevented with DOB treatment. In conclusion, DOB administration during HU effectively attenuates significant declines in total vBMD at PTM by mitigating associated decrements in bone formation rate. Positive effects of DOB were observed only in unloaded animals, with no effects observed in normal weight-bearing rats. These data provide evidence for the importance of Adrb1 signaling in maintaining osteoblast function during periods of mechanical unloading.

The associations between QCT-based vertebral bone measurements and prevalent vertebral fractures depend on the spinal locations of both bone measurement and fracture

We examined how spinal location affects the relationships between quantitative computed tomography (QCT)-based bone measurements and prevalent vertebral fractures. Upper spine (T4-T10) fractures appear to be more strongly related to bone measures than lower spine (T11-L4) fractures, while lower spine measurements are at least as strongly related to fractures as upper spine measurements. Vertebral fracture (VF), a common injury in older adults, is most prevalent in the mid-thoracic (T7-T8) and thoracolumbar (T12-L1) areas of the spine. However, measurements of bone mineral density (BMD) are typically made in the lumbar spine. It is not clear how the associations between bone measurements and VFs are affected by the spinal locations of both bone measurements and VF. A community-based case-control study includes 40 cases with moderate or severe prevalent VF and 80 age- and sex-matched controls. Measures of vertebral BMD, strength (estimated by finite element analysis), and factor of risk (load:strength ratio) were determined based on QCT scans at the L3 and T10 vertebrae. Associations were determined between bone measures and prevalent VF occurring at any location, in the upper spine (T4-T10), or in the lower spine (T11-L4). Prevalent VF at any location was significantly associated with bone measures, with odds ratios (ORs) generally higher for measurements made at L3 (ORs = 1.9-3.9) than at T10 (ORs = 1.5-2.4). Upper spine fracture was associated with these measures at both T10 and L3 (ORs = 1.9-8.2), while lower spine fracture was less strongly associated (ORs = 1.0-2.4) and only reached significance for volumetric BMD measures at L3. Closer proximity between the locations of bone measures and prevalent VF does not strengthen associations between bone measures and fracture. Furthermore, VF etiology may vary by region, with VFs in the upper spine more strongly related to skeletal fragility.

Feeding Blueberry Diets to Young Rats Dose-Dependently Inhibits Bone Resorption through Suppression of RANKL in Stromal Cells

Previous studies have demonstrated that weanling rats fed AIN-93G semi-purified diets supplemented with 10% whole blueberry (BB) powder for two weeks beginning on postnatal day 21 (PND21) significantly increased bone formation at PND35. However, the minimal level of dietary BB needed to produce these effects is, as yet, unknown. The current study examined the effects of three different levels of BB diet supplementation (1, 3, and 5%) for 35 days beginning on PND25 on bone quality, and osteoclastic bone resorption in female rats. Peripheral quantitative CT scan (pQCT) of tibia, demonstrated that bone mineral density (BMD) and content (BMC) were dose-dependently increased in BB-fed rats compared to controls (P<0.05). Significantly increased bone mass after feeding 5% BB extracts was also observed in a TEN (total enteral nutrition) rat model in which daily caloric and food intake was precisely controlled. Expression of RANKL (receptor activator of nuclear factor-κB ligand) a protein essential for osteoclast formation was dose-dependently decreased in the femur of BB animals. In addition, expression of PPARγ (peroxisome proliferator-activated receptor γ) which regulates bone marrow adipogenesis was suppressed in BB diet rats compared to non-BB diet controls. Finally, a set of in vitro cell cultures revealed that the inhibitory effect of BB diet rat serum on RANKL expression was more profound in mesenchymal stromal cells compared to its effect on mature osteoblasts, pre-adipocytes and osteocytes. These results suggest that inhibition of bone resorption may contribute to increased bone mass during early development after BB consumption.

Effect of finite element model loading condition on fracture risk assessment in men and women: The AGES-Reykjavik study

Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case–control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort. Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4–7years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (FPL), posterior (FP) and lateral (FL) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (FStance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p≤0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between FP and fracture in women fell short of statistical significance (p=0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, FPL was 424N (11%) less in subjects with fractures than in controls (p=0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD.

