Accuracy of peripheral quantitative computed tomography (pQCT) for assessing area and density of mouse cortical bone.
ABSTRACT Peripheral quantitative computed tomography (pQCT) is increasingly used for measurement of cortical bone geometry and density in mice. We evaluated the accuracy of pQCT for area and density measurements of thin-walled aluminum phantoms and mouse femora. Aluminum tubes with varying wall thicknesses and femora from 1- to 6-month-old C3H/HeJ (C3H) and C57B1/6J (B6) mice (average cortical thickness 0.14-0.29 mm) were scanned at 70- or 90-microm resolution. pQCT values of area were compared to optical values determined after sectioning, while pQCT density (vBMD) was compared to solid aluminum density or correlated to bone ash content. For the aluminum phantoms, the error in pQCT area and density depended strongly on wall thickness, and density was consistently underestimated. For mouse femora, threshold values were found that produced zero error in bone area for each strain and age group, although the optimal threshold differed between groups. pQCT vBMD correlated strongly with ash content (r2=0.7), although the regression equations differed between strains and the magnitude of the inter-strain difference in vBMD was fourfold greater than the difference in ash content. This finding suggests that pQCT can overestimate the differences in volumetric mineral density between inbred mouse strains whose bones are of different thickness (e.g., C3H vs. B6). In conclusion, both area and density values obtained by pQCT depend strongly on specimen thickness, consistent with a partial volume averaging artifact. Investigators using pQCT to assess cortical bones in mice should be aware of the potential for cortical thickness-dependent errors.
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ABSTRACT: We evaluated the accuracy and precision of a peripheral quantitative computed tomography (pQCT) scanner, the Stratec XCT-960, using 12 human cadaveric forearms. The accuracy was determined by comparing the total bone mineral content (BMC) with the ash weight (AW). We scanned and ashed three consecutive slices (thickness 2.5 mm) at the standard position (s-position) and at 2.5 mm both proximal and distal to the s-position. The correlation coefficient between the AW and total BMC using slices at the s-position was r = 0.87 with an accuracy error (random component) of 15.5%. The correlation coefficient using all slices was r = 0.90 with an accuracy error of 14.3%. The correlation coefficient improved to r = 0.95 with an accuracy error of 9.7% after averaging the results of all three slices for each forearm. The short-term precision error expressed as the coefficient of variation (CV) of bone mineral density (BMD) and BMC was determined by measuring the forearms five times either with repositioning or without repositioning. The CVs with repositioning were 2.77 and 1.15 for total BMD and BMC, 1.85 for trabecular BMD; without repositioning they were 0.29, 0.58 and 0.69 respectively. To further evaluate the influence of positioning, additional scans were performed at 1, 2 and 5 mm proximal, and 1 and 2 mm distal to the s-position. BMD and BMC were greatly influenced by the scan location; for example, the percentage differences in trabecular BMD 1 mm distal and proximal relative to the s-position were 2.5% +/- 5.1% and 0.18% +/- 6.3%, respectively. The Stratec XCT-960 appears to be a moderately accurate and highly precise scanner with potential usefulness for evaluating BMC and BMD of ultradistal radius.Osteoporosis International 02/1996; 6(3):207-12. · 4.04 Impact Factor
Article: Assessing bone quantity by pQCT.[show abstract] [hide abstract]
ABSTRACT: We have tested the ability of the XCT960A to detect bone loss in OVX-rats, as well as bone gain in the proximal tibial metaphysis of healthy rats treated with hPTH(1-34). The results demonstrated that high precision can be achieved, with CV's for most measurement parameters in the range of 1.6 to 5.9% being obtained in vivo with repositioning of animals. Significant changes in bone parameters in the tibia were observed already at 2 weeks following OVX or PTH-therapy, while whole bone mass measured in the tibia by DEXA ex vivo did not change significantly for up to 24 weeks. For the proximal rat tibia at location 5mm distal to the knee joint was identified as an optimal site. At this location, cortices are fairly parallel thus reducing the partial volume effect, the area is relatively rich in cancellous bone increasing the magnitude of bone gain or loss, and the site (2mm below the growth plate) is relevant for comparisons with histomorphometric measurements. The results demonstrate that pQCT can be adapted for use in small animals such as rats, and that it is a sensitive, reproducible, non-invasive method available to monitor changes in bone mass, bone density, and geometric properties. Future studies should help to establish whether the moment of inertia, moment of resistance and the newly added bone strength index provided by the machine are predictive in any way for bone strength as obtained from biomechanical testing procedures. Peripheral QCT in small animals is an important addition for drug evaluation because it is more sensitive than DEXA and allows for shorter duration of experiments. This non-invasive method can reliably measure changes in cancellous and cortical bone mass over time following ovariectomy or administration of the bone anabolic hormone hPTH(1-34). pQCT should be viewed as a complimentary technique to static and dynamic histomorphometry, which does not replace either of these methods. Its value in the field of basic research should be evaluated.Bone 11/1995; 17(4 Suppl):145S-154S. · 3.82 Impact Factor
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ABSTRACT: Previously, we identified two significant quantitative trait loci (QTLs) specifying the peak relative bone mass (bone mass corrected for bone size) on chromosomes (Chrs) 11 and 13 by interval mapping in two mouse strains, SAMP2 and SAMP6. The latter strain is an established murine model of senile osteoporosis and exhibits a significantly lower peak relative bone mass than SAMP2 mice. We recently designated the Chr 13 locus as Pbd2 (Peak bone density 2) and constructed a congenic strain, P6.P2-Pbd2(b), which carried a single genomic interval from the Chr 13 of SAMP2 on a SAMP6-derived osteoporotic background. In this study, we have constructed a congenic strain, P2.P6-Pbd2(a), carrying a SAMP6-derived susceptible interval on a SAMP2-derived resistance background. This congenic strain had a lower bone density than the background strain, SAMP2, based on three measurement methods, each utilizing a different principle for evaluating bone density: MD, DXA, and pQCT. Next, a candidate gene approach was used to find polymorphisms of Bmp6 (bone morphogenetic protein 6). The CAG trinucleotide repeat numbers in exon 1 of this gene differ among SAM strains. We found an association of CAG repeat length with relative peak bone mass in mice.Mammalian Genome 08/2002; 13(7):335-40. · 2.42 Impact Factor