Wednesday, September 18, 2013

Reducing Osteoporosis Fracture Risk


If you have been diagnosed with osteoporosis, or are at risk for this disease, you will need to strengthen your bones and reduce your risk for fracture. Options available to help reduce fracture risk include taking supplements, using prescribed medications, and/or making diet, exercise and lifestyle modifications. My philosophy is: “It doesn’t really matter how you get there…just so you get there….and, just so you don’t hurt yourself in the process.”  But I do admit to a bias for a whole-body approach. (1)

Supplements 
There is no one “best list” of supplements to take for reducing fracture risk. Sure, there are some basics that apply to pretty much everyone—calcium, magnesium, vitamins D and K—but to really be effective, we need to be a lot more specific. Everyone is unique; to gain optimal effect, each person will need to address his or her particular physiological strengths or shortcomings. Although I think OsteoNaturals products are great and they offer superior benefit to skeletal health, I still think people should continue to evaluate their progress. Loyalty to brand is fine but we still need to make sure that a product is providing benefit. If you require “X” and your supplement provides “Y,” then all the “Y” in the world, even if it is the best quality possible, won’t be of benefit. We should only care about one thing…results.

Medications
Many doctors recommend osteoporosis drugs as the primary mode of therapy to reduce fracture risk. This medical model is based on improving bone mineral density as opposed to bone quality. The bisphosphonate medications (currently the most commonly used osteoporosis drugs) significantly slow bone remodeling by essentially killing off bone resorbing osteoclast cells. Long-term use of these medications puts individuals at risk for serious adverse effects. In addition to a medication, the doctor may suggest 400 IU or so of vitamin D and some form of calcium carbonate, such as Tums. But in general, little or no focus, is placed on improving the overall health of the patient.

Nutrition/Lifestyle/Exercise
A growing contingent of health care providers, including me, recommend using nutrition/lifestyle/exercise as the primary therapeutic platform for reducing fracture risk – and prescribing medications short-term, and only when necessary. This alternative model completely avoids the possibility of serious adverse effects from long-term osteoporosis medication use; is more effective than simply taking a lot of supplements and hoping for the best; and has the added benefit of improving the patient’s overall health and reducing his or her risk of developing chronic disease co-morbidity.

Monitoring Options Scientifically
I also advocate using laboratory tests to determine efficacy of the chosen therapeutic protocol for reducing fracture risk.

Currently, a bone mineral density (BMD) test is the best way we have for determining the health of your bones. This test can identify osteoporosis, determine your risk for fractures (broken bones), and measure your response to osteoporosis treatment. The most widely recognized BMD test is called a dual-energy x-ray absorptiometry, or DXA test. Unfortunately, bone mineral density scores from DXA exams change extremely slowly (typically you usually have to wait two years between DXA exams) and there MUST be fairly large numerical improvement to confirm significant change that correlates with lower fracture risk. Also, what most people do not realize is that bone density is NOT a measure of bone strength and “there is only a weak relationship between the change in bone mineral density and fracture risk reduction.” (Primer on Metabolic Bone Disease, 6th ed. 2006, p. 274)

To make certain we are lowering fracture risk, I encourage changing lifestyle factors and improving certain laboratory biomarkers that have been correlated with bone health (2). When destructive lifestyle habits are improved and/or laboratory biomarkers are normalized, then the patient’s health benefits. Lab tests can be re-evaluated every 3 to 4 months and, by using multiple biomarkers, we can easily see “trends” in improvement that we can rely upon.

Let’s look at a comparison in order to understand this process
Note:  The result of the BMD test is given as a T-score. It stands for "standard deviation" and indicates how much ones bone density is above or below normal.
A T-score between +1 and -1 is normal bone density.
A T-score between -1 and -2.5 indicates low bone density or osteopenia.
A T-score of -2.5 or lower is a diagnosis of osteoporosis.

