Quantitative Computed Tomography Scans Research Articles

Habitual levels of higher, but not medium or low, impact physical activity are positively related to lower limb bone strength in older women: findings from a population-based study using accelerometers to classify impact magnitude

SummaryThis study assessed the effect of accelerometry-measured higher impacts resulting from habitual weight-bearing activity on lower limb bone strength in older women. Despite higher impacts being experienced rarely in this population-based cohort, positive associations were observed between higher vertical impacts and lower limb bone size and strength.IntroductionWe investigated whether the benefit of habitual weight-bearing physical activity (PA) for lower limb bone strength in older women is explained by exposure to higher impacts, as previously suggested by observations in younger individuals.MethodsFour hundred and eight women from the Cohort for Skeletal Health in Bristol and Avon (COSHIBA), mean 76.8 years, wore tri-axial accelerometers at the waist for a mean of 5.4 days. Y-axis peaks were categorised, using previously identified cutoffs, as low (0.5–1.0 g), medium (1.0–1.5 g), and higher (≥1.5 g) impacts. Mid and distal peripheral quantitative computed tomography scans of the tibia and radius were performed, as were hip and lumbar spine Dual X-ray Absorptiometry (DXA) scans. Regressions between (log transformed) number of low, medium and high impacts, and bone outcomes were adjusted for artefact error grade, age, height, fat and lean mass and impacts in other bands.ResultsEight thousand eight hundred and nine (4047, 16,882) low impacts were observed during the measurement week, 345 (99, 764) medium impacts and 42 (17, 106) higher impacts (median with 25th and 75th quartiles). Higher vertical impacts were positively associated with lower limb bone strength as reflected by cross-sectional moment of inertia (CSMI) of the tibia [0.042 (0.012, 0.072) p = 0.01] and hip [0.067 (0.001, 0.133) p = 0.045] (beta coefficients show standard deviations change per doubling in impacts, with 95 % confidence interval). Higher impacts were positively associated with tibial periosteal circumference (PC) [0.015 (0.003, 0.027) p = 0.02], but unrelated to hip BMD. Equivalent positive associations were not seen for low or medium impacts.ConclusionsDespite their rarity, habitual levels of higher impacts were positively associated with lower limb bone size and strength, whereas equivalent relationships were not seen for low or medium impacts.

Multiscale modeling of femur fracture

SummaryWe present two multiscale approaches for fracture analysis of full scale femur. The two approaches are the reduced order homogenization (ROH) previously developed by the first author and his associates and a novel accelerated ROH (AROH). The AROH is based on utilizing ROH calibrated to limited experimental data as a training tool to calibrate a simpler, single‐scale anisotropic damage model. For bone tissue orientation, we take advantage of so‐called Wolff's law, which states that bone tissue orientation is well correlated with principal strain direction in a stance position. The meso‐phase properties are identified by minimizing error between the overall cortical and trabecular bone properties resulting from the quantitative computed tomography (QCT) scans and those predicted by the two‐scale homogenization. The overall elastic and inelastic properties of the cortical and trabecular bone microstructure are derived from bone density that can be estimated from the Hounsfield units, which represent the measured grey levels in the QCT scans. For model validation, we conduct ROH and AROH simulations of full scale finite element model of femur created from the QCT and compare the simulation results with available experimental data. Copyright © 2016 John Wiley & Sons, Ltd.

