Bisphosphonates and PTH for Preventing Fractures - Skeletal Aging and Osteoporosis: Biomechanics and Mechanobiology - page 153

Fig. 3 Effects of
bisphosphonates on iliac crest
activation frequency.
Activation frequency, a
histological variable used to
evaluate the rate of bone
remodeling, has been
assessed in separate clinical
trials. These data show
significantly lower values in
BP-treated patients compared
to placebo controls in each of
the four trials. See text for
individual study references
crest [ 29 ] activation frequency. No such dose-response was shown in a similar
analysis using doses of alendronate in dogs [ 28 ]. Ovariectomized non-human
primates showed a dose-response in remodeling suppression after 18 months of
treatment with ibandronate [ 30 ]. Human studies hint at a dose-response in
remodeling suppression of the iliac crest in post-menopausal women treated with
alendronate yet this was only observed at doses below those used clinically [ 31 ].
Alendronate significantly suppresses remodeling more than risedronate [ 32 , 33 ]
and zoledronate suppresses more than risedronate [ 34 ]. There are no head-to-head
assessments of bone remodeling using histology, yet in separate studies the percent
suppression of remodeling relative to placebo controls tends to be relatively
similar over 3 years with daily risedronate [ 35 ], daily alendronate [ 36 ], intermit-
tent oral ibandronate [ 37 ], and intravenous yearly zoledronate [ 38 ] (Fig. 3 ).
The effect of BPs on bone turnover is highly location specific and when
assessed histologically can differ by an order of magnitude across skeletal sites.
There is also a time-dependent effect on remodeling suppression. Remodeling was
reduced only 15% in the mandible after 6 months of treatment with clinical doses
of alendronate [ 39 ], but treatment for three years at these same doses reduced
alveolar remodeling by 67% compared to vehicle-treated controls [ 40 ]. The same
time-dependent suppression was shown in the rib where clinical doses had no
effect after one year but reduced remodeling by more than 85% in the following
three years with osteoporosis treatment doses [ 41 , 42 ]. Clearly, the effect of BP
treatment on remodeling suppression is dose, time, and location dependent and
also differs among the specific BPs.
3.2 On and Off Effect of Remodeling Suppression
Animal studies show that normal trabecular bone remodeling tends to be
re-established sooner in animals previously treated with risedronate compared to