The Best Tools to Fight and Prevent Osteoporosis

by Krista Russ

The Epidemic of Broken Bones 

As many people struggle to get enough Vitamin D in the winter and early spring months with much of the country still patched in cloudy skies, March is an opportune time to consider bone health for your patients.

Bone health is particularly concerning in your aging patients, but even younger patients should be thinking about their bone health. After age 30, bone density slowly declines until it rapidly declines at menopause for women. Nearly 20 percent of women over 50 have osteoporosis of the femur neck and/or lumbar spine, according to the CDC [1]. And four percent of men over 50 have osteoporosis of the lumbar spine. 

Most patients won’t know they have osteoporosis until they break a bone, which is a problem because once a bone is broken it can have lasting effects like chronic pain, loss of height, loss of mobility and independence, and even increased mortality rate in the case of broken hips (per The CDC [2]). Osteoporosis is a chronic disease that affects 10 million Americans [3] and leads to significant morbidity and mortality, so what are we as physicians doing to treat and prevent osteoporosis? And more importantly, is our current standard of care safe and effective? 

Questionable Treatments

The core treatments for osteoporosis center around bisphosphonate drugs like Alendronate and Ibandronate (per Mayo Clinic [4]). Not only do these medications have unpleasant side effects like nausea, abdominal pain, heartburn, and gastric ulcers that can make compliance difficult, but they can only be used short term due to safety concerns.  

A better option that addresses the root of the problem is bioidentical hormone replacement therapy. 

For example, in a 2003 study [5] out of jama, healthy, postmenopausal women were treated with 0.25 mg/dL of micronized 17 beta-estradiol for 3 years and compared to women treated with a placebo in terms of bone mineral density and adverse events, as synthetic estrogen and progestin demonstrate potential health risks.  

According to the study results, “Mean BMD increased at all sites for participants taking low-dose estrogen (17β-estradiol) compared with placebo (P<.001). Compared with participants receiving placebo, participants taking low-dose estrogen had BMD increases of 2.6% for the femoral neck; 3.6%, total hip; 2.8%, spine; and 1.2%, total body. Markers of bone turnover, N-telopeptides of type 1 collagen, and bone alkaline phosphatase decreased significantly (P<.001) in participants taking low-dose estrogen compared with placebo…The adverse effect profile was similar; specifically, there were no statistically significant differences in breast tenderness, changes in endometrial thickness or pathological effects, or annual mammographic results between the 2 groups.”

The study went on to conclude that “In older women, a dosage of 0.25 mg/d of 17β-estradiol increased bone density of the hip, spine, and total body, and reduced bone turnover, with minimal adverse effects.”

One reason hormone therapy is often superior to bisphosphonates is that they increase osteoblast activity rather than merely slowing down or killing osteoclasts. As you know, osteoblasts are the cells that form new bone tissue by synthesizing and secreting bone matrices and participating in the mineralization of bone. Slowing down osteoclasts does little for aiding the osteoblast-driven bone growth process. In fact, in the case of some bisphosphonates like Fosamax, osteoclasts are effectively killed off, which is bad because as bones become denser due to the lack of breakdown, they actually become weaker as they lose the ability to remold themselves properly. This completely disrupts the normal physiological process of bone growth, which involves a continuous breakdown and rebuilding of bones needed to create healthy bone tissue. By disturbing osteoclast activity, this process can no longer occur. Bones become weaker in the long-run, even though they may appear denser initially. 

And while bisphosphonates can reduce vertebral fractures by 47-70 percent and hip fractures by 28-50 percent, their long-term safety is questioned (per a 2016 article [6] published in HSS journal). Outside of the unpleasant gastrointestinal effects, there are some scary adverse effects like osteonecrosis of the jaw, esophageal cancers, and (ironically) femur fractures reported by the FDA. The femur fractures and osteonecrosis of the mandible is due to the fact that the bone left behind by these drugs is not quality bone but instead consists of a honeycomb matrix with lots of open spaces and very thin, fragile bone comprising the matrix since the osteoclasts needed for normal bone remodeling were killed off by the drugs. 

