Introduction

It is estimated that over 14 million Americans will have osteoporosis by 2020. While it is primarily thought to be a disease of women, about 30% of all hip fractures occur in men. Yes, even you men better keep reading… 

Bones are living and growing tissues that make up the framework and support of the body. Granted, bones are not the most interesting parts of the body. They don’t really do much for our appearances–unless you have a great jawline or high cheekbones! Believe it or not, bones are very dynamic, and when they are ailing, they can cause serious health problems. 

Bones are made up of mostly collagen, calcium and phosphate and they are in a constant cycle of resorption and formation, meaning bone tissue is continually being lost and gained. During childhood, adolescence and the young adult life, bone formation is higher than bone resorption (breakdown), meaning bones are getting bigger, stronger and denser. After we get to a certain age, bone resorption starts becoming faster than bone formation, meaning bone density is lost.

Osteopenia is a systemic disease that is defined by the overall loss of bone density, causing weaker bones. It is a precursor to osteoporosis, which is a lot more severe and is treated more aggressively. Osteoporosis is not only the loss of bone mass but also bones becoming more porous, brittle and fragile, increasing their likelihood of fracture. Bone mineral density (BMD) is a measure of minerals in bone and is a marker of the degree of bone health or disease.   

 

Neither of these systemic diseases have any signs or symptoms until a fracture actually occurs, making them a silent disease. Although, some dull and sharp pains have been reported in patients in the later stages of the disease.

Bone Formation

Bone remodeling is the process where new bone replaces old bone. There are five stages:

• Resting phase is when there is minimal activity
• Activation phase is when osteoclasts (bone cells that break down bone) come to the surface of the bone.
• Resorption phase occurs when the osteoclasts make the environment more acidic which dissolved the bone so the minerals can be resorbed
• Reversal phase osteoclasts die and osteoblasts (bone cells that build bone) come to the surface.
• Formation phase occurs when osteoblasts deposit collagen that mineralizes into new

Causes of Osteoporosis

Osteoporosis is caused by an increased bone resorption rate (the second stage above), which can happen for a number of reasons, the first being advancing age. After a certain age, everyone starts to lose bone mass, which is why it is important to stay healthy and keep a balanced diet and build strong bones in the first few decades of life.

Another cause of increased bone resorption is genetics; never obtaining maximal bone density before adulthood, and people with a family history of osteoporosis are more likely to acquire it in the future.  Despite these, the leading cause of osteoporosis is lack of certain hormones, particularly estrogen in women and androgen in men. Radiation exposure used during the treatment of certain cancers can weaken bones further. Chronic steroid used in arthritis, asthma, emphysema, and autoimmune diseases are also agents that lead to osteoporosis.

Although osteoporosis can affect any gender, race or age group, it is most common in post-menopausal women of the Caucasian and Asian race. After menopause, estrogens levels drop drastically. Because estrogen promotes the activity of osteoblasts, which produce bone, a drop in estrogens after menopause increases the chance of developing osteoporosis. Females who have a small framework, an eating disorder, smoke, consume alcohol, and are less active are more prone to the condition. Hyperparathyroidism can also cause osteoporosis, but that specific disease won’t be covered in this article. However, rebuilding the bone is much the same as discussed here. 

 

Risk Factors for Osteoporosis

• Age
• Female gender
• Caucasian race
• Genetics
• Calcium intake and absorption
• Vitamin D status
• Lack of exercise
• Estrogen levels less than 5pg/ml have lower BMD and a higher risk of fractures
• High salt diet causes excess calcium to be excreted in the urine
• Sugar increases cortisol which increases calcium excretion
• Soda due to phosphorus
• High alcohol intake (greater than 2-3 drinks per day)
• Caffeine
• Smoking

 

Diagnosis of Osteoporosis vs Osteopenia 

Osteopenia and osteoporosis are diagnosed using a bone mineral density (BMD) test known as a DEXA (dual-energy X-ray absorptiometry) scan. It can help diagnose the disease before a fracture occurs so the right measures can be taken to prevent broken bones. It helps estimate the density of your bones and the risk you have for fracture. It is an ‘X-ray’ like machine that will test the mineral levels in your bones.

The results are described with a T-score. The lower the T- score, the lower the bone density. A normal T-score reading is anything above -1. If your T-score is in the -1 to -2.5 range, it is diagnosed with osteopenia. Osteoporosis is anything below -2.5. It is recommended at about age 55, men and women receive a bone mineral density test to determine their risk for osteoporosis. 

How to Assess the Risk of Osteoporosis or Fracture

 

The fracture risk for a person can be estimated using the FRAX (fracture risk assessment tool) questionnaire. It uses the results from your DEXA scan along with questions about your medical history and lifestyle to calculate a risk level over a period of ten years. Risk levels are low if less than a 10% chance in the next 10 years, moderate if between 10-20%, or high risk if greater than 20% chance of fracture. It is especially useful in women over 60 years of age because the DEXA may show an increase in BMD due to osteoarthritis and be misleading. 

Laboratory Tests to Detect Bone Loss

 

Plasma bone-specific alkaline phosphatase

This is a test that can indicate osteoblastic (bone building) activity and is used to monitor treatment progress. Alkaline phosphatase levels increase if your body is building bone and decrease if your body is breaking down bone.

 

Urinary calcium excretion

This is a urine test that measures the amount of calcium that is being excreted by the urinary system. The more bone that is being broken down, the more calcium you will urinate out, which can be measured. There are also other factors involved with this test, such as the amount of calcium consumed in your diet. 

High values >250mg/day

• High calcium and D intake
• Increased bone resorption
• Lasix

 

Normal values- 100mg/day- 250mg/day

Low values <100mg/day

• Decreased calcium intake
• Vit D deficiency
• Thiazide diuretics

 

Biochemical Marker of Bone Turnover

NTX is a bone marker called urinary collagen type 1 cross-linked N-telopeptide

• Measures collagen cross-links released during resorption (bone breakdown)
• High rate of bone turnover indicates a sign of rapid bone loss
• Helpful to monitor the response of treatment
• Not to be used as a screening test or as a replacement for a BMD study to determine osteopenia or osteoporosis
• It is used to assess response the therapy in patients  with osteoporosis, osteopenia, and Paget disease
• Assessment of the effectiveness of therapy in patients who have increased bone turnover due to other conditions such as rickets or excess thyroid

 

Who Should have their Bone Mineral Density (BMD) via DEXA Scan Tested?

• Women with a fracture
• Estrogen-deficient women or those who go off hormones in menopause
• History of prolonged steroid use
• Postmenopausal woman younger than 65 with one or more risk factors
• Women >65 years old
• Monitor response to therapy
• Only detects low bone mass-not the cause of the low bone mass
• People with normal BMD on first DEXA need not be screened again for 15 years
• The U.S. Preventive Services Task Force (USPSTF) guideline does not recommend a DEXA for chronic back pain

 

How often should DEXA scans be repeated to monitor treatment?

