Breast Cancer and Bone Density

This association is of critical significance. For the most part, Breast Cancer Risk is elevated with higher Bone Density in older women. This paradox needs an evaluation to clarify this observation. There are many possible variables; Estrogen levels, Dietary calcium intake and other bone building nutrients, Type of Dietary foods associated with higher bone densities like Dairy, Supplements such as vitamin D, E, & K, Type of Fats Consumed, Exercise influences, etc.  ref  ref   ref

One possibility is that greater bone density, associated with greater calcium uptake and thus greater dairy, is the result of higher IGF-1 levels from dairy foods. This does make sense. Check out these.  ref 

This next review is important, it shows how much calcium and vitamin D to take and blood levels for vitamin D to maintain for the lowest breast cancer risk from studies to date. Look at how close they are to recommendations of this new vitamin Criteria...interesting!  Would take some additional sun exposure to get vitamin D body levels to 30 ng/ml.

Breast Cancer Res Treat. 2012 Jul 25.

NEW TOPIC FOR DISCUSSION: OPG to RANKL balance

This is a very new direction for bone health that explains quite a few past mysteries and gives immense understanding to what should be the proper protocol for osteoporosis treatment. ref  Here are some of the issues:

• The normal bone building, maintenance, and repair process means more bone is built when young until about age 40 when a slight 1%/year reduction begins to occur until menopause when the accelerated reduction of estrogen production equates to between a 3-5% bone loss for a few years. Then a return to again about a 1% lost per year. But this pattern can be modified by diet and exercise. And it is probably influenced by gene polymorphism.

• Osteoporosis occurs when more bone is being torn down than is being re-built back up, and/or as bone structure suffers breakdown. Bone intregrity is a combination of density and structure. 

• How this occurs has been the subject of many theories in the past. 
• Calcium levels and vitamin D played a major role in some of these theories. 
• Long term research has now shot holes in most of these theories, they simply do not work at protecting against fractures or even to explain the observed events.

• Fosamax is one of the older bone drugs which tries to regulate the bone repair process by using an agent to kill some of the overactive tear down cells in an attempt to re-balance with the lower level action bone re-building cells.

• Today, new research is looking at a system called TNF for Tumour Necrosis Factor.
• This system includes 3 key proteins, RANK (the gene), RANKL (a ligand), and Osteoprotegerin, or OPG for the decoy that balances RANKL activity on cell receptors. ref
• These 3 proteins are influenced by many hormones, like estrogen, and body messengers; cytokines, PTH (directed by calcium blood levels), Vitamin D, and PGE2 (an inflammatory agent connected to fatty acids thru the omega 6 to omega 3 ratio)
• Up until menopause, estrogen controls RANKL activity thru OPG and maintains a normal and balanced bone re-building to renew and strengthen bones one section at a time.
• Recently it was found that in breast cancer and bone disease, the balance between RANKL and OPG needed for normal bone rebuilding was disturbed. Too much RANKL, the activator, and not enough of OPG, the regulator to control RANKL activity. ref
• RANKL is responsible for activating the development of bone cells (osteoclasts) that tear down small sections of bone as part of the repair process to allow bone rebuilding by osteoblasts in that empty space.
• Science is now looking for ways to get the body back into balance between RANKL and OPG. ref
• Resveratrol at non-toxic concentrations dose-dependently inhibited RANKL-induced osteoclast differentiation and induced apoptosis, and, suppressed RANKL-induced ROS generation  ref
• Magnesium also has RankL inhibitor actions, but at current consumption levels of only 68% of RDA level, it fails to protect bones. ref
• Higher magnesium levels associated with improved survival from breast cancer. ref
• The most recent drugs introduced to quiet RANKL activity, i.e. Prolia, have proved to be a disaster for side effects and were approved for and only used in very high risk osteoporosis patients. ref
• These drugs have simply pointed out that RANKL needs to be in balance and not almost completely shut down since it is necessary for functions in other vital body processes, like the immune system protection against infections and cancer. ref
• This OPG and RANKL balance is also the area of influence for Strontium initially on bone building. CAUTION: Strontium at 680 mg should only be used under medical supervision. There are some side effects, and after a number of years, Heart disease risk is increasing with more heart attacks.

Are there other NATURAL ways to CONTROL RANKL?

• Hinted above is that Fish oil Omega 3 (EPA exactly) is necessary to balance with Omega 6, largely from vegetable oils, to limit and control PGE2 production, a possible factor in creating inflammatory actions that increase RANKL. ref
• PTH, a parathyroid hormone activated when blood calcium levels get too low, can decrease OPG levels plus later increase RANKL.  ref
• Controlling PTH secretion is why certain amounts of calcium and vitamin D are needed in the diet. To balance out the calcium that is lost each day, an intake of about 600 mg. of calcium may be needed. This amount from research in the USA has varied from 300 to 720 mg in different diets and activity conditions.  Vitamin D appears not to be directly related to OPG or RANKL levels except through PTH levels. ref 
• Remember, other body and dietary conditions influence how much calcium gets absorbed. Since the average calcium absorption is about 33%, this means the calcium requirement in the USA is set at 1200+ milligrams a day. This is still to this day somewhat controversial since even at 1200+ mg, bones still fracture.  In the rest of the World, the calcium requirement is about 750 mg or less, and bones exhibit fewer fractures. WHY and HOW?
• Certain foods, herbs, and spices contain actives that possibly influence RANKL expression. Check out this article on Curcumin, an element in Tumeric.
• Plus, an element in Olive leaf extract has shown RANKL control on another level, thru Notch 1 cell to cell communication for TNF ref ref (listed by description only at bottom) 
• Or how about dried plums, yes only animal studies, but.. ref ref
• Tocotrienols, other vital Vitamin E family members, are mentioned here, especially number 4 & 5.   

What all this means to bone health is still to be worked out. But, in breast cancer...?

The take away is to avoid the drugs that block RANKL almost completely and possibly cause the jaw bone to deteriorate. Age would certainly play a major role in decisions. And bone fracture and cancer risks both need to be part of the calculations.

To be continued...

NOTE: While research continues to refine knowledge about RANK, RANKL, and OPG,  it appears that when there is a disruption between them, disease is often the result. Estrogen positive Breast cancers exhibit different expression levels versus estrogen negative cancers. How does this next study fit in with the above RANKL and OPG story for drug action. It says lower expression of RANK and RANKL is associated with greater bone metastasis and increased mortality from breast cancer while lower OPG is associated with better outcomes. Compare to this study. They seem to be at odds with each other. The important aspect appears to be that an upset ratio of RANKL to OPG is not healthy, regardless of expression level of RANKL compared to healthy tissues. Both RANKL and OPG may vary over the bone cell development process so absolute levels may not be as important as the overall balanced long term ratios, especially as demonstrated in cancers that matastize to bone. Prostate Cancer link to RANKL and OPG.

WRAP UP: Another Breast Cancer article for your consideration found under Health Theory Development. One last thought: Remember that this RANK system is involved in developing both the tear down and build up cells for healthy bone remodelling, a process that is necessary and lifelong to maintain healthy bones. The happenings after the bone cell development process are another story? Bone building nutrients and exercise forces still play a significant role in health of the finished bone. Bones need both the proper density of minerals as well as a strong and pliable STRUCTURE. article