Mary Ann is a 60 year-old woman. The result of her first BMD test: Lumbar/Spine T-score of -3.4.  She was obviously deeply concerned. She did not want to take medications because she had heard about the possibility of severe adverse side effects. She decided to try and improve her bone density by taking vitamins D and K and 1,000 mg calcium/day. Then she waited…for two years…until her next DXA scan.

Joan is a 60 year-old woman. The result of her first BMD test: Lumbar/Spine T-score of -3.4 (exactly the same as Mary Ann’s T-score).   Joan, like Mary Ann, was deeply concerned. She also did not want to take medications for the same reasons as Mary Ann. Joan’s health care provider ordered several laboratory tests that have correlation to fracture risk. The results from two of these tests indicated that Joan was at increased risk for fracture. In addition, Joan’s doctor took note of her complaints of constipation, abdominal bloating, and white spots on her fingernails; all signs and symptoms of a digestive and nutrient malabsorption issue. Joan and her doctor worked out a treatment regime that included the same supplements as Mary Ann but with different dosages, as well as several other products, diet changes, and an exercise program. Retesting every several months indicated improvement in the abnormal tests, plus Joan began feeling better. Two years after her first DXA Joan went for her second scan.

Here are the results from Mary Ann and Joan’s second DXA exams:

Mary Ann:  L/S T-score:  -3.5
Joan:          L/S T-score:  -3.5

Neither of these scores indicate a statistically significant change from the -3.4 reading that each woman measured two years ago. For an observable change in bone density we would have to see a “least significant change” for this spine reading of at least a 5.4 % increase or decrease in Mary Ann and Joan’s T-scores (or at least a 0.05 g/cm2 for the “smallest detectible difference”). We would have needed to see an improvement to at least 
a  -3.0 to be sure of improved bone density and reduced fracture risk, or a loss to -3.8 to be sure of a reduction in bone mineral density and an increased risk of fracture. The T-score of -3.5 only tells us that if there was a change in fracture risk due to a density change; it is too small to make a determination one way or the other.

Mary Ann was distraught. Even though she understood scientifically that the -0.1 change was not significant, she still felt it as a defeat emotionally. To her, a 0.1 loss in her T-score was just that, a LOSS. 

Joan, on the other hand, saw that during the two years between her DXA exams the following things had changed:
·       NTX (a marker for osteoclast bone resorption ): dropped from 78 nmol to 51
·       hsCRP (a marker for inflammation): dropped from 2.1 to 1.4.
·       Vitamin D: increased from 28 to 42 (ensuring that she would absorb more calcium and have greater muscle strength)
·       Urine pH (measure of the acidity of urine): increased from 5.5 to 6.6 (this would help reduce urinary losses of calcium and lower osteoclast bone resorption)
·       Plus Joan felt better, her bowel movements improved, she no longer experienced abdominal bloating, the white spots on her fingernails disappeared (indicating improved absorption of minerals), and she felt stronger and more stable.
In short, Joan felt encouraged (as she should be) that she was going in the right direction and that her risk for fracture was less…even though her bone density T-score did not show an improvement.

Monitoring change is important and relying completely on DXA scans and bone mineral density to determine fracture risk is frustrating and inadequate. Bone mineral density changes VERY slowly AND we must not forget that it is NATURAL to lose bone density as we age (we just don’t want to loose it too rapidly). When laboratory biomarkers are used with this natural method to scientifically guide the patient and health care provider, then this approach can be highly effective.
Improving bone quality, gaining over-all health, and becoming stronger with more coordination and agility do amazing things for helping reduce fracture risk…even if bone mineral density does not change. My suggestion is to meet with your doctor and talk about how you can reduce your fracture risk by monitoring change.

Whatever your level of bone loss and whatever your age or current condition, the great thing is that there is something that can be done to help strengthen your bones. Research has come a long way in the past 10 years; today we know so much more about osteoporosis prevention and treatment. There are supplements, prescription drugs, dietary recommendations, exercise regiments and lifestyle modifications that can be evaluated. There are also a number of factors and tests that can be used as baseline measures for monitoring progress toward reducing your fracture risks. Thankfully, it is never too late to make a positive impact on your skeletal health. All it takes is a game plan and a good dose of tenacity.