Limited short-term effect of palliative radiation therapy on quantitative computed tomography-derived bone mineral density in femora with metastases

PurposeThe aim of this study was to determine the effect of single fraction (SF) and multiple fraction (MF) radiation therapy (RT) on bone mineral density (BMD) in patients with cancer and bone metastases in the proximal femur. We studied this effect in the radiation field and within metastatic lesions, and differentiated between lytic, blastic, and mixed lesions. Methods and materialsThis prospective cohort study comprised 42 patients with painful bone metastases, including 47 irradiated femora with 52 metastatic lesions in the proximal femur. Patients received either 8 Gy SF or 20 to 24 Gy in 5 to 6 fractions (MF). Quantitative computed tomography scans were obtained before RT and 4 and 10 weeks after the initial scan. Patients who received MF additionally underwent quantitative computed tomography on the final day of their treatment. Automated image registration was performed. Mean BMD was determined at each time point for each proximal femur (region of interest [ROI]-PF) and in greater detail for a region of interest that contained the metastatic lesion (ROI-ML). Statistical analysis was performed using linear mixed models. ResultsNo significant differences in mean BMD were found between SF or MF RT over all time points in both ROI-PF and ROI-ML. Mean BMD did not change in ROI-PF with lytic and mixed lesions, but mean BMD in ROI-PF with blastic lesions increased to 109%. Comparably, when focused on ROI-ML, no differences in mean BMD were observed in lytic ROI-ML but mean BMD in mixed and blastic ROI-ML increased up to 105% and 121%, respectively. ConclusionsTen weeks after palliative radiation therapy in patients with femoral metastatic lesions, a limited increase in BMD was seen with no beneficial effect of MF over SF RT. BMD in lytic lesions was unchanged but slightly increased in mixed and blastic lesions.

Bone turnover predicts change in volumetric bone density and bone geometry at the radius in men

SummaryPeripheral quantitative computed tomography scans of the distal and midshaft radius were performed in 514 European men aged 40–79 years at baseline and a median of 4.3 years later. Age-related changes in volumetric bone mineral density (vBMD) and bone geometry were greater in men with higher biochemical markers of bone turnover at baseline.IntroductionThis study aimed to determine prospective change in bone density and geometry at the radius in men and examine the influence of bone turnover markers and sex hormones on that change.MethodsMen aged 40–79 years were recruited from population registers in Manchester (UK) and Leuven (Belgium). At baseline, markers of bone formation (P1NP and osteocalcin) and resorption (β-cTX and ICTP) were assessed. Total and bioavailable testosterone and oestradiol were also measured. Peripheral quantitative computed tomography (pQCT) was used to scan the radius at distal and midshaft sites at the baseline assessment and a median of 4.3 years later.ResultsFive hundred fourteen men, mean (SD) age of 59.6 (10.5) years, contributed to the data. At the midshaft site, there was a significant decrease in mean cortical vBMD (−0.04 %/year), bone mineral content (BMC) (−0.1 %/year) and cortical thickness (−0.4 %/year), while total and medullary area increased (+0.5 and +2.4 %/year respectively). At the distal radius, total vBMD declined (−0.5 %/year) and radial area increased (+0.6 %/year). Greater plasma concentrations of bone resorption and formation markers were associated with greater decline in BMC and cortical area at the midshaft and total vBMD at the distal site. Increased bone resorption was linked with an increase in total and medullary area and decrease in cortical thickness at the midshaft. Sex hormone levels were unrelated to change in pQCT parameters.ConclusionsAge-related changes in vBMD and bone geometry are greater in men with higher biochemical markers of bone turnover at baseline. Sex hormones have little influence on change in pQCT parameters.

Medial Patellofemoral Ligament Reconstruction Combined With Distal Realignment for Recurrent Dislocations of the Patella: 5-Year Results of a Randomized Controlled Trial