Besides hormone replacement therapy which is often not recommended due to risks associated with synthetic hormones–not bioidentical–the other treatments include drugs that mimic parathyroid hormones (teriparatide and abaloparatide), but those can only be used for up to two years, and we know bones will continue to weaken once those medications are stopped (per Mayo Clinic [4]). Even the newest osteoporosis medication, romosozumab, can only be given for up to a year. While better than nothing, there’s not much foreseeable long-term benefit with these drugs and plenty of potential harm. 

A New Approach

So while we do have some tools to treat osteoporosis like bisphosphonates, they help marginally at best and their extended use presents serious health and safety concerns. That’s not much of a win. As with most chronic illnesses, a better approach is more comprehensive. Rather than using medication alone, we should employ a multipronged approach that looks at all modifiable factors that influence bone health rather than medications alone. In our upcoming webinar, we will discuss many of the modifiable risk factors you can address with your patients like diet, weight-bearing exercise, and using bone screening tools like the DEXA bone mineral density scan [7] and FRAX Risk Assessment Tool [8]. 

The best tool to date you can use to assess your patients’ bone density and future risk for osteoporosis is the  N-Telopeptide Cross-links (NTx) urine test [9]. It is superior to DEXA because it can be repeated every three months and shows current bone loss. DEXA can only be tested every two years and only shows past bone loss rather than current bone health status. It is also typically only done once per lifetime.

Finally, in both the webinar and this blog, we will discuss several, research-supported supplements and other natural compounds proven to increase bone density and reduce fractures. Our goal for this blog is to dispel myths about what helps bones, review osteoporosis risk factors, and introduce compounds that can support aging bones, highlighting the prestigious research supporting them. But first, a word on prevention…

An Ounce Of Prevention

Every person has heard the saying that an ounce of prevention is worth a pound of cure. That is certainly true when it comes to bone health. If you take away nothing more, we hope that you will prioritize educating your younger patients about the importance of maintaining strong bones in their youth before osteoporosis is a problem. 

This is because the best way to treat osteoporosis is to prevent it altogether. According to the Mayo Clinic [4], a person’s likelihood of developing osteoporosis depends largely on how much bone mass they attain in their youth. Although peak bone mass is partly genetic, the higher your peak bone mass, the more bone mass a person has “in the bank” and the less likely they are to develop osteoporosis as they age in the future. Simply put, we should not be thinking of bone health as just an “old person’s” issue. It should be top of mind for all your patients. 

Osteopenia and Osteoporosis Risk Factors

• Aging due to a progressive loss of the sex hormones estradiol and testosterone 
• Lack of sunlight exposure
• Low blood Vitamin D levels
• Diet low in dark leafy greens (source of Calcium and Vitamin K)
• Chronic antibiotic use (depletes Vitamin-K producing bacterial flora)
• Lack of regular weight bearing exercise (walking, running, yoga, weight lifting, etc.)
• Sedentary lifestyle  
• Family history
• Caucasian or Asian descent 
• Female sex
• Anorexia Nervosa (chronically reduces estradiol levels)
• Low dietary calcium and vitamin D intake
• Smoking 
• Excessive alcohol intake 
• Small body frame (less bone mass to work with)
• Certain medications (long term use of glucocorticoids and some anticonvulsant drugs, as well as any medications that block estrogen such as certain breast cancer, prostate cancer, and fertility drugs like Lupron, Letrozole, or Anastrozole)
• Low bone mineral density, as indicated by a DEXA bone density scan [7] or better yet an N-Telopeptide Cross-links (NTx) urine test [9]

Dispelling Myths: What About Calcium Supplements?

If you haven’t already, you will soon notice that calcium is not included in the supplements and compounds we’ll be discussing for improving bone health. Why not? Shouldn’t all our patients take calcium supplements for healthy bones?

Well, the answer to that is a bit complicated. According to Erin Michos, MD, MHS, associate director of preventive cardiology for the Ciccarone Center for the Prevention of Heart Disease, “The truth is, the research is inconclusive. But there is a growing body of evidence that suggests no health benefit, or even worse, that calcium supplements may be harmful (per John Hopkins Medicine [11])”.  

Multiple studies have found little if any benefit from taking calcium supplements for preventing hip fractures and bone loss. And worse, newer studies are linking calcium supplements to an increased risk for precancerous colon polyps and painful kidney stones. Yikes. The news gets worse too. A 2016 study [12] linked calcium supplements to a buildup of arterial calcium in the heart which can lead to heart disease. 