(1)    In my book, The Whole-Body Approach to Osteoporosis, I provide a scientific rationale for this unique functions-based methodology to treat osteoporosis.   http://shop.osteonaturals.com/product/the-whole-body-approach-to-osteoporosis

(2)    Below is a partial list of factors and tests that are related to bone health and fracture risk.

Lifestyle Factors / Laboratory Tests
Impact on Bone Health and Fracture Risk
Weight
Under 127 pounds increases fracture risk
Body Mass Index (BMI)
A BMI of less than 18.5 increases fracture risk
Blood Pressure (BP)
High blood pressure is correlated to increased fracture risk
Pulse (resting heart is generally 60 to 80 beats per minute)
High pulse rate is indicative of inflammation and elevated sympathetic nervous system tone; both of which increase fracture risk.
Bone resorption markers (NTX, CTX, DPD)
A measure of collagen breakdown products from the resorption of bone by osteoclasts. These markers can indicate the rate of bone loss through blood and urine samples.
hsCRP  (High-sensitivity C-reactive Protein)
Measure of the level of inflammation which correlates to bone loss.  (Best if below 1.3mg/L)
Homocysteine (amino acid found in the blood)
Elevated homocysteine levels in the blood are correlated to inflammation and increased risk of heart disease and osteoporosis. It also causes collegen fibers to harden which makes bone more prone to breaking. (Best if kept below 8 micromoles per liter of blood)
Lipid peroxides  (index of oxidative stress)
Indirect measure of free radicals that promote bone loss.
8OH2dG   (index of oxidative stress)
Indirect measure of free radicals that promote bone loss.
Anti-tissue transglutaminase (tTG) and other gluten biomarkers such as AGA IgA and IgG
People sensitive to gluten in wheat, barley and rye often have increased bone loss.
AA to EPA ratio  [arachidonic acid (omega-6) (“bad” fats) to eicosapentaenoic acid (omega-3) (“good” fats) ratio]
Ideal ratio is less than 3 but not less than 1.5. If over 10, it is considered inflammatory.
Blood glucose  (blood sugar concentration)
Blood glucose that remains high over time can reduce bone quality and increase fracture risk.
A1C  (average level of blood sugar over 2-3 months)
Measure of glycemic control; the higher the level, the greater the development of advanced glycation end-products (AGES) which cause inflammation and make collagen fibers brittle, both of which increase fracture risk.
MPV   (Mean platelet volume) http://www.ncbi.nlm.nih.gov/pubmed/22684618
The higher the MPV the larger the platelet size and the greater the risk for inflammatory states. Elevated MPV is an early marker of platelet activation and heart disease.
TSH  (Thyroid stimulating hormone)
An underactive or overactive thyroid correlates to less than optimal bone health
Triglycerides  (type of fat found in the blood)
Elevated levels increase inflammation and is correlated with increased fat in the bone marrow which crowds out bone-building osteoblasts and promotes bone-resorbing osteoclast activity.
Mitochondrial function   (mitochondria are cell organelles that produce energy)
Functional tests that correlate to the body’s ability to produce energy; the more energy you have the healthier you will be.
DHEA  (hormone produced primarily in the adrenal glands – precursor to sex hormones)
Low DHEA concentration has been associated with low bone density in women.
Testosterone  (hormone primarily secreted in the testes of males and the ovaries of females)
Testosterone is known to decrease bone resorption and stimulate bone mineralization, so low levels could be cause for concern in both men and women.
Estrogen  (primary female sex hormone)
Estradiol, the primary estrogen in humans, aids in maintaining bone density. Postmenopausal levels below 10 to 12 pg/ml is cause for concern.
SHBG  (Sex hormone-binding globulin)
There is an inverse correlation between serum SHBG levels and bone mineral density in both males and females
Hypercalciuria (excessive urinary calcium excretion)
Loss of too much calcium is cause for concern.  Levels should be below 275 mg/day for women and 300 mg/day for men.
Vitamin D     (needed for calcium absorption and metabolism)
