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The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

ABSTRACT: How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains.Age-related changes in cortical and trabecular traits have been well studied; however, very little is known about how these bone tissues co-develop from day 1 of postnatal growth to establish functional structures by adulthood. In this study, we aimed to establish how cortical and trabecular tissues within the lumbar vertebral body change during growth for three inbred mouse strains that express wide variation in adult bone structure and function.Bone traits were quantified for lumbar vertebral bodies of female A/J, C57BL/6J (B6), and C3H/HeJ (C3H) inbred mouse strains from 1 to 105 days of age (n?=?6-10 mice/age/strain).Inter-strain differences in external bone size were observed as early as 1 day of age. Reciprocal and rapid changes in the trabecular bone volume fraction and alignment in the direction of axial compression were observed by 7 days of age. Importantly, the inter-strain difference in adult trabecular bone volume fraction was established by 7 days of age. Early variation in external bone size and trabecular architecture was followed by progressive increases in cortical area between 28 and 105 days of age, with the greatest increases in cortical area seen in the mouse strain with the lowest trabecular mass.Establishing the temporal changes in bone morphology for three inbred mouse strains revealed that genetic variation in adult trabecular traits were established early in postnatal development. Early variation in trabecular architecture preceded strain-specific increases in cortical area and changes in cortical thickness. This study established the sequence of how cortical and trabecular traits co-develop during growth, which is important for identifying critical early ages to further focus on intervention studies that optimize adult bone strength.

SUBMITTER: Ramcharan MA

PROVIDER: S-EPMC5890929 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

Ramcharan M A MA Faillace M E ME Guengerich Z Z Williams V A VA Jepsen K J KJ

Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 20161012 3

How cortical and trabecular bone co-develop to establish a mechanically functional structure is not well understood. Comparing early postnatal differences in morphology of lumbar vertebral bodies for three inbred mouse strains identified coordinated changes within and between cortical and trabecular traits. These early coordinate changes defined the phenotypic differences among the inbred mouse strains.<h4>Introduction</h4>Age-related changes in cortical and trabecular traits have been well stud ...[more]

PMID: 27734101

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Project description:We sought to determine if vertebral trabecular attenuation values measured on routine body computed tomography (CT) scans obtained for a variety of unrelated indications can predict future osteoporotic fractures at multiple skeletal sites. For this Health Insurance Portability and Accountability Act (HIPAA)-compliant and Institutional Review Board (IRB)-approved retrospective cohort study, trabecular attenuation of the first lumbar vertebra was measured in 1966 consecutive older adults who underwent chest and/or abdominal CT at a single institution over the course of 1 year. New pathologic fragility fractures that occurred after a patient's CT study date were identified through an electronic health record database query using International Classification of Diseases (ICD)-9 codes for vertebral, hip, and extremity fractures. Univariate and multivariate Cox proportional hazards regression were performed to determine the effect of L1 trabecular attenuation on fracture-free survival. Age at CT, sex, and presence of a prior fragility fracture were included as confounders in multivariate survival analysis. Model discriminative capability was assessed through calculation of an optimism-corrected concordance index. A total of 507 patients (mean age 73.4?±?6.3 years; 277 women, 230 men) were included in the final analysis. The median post-CT follow-up interval was 5.8 years (interquartile range 2.1-11.0 years). Univariate analysis showed that L1 attenuation values ?90 Hounsfield units (HU) are significantly associated with decreased fracture-free survival (p?<?0.001 by log-rank test). After adjusting for age, sex, prior fracture, glucocorticoid use, bisphosphonate use, chronic kidney disease, tobacco use, ethanol abuse, cancer history, and rheumatoid arthritis history, multivariate analysis demonstrated a persistent modest effect of L1 attenuation on fracture-free survival (hazard ratio [HR]?=?0.63 per 10-unit increase; 95% confidence interval [CI] 0.47-0.85). The model concordance index was 0.700. Ten-year probabilities for major osteoporosis-related fractures straddled the treatment threshold for most subcohorts over the observed L1 HU range. In conclusion, for patients undergoing body CT scanning for any indication, L1 vertebral trabecular attenuation is a simple measure that, when ?90?HU, identifies patients with a significant decrease in fracture-free survival. © 2018 American Society for Bone and Mineral Research.