 

It depends on the patient and is controversial, due to the radiation administered from DEXA. Two-year intervals while undergoing treatment seems reasonable but the evidence is lacking in this area of research. Even if bone mineral density does not show improvement on DEXA, the fracture risk may still be less due to non-density related improvements. This is something you and your physician will need to determine on a case-by-case basis, considering your personal and family history of cancer. 

According to an NIH study, osteoporosis will develop in fewer than 10% of older, postmenopausal women during the following time periods:

• In approximately 15 years for women with normal BMD or mild osteopenia  
• In about 5 years for women with moderate osteopenia 
• In about 1 year for women with advanced osteopenia 

 

Osteoporosis Management- How to Reverse Osteoporosis without Drugs!

 

The main goal is to lower the risk of fracture, slow bone loss, and increase bone mass and strength. Depending on the level of FRAX risk (remember the 10 year risk of fracture questionnaire mentioned earlier?), the general recommendations are:  

• Low Risk: Lifestyle changes and supplementation
• Moderate Risk: Same as Low Risk but may consider medication if high risk for fracture such as height decreasing, a prior fracture, taking an aromatase inhibitor, or on chronic steroids
• High Risk: same as the moderate risk

Of course, we will focus on the life style, diet, supplementation and hormone options in this article.

Lifestyle- Daily Habits to Reverse Osteoporosis

The first thing you will want to consider is exercise! Exercise must be weight-bearing and can be improved with hand-held weights while doing exercises such as step/stair climbing, lunges, squatting, heel drops, stomping, and getting up from a chair repeatedly. All of these types of exercises apply force to the bones which keep them healthy and build bone density. It is similar to strengthening muscles by lifting weights (which will be a nice side-effect!). 

Set a reminder on your watch or phone or whatever you can use to make sure you don’t forget to include these in your daily routine! You can do it! Best of all, it doesn’t cost you a dime but pays dividends to your health. If you’re not used to physical exercise, you will feel sore muscles. So, start slow and always consult your doctor first. 

 

Swimming, biking, and walking do not help bone mineral density much, but they will help overall fitness and reduce the risk of some diseases. Don’t be afraid to include these too!

Diet and Supplements- Major Nutrients to Reverse Osteoporosis

What you put into your body can have an enormous effect on your overall health and the health and density of your bones. And guess what…like with almost every other disease and health issue known to man, fruits and vegetables can prevent and reverse osteoporosis! In several studies, apples and prunes (especially prunes) significantly increased bone density in elderly women!  

• Fruits and Vegetables
• Legumes– higher phytate diets decrease hip fracture
• Almonds– inhibits bone breakdown cells
• Low sodium 
• Low sugar 
• No sodas
• No smoking or drinking!
• Low caffeine

While protein consumption doesn’t make a huge difference in osteoporosis or bone mineral density, several studies have shown that people with higher protein diets do tend to have higher bone mineral density. So, vegans/vegetarians beware! There are many great vegan proteins these days though!

Calcium

Calcium is the most abundant mineral in the human body, as nearly every section on calcium starts out. Most of it is stored in the bones and teeth as calcium hydroxyapatite, but it is also has many other uses in the body such as in muscular contractions, hormone secretion, cell signaling, etc.

In 2009, the U.S. Department of Agriculture conducted a review of the calcium, magnesium, vitamin D and phosphorus intakes of Americans from food and drink and compared it to the U.S. Institute of Medicine Dietary Reference Intakes. I’m going to include data from all age groups because building bone is a non-stop, life-long process and bone health in your early years reflects bone health in your later years:

•  Children
  • Only 5% of children aged 1-3 were below adequate intake (due to being formula-fed, as the report excluded breast-fed babies)
  • 32% of children aged 4-8 were below adequate intake (leads to me wonder if their “requirements” are too low)
• Males
  • Males 9-13: 83% were below adequate intake
  • Males 14-18: 78% were below adequate intake
  • Males 19-30: 44% were below adequate intake
  • Males 31-50: 42% were below adequate intake
  • Males 51-70: 34% were below adequate intake
  • Males Over 71: 86% were below adequate intake
• Females
  • Females 9-13: 88% were below adequate intake 
  • Females 14-18: 90% were below adequate intake
  • Females 19-30: 72% were below adequate intake
  • Females 31-50: 67% were below adequate intake
  • Females 51-70: 92% were below adequate intake
  • Females Over 71: 93% were below adequate intake
  • Pregnant Females 19-50: 27% were below adequate intake
• All Sexes
  • Everyone over 1 Year Old: 64% were below adequate intake

The report also states that 79% of all adult females and 56% of all adult males are not getting enough calcium to meet the Adequate Intake (1,000 mg at the time of the report). The Adequate Intake (AI) of calcium is “an approximation of the calcium intake that, in the opinion of the DRI Committee and its Panel on Calcium and Related Nutrients, would appear to be sufficient to maintain calcium nutriture while recognizing that lower intakes may be adequate for many.” Yes, it’s a bit ambiguous but probably a good amount for most healthy adults to shoot for. 

The reason the U.S. Institute of Medicine used Adequate Intake instead of Recommended Dietary Allowances was because of the lack of good data available on what appropriate calcium intakes should be at that time. The takeaway from the Department of Agriculture review is that most Americans don’t meet the Adequate Intake levels. 

However, in 2011, the Institute of Medicine (IOM) reconvened to write the “Dietary Reference Intakes for Calcium and Vitamin D (2011)” and were finally able to provide us with Recommended Dietary Allowances (RDA) on calcium, which reflect amounts that would be more than enough for 97.5% of the population in each age bracket. These turned out to be close to the previous Adequate Intake levels:

• Ages 19-50: 1,000 mg per day both sexes
• 51-70: 1,000 mg per day for males, 1,200 mg per day for females
• 71+: 1,200 mg per day both sexes

Source: https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/ 

The new 2011 IOM report also eliminated the Adequate Intakes and set the Estimated Average Requirements (EAR) “Average daily level of intake estimated to meet the requirements of 50% of healthy individuals.” to 800 mg for adults. So, somewhere between the EAR of 800 mg and Recommended Daily Allowance of 1,000 is where most adults would probably want to shoot for. This would cover 50% to 97.5% of the healthy population’s requirements. 

If you consider this new EAR level in the 2009 U.S. Department of Agriculture review of calcium mentioned previously, about 50% of the population actually hit or came close to the EAR. The major exception is women under 19 and over 50. If you or someone you love fall into those age groups, you might want to consider stepping up your calcium rich foods or grabbing a supplement. Of course, if you’re the 50% of the population that didn’t hit the EAR because you don’t eat a lot of legumes, greens or dairy (please stop the dairy though), you better start eating those things and/or grab a supplement too.