Ideally blood levels should be kept between 40 to 60 ng/ml. Levels below 32 ng/ml increase fracture risk.
Under-carboxylated osteocalcin
Measure of vitamin K functional capacity; elevated levels increase fracture risk.
Serum calcium (should be between 8.5 and 10.0 mg/dL)
Too much calcium in the blood (over 10 mg/dL) can indicate parathyroid disease. In most cases, this is from a benign tumor called an adenoma.
PTH  (parathyroid hormone) (should be below 50 pg/mL)
When the parathyroid glands release too much parathormone (most often, from an adenoma) osteoclast bone resorption is stimulated.
Red blood cell magnesium 
Measure of magnesium levels; magnesium acts as an anti-inflammatory and is needed for bone formation by osteoblasts
Urine Ph  (measure of the acidity of urine)
 An acidic body increases osteoclastic activity and causes more loss of calcium in the urine. Ideal value range of first morning urine pH is 6.6 – 7.2.
Eating Disorders
www.nationaleatingdisorders.org/learn
An adequate supply of nutrients is required if you are to have healthy bones.
Thiazolidinediones  (common drugs for glucose control for type 2 diabetics)
These drugs promote bone loss.  An alternative to these medications is to control blood glucose through diet, lifestyle, exercise and supplementation.
PPIs  (Proton pump inhibitors - medications used for Gastroesophageal reflux disease (GERD) / heartburn.)
These drugs promote bone loss.  An alternative to these medications is to eliminate the need through better digestion and improved gastrointestinal health.
SSRIs  (serotonin-specific reuptake inhibitors - class of compounds typically used as antidepressants)
These drugs used for treating anxiety and depression have been linked to bone loss. 
Cigarette smoking
Smoking reduces bone mass and increases fracture risk.
Inadequate exercise
Exercising regularly builds and strengthens bones. Weight-bearing exercises—where bones and muscles work against gravity—are best. These include aerobics, dancing, jogging, stair climbing, tennis, walking, and lifting weights. People who have osteoporosis may want to attempt gentle exercise, such as walking, rather than jogging or fast-paced aerobics, which increase the chance of falling. Exercising three to four times per week for 20-30 minutes each time helps.
Poor diet
A balanced diet rich in calcium, magnesium, vitamins D and K, and antioxidants reduces fracture risk.
Excess alcohol intake
Heavy drinking reduces bone mass. Limiting alcoholic drinks to no more than two per day reduces risks. An alcoholic drink is one-and-a-half ounces of hard liquor, 12 ounces of beer, or five ounces of wine.

Sunday, September 1, 2013

The Future: Targeting Bone-Cracks With Drug-Carrying Nanoparticles

Take a look at the future for osteoporosis drug therapy.

Research into drug delivery systems is hot, especially in the arena of nanotechnology. In a series of studies based at Penn State University and Boston University, researchers used self-powered nanoparticles to deliver medication (alendronate) right to the doorsteps of bone cracks themselves.

Molecules moving inside a nanotube
Interestingly, when microfractures occur in bone there forms a very small electric field. This small change in ionic gradient is all it takes for introduced negatively charged nanoparticles to migrate to the crack. When medication is attached to these particles, it can be delivered to the site where it can make the most impact...at the microfractures. When it comes to osteoporosis medications, this may help improve effectiveness and reduce adverse effects (by requiring less medication).

According to Yadav et al. in a paper published in Angewandte Chemie, "Bone cracks are detected by utilizing the damaged matrix itself as both the trigger and the fuel. A crack in a material with a high mineral content like bone generates ion gradients, which can be utilized for active targeting and treatment."

Yadav, V. et al. 2013. Bone-crack detection, targeting, and repair using ion gradients. Angewandte Chemie doi:10.1002/anle.201305759.
Website design and website development by Confluent Forms LLC, Easthampton MA