Last Section Update: 05/2022

Contributor(s): Shayna Sandhaus, PhD

1 Overview

Summary and Quick Facts for Osteoporosis

  • Osteoporosis is weakening of the bones. It increases the risk of breaking bones. A doctor can test for bone density. Older women are especially at risk for osteoporosis.
  • This protocol will help you understand the causes of osteoporosis and steps to take that may help strengthen bones. Eating a nutrient-dense diet and getting plenty of exercise are important for bone health. Drugs are also available to help, if your doctor deems it necessary.
  • Because hormones play a major role in bone health, working with a doctor to use bio-identical hormone replacement therapy may help keep bones healthy. Supplementation with vitamins D and K is also important for bone health.

What is Osteoporosis?

Osteoporosis is a disease in which bone mass or bone density is reduced. Bones are living tissue that is constantly being resorbed and reformed; when more bone is resorbed than reformed, osteoporosis results.

In the past, osteoporosis was believed to be caused by declining female hormone levels that is unique to aging women; it was treated primarily with estrogen therapy. Nowadays, the medical community is beginning to understand that osteoporosis is not so simple—it affects men as well and is caused by a host of factors, including hormonal imbalance, elevated blood sugar, oxidative stress, and inflammation.

Natural interventions such as isoflavones and vitamin K may help maintain healthy bones and prevent osteoporosis from developing.

What are the Causes and Risk Factors for Osteoporosis?

  • Sex – women are more likely to develop osteoporosis
  • Advanced age
  • Family history
  • Overweight/underweight
  • Sedentary lifestyle
  • Hormonal imbalance
  • Insulin resistance/high blood sugar
  • Insufficient vitamin and mineral intake
  • Chronic stress and depression, and others

What are the Signs and Symptoms of Osteoporosis?

  • Loss of height
  • Dowager’s hump
  • Bone fractures

Note: Osteoporosis is generally asymptomatic and goes undetected until a serious fracture occurs. It is therefore essential to take all measures to prevent the disease from developing.

What are the Conventional Medical Treatments for Osteoporosis?

  • Hormone replacement therapy (HRT)
    • Conventional HRT has fallen out of favor due to increased risk for breast cancer, stroke, and heart disease
    • Other hormone regimens include selective estrogen receptor modifiers (SERMs) for women and testosterone treatment for men
  • Bisphosphonates (eg, Actonel, Fosamax) to prevent further bone density loss
  • Calcium and vitamin D supplementation

What are Emerging Therapies for Osteoporosis?

  • Stem cell therapy
  • Bioidentical hormone replacement therapy

What Natural Interventions May Help Prevent Osteoporosis?

  • Isoflavones. Isoflavones, generally derived from soy, are often referred to as phytoestrogens and may work similarly to HRT. Several isoflavones have been shown in animal models to contribute to increased bone mineralization and strength, while reducing bone resorption.
  • Vitamin K. Vitamin K is essential for bone strength. Low vitamin K status is associated with decreased bone mineral density and increased risk of fracture.
  • Vitamin D and calcium. Vitamin D and calcium are commonly recommended for bone health. Vitamin D triggers the absorption of calcium and deposition in bone, where calcium provides hardness.
  • Magnesium. Magnesium regulates active calcium transport. Many older adults are deficient. Supplementation has been shown to reduce bone turnover, favoring bone formation over resorption.
  • Silica. Silica, or silicon dioxide, is a component of the Earth’s crust. It is also important in bone formation and health. The addition of silica to a calcium and vitamin D regimen improved production of bone proteins.
  • Collagen. Collagen provides essential tensile strength to bones. A collagen calcium chelate was developed and has been shown to improve bone mineral density and femur bone strength.
  • Vitamins E and C. Oxidative stress is an important contributor to osteoporosis. Vitamins E and C are antioxidants that play important roles in bone development and mineralization. Supplementation with both vitamins has been shown to help prevent bone loss in elderly men and women.
  • Omega-3 fatty acids. The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may reduce activity of bone-resorbing cells, increase that of bone-forming cells, and improve calcium balance. Consuming fish high in omega-3 fatty acids and/or supplementation has been shown to improve several indicators of bone health.
  • Other natural interventions that may support bone health and help prevent osteoporosis include boron, curcumin, resveratrol, quercetin, berberine, and hops.

