[IPk] important new research findings on the 'glitazones' Avandia/Actos etc
Basically while improving insulin sensitivity they also reduce bone density
in research mice and may also produce same effect in humans.
Since more and more of us are suffering from osteopenia or osteoporosis -
and this affects males as well as females - this is an important
For more info see below or at the URL.
This is an article from the
Diabetes in Control newsletter,(item #12)
this week says the following about the 'Actos/Avandia' type drugs:
Bone Is A Target For Rosiglitazone
Rosiglitazone administration results in significant bone loss.
Rosiglitazone improves insulin sensitivity through the activation of
the nuclear receptor, peroxisome proliferator-activated receptor-
In addition to sensitizing cells to insulin, the PPAR- 2 isoform
appears to be critical for the regulation of osteoblast and adipocyte
differentiation from common mesenchymal bone marrow progenitors. We
have demonstrated previously that PPAR- 2 activated with
rosiglitazone acts as a dominant inhibitor of osteoblastogenesis in
murine bone marrow in vitro.
It was shown that in vivo, rosiglitazone administration results in
significant bone loss.
When rosiglitazone (20 5g/g body weight/day) was given to 6 mo
non-diabetic C57BL/6 mice for seven weeks, a significant decrease in
total body bone mineral density was observed. Analysis of bone
microarchitecture, using micro-computed tomography, demonstrated a
decrease in bone volume, trabecular width, trabecular number, and an
increase in trabecular spacing. Histomorphometric analysis showed a
decrease in bone formation rate, with a simultaneous increase in fat
content in the bone marrow. Changes in bone morphology and structure
were accompanied by changes in the expression of osteoblast and
adipocyte-specific marker genes; the expression of the osteoblast-
specific genes Runx2/Cbfa1, Dlx5, and 1(I)collagen were decreased,
whereas the expression of the adipocyte-specific fatty acid binding
protein aP2, was increased.
These in vivo data suggest that rosiglitazone therapy may pose a
significant risk of adverse skeletal effects in humans. Endocrinology
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