Calcium Rich Foods

As always, the best source of this vital mineral is food. Calcium in food is already in the most absorbable form possible. If possible, you should always get as many of your vitamins and minerals from food. 

Here are some healthy food sources of calcium: 

• Legumes
• Broccoli 
• Sardines
• Tofu
• Bok Choi
• Kale

Source: https://www.osteoporosis.foundation/patients/prevention/calcium-content-of-common-foods    

Notice there are no dairy sources in there. Calcium is absorbed from greens such as broccoli and kale at nearly twice the amounts as from dairy (only about 30% of calcium is absorbed from dairy). Despite the huge budgeted marketing attempts by the dairy industry, dairy in general is a terrible food and has been linked to all sorts of immune responses, cancers, cardiovascular disease, toxins, etc., etc. Plus, milk has been shown to NOT be associated with bone health in later years. This would be a full and lengthy article in itself, but let’s focus on the topic at hand!

If, for some reason, you cannot get enough calcium from your food on a daily basis, there are calcium supplements you can use to SUPPLEMENT your needs. However, and this is important, you don’t want to take more than the recommended amounts of calcium. You probably didn’t start getting osteoporosis ONLY because your calcium intake dropped off. 

As we saw from the earlier reports, about 50% of Americans are meeting their daily requirements. You more than likely started getting osteoporosis because your calcium levels started to wane while your hormones started to decrease, or were cut off drastically from surgery, or your vitamin D levels dropped sharply from lack of sun exposure and supplementation, or a combination of many things. While a little extra calcium will help, too much won’t. 

You only want to take the amount of calcium your body needs to create new bone. More will not make it grow bone any faster! Providing an abundance of block at the construction site will not make the building go up any faster. You need more construction workers, more mortar, more tools, more time. It would be prudent to measure your intake over a few days and see just where you stand. You might be surprised. Besides, how else are you going to know how much calcium (or anything else) you’re getting? 

Calcium Supplements

The various calcium types include calcium carbonate, citrate, gluconate and microcrystalline hydroxyapatite concentrate (MCHC). Calcium carbonate is a very cheap and poorly absorbed version, has been associated with intestinal side effects and is not recommended. Calcium citrate is usually the go-to type of calcium used in supplements, as it has been shown to be much better absorbed in repeated studies. It is not dependant on stomach acid for absorption like calcium carbonate is, which makes it a better version for patients with hypochlorhydria (low stomach acid), on PPIs or similar issues.  

For bone growth specifically, there is a form of calcium called microcrystalline hydroxyapatite concentrate (MCHC). This form is taken directly from the bones of animals. There has not been a lot of research on this type of calcium supplement. However, what little data there is shows that it may be better utilized by the body than calcium carbonate or gluconate. The other benefit is that since it is taken directly from bone, it contains many of the smaller nutrients also used to build bone. Unfortunately, that is also the downside, since it contains phosphorus, and Americans already consume plenty of phosphorus in foods such as soda, chicken, turkey, pork and seafood. The jury is still out on this one as to its rank in calcium performance. Personally, I would probably use it occasionally to get my minerals from multiple sources. 

The last type of calcium I will touch on is calcium derived from various sea algae, such as red marine algae.  This is a much newer source of calcium and minerals. Like calcium hydroxyapatite, there is not much research performed on it, and the research that has been published is not really worth mentioning. Anecdotally, I would always prefer to obtain my nutrients from food or animal sources than from rock sources. So, obtaining minerals from algae seems like it would be a better source. However, more research is needed on this form of calcium before it truly proves it’s worth. 

Magnesium

Magnesium is an essential mineral for healthy human life. It is a cofactor (assistant) for over 300 enzymatic reactions (chemical processes) in the human body such as glycolysis (the transformation of glucose/sugar into energy), oxidative phosphorylation (the main source of energy (ATP) production in the body), blood pressure control, muscle and nerve function, DNA synthesis and repair, and protein synthesis…all critical functions. 

Some Osteoporosis Related Functions of Magnesium:

• Needed for calcitriol (vitamin D metabolite) synthesis
• Needed for normal calcium utilization
• Aids calcium gut absorption
• Shown to maintain bone mass

Let’s take another look at the results of the 2009 U.S. Department of Agriculture review for calcium, magnesium, vitamin D and phosphorus, but this time analyze magnesium. Again, the conclusions were disappointing:

•  Children
  • Less than 3% of children aged 1-3 were below estimated average requirements (due to being formula-fed, as the report excluded breast-fed babies)
  • Less than 3% of children aged 4-8 were below estimated average requirements (leads to me wonder if their “requirements” are too low)
• Males
  • Males 9-13: 22% were below estimated average requirements (leads to me wonder if their “requirements” are too low)
  • Males 14-18: 69% were below estimated average requirements
  • Males 19-30: 51% were below estimated average requirements
  • Males 31-50: 45% were below estimated average requirements
  • Males 51-70: 58% were below estimated average requirements
  • Males Over 71: 80% were below estimated average requirements
• Females
  • Females 9-13: 30% were below estimated average requirements (leads to me wonder if their “requirements” are too low)
  • Females 14-18: 89% were below estimated average requirements
  • Females 19-30: 65% were below estimated average requirements
  • Females 31-50: 48% were below estimated average requirements
  • Females 51-70: 55% were below estimated average requirements
  • Females Over 71: 70% were below estimated average requirements
  • Pregnant Females 19-50: 46% were below estimated average requirements 
• All Sexes
  • Everyone over 1 Year Old: 48% were below estimated average requirements

As bad as those numbers look, the story actually gets worse. Those are only the percent of people below the “Estimated Average Requirement”. The Estimated Average Requirement (EAR) is the “Average daily level of intake estimated to meet the requirements of 50% of healthy individuals.” So, the EAR is only enough to meet the minimum needs of  HALF of the HEALTHY people. So, HALF of the healthy people are still deficient at those numbers. 

Since the report states that 56% of all adult females and 53% of all adult males are not getting enough magnesium to meet the needs of healthy people, it means that, for those 44%-47% of adult Americans who are consuming enough magnesium adequate for half of the healthy people, 22%-23.5% of HEALTHY Americans (half of the 44-47%) are still NOT getting enough magnesium. 

Further, how many people in the U.S. are “healthy”? These amounts of magnesium are not enough for someone who has health issues, they are not enough to close the gap on deficiency, and by definition the EAR levels of magnesium are far from what is needed to meet the needs of everyone, which varies according to individual health status and unique requirements! 

