Thursday, January 17, 2019

Elevated Blood Glucose Increases Fracture Risk in Patients With Osteoporosis

When assessing a person's risk for breaking a bone, one of the things I like to look at are specific laboratory tests. Bone density exams are fairly good at showing us the QUANTITY of bone, but bone quantity does not equate to bone strength. Bone QUALITY, on the other hand, DOES correlate more to the actual strength of bone...its resistance to breaking. The problem is, we don't have tools readily available in the clinical setting to accurately assess bone's microarchitectural integrity (quality) first hand. We're getting closer with technology such as the trabecular bone score (TBS) (especially when evaluating fracture risk in patients with type 2 diabetes) but we still have a long way to go. What we do have in our diagnostic arsenal today are several lab tests that correlate well to
bone quality and fracture risk.

In the last Newsletter, I wrote about homocysteine, an inflammatory biomarker, that when elevated, is directly related to increased fracture risk in patients with osteoporosis. The reason for this correlation is that homocysteine compromises bone collagen molecules making them stiff and bone more prone to breaking.

Another biomarker I use to assess fracture risk is blood glucose. Like elevated homocysteine, high
blood glucose also increases an osteoporotic patient's risk to break a bone by compromising the quality of their bones.

Our skeleton is amazingly complex. It doesn't just act as an anchor for muscles and tendons, and as a storage vessel for vital minerals, and as a birthing place for blood cells, but our bones also act as an endocrine organ involved in energy regulation, specifically that of glucose metabolism. Because of this, elevated blood glucose levels (both in pre-diabetes and diabetes) results in, 1) an increased production of advanced glycation end products (AGEs) which compromises bone collagen structure, and 2) a compromise in osteoblast and osteoclast cell function which disrupts bone remodeling equilibrium. The end result is reduced bone quantity, quality, and bone strength.

Fasting blood glucose levels should remain below 100 mg/dL. Having fasting glucose levels consistently above 100 is a red flag not just for type 2 diabetes but also for increased fracture risk if you have osteoporosis. Bringing glucose levels under control is extremely important. OsteoNaturals' OsteoStim helps lower elevated blood glucose levels with its therapeutic amounts of alpha lipoic acid, lactoferrin, and berberine. All of these compounds (in addition to dietary considerations) are excellent for helping to lower blood glucose levels.  

Tuesday, December 11, 2018

Homocysteine and its Negative Impact on Bone

Elevated levels of homocysteine (Hcy) in the blood, a condition called hyperhomocysteinemia, is a common finding in patients with osteoporosis. Unfortunately, this not only increases a person's risk for fracture (by Hcy's adverse effects on bone quality), but for each 5 micromole/liter rise in Hcy, there is a 33.6% increase in all-cause mortality risk (Fan et al., 2017). 
Homocysteine is a byproduct from the metabolism of methionine, an amino acid found in meat (and nuts, soy, eggs, dairy). But even vegetarians can have elevated Hcy levels. This is because B12, a vitamin found in meat, is important for the conversion of Hcy into methionine and other metabolites. In addition to vitamin B12, several enzymes and the cofactors B2, B6, folate, betaine and magnesium are necessary to metabolize Hcy and lower its level in the blood. In cases of nutrient deficiency, and/or having the genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) enzyme, Hcy levels rise and create breeding grounds for chronic disease.   
Homocysteine levels above 15 micromoles/liter can damage nerve cells and blood vessels leading to cognitive decline and cardiovascular insufficiency (Ostrakhovitch, 2018). In addition, hyperhomocysteinemia reduces bone strength by slowing osteoblastic bone-building activity, stimulating osteoclastic bone resorption, and disrupting bone collagen cross-linking molecules making collagen stiff and bones extremely fragile. Hcy creates oxidative stress in the body and increases the production of advanced glycation end products (AGEs) which reduces both bone quantity and quality and, therefore, bone strength.  
One of my goals, when helping patients reduce fracture risk, is to stop rapid bone loss and falling bone density T-scores. Through serial assessment of bone resorption biomarkers (CTX, NTX, and/or DPD) we are able to identify rogue osteoclastic activity and provide safe, appropriate, and effective therapy. Hyperhomocysteinemia can be effectively treated through exercise, diet, and nutritional supplementation. By lowering Hcy levels, we are able to see improvements in bone health through the lowering of bone resorption biomarkers.            
Fan, R. et al. 2017. Association between homocysteine levels and all-cause mortality: a dose-response meta-analysis of prospective studies. Scientific Reports 7, 4769.  
Ostrakhovitch E.A. and S. Tabibzadeh. 2018. Homocysteine and age-associated disorders. Ageing Research Reviews,  

