New study on immune system and osteo

This is an interesting new study---I posted the whole thing because the link wouldn't work. It correlates high LDL with RANKL which has a sole purpose to destroy bone. Also, the immune system plays a bigger role in bone loss than they previously thought.
I wonder if this may be why so many people who have autoimmune diseases also have osteo---especially thyroid disease. Anyone know if you can you be tested for RANKL levels?

STUDY:
Immune System's Role In Bone Loss Uncovered; Finding Could Lead To New Therapies For Osteoporosis
ScienceDaily (Aug. 26, 2009) —

Got high cholesterol? You might want to consider a bone density test.
A new UCLA study sheds light on the link between high cholesterol and osteoporosis and identifies a new way that the body's immune cells play a role in bone loss.
Published Aug. 20 in the journal Clinical Immunology, the research could lead to new immune-based approaches for treating osteoporosis. Affecting 10 million Americans, the disease causes fragile bones and increases the risk of fractures, resulting in lost independence and mobility.
Scientists have long recognized the relationship between high cholesterol and osteoporosis, but pinpointing the exact mechanism connecting the two has proved elusive.
"We've known that osteoporosis patients have higher cholesterol levels, more severe clogging of the heart arteries and increased risk of stroke. We also knew that drugs that lower cholesterol reduce bone fractures, too," explained Rita Effros, professor of pathology at the David Geffen School of Medicine at UCLA. "What we didn't understand was why."
Effros suspected a clue to the mystery involved oxidation -- cell and tissue damage resulting from exposure of the fatty acids in cholesterol to molecules known as free radicals.
In the study, UCLA researchers focused on low-density lipoprotein (LDL), the so-called "bad" cholesterol. They examined how high levels of oxidized LDL affect bone and whether a type of immune cell called a T cell plays a role in the process.
Using blood samples from healthy human volunteers, the team isolated the participants' T cells and cultured them in a dish.
Half of the T cells were combined with normal LDL– the rest was combined with oxidized LDL. The scientists stimulated half of the T cells to mimic an immune response and left the other half alone.
"Lo and behold, both the resting and the activated T cells started churning out a chemical that stimulates cells whose sole purpose is to destroy bone," said Effros. Called RANKL, the chemical is involved in immune response and bone physiology.
To investigate further how the immune system participates in bone loss, the scientists repeated the experiment in a mouse model.
Half the animals were fed a high-fat diet starting at one month of age, while the control group ate a normal diet. At 11 months, the mice on the high-fat diet showed elevated cholesterol and thinner bones.
When Effros and her colleagues tested the T cells of the mice on the high-fat diet, they discovered that the cells acted differently than those of the mice on the normal diet.
The T cells switched on the gene that produces RANKL. The chemical also appeared in the animals' bloodstream, suggesting that the cellular activity contributed to their bone loss.
"It's normal for our T cells to produce small amounts of RANKL during an immune response," explained Effros. "But when RANKL is manufactured for long periods or at the wrong time, it results in excessive bone damage."
"That's exactly what happened to the mice on the high-fat diet," she said. "The animals' high cholesterol increased their levels of oxidized LDL, which told the T cells to keep generating RANKL. This discovery revealed to us how the immune system might play an entirely new role in bone loss."
The next step will be exploring methods to control T cell response to oxidized LDL in an effort to develop immune-based approaches to prevent or slow bone loss, Effros says.
The study was funded by the National Institute on Aging, the National Institute of Allergy and Infectious Diseases and the National Heart, Lung and Blood Institute.
Effros' coauthors were Lucia Graham, Farhad Parhami, Yin Tintut, Christina Kitchen and Linda Demer, all of UCLA.

By drizzit
Posted September 7, 2009 at 9:46 pm
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Interesting since the first RANKL drug is before the FDA awaiting approval now. This seems to reinforce the research that went into the drug.

I have an auto immune disease and the RANKL med has the promise to be incredible effective for me and hit at the root cause of my osteo.

By gishy
Posted September 8, 2009 at 9:29 am
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Thank you for the information Sante Fe.

I believe that multiple clinical trials are in progress to investigate the therapeutic potential of RANKL inhibition by denosumab, a fully human monoclonal anti-RANKL antibody, in the treatment of postmenopausal osteoporosis and other bone loss diseases.

I have read on here that some Members are taking this drug, perhaps it's passed the clinical trial stage?

Drizzit, I hope the research is a way forward for you.

Gishy

By VictoriaLynn
Posted September 8, 2009 at 10:00 am
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Wonder if this holds true for other auto immune diseases? I have celiac disease and my osteo has been blamed on that.
Anyone else get overwhelmed by the amount of info on Osteo... and how sometimes direct opposite advice is given. How do you make good choices?