Background: Tibial tubercle transfer (TTT) and medial patellofemoral ligament (MPFL) reconstruction have both shown, either in isolation or in combination, to provide improved patellofemoral joint (PFJ) stability. There are few studies that provide evidence that this remains true in the long term. Purpose: To compare the long-term results of patellar instability after TTT with and without MPFL reconstruction in 2 randomized groups. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: A total of 34 patients (36 knees) were randomized to 2 groups. The first group underwent lateral release (LR) and TTT for confirmed maltracking of the patella (control group). The second group underwent MPFL reconstruction in addition to TTT and LR (reconstruction group). Patients were followed up with validated questionnaires (Kujala score, Tegner activity score), a visual analog scale (VAS) assessing their insecurity, and a clinical assessment at a minimum of 5 years postoperatively. Participants also underwent quantitative computed tomography (CT) at 1 year for comparison. Two patients in the control group and 1 patient in the reconstruction group were lost to follow-up at 5 years. Results: There were no significant differences in the Kujala (P = .75), Tegner (P = .36), or VAS (P = .75) scores at any time period. One patient in the control group sustained a patellar redislocation at 3 years. Five patients in the control group and 2 in the reconstruction group had functional failures and required reoperations; however, this was not statistically significant (P = .30). There were no significant differences between groups in the time to return to school or work (P = .65) or sports (P = .38) after surgery. Overall patient satisfaction was higher in the reconstruction group compared with the control group (P = .04), and quantitative CT scans showed that the reconstruction group had a statistically significant improvement in the mean patellar tilt (6° vs −8°, respectively; P = .03) and mean congruence angle (13° vs −11°, respectively; P = .03) in the quadriceps-contracted state compared with the control group. Conclusion: Reconstruction of the MPFL in addition to TTT and LR resulted in improved alignment parameters (congruence angle, patellar tilt angle) as well as patient satisfaction. The Kujala and Tegner scores were no different between the 2 groups at any time period. There was insufficient evidence to conclude that the addition of MPFL reconstruction to TTT results in fewer redislocations or reoperations. This study concludes that MPFL reconstruction improves PFJ alignment and patient satisfaction; however, further studies with larger patient numbers are required to satisfy its significance with respect to redislocation rates and functional scores in the long term.

Are milk and alternatives and fruit and vegetable intakes during adolescence associated with cortical and trabecular bone structure, density, and strength in adulthood?

The purpose of this study was to investigate whether adolescents with high intake of milk and alternatives (M&A) or fruit and vegetables (F&V) had better adult bone structure and strength compared to those with low intake levels. We analyzed data from 47 males and 69 females enrolled in the Pediatric Bone Mineral Accrual Study (PBMAS 1991-2011), who had one peripheral quantitative computed tomography scan at age 29 ± 2years. We measured radius and tibia shaft total area (ToA), cortical area (CoA), cortical content (CoC), cortical density, bone strength (SSIp), and muscle area, as well as distal radius and tibia ToA, total density, trabecular area, trabecular content, trabecular density, and bone strength (BSIc). Sequential 24-h recalls were used to assess M&A and F&V intake; participants were grouped for their mean intake during adolescence (low = bottom quartile, moderate = middle quartiles, high = top quartile) and were compared using multivariate analysis of covariance while adjusting for adult height, muscle area, physical activity, energy and calcium intake and adolescent energy intake, and physical activity. Females with high M&A intake compared to low M&A intake group (mean 3.8 vs. 1.3 servings/day, respectively) had greater adult ToA (14%, p < 0.05), CoA (15%, p < 0.01), and CoC (16%, p < 0.01) at radius shaft. Females with moderate F&V intake compared to low F&V intake group (mean 3.7 vs. 2.1 servings/day, respectively) had greater adult ToA (8.5%, p < 0.05) at distal tibia. Higher intake of M&A or F&V during adolescence had a long-term beneficial effect on bone structure in females, an association not observed in males.

