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Drs. Adrian LeBlanc, Thomas Lang & John Jurist, Sunday, 5-6-12 May 6, 2012

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Drs. Adrian LeBlanc, Thomas Lang & John Jurist, Sunday, 5-6-12

NASA Bone Loss & Bisphosphonate Study

http://archived.thespaceshow.com/shows/1769-BWB-2012-05-06.mp3

Guests:  CLASSROOM:  Dr. Adrian LeBlanc, Dr. Tom Lang, Dr. John Jurist.  Topics:  Bone loss issues for human spaceflight & the use of bisphosphonates for mitigation.  You are invited to comment, ask questions, and discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com and The Space Show Classroom blog, http://spaceshowclassroom.wordpress.com.  Comments, questions, and any discussion must be relevant and applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright.  In addition, at the end of this summary, you will find links to relevant papers for our discussion as provided us by Dr. Lang.  We welcomed Dr. Adrian LeBlanc, Dr. Tom Lang and Dr. John Jurist as co-host to discuss the NASA bisphosphonate and bone loss study in progress.  Dr. LeBlanc along with his associate in Japan, Dr. Toshio Matsumoto, are leading this study and Dr. Lang is part of the team.  We started our discussion with Dr. LeBlanc providing us with a brief historical overview of bone loss issues of concern to NASA since the early days of the space program.  We talked about Skylab, Mir, the use of the DEXA scan, the use of quantitative computer tomography (QTC) and CT scans through to the ISS, Space Shuttle, and current research projects.  Our discussion was technical at times so if you need to look up or Google a technical term, please do so. In addition, we had some audio issues with the phone line used by Dr. LeBlanc as he faded in and out from time to time.  We apologize for any inconvenience this might have caused.  The first segment went through the bone loss issues, problems, consequences, & the methodologies involved in analyzing the conditions encountered by the astronauts participating in these studies.  Issues we discussed included the use of prescription drugs in space, long term use of bisphosphonates, risk factors for spontaneous hip fractures, exercise programs, bone strength, bone mass, the impact of radiation, skeletal recovery back on Earth after spaceflight to something different than before the spaceflight took place as well as the implications for astronauts as they age.  We talked about using artificial gravity to mitigate bone loss.  You might be surprised to learn that using partial gravity may not help matters.  Bisphosphonates do seem to help and will possibly play a role with exercise as we move to long duration spaceflight but we are in the very early stages of fact finding on these issues.  We also discussed informed consent with the astronauts regarding their participation in these and other experiments.

In the second segment, a listener asked about the relevance of this type of space research to the taxpayer who funds it and to the general population.  Our three guests responded to this question, explaining why the research is relevant and important. Don’t miss their answers.  We then talked about following the astronauts here on Earth to see the continued impact of having been in space on their bones as they age.  We learned that bone changes after being in space for four weeks or more and it is important to follow these changes as part of the aging process.  Our guests talked about calcium excretion issues in space and the risk this causes for a renal stones.  Bisphosphonates may inhibit calcium excretion which would help mitigate this risk.  Near the end of our discussion, we learned about new medications being developed that are more advanced than the bisphosphonates we have today.  We also talked about the competition with astronauts for different scientific experiments.  As Dr. Jurist pointed out, we really do need lots more human spaceflight!  At the end a listener asked about bed rest studies and our guests provided us with the basics.  If you are interested, visit https://bedreststudy.jsc.nasa.gov.  Our guests made important closing comments and take away points.

Please post comments/questions on The Space Show and Classroom blogs.

Dr. Lang provided us with these links that will be of interest to us all.  These documents can be accessed without a subscription to the journals. These papers provide some background to the problem of bone loss in spaceflight, the recovery of bone after spaceflight and use of CT and the use of CT-based finite element modeling to assess bone loss.

Cortical and Trabecular Bone Mineral Loss From the Spine and Hip in Long-Duration Spaceflight http://onlinelibrary.wiley.com/doi/10.1359/JBMR.040307/full

Adaptation of the Proximal Femur to Skeletal Reloading After Long-Duration Spaceflight http://onlinelibrary.wiley.com/doi/10.1359/jbmr.060509/full

Reduction in proximal femoral strength due to long-duration spaceflight http://scholar.google.com/citations?view_op=view_citation&hl=en&user=0zFSO9sAAAAJ&cstart=20&citation_for_view=0zFSO9sAAAAJ:4DMP91E08xMC

Click on link on right “[PDF] from http://cof.org.cn ” for free pdf copy of the report.