By caremanager
Posted September 8, 2009 at 10:07 am
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I also have an auto-immune disease, have osteoporosis, had to go off Forteo due to length of treatment, cannot tolerate biphosphonates and have been anxiously awaiting denosumab but have been told it is not yet on the market. Those of you who are using it--how are you getting it? Does anyone know if it is safe to use denosumab concurrently with Remicaide therapy which I receive every 6-7 weeks or will my immune system be over suppressed. Does anyone know if the Remicaide suppresses RANKL and I do not need denosumab? The correllation between LDL's is fascinating because that is something I have been battling but also cannot tolerate statins. Does anyone know who might have the answers to these questions because the doctors do not have much more information than I do so I guess these decisions will have to be mine based on a lot of personal research.
Thank you for this wonderful post--could not have shown up on my computer at a better time!!

By SantaFe
Posted September 8, 2009 at 11:22 am
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Hi Everyone,
Thanks for all your input---exciting new research gives us hope! Glad UCLA is so interested in pursuing it.

I hadn't heard of RANKL before so this was new to me---the connection with our immune systems. That's why I am curious if we can be tested for RANKL levels. I have Hashimotos--thyroid autoimmune with very high antibodies (TPO) and have a hard time stabilizing my thyroid with medication. Wonder if those antibodies are turning on the RANKL.

Quite a few people have had success suppressing their thyroid antibodies with 200mg selenium a day. So If we could measure our RANKL, we might be able to self-experiment with some of these less toxic/more natural therapies for the immune response until they get a safer medication out to deal with this.

Apparently, getting our LDL cholesterol down will help---but this has been so frustrating for me. I have been on an extremely healthy, low fat/good fat diet, mostly veggie for 30 years and my total cholesterol is still 204 and LDL at 129. I guess I am now motivated to work harder at getting it down lower---this must be why they are seeing the ability of statins to help increase bone density. I used a small amount of red rice yeast for just 3 weeks and it REALLY lowered my LDL, but I was nervous about it even though it is a natural statin and has been used for hundreds of years in Asia. Might reconsider it now they know LDL's connection to RANKL.
Caremanager, since you are in the health field, when you get a chance would you mind asking if we can get our RANKL levels tested and how is best--serum, urine?
Thanks so much,
Santa Fe

VictoriaLynn,---I totally relate to your getting osteo-information burnout, but I also feel excited and hopeful at all the positive and informed input we get here, so I keep loading it on!---keeps me motivated and hopeful. I learn more here than I ever would with my doctor !

By osteochick
Posted September 8, 2009 at 4:54 pm
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I also have hashimotos and fight high cholesterol. I eat really healthy. THe thyroid+family genes is keeping the levels elevated.

By SantaFe
Posted September 8, 2009 at 9:07 pm
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Osteochick,

RE: high cholesterol---I just read today that there have been many studies showing that pomegranate juice will stop the LDL's in our blood from oxidating, and even clears the plaque from arteries. It sounds like it is the LDL oxidation that releases the RANKL, not just the presence of LDL. You can buy a pure pomegranate juice at Trader Joe's called "Just Pomegranate"---I have been taking it for a while because I heard it was good for the heart and giving it to my husband for his prostate, but didn't know til today about that quality. Sounds like just what we need to reduce the RANKL. If you google pomegranate and LDL you'll see lots of studies: (It's being used for cancer a lot)

http://www.lef.org/magazine/mag2007/feb2007_report_pomegranate_01.htm

By osteochick
Posted September 9, 2009 at 1:17 am
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I will look into it. How much sugar? I find that sugar effects me, I think it is because of the thyroid issues. Didn't used to be that way. I really have to watch my sugar intake.

By bonafide
Posted September 9, 2009 at 10:16 am
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I know a Chinese medicine doctor who is also a Western MD who will preferentially recommend Red Rice Yeast extract over statins.
The Statins have horrendous side effects for some people whereas red rice yeast does not.
What is your HDL? Some practitioners feel the ratio of the HDL and LDL is more significant than the LDL by itself.
I regard it like a fish tank... how much "slime" is there on the walls (LDL) and how many snails (HDL) do I have to clean it up? If there is lots of slime and no snails I am in trouble.

In Chinese Medicine the link between bones and "kidney" (this function includes the thyroid and parathyroid) and brain is direct. This concept has been used to determine treatment for about 2000 years.
Western Medicine is very familiar with the parathyroid connection and Ca++.
Where Western medicine fails at times is in seeing the connections between everything.
Hence a drug is introduced without due consideration for all the subsequent connections and it is only after 10 years on the market that we see the harm.

A long way around Santa Fe to say keep trying the red rice yeast. It is always good to have a support system for blood work etc. to monitor.

By SantaFe
Posted September 9, 2009 at 11:41 am
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Osteochick,
There is no added sugar, just PJ and water. But the natural sugar is 32g for 8 oz. I only drink half a cup a day. I do remember on the Harvard Health Newsletter they were very excited about all the Pomegranate research with LDL oxidation and heart health, but one women did say it was too much sugar to be healthy. Yikes! I have been adding some OJ to make it taste sweeter...

