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TABLE 4.1
Vibrational spectroscopic study of oi Bones Comparison to normal Control
Mineral to
Matrix Ratio
Method
XST
XLR
Notes
Ref
Mouse models
Oim
/
oim
FTIRM
Altered
?
Mineral structure altered
5
FTIRI
Decreased
Smaller crystals
?
ALN treatment increased
mineral content but not XST
45
a
Raman
Crystals not well
aligned
Fibrils not well
aligned
Polarized Raman
Raman
?
Decreased
?
Rx with human stem cells -
male vs. female differences
11
Transgenic (col Iα1
mutation insert)
FTIR
Decreased
?
?
59
Brtl IV
Raman
Increased at 2
months
Smaller at 2 months
?
66
Brtl IV
FTIR
Increased
N
oim
/
oim
FTIRI
Increased
N
fro
/
fro
FTIRI
Increased
85
OOA mice (Amish)
Raman
Increased
?
Reduced
All backgrounds studied
67
Opt
FTIRI
Increased
Decreased
N
Transgenic
FTIRM
Increased
N
Human tissues
b
Classic OI (I, III, IV)
FTIRI
Slight Increase
Decreased
No change
2 patients
b
Type I C-cleavage site
mutation
FTIRI
Increased cortical
and cancellous
Decreased
Increased x-links in
trabeculae
2 patients
All comparisons are to age and background matched controls. XST = crystal size and perfection; XLR = collagen maturity; N = not published.
a
Raghavan M, Sahar ND, Wilson RH, et al. Quantitative polarized Raman spectroscopy in highly turbid bone tissue. J Biomed Opt 2010;
15:
037001.
b
Lindahl K, Barnes AM, Fratzl-Zelman N, et al. COL1 C-propeptide cleavage site mutations cause high bone mass osteogenesis imperfecta. Hum Mutat 2011;
32:
598-609.
Type I OI cases were not statistically different in crystal
sizes when the donors were adults. Although we now
know from FTIRI data that there are site-dependent
51
as well as age-dependent
52
variations in mineral prop-
erties, these studies are crucial in first demonstrating
that OI bone mineral crystals are smaller than normal,
which may contribute to the brittle behavior of bone.
Crystal size from these patients was later correlated
with the nature of the collagen defect,
53
with the small-
est crystals associated with the most severe OI cases.
Similarly, X-ray diffraction was used to show smaller
crystal size in the bovine models of OI.
20
For the X-ray diffraction experiment the bone is gen-
erally cleaned of soft tissue (including marrow) and
ground to a fine uniformly sieved powder. A sample
holder containing a minimum of 10 mg of powder is
needed for routine measurements, and preferably more
is loaded into the holder. Micro-diffraction uses slightly
smaller samples but these instruments are less widely
available. In either case, wide-angle X-ray diffraction
generates a fingerprint pattern (
Figure 4.5
) from which
the nature of the phases present, the dimension of the
crystal lattice, and the particle sizes of the crystals can
be determined.
20
No significant differences were found
in crystal sizes in the oim
/
oim mice and the fro
/
fro
mice at 6 months relative to their age- and background-
matched controls.
54
There have been no other published
X-ray diffraction studies of other types of OI bone.
Presumably these are limited due to the relatively large
amount of material needed for such analyses in contrast
to some of the methods listed below and the age-, back-
ground- and gender-dependent changes.
SMALL-ANGLE SCATTERING
Another X-ray-based technique, small-angle scatter-
ing or small-angle X-ray scattering (SAXS), provides
information on the distribution of particle sizes in the
tissue. There have been very few studies using SAXS
to evaluate human or murine OI tissues. An important
study by Fratzl
55
found thinner, more needle-like, crys-
tals in oim
/
oim cortical bone as compared to age- and
background-matched controls. The crystals were similar