AND, this is still not OPTIMAL magnesium intake level. To put it simply, according to their data, just about every person in the U.S. needs to increase their daily consumption of magnesium-rich foods and/or supplement with magnesium. It’s a complex analysis to a simple answer: consume more magnesium!

To serve as a better guide to what we should actually be consuming, here are the 2011 U.S. Institute of Medicine’s Recommended Dietary Allowances (RDA) of magnesium, which are higher than the amounts needed to reach the Estimated Average Requirements we had in the 90’s and reflect amounts that would be more than enough for 97.5% of the population in each age bracket.  These are generally agreed upon by most institutions: 

• Ages 19-30: 400 mg per day for males, 310 for females, 350 for pregnant females
• 31+: 420 mg per day for males, 320 mg per day for females, 360 for pregnant females

Source: https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ 

I’ll say it again, the best source of vitamins and minerals is food. I know this seems like I’m shooting myself in the foot, owning a supplement company and all, but my main goal is to improve your health and provide the best information possible. Many don’t typically eat like we have evolved to eat, consuming beans and kale at every meal. So, supplementation simply becomes the easiest route for many of us to ensure we’re meeting our needs (believe it or not, I don’t eat perfectly either).  

Magnesium Rich Foods

Healthy food sources of magnesium:

• Dark green vegetables
• Nuts such as almonds, cashews and brazil nuts
• Seeds like pumpkin, sunflower and sesame
• Buckwheat
• Brown rice

Source: https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/

Just to sum up what you would have to eat every day, day in, day out, to meet your daily requirements:

• 1 ounce of almonds
• ½ cup of cooked spinach
• 1 ounce of cashews
• 1 cup of organic soy milk
• ½ cup of cooked black beans 
• ½ cup of cooked and shelled edamame 
• 1 cup of avocado

That brings you to 400mg of magnesium! If you’re not eating that much healthy food every day, either step up your game or see the next section! 

Magnesium Supplements

Magnesium Supplement types:

aspartate, malate, glycinate, citrate, threonate and succinate

Dose of magnesium is 300-500 mg per day. It’s customary to couple calcium and magnesium in a ratio of 2 to 1 in divided doses due to the increased risk of diarrhea and absorption. Magnesium oxide should be avoided due to poor absorption and higher diarrhea rate. Magnesium glycinate has been shown to be the best absorbing form available. 

 

Vitamin D

Vitamin D is known as the sunshine vitamin, since your body makes it from being exposed to ultraviolet radiation. Blood levels of vitamin D (25-hydroxyvitamin D) below 20–25 nmol (8-10 ng/ml) is considered high risk for osteoporosis.  

Function

• Stimulation of osteoblasts
• Increases GI absorption of dietary Calcium
• Controls phosphorus absorption
• Interacts with hundreds of genes in the body

Since vitamin D is produced by the body, we’re going to ignore the U.S. Department of Agriculture’s review because they only took into consideration food sources. However, a review of a section of the National Health and Nutrition Examination Survey (NHANES) comprising 4,962 participants over 20 years old who were hospitalized between 2011 and 2012 show that about 40% of patients had vitamin D levels less than 50 nmol/L (20ng/ml), which is even below the level most agencies (Vitamin D Council, Endocrine Society) recommend. This means that a lot more than 40% of the population are below the optimal levels. This is the same result from the older 2005-2006 NHANES report. So, it doesn’t look like Americans are catching the hint, even though vitamin D has been a very popular health topic. 

There is some disagreement regarding vitamin D recommendations in general, for both frequency and dosage. As should have been obvious, since we evolved experiencing sunlight regularly, continuing research studying vitamin D in controlled trials have shown that daily dosages of vitamin D are superior to larger less frequent dosing. 

 

The daily vitamin D dosing recommendations vary quite a lot, depending on whom you ask, anywhere from the RDA of 600 IU per day for an adult to 5,000 IU per day by the Vitamin D Council, with safe upper limit daily doses at 10,000 IU per day, per Institute of Medicine. 

It is VERY important to note that the 2011 U.S. RDAs provided by the Institute of Medicine (this was a 1200 page book covering vitamin D and calcium, btw) are far below the current recommended amounts due to a statistical error in their reporting. It turns out, the amount of vitamin D from supplements or food it takes to bring your blood levels (serum 25(OH)D) to a recommended level of 50 nmol/L or more in a majority of the population is actually much higher than they published, as numerous published editorial letters have pointed out. The updated daily intakes are as follows:

• 1,000 IU for children <1 year who are on enriched formula
• 1,500 IU for those older than 6 months who are breastfed
• 3,000 IU for children >1 year of age 
• up to 8,000 IU for young adults and thereafter with adult doses adapted to the body mass index with the blood levels set to 100 nmol/L 

 

It should be noted that these amounts are estimates for people not getting any sunlight. If you’re getting direct sunlight on a regular basis, the dose you will have to take will be lower and will vary depending on the level of sunlight you experience. The best way to ensure you’re getting in the proper amount of vitamin D is to have it tested with your annual/semi-annual lab tests. Make sure you’ve been on a regular dosing schedule for a few months so that you’re levels are normalized. This way, you can know for sure you’re on the right path. Optimal blood levels for 25-hydroxyvitamin D range from 30 to 100 ng/ml (75-250 nmol/l).

If you don’t get atleast 30 minutes of direct sunlight on most of your body a few days a week, the best dosing schedule will probably be around 5,000 IU per day until you see some lab results in a couple months. It’s a good place to start before getting your blood levels tested. 

Vitamin D Sources

• Sunshine
• Fatty fish
• Supplements 

Vitamin D Supplements

There are two types of vitamin D supplements available on the market: D2 (ergocalciferol- produced by some plants and fungi) and D3 (cholecalciferol- produced by animals and humans). Many studies show that the D3 is the better all around version, and it is the version the human body makes. Remember, try to stick to what the body is meant to have and you’ll usually fare better. 

Phosphorus

Let’s take one last look at the results of the 2009 U.S. Department of Agriculture review for calcium, magnesium, vitamin D and phosphorus, but this time analyze phosphorus. For this mineral, most Americans actually consume plenty and I’ll only include the two age groups that might need a little attention:

• Females
  • Females 9-13: 34% were below estimated average requirements 
  • Females 14-18: 51% were below estimated average requirements
• All Sexes
  • Everyone over 1 Year Old: 95% were above estimated average requirements

If you’re a female age 9-18, you might want to consider upping your phosphorus intake. The most significant sources of phosphorus in the U.S. are grains, meat and dairy (please stop the dairy!). If you don’t consume any of those, you might want to consider adding some grass fed meat to your diet. Other than that, you are probably taking in adequate amounts of phosphorus. 