Is Obesity a Cardiovascular Risk Factor? Correlation of DXA Derived Fat Components & Cardiometabolic Features

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Comparisons of bone properties and keel deformities between strains and housing systems in end-of-lay hens

Susceptibility of caged layers to osteoporosis and cage layer fatigue has generated interest in newer housing systems that favor increased load-bearing activities. However, high incidences of fractures incurred during lay period have been reported in these newer systems. This study is aimed at determining the housing and strain effects on bone properties: dry weight, percentage ash content, cortical density (CBD), cortical thickness (CBT), and keel bone deformities. Tibia, femur, and keel from Hy-Line Brown (HB), Hy-Line Silver Brown (SB), and Barred Plymouth Rock (BR) hens housed in conventional cages (CC), cage-free (CF), and cage-free with range (outdoor access; R) were studied. At 78 wk, 60 hens from each strain and housing system combination were euthanized and bones were excised for analysis. Quantitative computed tomography (QCT) was used to measure CBD and CBT in each bone. Three-dimensional images of keels were generated from software using QCT scans to analyze the deformities. Tibiae CBT was greater (P < 0.01) in BR compared to other two strains. Between housing systems, CBT was greater (P < 0.05) for mid and distal tibia of R and CF compared to CC. Tibiae and femoral cortex were denser (P < 0.05) in BR compared to HB and SB. There was no effect of housing system for femur CBD, but CBD was greater (P < 0.05) for middle and distal tibia of birds housed in R compared to CC. CBD for keel bone was greater (P < 0.05) in CF and R birds compared to CC birds. The housing system did not influence the dry bone weight and ash percentage of tibiae and femur. Each housing system was associated with high prevalence (>90%) of keel deformities and the housing and genotype influenced the type of deformity. These findings indicate that range and cage-free housing may have beneficial impact on tibia and keel bone integrity compared to conventional cages but the improvement may not be sufficient to prevent fractures or deformities of keel.

Total Body Lean Mass, but Not Appendicular Lean Mass Least Significant Change Should be Calculated Separately for Older Men and Women

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Zhou et al. Validating high resolution peripheral quantitative CT scanning of bone

Zhou et al. Validating high resolution peripheral quantitative CT scanning of bone

A Novel Spirometric Measure Identifies Mild COPD Unidentified by Standard Criteria

In chronic obstructive pulmonary disease, both smaller and larger airways are affected. FEV1 mainly reflects large airways obstruction, while the later fraction of forced exhalation reflects reduction in terminal expiratory flow. In this study, the objective was to evaluate the relationship between spirometric ratios, including the ratio of forced expiratory volume in 3 and 6seconds (FEV3/FEV6), and small airways measures and gas trapping at quantitative chest CT scanning, and clinical outcomes in the Genetic Epidemiology of COPD (COPDGene) cohort. Seven thousand eight hundred fifty-three current and ex-smokers were evaluated for airflow obstruction by using recently defined linear iteratively derived equations of Hansen et al to determine lower limit of normal (LLN) equations for prebronchodilator FEV1/FVC, FEV1/FEV6, FEV3/FEV6, and FEV3/FVC. General linear and ordinal regression models were applied to the relationship between prebronchodilator spirometric and radiologic and clinical data. Of the 10,311 participants included in the COPDGene phase I study, participants with incomplete quantitative CT scanning or relevant spirometric data were excluded, resulting in 7,853 participants in the present study. Of 4,386 participants with FEV1/FVC greater than or equal to the LLN, 15.4%had abnormal FEV3/FEV6. Compared with normal FEV3/FEV6 and FEV1/FVC, abnormal FEV3/FEV6 was associated with significantly greater gas trapping; St. George's Respiratory Questionnaire score; modified Medical Research Council dyspnea score; and BMI, airflow obstruction, dyspnea, and exercise index and with shorter 6-min walking distance (all P< .0001) but not with CT scanning evidence of emphysema. Current and ex-smokers with prebronchodilator FEV3/FEV6 less than the LLN as the sole abnormality identifies a distinct population with evidence of small airways disease in quantitative CT scanning, impaired indexes of physical function and quality of life otherwise deemed normal by using the current spirometric definition.

Noninvasive Failure Load Prediction of Vertebrae with Simulated Lytic Defects and Biomaterial Augmentation.

