Re: Bisphosphonates
From: Terrence.Jones@kp.org
Fri Apr 28 15:22:11 2006
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Think Gary spelled it out: 5 years appears to be arbitrary. Without a
reasonable, validated, and reproducible method of volumetric assessment of
3-D architectural response (qCT) we're stuck with the areal 2-D surrogate
marker ( photon absptn.) for now. If she had gone from (-3.1) to (-1.5)
might consider the d/c, rechk and resume approach. If She is "stabilized"
at (-2.5), well that's the marker for Rx. The bisphosphonate is
incorporated into the matrix. It is released by the enzymatic degradation,
released from the ruffled border of the osteoclast, upon activation. It
then induces apoptosis via a prenyl protein mechanism. (The cell: "hoists
with its own petard".) So strictly speaking, there HAS to be some
osteoclast activity in order for the agent to exert its effect. So Gary,
the injectables, by getting higher serum (and thereby bone matrix) levels,
can not only avoid the major toxicity (esophageal stricture from reflux),
but space out the dosing inteval as well. Awaiting the US compnonent of
the "Horizon" trial - once yearly Zoledronic acid (Zometa). In certain
clinical situations, (ie: limited predictability WRT individual variation
and measurement validity), sometimes "shooting from the hip" is the
"right" answer - a sniper might be shooting blind. (Apologies to the NAPA
valley folks for the "Sniper" reference; as Beringer and Sharpshooter may
be a little too close to Home...) /tj
PS: YES, Anna - Wooley will watch Flight 93 - and send a critical scathing
to NPR movie reviews, outlining its inaccuracies. "The Sun Also Rises" &
and the bulls will run in Pamplona.
CONFIDENTIAL OR PRIVILEGED: This communication contains information intended only for the use of the
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garrys@mindspring.com (Garry E. Siegel, M.D.)
Sent by: ob-gyn-l@obgyn.net
04/28/2006 06:58 AM
Please respond to ob-gyn-l
To: Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net>
cc:
Subject: Re: Bisphosphonates
It sure is nice to be unencumbered with knowledge or knowledge of the
literature, as shooting from the hip is so easy. I'm optimistic that
one of the fine listers (Terrence) will give you the "right" answer
soon, should it exist.
Bone growth and loss are slow processes, like watching paint dry.
I don't think that there is much reason to repeat studies more often
than every few years. Arbitrarily, I go for 5, as 2 years (what we all
"grew up" with) is just not long enough to see much change, given the
slow nature of change and the inherent imprecision in any measurement.
I would keep her on them forever, as best we know.
Does anyone think that oral or IV Boniva is a fair/safe substiture for
Actonel weekly or Fosamax weekly?
Garry
At Fri, 28 Apr 2006, Joanne Bulley, MD wrote:
>
>When you are treating woment with a bisphosphonate do you
>
>1) leave her on it forever
>
>2) treat for 1-5 years and stop and observe
>
>3) something else.
>
>How long do you think she should remain on the bisphosphonates?
>
>I have a patient whose mother had horrible osteoporosis. Mom was put on
>Fosamax (After many fractures) and stayed on treatment until at end of
>life from other isseus. When they stopped the fosamax, the daughter
>said it was as if the bones started shanging shape - getting
>protuberances that could be seen and felt by the caregivers (primarily
>this daughter). Have any of you seen that sort of thing when coming off
>Fosamax after 10-15 years use?
>
>I have asked the question at a number of conferences regarding IF the
>bisphosphonate permanently blocks the osteoclasts - what happens IF the
>woman had a standard fracture after being on the drug for 5-10-20 years?
>Can the bone still remodel and if so does it remodel properly?
>
>I have never gotten any sort of straight answer - usually some skirting
>the issue and "we don't really know"
>
>This patient of mine has now been on Fosamax since 2001. Spinal BMD
>down to T score of -3.1 at its nadir and femur at -2.2. Both have come
>up some and staibilized at spine -2.5, femur -2.0 on treatment. I have
>explained the bone microarchitecture and the decrease fracture risk even
>if the numbers don't head back toward T score of 0. She has had a
>couple of significant falls without fracure.
>
>Anyhow - I have seen docs treat for 2-3 years then give a break - but
>what are Listers doing? As others have said - this is where I get
>valuable in-the-trenches information!
>
>--
>Joanne Bulley, MD
>Keene, NH, USA
>
>"Love is indescribable and unconditional.
>I could tell you a thousand things that it is not, but not one that it
is."
>? Duke Ellington, American jazz artist (1899-1974).
>
--
Garry E. Siegel, M.D.