The effects of multiple high-resolution peripheral quantitative computed tomography scans on bone healing in a rabbit radial bone defect model

The use of in vivo high-resolution computed tomography (CT) scanners provides the unique opportunity for evaluating temporal progression in healing of bone defects. However, these in vivo scanners impose ionizing radiation that could affect the healing and morphology of the bone. The primary objective of this study was to determine the effects of in vivo scanning at 2-week intervals on bone healing of a critical sized radial defect in rabbits and to investigate the effect of this radiation protocol on bone marrow cell viability using clinically applicable radiation doses. Thirty male rabbits were randomized into three groups: two groups received a 15mm defect in the left radius that was filled with an autologous bone graft (DEF-CT and DEF-SHAM), and one group acted as an intact control (INT-CT). The duration of the study was 6weeks. DEF-CT and INT-CT had high-resolution CT scans performed at 2-week intervals. The total cumulative radiation dose was 81.6mGy per animal. DEF-SHAM received sham CT scans at the same time points. In group DEF-CT, the bone volume (BV) in the defect increased significantly over time (p≤0.002, for all comparisons); the bone mineral density (BMD) in the defect decreased over time and was significantly lower at weeks 4 and 6 than at weeks 0 and 2 (p<0.001, for all comparisons). In group INT-CT, BV and BMD did not change over time (p=1, for all comparison). The BV (p=0.50) and the BMD (p=0.37) in the defect as measured by microCT scan during ex vivo analysis was not significantly different between DEF-CT and DEF-SHAM. Similarly, histomorphometry showed no significant difference in the total bone area (p=0.22) and percentage bone within the defect (p=0.24) between these groups.Bone marrow analysis of the left (radiated) and right (non-radiated) radius of the INT-CT group via a Colony Forming Units (CFU) assay demonstrated an average of 25.3 and 28.5 colonies for radiated and non-radiated radii, respectively (p=0.72).In conclusion, there was no significant difference in bone healing between radiated and non-radiated radius defects in rabbits. This is an important finding as it demonstrates that serial in vivo high resolution-CT imaging can not only provide accurate tissue regeneration data, but it can also be used to reduce the number of temporal cohorts within an experimental design.

Femoral and Vertebral Strength Improvements in Postmenopausal Women With Osteoporosis Treated With Denosumab

In the randomized, placebo-controlled FREEDOM study of women aged 60 to 90 years with postmenopausal osteoporosis, treatment with denosumab once every 6 months for 36 months significantly reduced hip and new vertebral fracture risk by 40% and 68%, respectively. To gain further insight into this efficacy, we performed a nonlinear finite element analysis (FEA) of hip and spine quantitative computed tomography (QCT) scans to estimate hip and spine strength in a subset of FREEDOM subjects (n = 48 placebo; n = 51 denosumab) at baseline, 12, 24, and 36 months. We found that, compared with baseline, the finite element estimates of hip strength increased from 12 months (5.3%; p < 0.0001) and through 36 months (8.6%; p < 0.0001) in the denosumab group. For the placebo group, hip strength did not change at 12 months and decreased at 36 months (–5.6%; p < 0.0001). Similar changes were observed at the spine: strength increased by 18.2% at 36 months for the denosumab group (p < 0.0001) and decreased by –4.2% for the placebo group (p = 0.002). At 36 months, hip and spine strength increased for the denosumab group compared with the placebo group by 14.3% (p < 0.0001) and 22.4% (p < 0.0001), respectively. Further analysis of the finite element models indicated that strength associated with the trabecular bone was lost at the hip and spine in the placebo group, whereas strength associated with both the trabecular and cortical bone improved in the denosumab group. In conclusion, treatment with denosumab increased hip and spine strength as estimated by FEA of QCT scans compared with both baseline and placebo owing to positive treatment effects in both the trabecular and cortical bone compartments. These findings provide insight into the mechanism by which denosumab reduces fracture risk for postmenopausal women with osteoporosis.