Biomedical Engineering Reference
In-Depth Information
acutely slow the initial rate of primary mineralization within the first month, but
that subsequent secondary mineralization occurs normally and allows the final
level of mineralization to be equivalent to that of untreated bone. However, more
recently, Fuchs et al. showed that administration of risedronate or alendronate had
no effect on the rate of either primary or secondary mineralization [
65
]. While both
drugs increase the overall mineralization of the tissue by suppressing remodeling
and allowing more sites to achieve full mineralization, they don't alter the rate at
which full mineralization is achieved. There also was no significant effect after one
year of treatment on the final level of BMU mineralization, suggesting that hyper
mineralization at the BMU does not occur.
Increased mineralization will increase both the strength and the stiffness of
bone—an important design goal for reducing the risk of fracture—but increased
material stiffness is inevitably associated with reduced energy absorption
(toughness) [
66
]. Post-yield stress and strain are also compromised by increasing
levels of mineralization [
67
]. In this regard, the 8-10% increases in mean degree
of mineralization reported following 2-3 years of alendronate treatment could be
cause for concern. On the other hand, more recent studies in animals [
68
] show no
relationship between small (*2%) increases in overall tissue mineralization
(percent ash weight) that occur with 1-3 years of bisphosphonate treatment, and
toughness.
4.2 Collagen and the Organic Matrix
Bone collagen contains both enzymatic and non-enzymatic collagen crosslinks that
stablize the matrix and have significant impact on the bone's mechanical prop-
erties. The organic matrix constitutes the principal toughening mechanism in bone,
and therefore plays a substantial role in determining properties of energy
absorption/toughness [
69
]. Changes in the organic matrix may have some effect on
pre-yield tissue strength and stiffness [
70
,
71
], although these properties are pre-
dominantly determined by the mineral fraction. Cross-links formed through non-
enzymatic processes are associated with tissue that is more brittle [
72
], and has
reduced post-yield deformation [
73
,
74
], work to fracture [
75
,
76
], and toughness
[
77
].
Following one-year of treatment with a wide-range of BP doses, the ratio of
pyridinoline to deoxypyridinoline (PYD/DPD, an index of increasing cross-link
maturity) in the trabecular bone of lumbar vertebrae was significantly increased
compared to vehicle-treated animals. The level of pentosidine, an advanced
glycation end-product (AGE) was significantly increased in vertebral trabecular
bone and cortical bone of the tibia from bisphosphonate treatment animals com-
pared to controls [
75
,
77
]. In a separate experiment, levels of pentosidine were
found to be increased in the rib of dogs following 3 years of treatment with
incadronate [
78
]. Limited data exist assessing collagen crosslinks in humans
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