 

Vitamin K

• Recent studies show that Vitamin K, especially K2, along with Vitamin D and calcium can reduce the fracture rate by 20-25% and increase survival among postmenopausal women
• There are four forms of K2: MK4, MK7, MK8, and MK9. The best type is MK7, a newer and long-acting form extracted from the Japanese fermented soy product called natto
• 180 mcg is the recommended daily dose

 

Vitamin C

 

Helps make collagen which makes up 30% of bones and stimulates bone-building cells, enhances calcium absorption and Vitamin D’s effect on bone metabolism.

 

• Typical dose is 1000 mg daily

 

Vitamins B6, B12 and B9/Folic Acid

The B vitamins have a physiologic role in the formation of bone, but clinical trials have not had much success with B vitamin supplementation alone increasing bone density, which probably seems obvious. It takes more than cofactors to build bone. Remember my construction site analogy earlier? 

People who are likely to be deficient are:

• People on antacids or medications to lower acid
• People over 50
• Regular alcohol or more than 4 cups of coffee
• Vegetarians and vegans
• People who consume a high-carbohydrate diet

 

 

Essential Fatty Acids

Essential fatty acids in humans are comprised of the omega 3 and omega 6 fatty acids, called essential because our bodies cannot make the fats but require them to function. Omega fatty acids in fish oils are composed almost entirely of omega 3 fatty acids, but supplements forms are usually highly refined to contain only the omega 3 fatty acid portion. Omega 6 fatty acids support inflammation in the body while omega 3 fights inflammation. Americans tend to have an excess of omega 6 fatty acids in our diet. So, consuming more omega 3 fatty acids is helpful for all body tissues, including bones. Omega 6 fatty acids also trigger osteoclasts (breaks down bones) via its inflammatory properties.

The daily omega 3 dose is about 1500 mg ( 800 EPA and 600 DHA, 100 other omega 3’s) but dosages in the 2-3 gram (2,000 to 3,000 mg) range are considered safe and therapeutic.

Strontium

This is a very important section. Strontium is a mineral that is only found in very low amounts in bone, naturally. There used to be a prescription drug in the form of strontium ranelate (Protelos) that came as a 2,000mg dose, but was discontinued due to severe side effects such as blood clots and heart attacks. While strontium is naturally found in our diets, we only consume about 2-4mg of it daily. So, to take 1000 times that dose was having a detrimental effect. 

Further, when taking higher doses of strontium, the body will store it as bone. However, it does so only to replace what should be calcium and other nutrients and it not necessarily healthy, even for the bone (though it may improve DEXA scan and other lab results). This is done in the same fashion as lead. If you have lead toxicity, the body will store it in the bone, improving DEXA scan results. Obviously, lead is not healthy for you! I think this example highlights the silliness of overdosing with strontium. In our current opinion, supplements should not contain hundreds of milligrams (mg) of strontium, which rules out some otherwise very good supplements. 

Isoflavones

 

Isoflavones are proteins naturally found in soy that act as estrogens on osteoblasts (cells that grow bones). In people who cannot take estrogen for osteoporosis prevention due to its adverse effect on the uterus and breast, isoflavones offer a good alternative and have been proven in research studies to provide significant improvements in bone mineral density and menopause symptom relief . These effects include the stimulation of osteoblasts growth and inhibit osteoclastic (bone breakdown) activity. In one study on 325 post-menopausal women, isoflavones increased bone mineral density almost as much as hormone replacement therapy ( 11.38% vs 15.32%). 

As bonus information, isoflavones have also been shown to inhibit the growth of post-menopausal breast cancer in research studies and higher dietary intakes of isoflavones have been repeatedly shown to be strongly associated with a lower incidence of prostate cancer. There was conflicting information about this because in petri dishes, breast tissue seem to grow cancer cells when exposed to isoflavones. However, in the human body, isoflavones have shown to actually be protective of cancer. The typical dose provided by supplements is usually 75-150 mg/dose. Research has shown doses of 900mg per day to be safe and effective.  

Unfortunately, isoflavones have not proved as effective in reversing osteoporosis in men as they have in women, though they still offer health benefits. Hormone replacement therapy, healthy diet and regular weight bearing exercise is still the best bet for men.  

Genistein

As mentioned above, there are 12 different types of isoflavones and genistein is one of those types that has been particularly well studied and sold commonly in supplement form. It has been a favorite of the isoflavones to be used in research trials due to its low side effects and  repeated significant improvements in bone mineral density in virtually every research study, even at fairly low doses. Further, when combined with hormone replacement therapy (HRT), participants also taking genistein improved bone mineral density, and all other bone-benefitting tests, more so than HRT alone. 

Similar to the isoflavones in general, genistein has been shown to prevent the spread of several cancers, including breast cancer, and increase the effectiveness of the cancer drug adriamycin/Doxorubicin in studies.  It also prevents the growth and spreading of prostate cancer! It’s definitely a multi-purpose supplement.  The general recommended daily dose of genistein is 125 to 250mg per day. 

Ipriflavone

Is a synthetic soy supplement that is helpful in reducing bone loss from a variety of reasons and may help bone-related pain. The typical dose is 200 mg, three times a day. However, with so many positive benefits of the real thing (isoflavones and genistein), I don’t see any reason to use this version. 

Hormones/Medications

Yes, even medications have their place in the treatment of osteoporosis. However, we will only cover hormones here, as they are a huge aspect of the disease, are produced naturally by the body and can be a very important part of treatment and overall wellbeing improvement.  

Estrogen has many purposes in both the male and female body. One of them is stimulating osteoblast cells to build bone. Once hormone levels diminish in men, and especially in women from menopause, osteoblasts no longer receive the signals from estrogen to build bone and many times osteoporosis ensues. 

This is when many people reach out to their physicians about hormone replacement therapy. Hormone replacement therapy can take the form of the natural or synthetic formulations. If a woman has a uterus, she will need to take progesterone along with estrogen, to prevent endometrial cancer, which also plays a positive role in bone formation.  

Forms of female hormone therapy include creams, pessaries and rings for intravaginal use. There are also oral formulations (though not recommended), transdermal patches, creams and gels and even implants. All of them can be estrogen alone or in combination with progesterone, DHEA, testosterone or other prescriptions.  

Four types of estrogen found in the human body:

• Estrone (E1)
• Estradiol (E2) 
• Estrione (E3)
• Estetrol (E4) (produced during pregnancy)

For men, increased testosterone will cause the body to naturally increase the production of estrogen, to aid in bone formation. However, androgens (testosterone, DHEA and others) also aid in bone formation on their own. 

Sometimes testosterone is boosted using the prescription drug clomid (clomiphene) or HCG (human chorionic gonadotropin). Otherwise, testosterone replacement therapy is given typically via a daily cream/gel on the skin or injections every few days and is also sometimes given with DHEA, progesterone and/or estrogen inhibitors to keep the estrogen levels in a healthy range.