The spine is the most common site for secondary bone metastases, and clinical management for fractures is based on size and geometry of the defect. About 75% of the bone needs to be damaged before lesions are detectable, so clinical tools should measure changes in both geometry and material properties. We have developed an automated, user-friendly, Spine Cancer Assessment (SCA) image-based analysis method that builds on a platform designed for clinical practice providing failure characteristics of vertebrae. The objectives of this study were to (1) validate SCA predictions with experimental failure load outcomes; (2) evaluate the planning capabilities for prophylactic vertebroplasty procedures; and (3) investigate the effect of computed tomography (CT) protocols on predicted failure loads. Twenty-one vertebrae were randomly divided into two groups: (1) simulated defect without treatment (negative control) [n = 9] and (2) with treatment [n = 12]. Defects were created and a polymeric biomaterial was injected into the vertebrae in the treated-defect group. Spines were scanned, reconstructed with two algorithms, and analyzed for fracture loads. To virtually plan for prophylactic intervention, vertebrae with empty lesions were simulated to be augmented with either poly(methyl methacrylate) (PMMA) or a novel bone replacement copolymer, poly(propylene fumarate-co-caprolactone) [P(PF-co-CL)]. Axial rigidities were calculated from the CT images. Failure loads, determined from the cross section with the lowest axial rigidity, were compared with experimental values. Predicted loads correlated well with experimental outcomes (R(2) = 0.73, p < 0.0001). Predictions from negative control specimens highly correlated with measured values (R(2) = 0.90, p < 0.0001). Although a similar correlation was obtained using both algorithms, the smooth reconstruction (B30) tended to underestimate predicted failure loads by ∼50% compared with the ∼10% underestimate of the sharp reconstruction (B70). Percent increase in failure loads after virtual vertebroplasty showed a higher increase in samples with PMMA compared with those with copolymer. The SCA method developed in this study calculated failure loads from quantitative computed tomography scans in vertebrae with simulated metastatic lytic defects, with or without treatment, facilitating clinical applicability and providing more reliable guidelines for physicians to select appropriate treatment options. Furthermore, the analysis could accommodate augmentation planning procedures that aimed to determine the optimum material that would increase vertebral body failure load.

Association of bone turnover markers with volumetric bone loss, periosteal apposition, and fracture risk in older men and women: the AGES-Reykjavik longitudinal study.

We assessed whether circulating bone formation and resorption markers (BTM) were individual predictors for trabecular and cortical bone loss, periosteal expansion, and fracture risk in older adults aged 66 to 93years from the AGES-Reykjavik study. The sample for the quantitative computed tomography (QCT)-derived cortical and trabecular BMD and periosteal expansion analysis consisted of 1069 participants (474 men and 595 women) who had complete baseline (2002 to 2006) and follow-up (2007 to 2011) hip QCT scans and serum baseline BTM. During the median follow-up of 11.7years (range 5.4-12.5), 54 (11.4%) men and 182 (30.6%) women sustained at least one fracture of any type. Increase in BTM levels was associated with faster cortical and trabecular bone loss at the femoral neck and proximal femur in men and women. Higher BTM levels were positively related with periosteal expansion rate at the femoral neck in men. Markers were not associated with fracture risk. This data corroborates the notion from few previous studies that both envelopes are metabolically active and that BTM levels may moderately reflect the cellular events at the endosteal and periosteal surfaces. However, our results do not support the routine use of BTM to assess fracture risk in older men and women. In light of these findings, further studies are justified to examine whether systemic markers of bone turnover might prove useful in monitoring skeletal remodeling events and the effects of current osteoporosis drugs at the periosteum.