While some supplements are great for supporting bone health, calcium is unfortunately not one of them. It’s much safer to get calcium through diet rather than supplements, which your patients can get by eating foods like beans, almonds, soybeans, dark leafy greens, unsweetened yogurt, or fortified milk substitutes like almond milk. But calcium supplementation just doesn’t increase bone density and may do more harm than good. 

*Studies added in addition to studies from the patient education are highlighted in blue

Vitamin D

Vitamin D is vital for the absorption and utilization of dietary calcium. It is probably the single nutrient people are lacking most, as nearly half of Americans are deficient (per FOX Weather [13]). Technically, in its active form, calcitriol, Vitamin D is a hormone rather than a vitamin. 

So besides increasing calcium absorption, how else does Vitamin D help bones? 

Well, osteoporosis is often considered an inflammatory condition, as the increase in pro-inflammatory cytokines may lead to an excessive breakdown of bone (per a 2010 paper [14]). Because Vitamin D reduces inflammation and regulates the immune system, it may have a positive effect on fracture risk via unknown immunoregulatory mechanisms. Vitamin D also improves muscle strength, which can greatly reduce the incidence of falls–one of the main reasons fractures occur in the first place.. 

A 2022 meta analysis [15] of 32 studies found that daily Vitamin D supplementation at a dose of 800-1,000 mg per day was linked to a lower risk of both osteoporotic related fractures and falls. Intermittent and sporadic Vitamin D supplementation did not correlate to a reduction in falls compared to daily supplementation. Also, patients with Vitamin D deficiency showed the most significant risk reduction in falls following Vitamin D supplementation. 

Vitamin K

Vitamin K is needed to synthesize the protein osteocalcin which is used to generate healthy bone tissue (per Harvard TH Chan [16]). Some studies demonstrate that higher Vitamin K intakes correlate with a lower occurrence of both hip fractures and low bone mineral density. Other studies have linked low blood levels of Vitamin K to lower bone mineral density (per a 2001 review [17]). 

In the Nurses’ Health Study, women who obtained at least 110 micrograms of Vitamin K per day saw nearly a one third decrease in the likelihood of fracturing a hip compared to women who obtained less than 110 mcg (per a comparative study [18]). In fact, the nurses who consumed as little as a single serving of dark leafy green vegetables per day slashed their risk of hip fractures by half compared to the nurses who ate only one serving of dark leafy greens per week. These results are better than many medications that are used to increase bone density. 

Data obtained from the Framington Heart Study also showed a correlation between higher vitamin K intake and decreased risk of hip fractures in both men and women. Increased bone mineral density in women was also correlated to higher Vitamin K intakes (a 2000 study [19] and a 2003 study [20]). 

Strontium

Strontium is a lesser-known trace mineral that can support bone health. Most of the strontium in nature is derived from seawater or soil, but it also occurs in small amounts in foods like seafood, whole milk, poultry, wheat bran, and root vegetables like carrots and onions (per Web MD [21]). 

It works in a similar fashion to calcium, helping the body synthesize new bone and slowing bone resorption. Strontium is also believed to activate genes that can increase osteoblast growth and replication. It even helps osteoblasts live longer and has been used for several bone-related conditions like tooth sensitivity, osteoarthritis, and osteoporosis. Finally, it reduces pain from metastatic bone cancer when given as an intravenous prescription called strontium-89 chloride. 

In one study, multiple bone-supportive nutrients were given at different levels to three different groups. While all three groups experienced increases in bone mineral density, the group that received the most strontium (680 mg per day) saw the greatest increases in bone mineral density (per Advanced Osteomolecular Research [22]) compared to the group who received the least strontium. 

A second study out of Alberta took a multi-pronged approach (per Advanced Osteomolecular Research [22]). Strontium citrate, vitamin K2, 2000 IU of vitamin D3, 25 mg of magnesium, and 250 mg of DHA omega-3 fatty acids from fish oil were administered to subjects. Subjects were encouraged to get their calcium from foods rather than calcium supplements and were also instructed to engage in physical activity. After a year, bone mineral density increased in both the spine and hip. Aside from this, the increases in bone mineral density were double what the same subjects who had taken bisphosphonates previously for a year experienced and equal or better than the results of patients who’d taken the drug strontium ranelate for a year before the study!