Project description:BackgroundThe quality of the vertebral body structures such as endplate, cortex, and trabecular bone is important for understanding the performance of implants, particularly at the bone-implant interface. Although vertebral body structures have been analyzed separately in the literature, there is no comprehensive study to assess these anatomical measurements along with their interrelationships in the lumbar spine. Therefore, the purpose of this study was to assess variations in trabecular microstructure, vertebral endplate thickness and concavity, and vertebral body cortex thickness within the lumbar spine.MethodsA total of 80 lumbar vertebrae (L1-L5) were dissected from 16 human cadaver specimens and imaged with microcomputed tomography to determine trabecular microstructure, vertebral cortex thickness, endplate thickness, and maximum endplate concavity depth. A paired t test and regression analysis were used to determine significant differences (P < .05) between different vertebral levels and correlations between the analyzed anatomical parameters.ResultsL1 vertebra had significantly better (P?<?.02) trabecular bone microstructure (eg, trabecular bone volume fraction) than all other lumbar vertebrae. However, L1 vertebra also had significantly thinner (P???.02) anterior, left, and right cortices compared to all other vertebral levels. Within L3-L5 intervertebral disc spaces, cranial endplates had significantly greater (P???.03) thickness and maximum concavity depth compared to their respective caudal endplates. No strong correlations were observed between trabecular bone microstructure, maximum endplate concavity depth, vertebral cortex, and endplate thickness parameters.ConclusionsDetailed reference data of these anatomical parameters for each lumbar vertebral body can aid in improved understanding of bone quality, particularly when assessing different implant designs and fixation approaches. Moreover, such anatomical knowledge may help clinicians with optimal implant design selection and surgical placement of these devices into their respective locations.

Project description:The spatial heterogeneity in trabecular bone density within the vertebral centrum is associated with vertebral strength and could explain why volumetric bone mineral density (vBMD) exhibits low sensitivity in identifying fracture risk. This study evaluated whether the heterogeneity and spatial distribution of trabecular vBMD are associated with prevalent vertebral fracture. We examined the volumetric quantitative computed tomography (QCT) scans of the L3 vertebra in 148 participants in the Framingham Heart Study Multidetector CT study. Of these individuals, 37 were identified as cases of prevalent fracture, and 111 were controls, matched on sex and age with three controls per case. vBMD was calculated within 5-mm contiguous cubic regions of the centrum. Two measures of heterogeneity were calculated: (i) interquartile range (IQR); and (ii) quartile coefficient of variation (QCV). Ratios in the spatial distributions of the trabecular vBMD were also calculated: anterior/posterior, central/outer, superior/mid-transverse, and inferior/mid-transverse. Heterogeneity and spatial distributions were compared between cases and controls using Wilcoxon rank sum tests and t tests and tested for association with prevalent fractures with conditional logistic regressions independent of integral vBMD. Prevalent fracture cases had lower mean ± SD integral vBMD (134 ± 38 versus165 ± 42 mg/cm3 , p < .001), higher QCV (0.22 ± 0.13 versus 0.17 ± 0.09, p = .003), and lower anterior/posterior rBMD (0.65 ± 0.13 versus 0.78 ± 0.16, p < .001) than controls. QCV was positively associated with increased odds of prevalent fracture (OR 1.61; 95% CI, 1.04 to 2.49; p = .034), but this association was not independent of integral vBMD (p = .598). Increased anterior/posterior trabecular vBMD ratio was associated with decreased odds of prevalent fracture independent of integral vBMD (OR 0.38; 95% CI, 0.20 to 0.71; p = .003). In conclusion, increased trabecular vBMD in the anterior versus posterior centrum, but not trabecular vBMD heterogeneity, was associated with decreased risk of prevalent fracture independent of integral vBMD. Regional measurements of trabecular vBMD could aid in determining the risk and underlying mechanisms of vertebral fracture. © 2019 American Society for Bone and Mineral Research.