Dr. John Jurist, Tuesday, 3-27-12 March 27, 2012

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Dr. John Jurist, Tuesday, 3-27-12

http://archived.thespaceshow.com/shows/1744-BWB-2012-03-27.mp3

Part 1, Bisphosphonate Usage in Microgravity

Guest:  Dr. John Jurist.  Topics:  This is the first in a series of programs focused on the use of bisphosphonates to mitigate bone loss in long duration spaceflight.  You are invited to comment, ask questions, & discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com. Comments, questions, & any discussion must be relevant & applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright.  We welcomed back Dr. John Jurist for the first of several programs devoted to understanding bone loss in microgravity & the use of prescription the bisphosphonate family of drugs to mitigate the problem.  Dr. Jurist provided talking points which you can find below this summary on The Space Show blog.  A significant portion of the second segment is devoted to understanding these talking points so follow along.  We started our discussion with an explanation of the bone loss problem facing those in microgravity.  Following this brief overview, Dr. Jurist told us about bisphosphonates, the origins of this drug, how it was developed, how its usage, what some of the side effects are, some of the trials that have been associated with the drug, & space/NASA studies.  Later in this nearly hour long segment, we talked about the human population & what happens to our bone mass at various stages in our life. We talked about gender, racial, & ethnic differences in human bone mass issues.  As you will hear, there are gender & other differences among our diverse population.  This led us to asking about using targeted genetics in selecting crews for longer spaceflight missions.  Genetic modification was mentioned, especially for the long term, but for the near term, looking for better exercise routines & pharmaceutical modification/treatment seem to hold the most promise.  Dr. Jurist then talked about bisphosphonate side effects.  Fast transit time to Mars or a long duration mission destination came up. As you will hear, even if you get to Mars faster, you still have the problem on the surface of Mars.  The big problem is we have no credible information on what the gravity prescription for humans needs to be so we do not know if Martian gravity is sufficient to mitigate the problem.  Next, we focused on the need for an orbiting centrifuge, we talked about the size & spin rate of the centrifuge, & what to actually test for in experiments.  Dr. Jurist suggested that starting with 1/6th lunar gravity made sense because if it was sufficient, we would know that anything stronger than 1/6th would work.  If not, we should probably next experiment with Martian gravity which is about 1/3rd Earth gravity.

In our second segment, Dr. Jurist referred to his talking points which you will find on The Space Show blog. We went line by line so follow along with us.  Despite interruptions, John stayed on topic with the talking points.  Listener questions asked about how gravity & having a load on bones works & what happens in space when that load is no longer present.  We talked about the time prescription as well as the load factor (G force).  Toward the end, John told us about a reviewed radiation article from 2010 showing that radiation impacted bone loss so the issue in space is more complex than just microgravity.  Near the end, John got a question asking about ETs & their thin, pencil like shape making them perfectly designed for microgravity.  This was both an interesting & fun discussion, bordering on science fiction.  Another question asked about fish, reptilian, sea mammal, & bird bones.  Our final topic dealt with the release of personal astronaut medical information & others & the ways for private information to be legally released to the public.

Please post your comments/questions on The Space Show blog URL above.  Email for Dr. Jurist can be sent to me for forwarding.

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Dr. John Jurist Bisphosphonate Talking Points:

Bisphosphonate show Tues 8:00-9:30 MDT Talking Points

Introduction:             Bone is incredibly complex with many inter-related factorsGoal:                          Brief outline of cellular, structural, and functional aspects of bone metabolism in order to help listeners better understand and appreciate the potential role of bisphosphonates (which is the subject of a future show)

Bone Function:          Two types of bone – compact and trabecular: Compact is outer shell, very dense, and fairly strong

Trabecular – also called spongy, contains spicules, plates, and struts of bone tissue with lots of vascular and fatty marrow, called trabecular

Remodeling:             Bone is constantly being turned over or remodeled with portions being torn down and constituents dumped into bloodstream and other portions being built up from nutrients supplied by blood

Very rapid bone loss can lead to kidney stone formation from calcium dumped into blood

Turnover rate and the volume of total skeleton undergoing remodeling at any given time tends to go down with increasing age (remember this – important)

Balance between formation and resorption (tearing down) also tends to be lost after about age 30, lack of activity, certain hormonal imbalances, diseases, etc. with resorption predominating – one rationale for estrogen replacement therapy after menopause

Coordination between formation and resorption partly controlled by mechanical strains on bone tissue (called Wolff’s Law and issue in microgravity) – some evidence that mechanism is electrical in nature – rationale for electric and electromagnetic bone growth stimulators used to treat problematic fractures and improve incorporation of bone grafts

Cells:                          Stem cells differentiate (or specialize) into osteoprogenitor cells which differentiate into osteoblasts which are the bone formers