2 Introduction

Osteoporosis, defined as a reduction of bone mass or bone density, was long viewed as a disease unique to aging women, and has been treated primarily with conjugated equine estrogens (CEE) in hopes of mitigating the decline in endogenous female hormone levels that occurs during menopause (Leong 1998, Wylie 2010). Sadly, much of what conventional wisdom held true about osteoporosis turns out to be flawed; it is now clear that osteoporosis (like many age-related conditions) is not a disease with a singular cause affecting a specific population. Rather, it is a multi-faceted disease driven by a barrage of interrelated factors, and must be addressed as such for optimal prevention and treatment (Clarke 2010).

Today we realize that osteoporosis not only impacts the lives of women, but of men as well; fully one third of those affected by the condition are males (about 2.8 million of them as of 2011), and that number is likely to grow as the population ages (Cawthon 2011, Kawate 2010, Nuti 2010). Indeed, one out of every four men will sustain an osteoporotic fracture during their lifetime (Ahmed 2009). Conventional physicians have been slow to recognize the prevalence of osteoporosis in men; as a result the diagnosis is often delayed even more than it is in women, allowing the disease to progress to an advanced stage before it is detected. (Kawate 2010).

Scientific advancements have revealed that the etiology of osteoporosis stems not only from hormonal imbalances, but oxidative stress, elevated blood sugar, inflammation, and components of the metabolic syndrome as well (Clarke 2010, Confavreux 2009, Lieben 2009; Zhou 2011).

Overlooked by mainstream medicine is the critical role that micronutrients play in bone health. For instance, emergent research on vitamin K has attracted great scientific interest through the revelation of its involvement, along with vitamin D, in both bone health and atherosclerosis, a condition to which osteoporosis is intimately related (Baldini 2005, Abedin 2004). In fact, these two conditions can be thought of as mirror images of one another (McFarlane 2004, D'Amelio 2009). Osteoporosis is characterized by loss of calcium from bones, shifting them from their healthy hard state to a diseased state of softness. Atherosclerosis, on the other hand, is characterized by excessive influx of calcium into arterial walls, shifting them from their healthy flexible state to a diseased state of hardness. Insufficiency of vitamin K contributes to this unhealthy balance.

Similarly underappreciated contributors to bone loss in both men and women are advanced glycation end products (AGE’s); byproducts of high blood sugar. AGE’s interact with proteins in bone causing impaired mineralization and increases in the number of osteoclasts – bone resorbing cells. Moreover, AGE’s encourage vascular calcification by activating a specialized receptor called RAGE, which recruits calcium into vascular smooth muscle cells, leading to hardening of the arteries. This relationship between elevated blood sugar, osteoporosis, and atherosclerosis comprises a vicious cycle linking the conditions in a manner unknown to the majority of mainstream physicians (Tanikawa 2009; Franke 2007; Hein 2006; Zhou 2011).

Pharmaceuticals, such as Actonel® or Fosamax®, have shown limited success, and are associated with some potentially serious side effects including atrial fibrillation and osteonecrosis of the jaw (Jager 2003, Howard 2010). These drugs work chiefly by inhibiting the cells responsible for breaking down bone tissue, but neglect multiple other factors responsible for osteoporosis (Roelofs 2010, Varenna 2010). Although these drugs do increase bone density, poorly appreciated is that they disrupt the natural cycle of regeneration and resorption that is important for the strength of the bone (Abrahamsen 2010).

An integrative approach, based on the human body’s finely tuned relationship with its environment and the nutrients that support bone health, makes much more sense (Confavreux 2009, Hanley 2010). This realization has led to an awakening to the tremendous potential of nutrient and mineral supplements along with hormonal optimization in the prevention and management of osteoporosis.  The myriad complexities of osteoporosis necessitate the need to integrate pharmaceutical, nutritional, and lifestyle interventions in order to maintain bone health into advancing age.

3 The Truth About Osteoporosis: Multiple Causes, Multiple Targets

Most of us assume that our bones are like pieces of rocks or hard shells. However, bone is a living tissue, constantly undergoing demolition and renewal as it responds to changing forces in the environment (Martin 2009, Body 2011). Bone is also the body’s primary reservoir of the calcium needed for a wide variety of biological processes (de Baat 2005). Bone is now recognized as an endocrine organ, secreting compounds that function like hormones throughout the body (Kanazawa 2010).

Our bones are made of crystals of calcium salts in a protein matrix. Specific cells, called osteoblasts, produce the matrix and attract calcium compounds to form new bone, while a different set of cells, called osteoclasts, resorbs the bone tissue to allow new shapes and structures to form in response to gravity and the pull of muscles. This process of remodeling helps repair microdamage that occurs as a result of daily activity and prevents the accumulation of old fragile bone (Martin 2009, Mitchner 2009, Body 2011).

