Dual energy X-ray absorptiometry derived bone quantity in an ovine model of osteoporosis.
Citation:
Dr Nick Mahony, Dual energy X-ray absorptiometry derived bone quantity in an ovine model of osteoporosis., TCD, 2013Download Item:
Abstract:
Dual energy X-ray absorptiometry (DXA) is the most widely used bone quantity
investigation in human osteoporosis; it is so ubiquitous that many clinicians now
mistakenly equate DXA derived areal BMD with bone strength. Bone strength partly
depends on bone
mass and the distribution of this mass in terms of size and shape
but also depends on bone quality factors of microarchitecture, material properties,
accumulated microdamage and remodelling rate. In osteoporosis research, sheep
have emerged as a useful lar
ge animal model due to size and physiological
similarities to humans; and, as a flock animal, large numbers of sheep can be reared
at reasonable costs. The aim of this research, part of the ‘Bone for Life’ group of
studies, was to evaluate; DXA scanner val
idity in the ovine animal model, DXA
derived bone quantity (aBMD) change in an ovine animal model of osteoporosis, and
following on from these preliminary studies; to examine the influence of DXA derived
aBMD on cortical and trabecular bone mechanical prop
erties.
In initial validation studies of DXA scanner reliability and assessment of natural
variation in aBMD in the Irish sheep population
ex
-
vivo
bone samples were sourced
from heal
thy Irish mixed breed ewes (age
>5yr) at routine commercial sacrifice.
Fur
ther samples were also harvested from control (CON) and ovariectomised (OVX)
sheep in a specially reared flock at two time points, 12 and 31 month post
-
ovariectomy, to determine the short
-
and long
-
term effect of ovariectomy on bone
quantity (aBMD); and in
further collaborative studies, bone quantity and quality
relationships to mechanical properties. The DXA scan protocol consisted of
standardised alignment of the whole sample (WB) on a holding jig within a tank filled
with normal saline, followed by basel
ine repeat data acquisition scans using a
standard algorithm. The same algorithm allowed further analysis (SRA) of six sub
-
regions down the length of selected long bones femur (FMR), tibia (TBR), humerus
(HMR) and radius (RDR); and, the six vertebrae spina
l samples (LS); as well as
smaller region of interest (ROI) analyses in areas of high trabecular bone content.
Statistical analysis was made of initial repeat test data to determine DXA scanner
reliability, establish measurement limits; and assess biologic
al variability; and for the
specially reared flock, inter
-
group differences in aBMD were analysed for effect of
ovariectomy, and then re
-
analysed in conjunction with bone quality variables to
assess the strength of aBMD and bone quality relationships to me
chanical test data.
xxiii
The results of preliminary studies confirmed an acceptable level of; repeatability (ICC
>0.9), reliability (%TEM 3
-
5%) and measurement limits (95%LOA
±
0.035 g.cm
-
2
) of
the adapted DXA scanning protocol for large ovine bone samples. In
a representative
sample of the Irish ewes evaluation of biological variability revealed; an aBMD range
of approximately 0.60 to 1.20 g.cm
-
2
, minimal inter
-
breed variation and a small
seasonal effect toward lower density in Spring months at some sites. Ana
lysis of
inter
-
group differences between CON and OVX detected no significant difference in
aBMD post
-
ovariectomy at any spinal or long bone site at 12 month; but did detect a
significant reduction in aBMD in the proximal humeral region and an unexpected
fi
nding of increased aBMD in the mid
-
region of the tibia, both with large effect size, at
the 31 month time point. In follow on studies; aBMD (r
2
~0.83) and then structural
geometric properties of CSMI (r
2
~0.75) and section modulus (r
2
~0.65) had the
stronges
t association with breaking strength (Fmax) of ovine radii in three point
bending. In microdamage analysis of radii exposed to cyclic loading, and stratified as
high, medium or low aBMD, results also suggested significantly higher microcrack
numerical and
surface density in bones with lower aBMD. Analysis of compressive
strength of isolated trabecular cores was less clear, but significant inter
-
group
differences in trabecular thickness of large effect size were detected in the CON vs.
OVX comparison at the
31 month time point, and in terms of relationships to strength,
trabecular number and spacing (r
2
~0.4 to 0.5) were better related to compressive
strength and modulus than any DXA or microCT derived bone quantity variable.
In conclusion this
work
has further validated DXA bone quantity measurement and
defined measurement limits for scanning and sub
-
regional analysis of whole bone
samples in this animal model. Bone quantity data for Irish s
heep were of a similar
range to those seen in human female populations, and exhibited some seasonal
variation again similar to human populations living in northern latitudes. In this animal
model ovariectomy alone
however
, did not prove a sufficient enough
stimulus in the
short
-
term to produce
a
significant reduction in bone quantity detectable by DXA in
time frames suitable for research; however longer term changes detected in the
proximal humerus and tibia require further evaluation. In terms of relations
hips to
strength DXA derived aBMD data was the better predictor of bending strength in a
typical long bone
mid
-
shaft site
; but in compression of isolated trabecular cores, bone
quality factors were more closely associated to mechanical properties.
Author's Homepage:
http://people.tcd.ie/njmahonyDescription:
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Author: Mahony, Nicholas
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