Osteoblasts create and secrete a protein and polysaccharide matrix called osteoid which is then calcified later to form the stuff we call bone

Interference in that calcification leads to rickets in children and osteomalacia (Greek for soft bones) in adults

Osteomalacia is often a result of interference in Vitamin D metabolism or dietary deficiencies

During bone formation, some osteoblasts “paint” themselves into a corner and get surrounded by bone – they are then called osteocytes and somehow maintain bone tissue

If osteocytes die in a volume of bone, that devitalized bone no longer undergoes remodeling but can eventually be replaced by a process called creeping substitution (remember comment about remodeling volume going down with age)

Devitalized bone can accumulate fatigue defects and eventually suffer fatigue fractures (called stress fractures – common in military recruits and deconditioned people who recondition too rapidly) if the defects are not replaced by new bone during creeping substitution

Other cells, with multiple nuclei and called osteoclasts, differentiate from marrow cells (monocytes and macrophages) which in turn differentiate from stem cells

Osteoclasts are the bone resorbers and destroyers

Autoradiographic studies show that their nuclei also came from osteocytes as well – presumably as they are resorbed during bone destruction process

Osteoclasts are related to multinucleated “giant cells” which are associated with inflammation in ways I do not understand

Bisphosphonates:      Used over past 20-30 years in clinical medicine – brands include Actonel, Boniva, Fosamax, Aredia, etc.

Multiple mechanisms with different dose-response properties results in clinicians juggling doses and brands to get effects they want without effects they do not want

Bind to hydroxyapatite – the mineralized  portion of bone tissue (calcified osteoid)

Inhibit bone resorption by inhibiting osteoclastic activity

Inhibition of resorption signals osteoblasts to slow down formation rates after a delay (but increases their lifetimes (anti-apotosis)

Bisphosphonates also inhibit mineralization of osteoid – especially at higher doses

That eventually reduces turnover rate and can lead to fatigue fractures with prolonged treatment (remember to call 1-800-BAD-DRUG)

Orthopedic surgeon (Frost atHenryFordHospital) figured out that cyclic therapy exploits delay in osteoblast inhibition relative to osteoclast activity and results in better bone mass gains

Bisphosphonates used in oncology to preserve bone and reduce pathological fractures with osteolytic tumors such as breast and prostate cancers.  Also to counter hormonal blocking therapy used for prostate and breast cancers, but side effects increase with duration of treatment

Interesting sidelight with oncology is some evidence that bisphosphonates reduce risk of tumor metastasis to bone and other sites (somehow involving same signaling pathway as giant cells?)

Oral bisphosphonates cause stomach upset – advise staying upright for an hour or two after taking pill – how does this affect microgravity exposure?

Intravenous bisphosphonates get around oral gastric upset, but placing line or port has risks too (most oncology patients have ports during active treatment)

Also cause osteonecrosis – especially jaw which I believe is septic or infective – and atrial fibrillation (talk to Bill Rowe on this one since he is interested in heart physiology in space)

Bone quality:             Turnover rates and percent of skeleton not devitalized important factors in determining bone strength – measuring bone mass by DEXA or other means is not the be all and end all in evaluating bone strength and risk of fracture.

My Goal:                   General background on bone physiology and function to aid in appreciating upcoming show(s) on bisphosphonates in space medicine

John Batchelor “Hotel Mars,” Wednesday, 12-7-11 December 8, 2011

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John Batchelor “Hotel Mars,” Wednesday, 12-7-11

This segment features Mr. Batchelor,  Dr.Space and Dr. John Jurist discussing bone loss in space