Finding a qualified doctor very experienced in hormone therapy is important for both men and women. Hormones (or lack of normal hormone levels) can completely change the way you feel and think and even the way you cope with stress. The American Academy of Anti-Aging Medicine (A4M) is a good place to find a qualified hormone doctor. 

Conclusion

We always have to remember to go back to the broad picture when it comes to your health. Even though many things in isolation have shown to make improvements to bone density, humans and the real world don’t work in isolation like a research study does. Sure calcium alone might benefit your bones, but why would you ever just take calcium when the bones (and the rest of the body) benefit so much more from calcium with magnesium, phosphorus, vitamin D, potassium, zinc, vitamin C, isoflavones, probably 50 other things found in fruits and vegetables, normalized hormones, exercise and other healthy lifestyle choices? I hope you wouldn’t. I would love to see you on a path to healing, not annoyed that the calcium supplement you bought isn’t working. 

It would be very plausible that also adding in lifestyle changes such as exercise and some of the diet modification mentioned earlier such as lower sugar, salt and alcohol, could increase your bone mineral density by much more significant amounts and make a drastic improvement to your health. What do you have to lose? I challenge you to grab your phone or calendar right now and schedule a regular time atleast three days a week to incorporate just 15 minutes of weight bearing exercise. And tonight, grab that bowl of strawberries instead of that pint of ice cream in the freezer. Reply below and let me know you did it!

Shoot me an email for my list of recommended supplements!

Would you like some personalized help with osteoporosis or other health concerns? Use the contact form at the bottom of this page for a consult! 

Cheat Sheet

• Calcium-
  • Ages 19-30: 400 mg per day for males, 310 for females, 350 for pregnant females 
  • 31+: 420 mg per day for males, 320 mg per day for females, 360 for pregnant females
• Magnesium-
  • Ages 19-30: 400 mg per day for males, 310 for females, 350 for pregnant females
  • 31+: 420 mg per day for males, 320 mg per day for females, 360 for pregnant females
• Vitamin D- Up to 8,000 IU per day until blood levels reach 100 nmol/L 
• Vitamin K- 180 mcg is the recommended daily dose
• Vitamin C- Typical dose is 1000 mg daily
• Essential Fatty Acids- 2-3 grams per day
• Isoflavones/Genistein- 150mg- 250mg per day

