Accuracy and Precision of PIXImus Densitometry for Ex Vivo Mouse Long Bones

Franco, Gloria E. Lopez; O’Neil, Tyriina K.; Litscher, Suzanne J.; Urban-Piette, Michael; Blank, Robert D.

doi:10.1385/jcd:7:3:326

Cited by 21 publications

(11 citation statements)

References 14 publications

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“…Specimens were subjected to two freeze thaw cycles, one prior to DXA, and the second prior to biomechanical testing. Using DXA we measured areal BMD of isolated femura twice with repositioning, as previously described [26]. Prior to biomechanical analysis, femora were gradually warmed by placing them at 4°C for at least 12 hours, and then allowing them to come to room temperature prior to analysis.…”

Section: Methodsmentioning

confidence: 99%

Low Bone Strength Is a Manifestation of Phenylketonuria in Mice and Is Attenuated by a Glycomacropeptide Diet

et al. 2012

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PurposePhenylketonuria (PKU), caused by phenylalanine (phe) hydroxylase loss of function mutations, requires a low-phe diet plus amino acid (AA) formula to prevent cognitive impairment. Glycomacropeptide (GMP), a low-phe whey protein, provides a palatable alternative to AA formula. Skeletal fragility is a poorly understood chronic complication of PKU. We sought to characterize the impact of the PKU genotype and dietary protein source on bone biomechanics.ProceduresWild type (WT; Pah+/+) and PKU (Pahenu2/enu2) mice on a C57BL/6J background were fed high-phe casein, low-phe AA, and low-phe GMP diets between 3 to 23 weeks of age. Following euthanasia, femur biomechanics were assessed by 3-point bending and femoral diaphyseal structure was determined. Femoral ex vivo bone mineral density (BMD) was assessed by dual-enengy x-ray absorptiometry. Whole bone parameters were used in prinicipal component analysis. Data were analyzed by 3-way ANCOVA with genotype, sex, and diet as the main factors.FindingsRegardless of diet and sex, PKU femora were more brittle, as manifested by lower post-yield displacement, weaker, as manifested by lower energy and yield and maximal loads, and showed reduced BMD compared with WT femora. Four principal components accounted for 87% of the variance and all differed significantly by genotype. Regardless of genotype and sex, the AA diet reduced femoral cross-sectional area and consequent maximal load compared with the GMP diet.ConclusionsSkeletal fragility, as reflected in brittle and weak femora, is an inherent feature of PKU. This PKU bone phenotype is attenuated by a GMP diet compared with an AA diet.

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Section: Methodsmentioning

confidence: 99%

Low Bone Strength Is a Manifestation of Phenylketonuria in Mice and Is Attenuated by a Glycomacropeptide Diet

et al. 2012

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“…We measured areal BMD of isolated femora by DXA as previously described [8]. Briefly, each bone was scanned twice with repositioning.…”

Section: Methodsmentioning

confidence: 99%

Linkage mapping of principal components for femoral biomechanical performance in a reciprocal HCB-8 × HCB-23 intercross

Saless

Litscher

Vanderby

et al. 2011

Bone

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Studies of bone genetics have addressed an array of related phenotypes, including various measures of biomechanical performance, bone size, bone, shape, and bone mineral density. These phenotypes are not independent, resulting in redundancy of the information they provide. Principal component (PC) analysis transforms multiple phenotype data to a new set of orthogonal “synthetic” phenotypes. We performed PC analysis on 17 femoral biomechanical, anatomic, and body size phenotypes in a reciprocal intercross of HcB-8 and HcB-23, accounting for 80% of the variance in 4 PCs. Three of the 4 PCs were mapped in the cross. The linkage analysis revealed a quantitative trait locus (QTL) with LOD = 4.7 for PC2 at 16 cM on chromosome 19 that was not detected using the directly measured phenotypes. The chromosome 19 QTL falls within a ~10 megabase interval, with Osf1 as a positional candidate gene. PC QTLs were also found on chromosomes 1, 2, 4, 6, and 10 that coincided with those identified for directly measured or calculated material property phenotypes. The novel chromosome 19 QTL illustrates the power advantage that attends use of PC phenotypes for linkage mapping. Constraint of the chromosome 19 candidate interval illustrates an important advantage of experimental crosses between recombinant congenic mouse strains.

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“…BMD scans were preformed using a Lunar PIXImus II Densitometer (GE Healthcare, Piscataway, NJ, USA). Positional scanning effects have been documented for PIXImus Densitometers.

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To determine whether scanning position affected the DXA used in this study, we recorded the x and y coordinates for each scan. Using ANOVA, we found no difference in BMD dependent on x ‐axis position; however, there was a small increase in BMD from top to bottom on the y ‐axis (right femur: r 2 = 0.01, p = 0.04; left femur: r 2 = 0.02, p = 0.006).…”

Section: Methodsmentioning

confidence: 99%

An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

Farber

Nas

Ghazalpour

et al. 2009

Journal of Bone and Mineral Research

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Numerous quantitative trait loci (QTLs) affecting bone traits have been identified in the mouse; however, few of the underlying genes have been discovered. To improve the process of transitioning from QTL to gene, we describe an integrative genetics approach, which combines linkage analysis, expression QTL (eQTL) mapping, causality modeling, and genetic association in outbred mice. In C57BL/6J × C3H/HeJ (BXH) F 2 mice, nine QTLs regulating femoral BMD were identified. To select candidate genes from within each QTL region, microarray gene expression profiles from individual F 2 mice were used to identify 148 genes whose expression was correlated with BMD and regulated by local eQTLs. Many of the genes that were the most highly correlated with BMD have been previously shown to modulate bone mass or skeletal development. Candidates were further prioritized by determining whether their expression was predicted to underlie variation in BMD. Using network edge orienting (NEO), a causality modeling algorithm, 18 of the 148 candidates were predicted to be causally related to differences in BMD. To fine-map QTLs, markers in outbred MF1 mice were tested for association with BMD. Three chromosome 11 SNPs were identified that were associated with BMD within the Bmd11 QTL. Finally, our approach provides strong support for Wnt9a, Rasd1, or both underlying Bmd11. Integration of multiple genetic and genomic data sets can substantially improve the efficiency of QTL fine-mapping and candidate gene identification.

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Accuracy and Precision of PIXImus Densitometry for Ex Vivo Mouse Long Bones

Cited by 21 publications

References 14 publications

Low Bone Strength Is a Manifestation of Phenylketonuria in Mice and Is Attenuated by a Glycomacropeptide Diet

Low Bone Strength Is a Manifestation of Phenylketonuria in Mice and Is Attenuated by a Glycomacropeptide Diet

Linkage mapping of principal components for femoral biomechanical performance in a reciprocal HCB-8 × HCB-23 intercross

An Integrative Genetics Approach to Identify Candidate Genes Regulating BMD: Combining Linkage, Gene Expression, and Association

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