http://archived.thespaceshow.com/shows/1668-BWB-2011-12-07.mp3

Guests:  John Batchelor, Dr. David Livingston, Dr. John Jurist.  Topics:  Bone loss issues for short and long duration spaceflight.  You are invited to comment, ask questions, and discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com.  Comments, questions, and any discussion must be relevant and applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright. The Space Show/OGLF is now engaged in its annual fundraising drive. Please see & act upon our appeal at https://thespaceshow.wordpress.com/2011/11/21/space-show-2011-fundraising-campaign.  As many of you know, I have been doing a weekly segment on the John Batchelor Radio Show with Mr. Batchelor on various space topics.  Sometimes I appear with John as the only guest on the segment, at other times I co-host the segment with John and bring on board an expert in the subject being discussed. Mr. Batchelor has given The Space Show permission for these segments to be archived on The Space Show site and blog.  Mr. Batchelor calls these segments “Hotel Mars” and they are targeted toward his significant live and podcast highly educated general audience.  Find out more about the excellent John Batchelor Show and listen to his archived segments at http://johnbatchelorshow.com.  You can hear the live stream of his show if it is not carried live in your radio market at www.wabcradio.com/article.asp?id=531472.  For this segment of Hotel Mars, we discussed bone loss in space and the use of the class of drugs known as bisphosphonates in treating bone loss issues.  This discussion was prompted by various news reports such as this one:  www.dispatch.com/content/stories/national_world/2011/12/06/osteoporosis-drugs-helped-astronauts-scientists-say.html.  Our special guest was Dr. John Jurist and I co-hosted the segment with Mr. Batchelor.  During our eleven minute segment, we addressed bone loss issues for both short duration and long duration spaceflight.  We talked about the use of bisphosphonates, the benefits and the risks associated with them.  We also addressed artificial gravity, issues of both lunar and Martian gravity, and the seriousness of the bone loss issue as well as the other human factors issues primarily for the longer duration voyages.  Post any comments/questions that you might have regarding this John Batchelor Show segment on The Space Show blog URL above.  We thank Mr. Batchelor for allowing us to archive this segment on The Space Show website and blog.  Please note that the copyright to this material remains with The John Batchelor Show.  Any and all uses of this material must be approved by John Batchelor.

Open Lines, Tuesday, 12-6-11 December 7, 2011

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Open Lines, Tuesday, 12-6-11

http://archived.thespaceshow.com/shows/1667-BWB-2011-12-06.mp3

Guest:  Open Lines with Dr. David Livingston.  Topics: Bone loss issues, Droid podcast suggestions, bisphosphonates in space, reusability, flyback boosters.  You are invited to comment, ask questions, and discuss the Space Show program/guest(s) on the Space Show blog, https://thespaceshow.wordpress.com.  Comments, questions, and any discussion must be relevant and applicable to Space Show programming. Transcripts of Space Show programs are not permitted without prior written consent from The Space Show (even if for personal use) & are a violation of the Space Show copyright.  The Space Show/OGLF is now engaged in its annual fundraising drive. Please see & act upon our appeal at https://thespaceshow.wordpress.com/2011/11/21/space-show-2011-fundraising-campaign. During the announcement part of the program at the beginning, I talked about another Droid podcast possible solution from a listener using the DoggCatcher app. I also mentioned recent general press articles about success being claimed with the use of bisphosphonates to stop bone loss in space: www.dispatch.com/content/stories/national_world/2011/12/06/osteoporosis-drugs-helped-astronauts-scientists-say.html.  As mentioned on the air, I’m on the nationally syndicated radio show, The John Batchelor Show, tonight, Wednesday, Dec. 7, 6:30-6:45 PM PST discussing this as co-host with John.  The expert guest is Dr. John Jurist, a lifetime member of the aerospace medical association and one of the early researchers on this issue back when NASA was starting such research.  You can hear us live at www.wabcradio.com/article.asp?id=531472.  If you miss the live stream, the segment will be archived the next day at John’s website, http://johnbatchelorshow.com.  For your information, I typically do the Wednesday evening segment at either 6:30 PM or at 6:45 PM PST.  I am often on air alone with John but sometimes I bring in an expert to discuss a specific topic such as tonight with Dr. Jurist.  I also went over my December schedule for programming as my travel plans to Los Angeles are now known as are Space Show plans for the balance of the year.  Our first caller was Jeff from the UK who wanted to talk mostly about the new Earth-like planet that Kepler has found, the Kepler-22b.  We also talked about faster than light travel, the recent neutrino experiment, photons, and more.  Charles was the next caller and we talked more about the new planet found by the Kepler Space Telescope. Charles mentioned the two planet finding methods, the transit and the wobble methods.  He also mentioned Armadillo Aerospace and their recent success with the STIGA A launch vehicle. You can read about it and see the video at www.rlvnews.com.  Scroll down to this headline:  STIG A – another video + recovery info.  In the next segment, Tim called in with questions about the Air Force contract for the flyback booster which went to Lockheed and will use Spaceport America. This prompted quite a discussion on reusability, flyback boosters and their payload penalties, ocean recovery for the first stage, and expendable, renewable, and disposable rockets.  Our caller also inquired about nuclear power and the plan to do a ballot initiative in California to shut down the California nuclear power plants though they generate 16% of California’s electrical power.  John from Atlanta called in to talk about ocean recovery, the faster than light experiment and his thoughts that tachyons provide a reasonable explanation for the faster than light experiment.  During the program, we also discussed on orbit repair for both LEO and GEO satellites and what the future might hold for such efforts.  Please post your comments/questions on The Space Show blog URL above.