Ipriflavone (IP)

Ipriflavone is a compound derived from soy that is synthesized in a laboratory and is available as a prescription in some countries (per Web MD [23]). Because it is created in a laboratory, it can only be obtained from supplements or prescriptions. IP is often used to treat bone-related conditions like osteoporosis and Paget’s disease and works by blocking bone resorption (per Web MD [23]). Studies show that it can help prevent bone loss in postmenopausal women who have osteoporosis and might even decrease the bone pain caused by osteoporosis. When taken in conjunction with the hormone estradiol, it may even prevent osteoporosis and increase bone density by amplifying the bone-building effects of estrogen on bone tissue.  

A double-blind, placebo-controlled study [24] conducted on 453 postmenopausal women with low bone mass found that biochemical markers for bone turnover reduced in patients treated with IP, which suggested a reduced bone turnover rate. The study ultimately showed that IP prevented both axial and peripheral bone loss in postmenopausal women with low bone mass, and the treatment was well-tolerated by most. 

Another placebo-controlled study [25] showed that oral IP supplementation for two years prevented radial bone loss in postmenopausal women compared to women who did not supplement with IP.

And yet another exciting study [26] out of the journal of The North American Menopause Society found that while bone density declined after two years in early menopausal women who only took calcium (placebo group), bone density did not decline in women who also took ipriflavone in addition to calcium, concluding that taking ipriflavone prevents rapid bone loss following menopause onset. 

The Power of Bone-Building Hormones

While Vitamin D is one hormone important for bone health, there are five more the body also makes. These natural compounds all support bone health but tend to decline with age. Fortunately, you can learn how to safely replace them in your patients by attending our comprehensive training on Bioidentical Hormone Replacement Therapy (BHRT), giving you the expertise to effectively prescribe these hormones.

Estradiol

Because menopause significantly accelerates bone loss and increases the risk of osteoporosis, the prevention of bone loss should be top of mind for women undergoing menopausal changes, according to The Endocrine Society [27]. In fact, research shows that as much as 20 percent of the bone loss that occurs in the lifespan occurs during menopause, and 10 percent of women over age 60 are affected by osteoporosis as a direct result. After menopause, the stats are even worse, as half of postmenopausal women develop osteoporosis, many of which will go on to suffer debilitating fractures which decreases quality of life and increases mortality. 

But this isn’t inevitable if we replace the missing estradiol, which can be done safely and effectively with bioidentical hormone replacement therapy (BHRT). For instance, a place-controlled, double blind study [28] out of Jama found that bone mineral density increased significantly in the lumbar spines of elderly women who underwent estrogen replacement therapy for just nine months.

Estradiol also plays an important role in bone health for males and has been recently implicated in the pathogenesis of male osteoporosis (per a 2000 study [29] out of the journal Osteoporosis International). The study aimed to determine if estrogen deficiency was a cause of osteoporosis in men and found that a third of male subjects had low estradiol levels compared to only three percent of males having low testosterone. The study concluded that estrogen deficiency is more strongly linked to male osteoporosis than androgen deficiency and went on to suggest that screenings for osteoporosis in males should include an assessment on serum estradiol levels. 

Testosterone

Testosterone levels decline in both sexes with age, though the effects are more observable in men since they produce more to begin with. This gradual loss of testosterone can have negative effects on bone mineral density in both sexes, but as with estradiol replacement, testosterone replacement has been shown to offset the loss of bone mineral density. 

For instance, the Framington Study [30] found that while men with low estradiol levels were at an increased risk for hip fractures in the future, emphasizing the importance of estradiol in men, men with low estradiol and low testosterone levels had the greatest risk of future hip fractures. 

In an interventional 2000 study [31] that aimed to determine if either estrogen or testosterone deficiency was more important in causing increased bone resorption and reduced bone formation in men (both hormones decline in aging men), 59 elderly men were given drugs to block their endogenous T (testosterone) and E(estradiol) production, and then T and E were replaced in a controlled manner. 