Sunday, November 11, 2018

Lactoferrin and Alpha Lipoic Acid for Osteoporosis

One of my goals as president of OsteoNaturals is to provide our customers with up to date information about osteoporosis and therapeutic options. To do this I typically peruse hundreds of medical research articles each month while sitting in the basement of the University of Massachusetts library. Scouring PubMed for exciting (yes, I love it!) research is rewarding...and fun (yes, I'm a nerd). The more I learn about the pathophysiology of osteoporosis and possible therapeutic options--both pharmacological and nutritional--the better I can help others combat their bone loss. In the last blog, I wrote about the beneficial epigenetic effects of three biocompounds in OsteoStim. In this Newsletter I want to briefly mention two articles I came across this week, one about the bone building effects of lactoferrin and the other about alpha lipoic acid-- both of which are ingredients in our
Lactoferrin is a natural protein supplied by Bioferrin 1000 in our OsteoStim product. Lactoferrin boosts bone health in two ways: 1) it stimulates osteoblast bone formation activity, and, 2) it curtails bone loss by calming aggressive osteoclastic bone resorption. The overall effect of lactoferrin is that of improving bone quality and quantity for better strength and reduced fracture risk.  
In an article from the International Journal of Biological Macromolecules, researchers explore the molecular mechanisms of lactoferrin on bone building activity. Using cell cultures, Liu, et al. (2018)  investigated the enzymatic effects of various mitogen-activated protein kinase (MAPK) pathways on osteoblast cell function. They concluded that lactoferrin induced osteoblast cell proliferation and that it is "an osteogenic growth factor" and has the potential as a "therapeutic agent to treat low bone mass in patients with diseases such as osteoporosis." Yes, we have certainly found that to be true as we are hearing of great results from those who take OsteoStim!  
The second article is by Roberts and Moreau from the University of Nebraska. This article (2015, Nutrition Reviews) gives a fairly good explanation of the mechanisms alpha lipoic acid (ALA) has on improving bone health. This bioactive compound scavenges reactive oxygen species (ROS), disposes of heavy metals, regenerates vitamins C and E, and increases CoQ10 levels (for cell energy). ALA's antioxidant properties and ability to reduce oxidative stress and inflammation are the reasons it has been used successfully for years to treat chronic diseases such as diabetic neuropathy and liver disease...but it also works wonders for bone. 
Oxidative stress and chronic systemic inflammation are the prime destructive forces behind the accelerated bone loss of osteoporosis. ALA reduces bone loss by lowering ROS and inflammation which creates a calming effect on hyperaggressive osteoclastic bone-resorbing activity.  
What I have found over the years is that the unique combination of ingredients in OsteoStim produces a beneficial composite effect on bone, and that "the whole is far greater than the sum of its parts".  

