Biomedical Engineering Reference
In-Depth Information
postmenopausal women. Estimates place the prevalence without bisphosphonate
treatment at about 7/100,000 person-years in women 55-74 years old, and 34-74/
100,000 person-years in women older than 75 years [
50
]. However, atpypical
femoral fractures—defined as low energy fractures that result in a transverse or
oblique fracture orientation, with a medial spike and a lateral periosteal stress
reaction-may only account for about one-third of all subtrochanteric fractures,
many of which are spiral and not transverse [
51
,
52
].
The investigators found that only 7% of patients who presented with atypical
femoral fractures had been exposed to alendronate, the same percentage as those
with a typical hip fracture. As alendronate is known to reduce the risk for hip
fracture, this would suggest that alendronate use does not contribute to atypical
femoral fractures. The risk associated with ''subtrochanteric/diaphyseal'' femoral
fractures in patients on alendronate was 1.46, compared to 1.45 for hip fracture,
after adjustment for co-morbidity and co-medications. The overall conclusion is
that atypical femoral fractures are probably another brand of osteoporotic fracture,
and that fracture risk is not increased by the use of alendronate. A more recent
study [
53
] that re-analyzed subtrochanteric/diaphyseal fractures from three large
clinical trials of BPs suggest calculated relative hazard ratios from 1.03 for those
treated with alendronate, to 1.5 for those women treated with zoledronate. They
conclude that treatment for three years with alendronate would prevent 10-fold
more hip fractures than it would cause, and that treatment even for 10 years does
not pose a significant risk for atypical femoral fractures.
The concept of BPs increasing fracture risk is certainly counterintuitive given
these agents are prescribed for, and known to be effective in, reducing fractures.
However, BPs exert well-known effects on bone tissue that tend to make the tissue
more brittle (see
Sect. 4
). It is possible that in the short term, increases in BMD
offset negative changes in the tissue level, yet over the long term (or in some
patients) the detrimental effects on the tissue reach a point that even with a higher
BMD the patient fractures.
4 The Effects of BPs on Bone Matrix Properties
BPs are effective in reducing the risk of fracture in postmenopausal women at least
over 10 years [
54
], but numerous studies demonstrate that they negatively affect
bone tissue quality. This means that the benefit of BPs for reducing fracture is due
primarily to maintenance/small increases in bone mass and volume. BP treatment
is associated with increases in bone mineralization, microdamage, and alterations
in the cross-linking of collagen (Fig.
4
). Any of these changes, either alone or in
combination, could potentially compromise the mechanical properties of the tis-
sue. Pre-clinical studies have shown consistently that the mechanical properties of
the tissue, specifically material toughness (the normalized energy to fracture) are
reduced with BP-treatment. Following 1-3 years of treatment at doses at or above
those used in postmenopausal women, bone toughness is 20-30% lower compared
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