Blueberry Diet Derived 3‐(3‐hydroxyphenyl) Propionic Acid (PPA) Suppresses Osteoblastic Cell Senescence to Promote Bone Accretion in Mice

A blueberry (BB) supplemented diet has been previously shown to significantly stimulate bone formation in rapidly growing male and female rodents. Phenolic acids (PAs) are metabolites derived from polyphenols found in fruits and vegetables as a result of the actions of gut bacteria, and the levels of seven individual PAs were found to be at least 10 times higher in the serum of rats fed a BB‐containing diet compared to those fed a control diet. We have characterized the effects of one such BB‐associated serum PA, 3‐(3‐hydroxyphenyl) propionic acid (PPA), on stimulating osteoblastogenesis. To better understand the mechanistic actions of PPA on bone formation, we administered four doses of PPA (0.1, 0.5, 1 and 5 mg/kg/d) to one‐month‐old female C57BL6/J mice for thirty days. We found that stimulation of osteoblast differentiation and proliferation occurred in PPA treated osteoblastic cells. Using peripheral quantitative CT scan (pQCT) and micro‐CT analyses, we demonstrated differences in bone phenotypes between control and PPA‐treated animals, i.e., bone mass was significantly higher in 1 to 5 mg/kg/d PPA‐treated animals compared to controls (p&lt;0.05). Micro‐CT showed bone volume and trabecular number in 1 mg/kg/d treated animals were 0.14±0.007 and 4.76±0.095 versus 0.12±0.02 and 4.33±0.33 in control animals (p&lt;0.05). The bone formation marker alkaline phosphatase in both serum and bone marrow plasma was dose‐dependently increased in PPA‐treated animals. After aspiration of bone marrow, femur bone protein and RNA were isolated for Western blot and real‐time PCR analysis of signaling transduction. We found that PPA was able to suppress bone senescence signaling as evaluated by measuring senescence‐associated beta‐galactosidase activity, PPARγ, p53 and p21 expression (p&lt;0.05 vs control). In conclusion, blueberry‐derived PPA is capable of altering the mesenchymal stem cell differentiation program and bone cell senescence. Thus, PPA or blueberry‐rich diets merit investigation as potential dietary alternatives to drugs for degenerative bone disorders or to promote bone growth during development. Supported in part by USDA‐ARS Project 6026‐51000‐010‐05S.Support or Funding InformationSupported in part by USDA‐ARS Project 6026‐51000‐010‐05S

Evaluation of Quantitative Computed Tomography Cortical Hip Quadrant in a Clinical Trial With Rosiglitazone: A Potential New Study Endpoint

Quantitative computed tomography (QCT) measurements have been used extensively to ascertain information about bone quality and density due to the 3-dimensional information provided and the ability to segment out trabecular and cortical bones. QCT imaging helps to improve our understanding of the role that each bone compartment plays in the pathogenesis and prognosis of fracture. This study was conducted to explore longitudinal changes in femoral neck (FN) cortical bone structure using both volumetric bone mineral density (vBMD) and cortical shell thickness assessments via QCT in a double-blind, randomized, multicenter clinical trial in postmenopausal women with type 2 diabetes mellitus. This study also examined whether treatment-associated changes in the cortical bone vBMD and thickness in femoral neck quadrants could be evaluated. Subjects were randomized to rosiglitazone (RSG) or metformin (MET) for 52 wk followed by 24 wk of open-label MET. A subset of 87 subjects underwent QCT scans of the hip at baseline, after 52 wk of double-blind treatment, and after 24 wk of treatment with MET using standard full-body computed tomography scanners. All scans were evaluated and analyzed centrally. Cortical vBMD at the FN was precisely segmented from trabecular bone and used to assess a possible therapeutic effect on this bone compartment. QCT analysis showed reductions in adjusted mean percentage change in vBMD and in absolute cortical thickness occurred with RSG treatment from baseline to week 52, whereas changes with MET were generally minimal. The reductions observed during RSG treatment for 1 yr appeared to partially reverse during the open-label MET phase from weeks 52 to 76. The femoral neck quadrant may provide utility as a potential endpoint in clinical trials for the understanding of the therapeutic effect of new entities on cortical bone vs trabecular bone; however, further clinical validation is needed. Trial registration: The protocol (GSK study number AVD111179) was registered on ClinicalTrials.gov as NCT00679939.