At the simplest level, osteoporosis occurs when more bone is resorbed than formed (Banfi 2010, Chang 2009). There are multiple causes for osteoporosis including suboptimal nutrition, age-related hormonal imbalance, and lack of weight-bearing exercise, to name a few (Body 2011).

Sedentary Lifestyle

Perhaps the earliest contributing lifestyle factor is lack of weight-bearing exercise, as many as 20% of young and middle aged women already have an abnormal spinal curvature related to bone loss in their vertebrae, a situation that only get worse as one ages (Dwyer 2006, Cutler 1993). A sedentary lifestyle reduces the constant forces that bone needs to experience in order to continue its normal process of remodeling (Akhter 2010). Studies show that both women and men who engage in regular exercise have much lower risk of osteoporosis and fracture (Ebeling 2004, Englund 2011).

Vital Hormones

Vital hormones such as estrogen and testosterone promote bone formation and regulate bone resorption, and when those hormone levels drop, osteoporosis can occur. At puberty, bone production increases dramatically, producing the growth spurt of the early teen years. This effect seems to be driven mostly by estrogens, the “female” hormones, in both boys and girls (Gennari 2003, Clarke 2009). Near the end of puberty, androgens, the “male” hormones, increase in both women and men. The androgen surge fuses the bone growth plates, with the result being that the bones can no longer elongate. Young adults generally maintain a steady-state balance in which new bone formation is nearly equal to bone resorption.

Sex hormones also remain at roughly steady levels throughout young adulthood and early middle age (Clarke 2009). After about the age of 35, however, the total amount of bone in the body begins to diminish. In women, the process begins fairly sharply with the onset of menopause, when estrogen levels drop dramatically. In postmenopausal women, bone is lost both from the inner and outer surfaces of bones, as bone resorption by osteoclasts exceeds the already reduced new bone formation by osteoblasts. In men, however, new bone formation on the outer surface of bone keeps pace with resorption on the inner surface for much longer (Seeman 1999). This obvious connection probably accounts for the fact that osteoporosis was thought for so long to be a problem unique to women, and may account for the fact that men begin to suffer fractures from osteoporosis about a decade later than women (Hagino 2003), but similar factors are involved (Ducharme 2009).

The discovery that primary control of bone mineralization in both men and women is mediated by estrogens not only enhances our understanding of how osteoporosis occurs in men, but also has dramatic implications for how we can prevent and treat it (Gennari 2003).

Sex Hormone Binding Globulin (SHBG)

SHBG is a protein produced primarily in the liver, and serves to bind estrogen and testosterone (Nakhla 2009). It has long been known that declining estrogen levels in both sexes are significant contributors to bone mineral loss with aging. Experts now recognize that the steady rise in SHBG with aging is directly correlated with bone loss and osteoporosis in both men and women (Hofle 2004, Lormeau 2004). As a general rule the higher the SHBG level, the less estrogen is available to contribute favorably to bone health.

Evidences indicate that the SHBG molecule itself plays another key role in the body: conveying essential signals to the heart, the brain, the bone and adipose (fat) tissue that ensure their optimal function (Caldwell 2009). There’s even a special SHBG receptor molecule on cell surfaces that functions much like the ubiquitous vitamin D receptor protein, helping cells communicate with one another (Adams 2005, Andreassen 2006). In other words, SHBG itself functions much like a hormone.

New studies are finding a direct role for SHBG and its cell surface receptor in bone loss (Hoppe 2010). The association is so strong that some experts are now suggesting routine measurement of SHBG as a useful new marker for predicting severity of osteoporosis (Hoppe 2010).

Insulin Resistance, Blood Sugar, and Glycation

Bone functions as an endocrine organ secreting compounds that act like hormones (Kanazawa 2010). Healthy production of bone matrix protein increases insulin sensitivity in other tissues (Kanazawa 2010, de Paula 2010). Conversely, people with the metabolic syndrome who are insulin resistant have poorer bone quality and an increased risk of osteoporotic fracture (Hernandez, McClung 2010). Metabolic syndrome also raises SHBG levels, further reducing bioavailable levels of estrogen and testosterone (Akin 2009).

Research suggests that advanced glycation end products, or AGEs, are implicated in bone loss. AGEs are formed when proteins interact with glucose molecules to form damaged structures in the body. One study examined the proteins in osteoporotic bones to determine if there was damage by AGEs. More AGEs present resulted in fewer bone-building osteoblasts (Hein 2006). It is suggested that limiting AGE formation by maintaining a healthy blood sugar level may slow the osteoporotic process (Valcourt 2007).