Monday, October 29, 2018

Bio-Active Compounds and the Epigenetics of Osteoporosis

To better understand how bio-active compounds in food and certain supplements (such as the berberine, milk thistle, and taurine found in OsteoStim) work to improve health, we first need to understand the epigenetics of nutrigenomics (a fancy word for how nutrition affects our genetics).
Epigenetics: We know what genetics is about: a biological map of how we are put together and what makes us who we are...what makes us unique...but what about epigenetics? Epigenetics refers to external modifications to DNA (not actual changes to DNA sequencing) that turn genes "on" or "of". A good example of this is methylation. Methyl groups are molecules consisting of one carbon and 3
hydrogen atoms. When a methyl group is added to other molecules it is called methylation, and when a methyl group is taken away it is called demethylation. When adding or detaching methyl groups to molecules, it has the effect of 'turning on" or "turning off" a biochemical reaction. It's kind of like turning a light on or off with a switch. This is epigenetics at work. In epigenetics, the DNA sequence has not changed, only how that DNA is being read. The modifications caused by methylation (and other histone modifications) only affect how that genetic information is going to be used: for example how the DNA will or won't produce proteins.
When it comes to nutrigenomics and bone health, DNA methylation is extremely important. (Too much is not good and too little is not good...both can lead to osteoporosis and other chronic diseases.) "Methyl switches" (and other switch forms) work to control just about everything in the body, including how bone forms and how it is broken
down; how it is remodeled. We usually hear of methylation as it relates to cardiovascular and neurological disease, but methylation is also important for skeletal health.  
We know that when bone remodeling gets out of balance, it leads to osteoporosis. Bone cells (the osteoclasts and osteoblasts) must stay in harmony, balanced in their activity for bone to stay healthy. It is through cytokine-orchestrated genetic expression that this activity remains in sync. A person may have genes for strong bones, but the regulators of how those genes manifest are, for some reason or other, not turned on or off correctly and the bone strength is not realized. Epigenetics--how genes are expressed--becomes important when we talk about nutrition beyond the basic bone-building blocks of protein and minerals. Good nutrition encourages a person's genetic makeup to be expressed fully. It allows the epigenetics to engage and bring that person's genetic potential to its optimal expression. But poor nutrition may lead to an under-expression of the genetic code and result in physiological dysfunction and disease.   
DNA methylation also plays a major part in the immune system's response. It therefore is a major regulator of inflammation and that of the chronic systemic inflammation we see in accelerated bone loss.  
One of the reasons it is so important to eat lots of vegetables is because they are a great source of bio-active compounds that are methyl switches and have anti-inflammatory properties. This is also why we put several bone-specific bioactive compounds in our OsteoStim formula. Berberine, milk thistle (silymarin), and taurine are all active bio-compounds involved in either the promotion or reduction of methylation and the regulation of skeletal epigentics.    

Saturday, October 13, 2018

Berberine, a key ingredient in OsteoStim

Berberine is one of the key ingredients in OsteoStim. OsteoStim is our unique (there is nothing even close to it on the market) bone-health supplement that
promotes normal bone remodeling activity through bio-active compounds such as berberine. A strategic blend of antioxidants, vitamins, and medicinal herbs, OsteoStim aids skeletal health by calming osteoclastic bone resorption and boosting osteoblastic bone formation.  
Berberine is a traditional Chinese medicinal herb that is recognized around the world for its health-promoting benefits and treatment of disease. Not only does berberine lower blood sugar and cholesterol levels, but it is extremely effective for dampening chronic systemic inflammation and reducing oxidative stress...two major reasons for osteoporosis and accelerated bone loss as we get older. In addition, berberine activates an enzyme, AMP activated protein kinase (AMPk), within cells. AMPk acts as a chemical sensor to help maintain energy mechanisms including the formation of mitochondria, the power generators within cells. It is through the stimulation of AMPk that berberine is able to reduce osteoclastic bone resorption when RANKL (a cell signaling molecule) is excessively elevated.
Some of you may be familiar with the medication, Prolia (denosumab), for osteoporosis. This drug is an antibody against RANKL (you can read more about RANKL in my book, The Whole-Body Approach to Osteoporosis). By blocking RANKL, Prolia dramatically lowers osteoclast cell activity and thus bone resorption. The end result is higher bone mineral density and less fracture risk, at least initially.  
One of the actions of berberine is similar to Prolia in that it reduces RANKL activity. But, unlike Prolia, berberine does not carry the high risk for serious allergic reactions or adverse side effects. The reasons:
1) Prolia can excessively reduce RANKL levels: RANKL is important not only for activating bone resorbing osteoclasts (some resorption of bone is necessary to keep the skeleton youthful and devoid of excessive microfracture accumuation) but also for a healthy immune response. Excessive lowering of RANKL can cause bone to become "old" and brittle from overly limiting osteoclastic activity. Excessive lowering of RANKL also compromises the immune response, and creates increased risk for infection and serious allergic reactions. Long term use of Prolia (over 3 years) can increase the risk for atypical femur fractures and osteonecrosis of the jaw.  
2)  The Prolia rebound effect: There is an increased risk of broken bones if Prolia therapy is discontinued. When the anti-resorptive effects of Prolia wear off, the body senses the absence of the RANKL antibodies and reacts by hyper-producing RANKL. This leads to accelerated osteoclastic activity and rapid bone loss.  
Berberine, on the other hand, does not excessively reduce RANKL levels. Berberine works to NATURALLY lower inflammation and oxidative stress which are promoters of excess RANKL production. By lowering RANKL to normal levels, berberine does not cause bone to get "old" or brittle.  And, with berberine, there is no accelerated bone loss if for any reason it is discontinued.  
Bio-active berberine is just one of the reasons that makes OsteoStim your number one choice for supplemental bone health. In addition to berberine, OsteoStim also contains therapeutic amounts of vitamins D3 and K2 (MK4 and MK7), biotin, alpha-lipoic acid, N-acetyl cysteine, taurine, Bioferrin 1000, MBP (milk basic protein), and silymarin (milk thistle).
Many of you have been asking, "What can I do in the short term until OsteoStim is available?" My suggestions are:
1) It is not harmful to take intermittent supplement "holidays". Going for a week or two without taking OsteoStim is perfectly fine as long as you are continuing to eat a healthy diet rich in vegetables and devoid in bone robbing food stuffs.
2) If, after two weeks or so, you want to supplement your diet with alpha-lipoic acid (200 mg/day) and berberine (250 mg/day) this will hold you over until OsteoStim is back on our shelves.   