Association of 3D Geometric Measures Derived From Quantitative Computed Tomography With Hip Fracture Risk in Older Men.

We investigated the associations of 3D geometric measures and volumetric bone mineral density (vBMD) of the proximal femur assessed by quantitative computed tomography (QCT) with hip fracture risk among elderly men. This study was a prospective case-cohort design nested within the Osteoporotic Fractures in Men Study (MrOS) cohort. QCT scans of 230 men (65 with confirmed hip fractures) were evaluated with Mindways' QCTPRO-BIT software. Measures that are indicative of bone strength for the femoral neck (FN) and for the trochanteric region (TR) were defined. Bending strength measures were estimated by minimum section modulus, buckling strength by buckling ratio, and a local thinning index (LTI). Integral and trabecular vBMD measures were also derived. Areal BMD (aBMD) of the total proximal femur from dual-energy X-ray absorptiometry (DXA) is presented for comparison. Associations of skeletal measures with incident hip fracture were estimated with hazard ratios (HR) per standard deviation and their 95% confidence intervals (CI) from Cox proportional hazard regression models with adjustment for age, body mass index (BMI), site, and aBMD. Men with hip fractures were older than men without fracture (77.1 ± 6.0 years versus 73.3 ± 5.7 years, p < 0.01). Age, BMI, and site-adjusted HRs were significant for all measures except TR_LTI. Total femural BMD by DXA (HR = 4.9, 95% CI 2.5-9.9) and QCT (HR = 5.5, 95% CI 2.5-11.7) showed the strongest association followed by QCT FN integral vBMD (HR = 3.6, 95% CI 1.8-6.9). In models that additionally included aBMD, FN buckling ratio (HR = 1.9, 95% CI 1.1-3.2) and trabecular vBMD of the TR (HR = 2.0, 95% CI 1.2-3.4) remained associated with hip fracture risk, independent of aBMD. QCT-derived 3D geometric indices of instability of the proximal femur were significantly associated with incident hip fractures, independent of DXA aBMD. Buckling of the FN is a relevant failure mode not entirely captured by DXA. Further research to study these relationships in women is warranted. © 2016 American Society for Bone and Mineral Research.

Software-assisted morphometry and volumetry of the lumbar spine

The aim of the study was to measure volumes of the lumbar vertebral bodies with use dedicated Computed Tomography (CT) workstation software to predict expected volume of PMMA for vertebroplasty and supplement calculations using computed tomography scanogram. Quantitative CT scans of 87 women's (mean age 69.4 years; SD 10.9) and 15 men's (mean age 64.3 years; SD 11.8) lumbar spines were analyzed; this made a total of 379 vertebrae. The population of patients was divided into three groups depending on measured BMD value, in accordance with American College of Radiology Practice Parameter for the Performance of Quantitative Computed Tomography (QCT) Bone Densitometry. With the use of the general linear model and least squares means groups were compared regarding vertebral volume, anterior, middle, and posterior vertebral heights.Morphometric parameters tended to be greater in males than in females, in a population of diversified bone mineral density. BMD result should be considered as the modifying factor for preoperative planning of the bone cement volume to be deposited inside the vertebra. Vertebral body volumetry might prove to be a useful tool in pre-operative planning as well as an alternative for treatment monitoring after minimally invasive spinal procedures.