Bonafide,
Love your snail and slime metaphor!
My ratios are really good, so I only tried the red yeast to experiment in bringing my LDL down which is 129 and "optimal" is below 120 on my lab numbers. But now after reading these articles on RANKL (whose soul purpose is to destroy bone!) , I think I am more focused on stopping the LDL oxidation (pomegranate juice) to reduce the RANKL than on the "quantity" of LDL---you do have to watch your liver enzymes on red rice yeast as it still IS a statin, although in a more natural form. But I agree it is less dangerous and has a longer history than the synthetic statins. I also read that onions can really reduce RANKL.
Onions, pomegranates, prunes, red yeast..........ugh.
warmly, Santa Fe

By bonafide
Posted September 9, 2009 at 1:00 pm
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Santa Fe
very good point about the liver enzymes... I always tell all my clients to monitor what they do with blood work and follow ups. Western medicine does that very well.
And as good as natural can be, anything taken in concentrations different than what occur naturally in food still needs monitoring...

What bugs me though, is ONE case of an interaction between something "herbal" and whatever else makes the news. whereas with drug side effects it takes at least 500 cases before it makes any headlines and thousands before they withdraw it.

A very good Herbalist will know their stuff though, that is why making sure of a person's qualifications is so important.

There are some drugs, I absolutely will not mix with anything herbal because the drugs are so toxic on their own.

It can be more of a tightrope than a path sometimes.

Interesting to note all the foods you named have wonderful effects on the bowels and it is becoming clearer how much of our immune system health stems from the bowel system.

By SantaFe
Posted September 9, 2009 at 3:03 pm
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I couldn't agree more regarding the overplay of herbal/supplement problems and the extraordinary downplaying of some pharmaceutical drugs' dangers.
I am playing close attention to the Merck lawsuit (Fosamax/ONJ) going on right now as it is indicative of that problem. The jury was just told to deliberate more last night. I hope they had some dentists testify. If the plaintiff wins, it will really be a pandoras box for Merck because apparently there are about 900 other lawsuits pending the decision (many of them with multiple cases).
I wonder if they were allowed to tell about Merck "faking" an Australian bone and mineral medical journal and then citing it with false info?

By bonafide
Posted September 9, 2009 at 4:55 pm
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I, too, am following that case....
There was a brilliant article written about Merck and the Placebo effect.
See if you can access this site for some VERY interesting reading
http://www.wired.com/medtech/drugs/magazine/17-09/ff_placebo_effect?current Page=all

By gishy
Posted September 10, 2009 at 8:10 am
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Hi there

This morning I found an article from Mercola.com in my inbox about Red Rice Yeast.

Here is an Paragraph that is interesting

*****************
The "active" compounds in red yeast rice are known as monacolins, and are substances known to inhibit cholesterol synthesis. One type of monacolin, "monacolin K," is also known as mevinolin or lovastatin.[3]

Lovastatin, as you might now recognize, is the first statin drug to be approved by the U.S. Food and Drug Administration, and it goes by the brand names of Mevacor and Altocor. So if you’re taking red yeast rice in the hopes of avoiding a statin drug -- surprise!

They’re essentially the same drug.

************

Dear Bonfide, would you be kind enough to ask your Doctor how he views this info. Many thanks. Or indeed, if anyone else has a view.

Gishy

By reets
Posted September 10, 2009 at 1:01 pm
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I am interested in getting any type of feedback /information regarding denosumab. I didn't think it was available and hope to start taking it as soon as it is FDA approved. Looking for that miracle because I've been diagnosed with osteoporosis and haven't taken any meds , other than calcium. Thanks

By Raven1
Posted September 10, 2009 at 4:40 pm
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Denosumab was approved by the FDA within the last couple of weeks to be used to treat osteoporosis. Google it and see what you get. I'd like to take it when I finish Forteo in November. I also have low cholestorol and I always have.

By windblown
Posted September 10, 2009 at 7:33 pm
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Hi Sante Fe, thanks for the interesting article. I don't know if anyone else answered your question or not but you can test RANKL serum levels. I've never had the test but it can be done, if you were looking for it.

Denosumab's potential final approval won't come until Oct 16th or later. It did get preliminary FDA approval but not the final one, so until that happens we won't know for sure if it will be marketed. The FDA does things really slow like most medical studies/clinical trials etc. for a really good reason, so we just have to wait and see what that will be, but I do hope it does get the final FDA nod.

If anyone is looking to get involved in a free Denosumab study in their state just email me, there's a lot going on right now and the results will be included in the final FDA decision. The study is with one group getting Denosumab and the other Boniva, no placebo group which is good imho :-).

Good luck with whatever you choose for treatment!!

And kudos to UCLA; I'm glad I can use that facility if need be as my husband does. Hope I don't sound to prejudice since some of my family are alums.

By windblown
Posted September 10, 2009 at 7:36 pm
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Hi Gishy, if some of our members are getting Denosumab it would have to be through a clinical trial since the final FDA approval is still forthcoming.

If anyone is interested in enrolling in a free Denosumab trial in their state just email me and I'll give you the info for your location or the nearest one to you.

By SantaFe
Posted September 10, 2009 at 11:47 pm
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Hi Windblown,
Thanks for the heads up on getting a RANKL test. I will ask my doctor about it---may be a good way to keep track of progress like the bone turnover tests.

Just read your profile and am amazed at what you have been thru! Your courage and spirit are really inspiring.
I'll put good thoughts out for your progress.
warmly, Santa Fe

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