REFERENCES

1. Burge, R., Dawson-Hughes, B., Solomon, D., Wong, J., King, A., & Tosteson, A. (2006). Incidence and Economic Burden of Osteoporosis-Related Fractures in the United States, 2005-2025. Journal Of Bone And Mineral Research, 22(3), 465-475. doi:10.1359/jbmr.061113 https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.061113
2. Guideline] National Osteoporosis Foundation. Clinician’s Guide to Prevention and Treatment of Osteoporosis: 2014 Issue, Version 1. Available at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4176573/. April1 2, 2014; Accessed: May 4, 2017.
3. [Guideline] Schousboe JT, Shepherd JA, Bilezikian JP, Baim S. Executive summary of the 2013 International Society for Clinical Densitometry Position Development Conference on bone densitometry. J Clin Densitom. 2013 Oct-Dec. 16(4):455-66. [PubMed].
4. Gosfield E 3rd, Bonner FJ Jr. Evaluating bone mineral density in osteoporosis. Am J Phys Med Rehabil. 2000 May-Jun. 79(3):283-91. https://pubmed.ncbi.nlm.nih.gov/10821315/
5. Gallagher and Tella ,J Steroid Biochem Mol Biol. Author manuscript; available in PMC 2015 July 01.
6. Brown, SA, Guise, TA. 2009. Cancer treatment‐related bone disease. Crit Rev Eukaryot Gene Expr 19( 1): 47– 60. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762110/
7. Kanis JA, Johansson H, Oden A et al. A meta-analysis of prior corticosteroid use and fracture risk. J. Bone Miner. Res. 19, 893–899 (2004). https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/JBMR.040134
8. Angeli A, Guglielmi G, Dovio A et al. High prevalence of asymptomatic vertebral fractures in post-menopausal women receiving chronic glucocorticoid therapy: a cross-sectional outpatient study. Bone 39, 253–259 (2006). https://www.sciencedirect.com/science/article/abs/pii/S8756328206002626?via%3Dihub
9. Osteopenia Treatment, Symptoms, Signs & Causes [Internet]. eMedicineHealth. [cited 2019 Feb 24]. Available from: https://www.emedicinehealth.com/osteopenia/article_em.htm
10. Sözen T, Özışık L, Başaran NÇ. An overview and management of osteoporosis. Eur J Rheumatol. 2017 Mar;4(1):46–56.
11. Osteoporosis Treatment, Signs & Symptoms [Internet]. eMedicineHealth. [cited 2019 Feb 23]. Available from: https://www.emedicinehealth.com/osteoporosis/article_em.htm
12. Bone Density Test, Osteoporosis Screening & T-score Interpretation [Internet]. National Osteoporosis Foundation. [cited 2019 Feb 24]. Available from: https://www.nof.org/patients/diagnosis-information/bone-density-examtesting/
13. Howe TE, e. (2019). Exercise for preventing and treating osteoporosis in postmenopausal women. – PubMed – NCBI . Ncbi.nlm.nih.gov. Retrieved 26 June 2019, from https://pubmed.ncbi.nlm.nih.gov/21735380/ 
14. Prynne, C., Mishra, G., O’Connell, M., Muniz, G., Laskey, M., & Yan, L. et al. (2006). Fruit and vegetable intakes and bone mineral status: a cross-sectional study in 5 age and sex cohorts. The American Journal Of Clinical Nutrition, 83(6), 1420-1428. doi:10.1093/ajcn/83.6.1420 https://academic.oup.com/ajcn/article/83/6/1420/4632973
15. Tucker, K., Hannan, M., Chen, H., Cupples, L., Wilson, P., & Kiel, D. (1999). Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. The American Journal Of Clinical Nutrition, 69(4), 727-736. doi:10.1093/ajcn/69.4.727 https://academic.oup.com/ajcn/article/69/4/727/4737412 
16. Hooshmand, S., Chai, S., Saadat, R., Payton, M., Brummel-Smith, K., & Arjmandi, B. (2011). Comparative effects of dried plum and dried apple on bone in postmenopausal women. British Journal Of Nutrition, 106(6), 923-930. doi:10.1017/s000711451100119x https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/comparative-effects-of-dried-plum-and-dried-apple-on-bone-in-postmenopausal-women/96CBAFC8762838C62C36F5B57ACF0733# 
17. Platt, I., Josse, A., Kendall, C., Jenkins, D., & El-Sohemy, A. (2011). Postprandial effects of almond consumption on human osteoclast precursors—an ex vivo study. Metabolism, 60(7), 923-929. doi:10.1016/j.metabol.2010.08.012 https://www.maturitas.org/article/S0378-5122(07)00255-1/fulltext
18. López-González, Á., Grases, F., Monroy, N., Marí, B., Vicente-Herrero, M., Tur, F., & Perelló, J. (2012). Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women. European Journal Of Nutrition, 52(2), 717-726. doi:10.1007/s00394-012-0377-6 https://link.springer.com/article/10.1007/s00394-012-0377-6
19. Tucker, K. (2014). Vegetarian diets and bone status. The American Journal Of Clinical Nutrition, 100(suppl_1), 329S-335S. doi:10.3945/ajcn.113.071621
20. Dietary Reference Intakes for Calcium and Vitamin D. (2011). doi:10.17226/13050 https://www.nap.edu/catalog/13050/dietary-reference-intakes-for-calcium-and-vitamin-d 
21. Shams-White, M., Chung, M., Du, M., Fu, Z., Insogna, K., & Karlsen, M. et al. (2017). Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. The American Journal Of Clinical Nutrition, ajcn145110. doi:10.3945/ajcn.116.145110 https://academic.oup.com/ajcn/article/105/6/1528/4633993?searchresult=1
22. Michaelsson, K., Wolk, A., Langenskiold, S., Basu, S., Warensjo Lemming, E., Melhus, H., & Byberg, L. (2014). Milk intake and risk of mortality and fractures in women and men: cohort studies. BMJ, 349(oct27 1), g6015-g6015. doi:10.1136/bmj.g6015 https://www.bmj.com/content/349/bmj.g6015
23. Feskanich, D., Bischoff-Ferrari, H., Frazier, A., & Willett, W. (2014). Milk Consumption During Teenage Years and Risk of Hip Fractures in Older Adults. JAMA Pediatrics, 168(1), 54. doi:10.1001/jamapediatrics.2013.3821 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3983667/
24. Institute of Medicine 2011. Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press. https://www.nap.edu/catalog/13050/dietary-reference-intakes-for-calcium-and-vitamin-d.
25. NHANES – National Health and Nutrition Examination Survey Homepage. (2019). Cdc.gov. Retrieved 5 July 2019, from https://www.cdc.gov/nchs/nhanes/index.htm 
26. Office of Dietary Supplements – Calcium. (2019). Ods.od.nih.gov. Retrieved 6 July 2019, from https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/#en1 https://ods.od.nih.gov/factsheets/Calcium-HealthProfessional/#en1
27. Veugelers, P., & Ekwaru, J. (2014). A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients, 6(10), 4472-4475. doi:10.3390/nu6104472 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4210929/
28. Heaney, R., Garland, C., Baggerly, C., French, C., & Gorham, E. (2015). Letter to Veugelers, P.J. and Ekwaru, J.P., A Statistical Error in the Estimation of the Recommended Dietary Allowance for Vitamin D. Nutrients 2014, 6, 4472–4475; doi:10.3390/nu6104472. Nutrients, 7(3), 1688-1690. doi:10.3390/nu7031688 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4377874/
29. Papadimitriou, D. (2017). The Big Vitamin D Mistake. Journal Of Preventive Medicine And Public Health, 50(4), 278-281. doi:10.3961/jpmph.16.111 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541280/
30. Epstein, O., Kato, Y., Dick, R., & Sherlock, S. (1982). Vitamin D, hydroxyapatite, and calcium gluconate in treatment of cortical bone thinning in postmenopausal women with primary biliary cirrhosis. The American Journal Of Clinical Nutrition, 36(3), 426-430. doi:10.1093/ajcn/36.3.426 https://academic.oup.com/ajcn/article-abstract/36/3/426/4693441?redirectedFrom=fulltext
31. Castelo-Branco, C., & Dávila Guardia, J. (2014). Use of ossein–hydroxyapatite complex in the prevention of bone loss: a review. Climacteric, 18(1), 29–37. doi:10.3109/13697137.2014.929107 https://www.tandfonline.com/doi/abs/10.3109/13697137.2014.929107?journalCode=icmt20
32. Bristow, S., Gamble, G., Stewart, A., Horne, L., House, M., & Aati, O. et al. (2014). Acute and 3-month effects of microcrystalline hydroxyapatite, calcium citrate and calcium carbonate on serum calcium and markers of bone turnover: a randomised controlled trial in postmenopausal women. British Journal Of Nutrition, 112(10), 1611-1620. doi:10.1017/s0007114514002785 https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/acute-and-3month-effects-of-microcrystalline-hydroxyapatite-calcium-citrate-and-calcium-carbonate-on-serum-calcium-and-markers-of-bone-turnover-a-randomised-controlled-trial-in-postmenopausal-women/C7B53D8B50F5372304C6B7CB020FD0C6 