Oxidation and Inflammation

Oxidation of fatty acids and other molecules produces reactive oxygen species that directly and indirectly impair new bone formation and promote excessive bone resorption (Graham 2009, Maziere 2010). In a similar fashion, chronic inflammation hastens the absorption of existing bone while impeding normal production of new bone (Chang 2009). Fat cells produce a steady efflux of inflammatory cytokines while diminishing cells’ insulin sensitivity; both factors further impede normal bone production (Mundy 2007, Kawai 2009).

Vitamin K

For healthy, mineral-rich bone to form, healthy bone matrix protein must be produced (Bugel 2008, Wada 2007). Over the past decade scientists have realized that vitamin K is an essential co-factor for production of the major bone protein, osteocalcin (Bugel 2008, Iwamoto 2006). Vitamin K-dependent enzymes produce changes in osteocalcin that allow it to tightly bind to the calcium compounds that give bone its incredible strength (Bugel 2008, Wada 2007, Rezaieyazdi 2009).

Calcium and Vitamin D

Many other environmental and nutritional factors contribute to the gradual development of osteoporosis. The role of low intake of vitamin D and calcium are well known (Cherniack 2008, Lips 2010). Adequate calcium intake is required to allow healthy bone remodeling and prevent osteoporosis. Vitamin D promotes intestinal absorption of calcium, and also regulates how much calcium enters and leaves bone tissue in response to the body’s other calcium requirements.

Trace Minerals

While bone is primarily composed of matrix protein and calcium compounds, small amounts of other trace minerals are essential for normal bone function. These include magnesium, which regulates calcium transport; silicon, which reverses loss of calcium in the urine; and boron, which interacts with other minerals and vitamins and also has anti-inflammatory effects (Aydin 2010 Mizoguchi 2005, Kim 2009, Li 2010, Spector 2008, Scorei 2011).

The conventional model of osteoporosis predicts that simple restoration of declining sex hormone levels and provision of modest amounts of calcium and vitamin D should be sufficient to prevent osteoporosis. When those steps fail (which they inevitably do), conventional medicine resorts to suggesting that osteoporosis must be an inevitable consequence of aging.

Life Extension’s® position, however, is much more nuanced and incorporates the truth about the complex, interrelated factors that genuinely contribute to osteoporosis. Life Extension recommends a lifelong commitment to an active lifestyle, and supplementation with targeted vitamins, minerals and nutrients that quench reactive oxygen species (ROS), reduce inflammation, control obesity and insulin resistance, promote healthy bone matrix protein synthesis, and supply sufficient trace minerals to support healthy bone.

Risk Factors for Osteoporosis

The risk factors for osteoporosis, like those for all chronic, multifactorial conditions, are many, and they interact with one another. Here is a summary of those we understand best, and that we can take steps to incorporate in our prevention strategies.

Gender - Women are more likely to develop osteoporosis than men. This difference is related to several reasons including: the abrupt loss of estrogen at menopause, women start with a lower bone density and lose bone more quickly than men and women live longer than men.

Age - Increasing age is associated with falling production of estrogen and testosterone, which increases osteoporosis risk. Levels of sex hormone binding globulin (SHBG) rise with age, binding to the sex hormones and reducing their total bioavailable levels, which further aggravates bone loss. Advancing age also means longer total exposure to chronic oxidant stress and inflammation, both of which contribute to development of osteoporosis (Mundy 2007, Maziere 2010, Seymour 2007, Ruiz-Ramos 2010).

Ethnicity - Caucasian and South Asian people have greater risk of osteoporosis (Dhanwal 2011, Golden 2009).

Family History - A family history of hip fracture carries a twofold increased risk of fracture among descendants (Ferrari 2008).

Estrogen Exposure - Women with late puberty or early menopause are at higher risk due to a decrease in estrogen exposure over their lifetime (Vibert 2008, Sioka 2010).

Vertigo - Several recent studies have shown an association between “benign positional vertigo” (BPV) and lower bone mineral density (Vibert 2008, Jeong 2009, Vibert 2003). The inner ear, where balance is maintained, contains tiny bone particles (otoconia) that may be affected in osteoporosis (Vibert 2008). Some experts recommend that people with BPV should undergo screening for osteoporosis (Jeong 2009).

Slim stature (underweight) - People with a body mass index of 19 or less or have small body frames tend to have a higher risk because they may have less bone mass to draw from as they age (El Maghraoui 2010).

