Biomedical Engineering Reference
In-Depth Information
was associated with this reduction in microdamage, such a conclusion seems
eminently plausible.
Notably, even though the co-administration or prior administration of a bis-
phosphonate will blunt the subsequent effect of PTH on BMD, the response of co-
treatment is still better than switching entirely to PTH once the bisphosphonate
therapy has begun. Adding teriparatide to ongoing therapy with either alendronate
or raloxifene improves BMD more than stopping the anti-resorptive therapy and
switching to PTH [ 122 ]. Co-administration of an anti-resorptive (either raloxifene
or alendronate) with PTH (1-84) still provides greater increases in hip BMD than
did PTH (1-84) alone [ 120 , 130 ]. Whether this is true for other skeletal sites is not
clear; these results may be both a function of the regulation of the PTH-stimulated
effects on bone remodeling specifically at the hip, and the short period of PTH
administration (6 months).
Concurrent administration of PTH with a BP does not appear to generate either
additive or synergistic effects. To some extent, any advantage appears dominated
by the role of BPs. Thus, increases in spine BMD are not greater with co-
administration of PTH + alendronate than either drug alone, and BMD at the hip is
greater in the groups treated with alendronate, whether in combination with PTH
or not, than with administration of PTH alone [ 120 , 131 ]. However, when PTH
treatment is followed by administration of alendronate, BMD continues to increase
in the spine [ 131 ]. A meta-analysis of combination treatments showed that PTH
treatment either with or without co-administration with a BP reduced the risk of
vertebral fracture by 64%, and of non-vertebral fracture by 38%, compared to 48
and 49% respectively for alendronate alone. This would suggest that PTH alone or
in combination has a greater positive benefit on the spine, whereas administration
of a BP alone has a better profile for the hip. However, these results are prob-
lematic in that they pool studies in which inclusion criteria, dose and duration
vary.
Current treatment regulations only allow administration of teriparatide for up to
2 years, because of a perceived risk of osteosarcoma that was identified in pre-
clinical trials in rats which received lifetime administration of PTH [ 132 ]. How-
ever, cessation of treatment with PTH will, within 18-30 months [ 96 , 133 ], result
in a reduction in BMD and an increase in vertebral fracture risk. Subsequent
treatment with a BP after full exposure to teriparatide will stabilize or increase
BMD and reduce fracture risk [ 96 ].
9 Conclusion
Bisphosphonates are the most widely used anti-catabolic agents to prevent frac-
tures in various forms of osteoporosis, and to prevent metastasis to bone in certain
kinds of cancer. Teriparatide (rhPTH 1-34) currently is the only anabolic agent
available to treat osteoporosis. Both classes of therapy have their own specific
profile, mechanisms of action, and effects on bone mass, architecture and tissue
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