33. Zenk, J. L., Frestedt, J. L., & Kuskowski, M. A. (2018). Effect of Calcium Derived from Lithothamnion sp. on Markers of Calcium Metabolism in Premenopausal Women. Journal of Medicinal Food, 21(2), 154–158. doi:10.1089/jmf.2017.0023 https://www.liebertpub.com/doi/10.1089/jmf.2017.0023
34. Aslam, M., Kreider, J., Paruchuri, T., Bhagavathula, N., DaSilva, M., & Zernicke, R. et al. (2010). A Mineral-Rich Extract from the Red Marine Algae Lithothamnion calcareum Preserves Bone Structure and Function in Female Mice on a Western-Style Diet. Calcified Tissue International, 86(4), 313-324. doi:10.1007/s00223-010-9340-9 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2877502/
35. Office of Dietary Supplements – Magnesium. (2016). Ods.od.nih.gov. Retrieved 9 November 2016, from https://ods.od.nih.gov/factsheets/magnesium-HealthProfessional/#en1
36. Office of Dietary Supplements – Magnesium. (2019). Ods.od.nih.gov. Retrieved 6 July 2019, from https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/ https://ods.od.nih.gov/factsheets/Magnesium-HealthProfessional/
37. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. (1997). doi:10.17226/5776 https://www.ncbi.nlm.nih.gov/books/NBK109825/ 
38. Parva, N., Tadepalli, S., Singh, P., Qian, A., Joshi, R., & Kandala, H. et al. (2018). Prevalence of Vitamin D Deficiency and Associated Risk Factors in the US Population (2011-2012). Cureus. doi:10.7759/cureus.2741 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075634/
39.  Hanley, D., & Davison, K. (2005). Vitamin D Insufficiency in North America. The Journal Of Nutrition, 135(2), 332-337. doi:10.1093/jn/135.2.332 https://academic.oup.com/jn/article/135/2/332/4663654
40. Stephensen, C., Zerofsky, M., Burnett, D., Lin, Y., Hammock, B., Hall, L., & McHugh, T. (2012). Ergocalciferol from Mushrooms or Supplements Consumed with a Standard Meal Increases 25-Hydroxyergocalciferol but Decreases 25-Hydroxycholecalciferol in the Serum of Healthy Adults. The Journal Of Nutrition, 142(7), 1246-1252. doi:10.3945/jn.112.159764 https://academic.oup.com/jn/article/142/7/1246/4630809?searchresult=1
41. Armas, L., Hollis, B., & Heaney, R. (2004). Vitamin D2Is Much Less Effective than Vitamin D3in Humans. The Journal Of Clinical Endocrinology & Metabolism, 89(11), 5387-5391. doi:10.1210/jc.2004-0360 https://academic.oup.com/jcem/article/89/11/5387/2844259 
42. McClure, S., Chang, A., Selvin, E., Rebholz, C., & Appel, L. (2017). Dietary Sources of Phosphorus among Adults in the United States: Results from NHANES 2001–2014. Nutrients, 9(2), 95. doi:10.3390/nu9020095 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5331526/ 
43. Dai, Z., & Koh, W. (2015). B-Vitamins and Bone Health–A Review of the Current Evidence. Nutrients, 7(5), 3322-3346. doi:10.3390/nu7053322 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4446754/
44. J. Agric. Food Chem.201462297268-7278. Publication Date:June 28, 2014. https://pubs.acs.org/doi/10.1021/jf5016973 
45. Mangano, K., Sahni, S., Kerstetter, J., Kenny, A., & Hannan, M. (2013). Polyunsaturated Fatty Acids and Their Relation with Bone and Muscle Health in Adults. Current Osteoporosis Reports, 11(3), 203-212. doi:10.1007/s11914-013-0149-0 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3884553/
46. Tolerable Upper Intake Level of EPA, DHA and DPA. (2012). European Food Safety Authority. Retrieved 17 July 2019, from https://www.efsa.europa.eu/en/efsajournal/pub/2815
47. Fogelman, I., & Blake, G. (2005). Strontium ranelate for the treatment of osteoporosis. BMJ, 330(7505), 1400-1401. doi:10.1136/bmj.330.7505.1400 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC558360/
48. (2019). Jarrow.com. Retrieved 27 June 2019, from https://jarrow.com/blogs/articles-posts/smart-supplementing-for-bone-health
49. Pors Nielsen, S. (2004). The biological role of strontium. Bone, 35(3), 583-588. doi:10.1016/j.bone.2004.04.026https://www.sciencedirect.com/science/article/abs/pii/S8756328204001814 
50. Wei, P., Liu, M., Chen, Y., & Chen, D. (2012). Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pacific Journal Of Tropical Medicine, 5(3), 243-248. doi:10.1016/s1995-7645(12)60033-9 https://www.sciencedirect.com/science/article/pii/S1995764512600339?via%3Dihub
51. Zhang G, Qin L, Shi Y. Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial. J Bone Miner Res.  2007;22:1027-1079. https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.070405
52. Xiao, Y., Zhang, S., Tong, H., & Shi, S. (2017). Comprehensive evaluation of the role of soy and isoflavone supplementation in humans and animals over the past two decades. Phytotherapy Research, 32(3), 384-394. doi:10.1002/ptr.5966 https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.5966
53. Nahas, E., Nahas-Neto, J., Orsatti, F., Carvalho, E., Oliveira, M., & Dias, R. (2007). Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study. Maturitas, 58(3), 249-258. doi:10.1016/j.maturitas.2007.08.012 https://www.maturitas.org/article/S0378-5122(07)00255-1/fulltext
54. Koh, W., Wu, A., Wang, R., Ang, L., Heng, D., Yuan, J., & Yu, M. (2009). Gender-specific Associations Between Soy and Risk of Hip Fracture in the Singapore Chinese Health Study. American Journal Of Epidemiology, 170(7), 901-909. doi:10.1093/aje/kwp220 https://academic.oup.com/aje/article/170/7/901/92802
55. Sivoňova, M., Kaplan, P., Tatarkov, Z., Lichardusova, L., Dušenka, R., & Jurečekova, J. (2018). Androgen receptor and soy isoflavones in prostate cancer (Review). Molecular And Clinical Oncology. doi:10.3892/mco.2018.1792 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6327222/
56. Ziaei, S., & Halaby, R. (2017). Dietary Isoflavones and Breast Cancer Risk. Medicines, 4(2), 18. doi:10.3390/medicines4020018 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5590054/
57. Yamaguchi, M. Regulatory mechanism of food factors in bone metabolism and prevention of osteoporosis. Yakugaku zasshi. 2006; 126:1117-1137. https://www.jstage.jst.go.jp/article/yakushi/126/11/126_11_1117/_article
58. Marini H, Minutoli L, Poilito F, et al. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women.  Ann Intern Med. 2007; 146:839-847. https://annals.org/aim/article-abstract/734995/effects-phytoestrogen-genistein-bone-metabolism-osteopenic-postmenopausal-women-randomized-trial?volume=146&issue=12&page=839 
59. Morabito N, Crisaffuli A, Gaudio A, et al. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res. 2002; 17: 1904-1912. https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.2002.17.10.1904 
60. Pavese, J., Krishna, S., & Bergan, R. (2014). Genistein inhibits human prostate cancer cell detachment, invasion, and metastasis. The American Journal Of Clinical Nutrition, 100(suppl_1), 431S-436S. doi:10.3945/ajcn.113.071290 https://academic.oup.com/ajcn/article/100/suppl_1/431S/4576581?searchresult=1  
61. Pop, E., Fischer, L., Coan, A., Gitzinger, M., Nakamura, J., & Zeisel, S. (2008). Effects of a high daily dose of soy isoflavones on DNA damage, apoptosis, and estrogenic outcomes in healthy postmenopausal women. Menopause, 15(4), 684-692. doi:10.1097/gme.0b013e318167b8f2 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2574732/ 
62. Weitzmann, M. (2006). Estrogen deficiency and bone loss: an inflammatory tale. Journal Of Clinical Investigation, 116(5), 1186-1194. doi:10.1172/jci28550 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1451218/
63. Seifert-Klauss, V., & Prior, J. (2010). Progesterone and Bone: Actions Promoting Bone Health in Women. Journal Of Osteoporosis, 2010, 1-18. doi:10.4061/2010/845180 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2968416/
64. Clarke, B., & Khosla, S. (2009). Androgens and bone. Steroids, 74(3), 296-305. doi:10.1016/j.steroids.2008.10.003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2679948/