Wednesday, August 29, 2018

RBC Level Can Be An Important Therapeutic Target

If you have read my book, The Whole-Body Approach to Osteoporosis, you know that I focus on therapeutic targets (especially lab test results) to design bone-strengthening therapy and monitor progress.

One of the tests I look at when evaluating patients with bone loss is the CBC (complete blood count) and specifically the index, RBC (red blood cell) count. People with osteoporosis often have lower RBC counts than individuals with normal bone density. The reason for this seems to be two fold: 1) lower sex hormones, estradiol and testosterone (a risk factor for osteoporosis), in both women and men is correlated to higher bone marrow fat, and 2) chronic systemic inflammation and higher oxidative stress (also risk factors for osteoporosis) lead to a build-up of bone marrow fat and PPAR-
More than 50% bone marrow fat (round white objects) in severely osteoporotic bone
gamma (nuclear) receptors. High levels of bone marrow fat (over 50%) crowds out the hematopoetic stem cells that form RBCs. The PPAR-gamma receptors, when activated, pull a "molecular switch" that converts mesenchymal stem cells into fat cells instead of bone-forming osteoblasts.  
In plain English...this means that low RBCs in people with osteoporosis can mean higher rates of bone loss, lower rates of bone formation, deficient levels of sex hormones, and higher chronic systemic inflammation. Proper therapy not only increases RBC levels over time, but also improves skeletal health and reduces fracture risk.   
OsteoNaturals OsteoStim is a unique complex designed to repress PPAR-gamma activity, lower free radicals and oxidative stress (thus, chronic systemic inflammation), reduce osteoclastic bone resorption, stimulate osteoblastic bone formation...and yes, increase RBCs.    

Saturday, May 12, 2018

Long-Term Effects of Bisphosphonate Therapy

In a March 6, 2017 Scientific Report article, Dr. Ma (Dept. of Mechanical Engineering, Imperial College, London), et al. presented findings from a study that investigated the effects of bisphosphonate therapy on the microstructure and strength of bone. Dr. Ma looked at three cohorts of individuals from a total of 21 bone samples: 1) eight were from bisphosphonate-treated patients who
had sustained bone fractures, 2) eight were from patients who had sustained bone fractures but who had not received bisphosphonate therapy, and 3) five samples from cadavers of healthy, ageing, non-fracture individuals.

By using X-ray micro-CT and image segmentation technology, the researchers could assess both trabecular microdamage and mechanical strength of the bone samples. What they found was that bisphosphonate therapy is capable of reducing trabecular perforations (A phenomenon that weakens bones when excessive and one which I describe as "disconnected trabeculae" in my book - pages 14 and 15 - The Whole-Body Approach to Osteoporosis.) but causes an accumulation of microcracks. This abundance of microcracks (compared to the cohort that did not receive bisphosphonate therapy) lead to a loss of microstructural integrity and bone strength.

This study explains why short-term bisphosphonate use (2 years or less) can be beneficial (especially in a person with elevated osteoclastic bone resorption that is not being controlled through diet, lifestyle changes, and nutritional supplementation), but that long-term use of these drugs can be detrimental to skeletal health and strength.

The bottom line is that bisphosphonate medications can be of help in reducing immediate fracture risk in the short term but should not be used as the primary long-term treatment for osteoporosis. What SHOULD be used as primary long-term therapy for bone loss is bone-healthy nutrition and exercise, ensuring optimal GI health, and making changes in life style to promote overall health. 

Ma, et al. 2017. Long-term effects of bisphosphonate therapy: perforations, microcracks and mechanical properties.
Scientific Reports DOI: 10.1038/srep43399
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