Private Practice
Roswell, GA
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<br><font size=2 face="sans-serif">Think Gary spelled it out: 5 years appears to be arbitrary. Without a reasonable, validated, and reproducible method of volumetric assessment of 3-D architectural response (qCT) we're stuck with the areal 2-D surrogate marker ( photon absptn.) for now. If she had gone from (-3.1) to (-1.5) might consider the d/c, rechk and resume approach. If She is "stabilized" at (-2.5), well that's the marker for Rx. The bisphosphonate is incorporated into the matrix. It is released by the enzymatic degradation, released from the ruffled border of the osteoclast, upon activation. It then induces apoptosis via a prenyl protein mechanism. (The cell: "hoists with its own petard".) So strictly speaking, there HAS to be some osteoclast activity in order for the agent to exert its effect. So Gary, the injectables, by getting higher serum (and thereby bone matrix) levels, can not only avoid the major toxicity (esophageal stricture from reflux), but space out the dosing inteval as well. Awaiting the US compnonent of the "Horizon" trial - once yearly Zoledronic acid (Zometa). In certain clinical situations, (ie: limited predictability WRT individual variation and measurement validity), sometimes "shooting from the hip" is the "right" answer - a sniper might be shooting blind. (Apologies to the NAPA valley folks for the "Sniper" reference; as Beringer and Sharpshooter may be a little too close to Home...) /tj</font>
<br>
<br><font size=2 face="sans-serif">PS: YES, Anna - Wooley will watch Flight 93 - and send a critical scathing to NPR movie reviews, outlining its inaccuracies. "The Sun Also Rises" & and the bulls will run in Pamplona. <br>
<br>
</font><font size=1 color=blue face="Arial"><b>CONFIDENTIAL OR PRIVILEGED:</b></font><font size=1 face="Arial"> This communication contains information intended only for the use of the individuals to whom it is addressed and may contain information that is privileged, confidential or exempt from other disclosure under applicable law. If you are not the intended recipient, you are notified that any disclosure, printing, copying, distribution or use of the contents is prohibited. If you have received this in error, please notify the sender immediately by telephone or by returning it by reply email and then permanently deleting the communication from your system. Thank you.<br>
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<td><font size=1 face="sans-serif"><b>garrys@mindspring.com (Garry E. Siegel, M.D.)</b></font>
<br><font size=1 face="sans-serif">Sent by: ob-gyn-l@obgyn.net</font>
<p><font size=1 face="sans-serif">04/28/2006 06:58 AM</font>
<br><font size=1 face="sans-serif">Please respond to ob-gyn-l</font>
<br>
<td><font size=1 face="Arial"> </font>
<br><font size=1 face="sans-serif"> To: Multiple recipients of list OB-GYN-L <ob-gyn-l@dns.obgyn.net></font>
<br><font size=1 face="sans-serif"> cc: </font>
<br><font size=1 face="sans-serif"> Subject: Re: Bisphosphonates</font></table>
<br>
<br><font size=2 face="Courier New">It sure is nice to be unencumbered with knowledge or knowledge of the<br>
literature, as shooting from the hip is so easy. I'm optimistic that<br>
one of the fine listers (Terrence) will give you the "right" answer<br>
soon, should it exist.<br>
<br>
Bone growth and loss are slow processes, like watching paint dry.<br>
<br>
I don't think that there is much reason to repeat studies more often<br>
than every few years. Arbitrarily, I go for 5, as 2 years (what we all<br>
"grew up" with) is just not long enough to see much change, given the<br>
slow nature of change and the inherent imprecision in any measurement.<br>
<br>
I would keep her on them forever, as best we know.<br>
<br>
Does anyone think that oral or IV Boniva is a fair/safe substiture for<br>
Actonel weekly or Fosamax weekly?<br>
<br>
Garry<br>
<br>
At Fri, 28 Apr 2006, Joanne Bulley, MD wrote:<br>
><br>
>When you are treating woment with a bisphosphonate do you<br>
><br>
>1) leave her on it forever<br>
><br>
>2) treat for 1-5 years and stop and observe<br>
><br>
>3) something else.<br>
><br>
>How long do you think she should remain on the bisphosphonates?<br>
><br>
>I have a patient whose mother had horrible osteoporosis. Mom was put on<br>
>Fosamax (After many fractures) and stayed on treatment until at end of<br>
>life from other isseus. When they stopped the fosamax, the daughter<br>
>said it was as if the bones started shanging shape - getting<br>
>protuberances that could be seen and felt by the caregivers (primarily<br>
>this daughter). Have any of you seen that sort of thing when coming off<br>
>Fosamax after 10-15 years use?<br>
><br>
>I have asked the question at a number of conferences regarding IF the<br>
>bisphosphonate permanently blocks the osteoclasts - what happens IF the<br>
>woman had a standard fracture after being on the drug for 5-10-20 years?<br>
>Can the bone still remodel and if so does it remodel properly?<br>
><br>
>I have never gotten any sort of straight answer - usually some skirting<br>
>the issue and "we don't really know"<br>
><br>
>This patient of mine has now been on Fosamax since 2001. Spinal BMD<br>
>down to T score of -3.1 at its nadir and femur at -2.2. Both have come<br>
>up some and staibilized at spine -2.5, femur -2.0 on treatment. I have<br>
>explained the bone microarchitecture and the decrease fracture risk even<br>
>if the numbers don't head back toward T score of 0. She has had a<br>
>couple of significant falls without fracure.<br>
><br>
>Anyhow - I have seen docs treat for 2-3 years then give a break - but<br>
>what are Listers doing? As others have said - this is where I get<br>
>valuable in-the-trenches information!<br>
><br>
>--<br>
>Joanne Bulley, MD<br>
>Keene, NH, USA<br>
><br>
>"Love is indescribable and unconditional.<br>
>I could tell you a thousand things that it is not, but not one that it is."<br>
>— Duke Ellington, American jazz artist (1899-1974).<br>
><br>
<br>
--<br>
Garry E. Siegel, M.D.<br>
Private Practice<br>
Roswell, GA<br>
</font>
<br>