Following replacement, in order to assess the impact of T and E in isolation on bone turnover, either T and E were withdrawn, only T was withdrawn, only E was withdrawn, or nothing was withdrawn (control group) then the four groups were compared to each other. As expected, bone resorption increased most greatly in men whose T and E were both withdrawn. It was determined by two-factor ANOVA that E is needed to prevent bone tissue resorption–not T–while both T and E were vital for maintaining bone formation as a lack of either hormone inhibited bone-promoting osteocalcin, demonstrating testosterone’s importance for forming new bone rather than preventing the resorption of old bone like estradiol does. 

DHEA

DHEA’s (Dehydroepiandrosterone) ability to improve bone density lies in its dual ability to convert into two important bone-building hormones: estradiol and testosterone, but our levels drop with age, as with most hormones. So what does research say about its bone-building effects?

A double-blinded, placebo controlled trial [32] out of the journal of endocrinology investigated the mechanism behind DHEA’s ability to increase bone density. The objective was to see if DHEA supplementation increased sex hormones and resulted in positive changes in bone mineral density. The participants included 58 women and 61 men who were middle aged to elderly and had low DHEA levels, divided into either a treatment or a control group. 

The treatment group was given 50 mg of DHEA per day for a year. The treatment group not only experienced positive sex hormone changes like an increase in bone-building estradiol, but they also also enjoyed significant increases in bone mineral density (increased by 1.1-1.6 percent) of the hip and spine bones when compared to the control group. 

Thyroid Hormone

You are probably aware that there are two main types of thyroid hormones: thyroxine or T4 and triiodothyronine or T3 (per The Endocrine Society [33]). T3 is the more biologically active of the two and is derived from the conversion of T4 into T3, which many people have problems with–not just middle aged or elderly people. Furthermore, even people with seemingly sufficient levels of T3 may experience a cellular resistance to the hormone, rendering it inefficient in the standard amount the body creates. 

Unfortunately, most conventional doctors only look at a very narrow range of thyroid hormones despite the fact that many people still have problems whose levels fall well within the “normal” range. Typically, thyroid hormones themselves are not even measured; rather, an indirect measure called thyroid stimulating hormone (TSH) is measured, which is a poor indicator of active thyroid hormone status. That’s why it’s so important to attend our BHRT training, where you will learn to look beyond these numbers.

You may have been taught to associate elevated thyroid hormones with bone loss, but this is only observed in Grave’s Disease which causes thyrotoxicosis. This phenomenon is not observed in euthyroid patients who are given exogenous thyroid hormone supplementation. On the contrary, low levels of thyroid hormone can negatively impact bones because thyroid hormones are required for bone growth, fracture repair, and overall skeletal maintenance (per a 2009 review [34]). 

Human Growth Hormone (HGH/GH)

Growth Hormone’s impressive effects on bone mass are definitely worth mentioning. For example, one study [35] out of the journal of endocrinology looked at the effects of GH replacement therapy on bone mass and body composition in adults with GH deficiency over the course of five years. 

Not only did GH therapy result in a positive increase in lean body tissue and decreases in fat mass, but it also resulted in an increase in total body bone mineral density, including increased bone mass in the lumbar spine and femur bones. 

Positive metabolic changes were also observed like reduced total and LDL cholesterol, increased HDL cholesterol, decreased triglycerides, and reduced triglycerides and HbA1c. 

What’s Next?

We encourage you to enroll in our exciting course on bone health which will dive deeper into ways to help your patients such as:

• Bone supplement dosages
• Best supplement forms for superior absorption 
• Concerns and special considerations 
• Explore a comprehensive approach to bone health, including the best diet for bone health, according to the most up-to-date research
• Highlight a few other key bone-promoting supplements 

To learn how to use bioidentical hormones in your practice to support bone health, we strongly encourage you to attend our BHRT training series which delves comprehensively into all therapeutic hormones, their mechanisms of action, dosages, indications (including and beyond bone health), and most importantly, how to get started prescribing them as soon as you return to work. 

Because the inevitable decline in hormones that occurs with age is the primary cause of bone loss and osteoporosis, this training is invaluable if you wish to give your patients the best chance of improving their bone health, preventing fractures, and ultimately enjoying a graceful, happier old age. 

References 

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