Biomedical Engineering Reference
In-Depth Information
Table 1 Increased vertebral BMD and reduced fracture incidence after 3 years treatment with
different bisphosphonates
6
Compound
Suppression of turnover
5
Increased BMD
Reduction in fracture indicies
Alendronate
1
6.2%
50%
92%
Risedronate
2
5.4%
41%
40%
Ibandronate
3
6.5%
50%
50%
Zoledronate
4
6.7%
70%
63%
1
See references [
134
,
135
]
2
See reference [
136
]; this varies depending on the dose
3
See reference [
137
]
4
See reference [
138
]
5
See text for references
6
For comparison of vertebral fracture rates among bisphosphonate treatments, see [
139
]
3 The Effects of BPs on Remodeling Suppression
Binding affinity of the drug can have a significant effect on the accumulation of
the BP within the bone matrix, the speed with which its effect is initiated, the
reversibility of effect once the drug is withdrawn [
17
], as well as diffusion of
the drug into the bone [
12
,
14
] and potential recycling of BP released consequent
to bone remodeling [
18
]. Differences in the mineral binding affinities of BPs used
clinically are, in rank order from highest mineral affinity, with their affinity con-
stants (K
L
9 10
6
)[
19
,
20
]:
zoledronate 3
:
ðÞ
[ alendronate 2
:
ð
[ ibandronate 2
:
ðÞ
[ risedronate 2
:
ðÞ
Consistent with the affinity constants, approximately 50% more risedronate is
excreted than alendronate after 24 h [
21
,
22
], resulting in significantly greater
skeletal retention of alendronate compared to risedronate after 28 days.
BPs also demonstrate different potencies in their effect on osteoclast FPPS.
Differences in FPPS inhibition of bisphosphonates used clinically are, in rank
order from the highest to lowest [
23
,
24
]:
zoledronate [ risedronate [ ibandronate [ alendronate
It is these two properties—binding affinity and potency on osteoclasts-along
with the dose and route of administration-that determine the physiological effects
on bone remodeling which are similar in some respects yet differ with regard to the
magnitude of suppression, speed of onset of effect, and skeletal retention.
3.1 Magnitude and Site Specificity of Remodeling Suppression
Bisphosphonates accumulate in the skeleton in a dose-dependent manner [
25
-
27
].
Treatment of dogs with a wide range of risedronate doses (including the post-
menopasual osteoporosis dose) show a dose-response in vertebral [
28
] and iliac
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