Biomedical Engineering Reference
In-Depth Information
treated with BPs. Using FTIR (Fourier Transformed Infrared Spectroscopy) BPs
had no effect on collagen maturity in iliac crest biopsies [
79
].
4.3 Microdamage
Bisphosphonate treatment is associated with changes in both the initiation and
repair of microdamage. This has been demonstrated repeatedly in animal models
using various different oral bisphosphonates at doses ranging from to 69 the
dose used for treatment of post-menopausal osteoporosis, and with treatment
durations lasting from 1 to 3 years. Significantly higher levels of microdamage are
consistently noted in the trabecular bone of the lumbar vertebrae and cortical bone
of the rib with bisphosphonate treatment [
80
]. Although increased levels of mi-
crodamage have also been noted in the ilium, thoracic spinous process, and
femoral neck of dogs treated with bisphosphonates, these sites appear less prone to
significant microdamage accumulation (\2-fold relative to untreated) [
57
,
80
].
This site-specificity may be important in evaluating damage accumulation in bone
from human patients; as such evaluations can only occur from iliac crest biopsies
which may underestimate the amount of damage accumulating in the spine or ribs.
Recent data from iliac crest biopsies of treatment naïve women and women treated
for 5 years with alendronate show increased microdamage accumulation with
bisphosphonate treatment [
81
]. Both low femoral neck BMD and increasing age
were associated with greater microdamage formation, suggesting that older
patients with especially low BMD might be more at risk for damage accumulation.
A separate study in which iliac crest biopsies of women treated with alendronate
were compared to cadaveric bone showed no significant difference in micro-
damage levels, although in this study the cadavers used as ''untreated controls'
were almost 10 years older than the treated patients [
82
]. The well-known age-
related increase in microdamage [
83
-
85
], therefore, may make this an unsuitable
control population. Moreover, there was no independent verification that the
control population had not used bisphosphonates while alive.
The increased brittleness caused by changes to bone's organic matrix and
mineralization allow for greater initiation of microdamage [
80
]. In the majority of
studies that have documented increased microdamage with BP-treatment, a con-
comitant decrease in bone toughness has also been quantified [
28
,
55
-
57
,
86
].
However, recent studies assessing microdamage and biomechanical properties in
dog vertebra suggest microdamage accumulation may not be the predominant
reason for reduced toughness [
55
]. In a one year study using various doses of
alendronate or risedronate, there was minimal congruence between changes in
microdamage accumulation and material-level toughness in vertebrae from several
groups of bisphosphonate-treated dogs [
28
]. Although these data do not eliminate
the possibility of a direct cause/effect connection, they suggest factors other than
microdamage contribute significantly to the material-level biomechanical changes
associated with bisphosphonate treatment. This conclusion is supported by data
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