Biomedical Engineering Reference
In-Depth Information
with age may lead to a net increase in tissue mineralization due to accumulation of
elderly tissue fragments [
113
].
Bone mineral also displays osteoporosis-related alterations in elemental com-
position and crystallinity. Biochemical analysis of iliac crest biopsies from oste-
oporotic subjects exhibited mineral with decreased CO
3
and Ca/P ratio [
107
],
while Cohen and Kitzes found decreased Mg content [
114
]. Moreover, a Fourier
Transform Infrared Microscopy (FTIRM) study indicated that fracture risk was
increased with the mineral-to-matrix ratio and crystallinity [
115
]. For cortical bone
from iliac crest biopsies, the mineral phase was more crystalline/mature in samples
from osteoporotic donors than bone from normals [
116
]. (Changes in bone mineral
are also reviewed in Changes in Cortical Bone Mineral and Microstructure with
Aging and Osteoporosis).
4.1.3 Collagen Matrix
The age-related changes causing a functional deficiency of collagen are primarily
due to increased intermolecular cross-linking [
99
,
117
-
124
]. The intermolecular
cross-linking of collagen molecules within the tissues involves two different
mechanisms: enzymatic and non-enzymatic crosslinks. Among the two, the non-
enzymatic crosslinking, known as glycation, is the major cause of dysfunction of
collagen matrix associated with aging. The non-enzymatic crosslinking involves
reaction with glucose and subsequent oxidation products of the complex. The
process may be accelerated in diabetic patients due to higher levels of serum
glucose. Non-enzymatic crosslinks are actually the outcome of so-called Advanced
Glycation End Products (AGEs). Pentosidine, one of collagen crosslinks by AGEs
found in bone, is commonly used as a biomarker of AGEs [
125
]. Higher urinary
pentosidine levels were associated with bone fractures in elderly diabetic patients
and may in part account for the reduced bone strength in type 2 diabetes [
102
].
In addition, aging may lead to a decrease in collagen content, thereby resulting in
the increased stiffness, enzyme resistance, and permeability and the decreased
swelling of bone [
112
]. Moreover, the effect of glycation on cell-matrix interac-
tions has also shown to be an equally important aspect of aging of bone [
23
].
Recent findings provide important evidence that bone proteins are affected by
AGEs modification, showing that glycation of bone matrix influences osteoclasts
(bone resorption) and osteoblasts (bone formation) [
126
]. Finally, recent studies
show that tissue age-dependent collagen maturity may also be correlated to frac-
ture risk of bone [
115
].
As the major part of extracellular matrix of bone, the thermostability of the
collagen network decreases with increasing age in terms of shrinking and melting
temperatures. Age related decreases in collagen shrinkage temperature have been
correlated to decreased bone toughness, thus substantiating the view that detri-
mental changes in the collagen network may lead to increased bone fragility with
aging [
127
].
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