Project description:BACKGROUND:Intervertebral motion impairment is widely thought to be related to chronic back disability, however, the movements of inter-vertebral pairs are not independent of each other and motion may also be related to morphology. Furthermore, maximum intervertebral range of motion (IV-RoMmax) is difficult to measure accurately in living subjects. The purpose of this study was to explore possible relationships between (IV-RoMmax) and lordosis, initial attainment rate and IV-RoMmax at other levels during weight-bearing flexion using quantitative fluoroscopy (QF). METHODS:Continuous QF motion sequences were recorded during controlled active sagittal flexion of 60° in 18 males (mean age 27.6 SD 4.4) with no history of low back pain in the previous year. IV-RoMmax, lordotic angle, and initial attainment rate at all inter-vertebral levels from L2-S1 were extracted. Relationships between IV-RoMmax and the other variables were explored using correlation coefficients, and simple linear regression was used to determine the effects of any significant relationships. Within and between observer repeatability of IV-RoMmax and initial attainment rate measurements were assessed in a sub-set of ten participants, using the intra-class correlation coefficient (ICC) and standard error of measurement (SEM). RESULTS:QF measurements were highly repeatable, the lowest ICC for IV-RoMmax, being 0.94 (0.80-0.99) and highest SEM (0.76°). For initial attainment rate the lowest ICC was 0.84 (0.49-0.96) and the highest SEM (0.036). The results also demonstrated significant positive and negative correlations between IV-RoMmax and IV-RoMmax at other lumbar levels (r?=?-0.64-0.65), lordosis (r?=?-0.52-0.54), and initial attainment rate (r?=?-0.64-0.73). Simple linear regression analysis of all significant relationships showed that these predict between 28 and 42 % of the variance in IV-RoMmax. CONCLUSIONS:This study found weak to moderate effects of individual kinematic variables and lumbar lordosis on IV-RoMmax at other intervertebral levels. These effects, when combined, may be important when such levels are being considered by healthcare professionals as potential sources of pain generation. Multivariate investigations in larger samples are warranted.

Project description:PurposeTo design and validate a fully automated computer system for the detection and anatomic localization of traumatic thoracic and lumbar vertebral body fractures at computed tomography (CT).Materials and methodsThis retrospective study was HIPAA compliant. Institutional review board approval was obtained, and informed consent was waived. CT examinations in 104 patients (mean age, 34.4 years; range, 14-88 years; 32 women, 72 men), consisting of 94 examinations with positive findings for fractures (59 with vertebral body fractures) and 10 control examinations (without vertebral fractures), were performed. There were 141 thoracic and lumbar vertebral body fractures in the case set. The locations of fractures were marked and classified by a radiologist according to Denis column involvement. The CT data set was divided into training and testing subsets (37 and 67 subsets, respectively) for analysis by means of prototype software for fully automated spinal segmentation and fracture detection. Free-response receiver operating characteristic analysis was performed.ResultsTraining set sensitivity for detection and localization of fractures within each vertebra was 0.82 (28 of 34 findings; 95% confidence interval [CI]: 0.68, 0.90), with a false-positive rate of 2.5 findings per patient. The sensitivity for fracture localization to the correct vertebra was 0.88 (23 of 26 findings; 95% CI: 0.72, 0.96), with a false-positive rate of 1.3. Testing set sensitivity for the detection and localization of fractures within each vertebra was 0.81 (87 of 107 findings; 95% CI: 0.75, 0.87), with a false-positive rate of 2.7. The sensitivity for fracture localization to the correct vertebra was 0.92 (55 of 60 findings; 95% CI: 0.79, 0.94), with a false-positive rate of 1.6. The most common cause of false-positive findings was nutrient foramina (106 of 272 findings [39%]).ConclusionThe fully automated computer system detects and anatomically localizes vertebral body fractures in the thoracic and lumbar spine on CT images with a high sensitivity and a low false-positive rate.

Dataset Information

The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

Publications

The development of inter-strain variation in cortical and trabecular traits during growth of the mouse lumbar vertebral body.

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