MPFL Reconstruction with TTT Versus TTT Alone for Recurrent Patella Instability

Purpose:Reconstruction of the medial patellofemoral ligament (MPFL) is increasingly used to restore the primary ligamentous restraint to patella dislocation. The purpose of this randomised controlled trial is to compare the 5 year results of the addition of autograft MPFL reconstruction to tibial tubercle transfer (TTT) and lateral release (LR) (reconstruction group) to TTT and LR alone (control group) for recurrent patella dislocation.Methods:Thirty-four patients (36 knees) were randomised to two groups. Two patients in the control group (TTT + LR) and three patients in the reconstruction group (MPFL + TTT + LR) group were lost to follow up at 5 years.Results:There were no significant differences in Kujala and Tegner scores or “insecurity” Visual Analogue Scale (VAS) at any time period. There was a trend to a lower average VAS in the reconstruction group at six weeks but also poorer average flexion. There were no significant differences in time to return to school, work or sports. Quantitative CT scans showed the reconstruction group had a significant improvement in average patella tilt (6 degrees vs -8 degrees, p = 0.03) and average congruence angle (13 degrees vs -11 degrees, p = 0.03) in the quadriceps contracted state. At 5 years the MPFL/TTT reconstruction group had a lower revision rate (2/17) compared to the control group of TTT alone (5/16).Conclusion:Patients who underwent an MPFL reconstruction in addition to a TTT had a comparatively significant improved patella congruence on quantitative CT Scan. At 5 years the MPFL/TTT reconstruction group had a lower but non significant revision rate compared to the control group of TTT alone.

Lung density associates with survival in alpha 1 antitrypsin deficient patients

IntroductionCT density correlates with quality of life (QOL) scores and impaired upper zone lung density associates with higher mortality in alpha one antitrypsin deficiency (A1ATD). We hypothesised that decline in CT densitometry would relate to survival or deterioration in QOL in A1ATD. MethodsAll augmentation naïve PiZZ patients in the UK A1ATD registry with ≥two successive quantitative CT scans were selected. Patients were divided into groups based on CT density decline and the relationship to survival and change in QOL compared by univariate analyses and multivariate Cox regression. Analyses were performed for whole lung, upper zone and lower zone density separately. Exploratory analyses of FEV1 subgroups were conducted. Results110 patients were identified; 77 had whole lung and lung zone density recorded on two CT scans, 33 patients had upper zone data only on four scans. Decline in lower zone density associated with survival, even after adjustment for baseline lung density (p = 0·048), however upper zone density and whole lung density decline did not. This difference appeared to be driven by those with FEV1 >30% predicted. ConclusionRate of change in lung densitometry could predict survival in A1ATD.

Bioactive glass can potentially reinforce large bone defects

Introduction: Bioactive glass (BAG) has been studied widely and seems to be a very promising biomaterial in regeneration of large bone defects and osteomyelitis treatment, because of its bone bonding and antibacterial properties[1]-[5]. Potentially, it could also mechanically reinforce large defects, thus making it suitable for load-bearing applications. However, the mechanical properties of the reconstructive layer and its dependence on BAG:bone allograft mixture composition are unknown. In this study, we measured the mechanical properties of different impacted BAG/bone graft mixtures. Then these properties were used in micro-Finite Element (FE) patient-specific models to investigate whether these mixtures could restore mechanical properties of large bone defects. Materials and Methods: Five different S53P4 BAG/bone graft mixtures were impacted in a cylindrical holder, mechanically tested in confined compression and scanned with micro-CT. From these images, the mixture was identified by its three phases: bone, glass or interface region. Micro-Finite-Element (FE) models of the composites were made using a Young’s modulus of 2.5 GPa for bone and 35 GPa for BAG. The Young’s modulus for the interface region was determined by fitting experimental and micro-FE results for the same specimens. High-Resolution peripheral quantitative CT scans of a 9 mm region of the distal tibia of seven subjects were used for studying the reinforcement potential. Micro-FE models of this region were made to determine its stiffness in the original state, with a simulated cortical defect, and after that a mixture of BAG/bone or BAG alone was simulated in the defect. Results: The confined compression tests showed a strong dependence of the Young’s modulus of the BAG/bone composite on the amount of BAG, ranging from 116.7±18.2 to 654.2±35.2 MPa. The micro-FE results could fairly reproduce these measured moduli, when using a stiffness of 25 MPa for the interface layer (R2=0.678, see Figure 1).