Obesity - Increased body fat was long thought to be protective against osteoporosis (Bredella 2010). Accumulating evidence, however, suggests that obesity-related components such as insulin resistance, hypertension, increased triglycerides, and reduced high-density lipoprotein cholesterol are all risk factors for low bone mineral density (Bredella 2010, Kim 2010).

Cardiovascular Disease - Cardiovascular disease and mortality are associated with osteoporosis and bone fractures (Baldini 2005). That’s not surprising since the two conditions share many mechanisms and risk factors, such as oxidant damage and inflammation (Baldini 2005, Vermeer 2004).

Chronic Stress & Depression - Both condition increase cortisol production, leading to suppression of sex hormone production, increased insulin resistance, and enhanced release of inflammatory cytokines (Kiecolt-Glaser 2003, Kaplan 2004, Berga 2005). All of these effects increase the risk of bone mineral loss and osteoporosis (Berga 2005, Bab 2010, Diem 2007, Haney 2007).

Other risk factors for osteoporosis include: HIV infection (Ofotokun 2010), anorexia (Mehler 2011), cancer (Ewertz 2011, Lim 2007), smoking (Kanis 2009), caffeine (Tsuang 2006, Tucker 2006), and alcholism (Matsui 2010).

Medication Use - A variety of medications increase one’s risk for osteoporosis. These include:

Corticosteroids. These immune-suppressive drugs mimic the effect of stress-induced cortisol, with all of its suppression of sex hormones, weight gain, and insulin resistance.

Selective Serotonin Reuptake Inhibitors (SSRIs). Both depression and medications used in its treatment, such as SSRIs, increase the risk of osteoporosis (Bab 2010).

“Blood thinning” Medications (Anticoagulants). The drug Coumadin, used to prevent clot formation in patients with cardiovascular disease, acts to block the beneficial effects of vitamin K and is associated with decreased bone mineralization in some patients (Deruelle 2007). Low molecular weight heparin, an unrelated blood thinner, can also cause reduced bone mineral content (Rezaieyazdi 2009).

4 Symptoms and Diagnostic Tests

Signs and Symptoms

Anyone who is losing height with age may have osteoporosis; unfortunately, osteoporosis typically has no symptoms at all until a serious fracture occurs, usually from a relatively minor injury (Walker 2010; Azagra 2011). All the while, however, the disease is actually progressing, which is why early prevention is so important (Kawate 2010). Diagnosis and treatment are often substantially delayed, especially in men, because the concept of male osteoporosis is still unfamiliar to many practitioners as well as patients (Kawate 2010).

In women, the “dowager’s hump” that is classically associated with the disease is also a late finding, caused by gradual collapse of the front portion of the bones of the spinal column (Cutler 1993). It is predictive of decreased mobility over the coming years (Katzman 2011). Once fractures are evident, of course, they are associated with symptoms such as pain and immobility. If the hip is fractured, patients are often bedridden for weeks or months, putting them at major risk of pneumonia and blood clots. Hip fracture continues to be a leading cause of death in older adults (Dhanwal 2011).

Diagnostic Tests

Dual energy X-ray absorptiometry (or DXA) is considered the gold standard technology for assessing bone mineral density as of the time of this writing (National Osteoporosis Foundation 2013; Clinical Key 2013). It uses X-rays to measure bone density and renders results in grams per square centimeter (g/cm2), with a larger number indicating greater bone mineral density (BMD).

Another technology utilized to determine bone density is quantitative computed tomography (QCT). Like DXA, QCT utilizes X-ray technology to generate a measurement of bone mineral density and expresses results in milligrams per cubic centimeter (mg/cm3) (National Osteoporosis Foundation 2013; Li 2013; Santos 2010). Some evidence suggests that QCT may be more sensitive, relative to DXA, in the detection of osteoporosis; and measures of BMD by QCT may remain somewhat more stable in the context of fluctuating body weight and adiposity (Li 2013; Yu 2012; Smith 2001).

There are some important distinctions between DXA and QCT. First, DXA is associated with modestly less exposure of the patient to ionizing radiation compared to QCT. Specifically, a DXA scan exposes the patient to about .001 – .006 millisieverts (mSv), while a QCT scan of the lumbar spine exposes them to about .09 mSv. (One mSv represents the cumulative background radiation that, on average, a person is exposed to each year in the United States.) However, radiation exposure associated with a QCT scan is still relatively low by comparison to some other common medical scanning techniques. For example, a spinal radiograph exposes the patient to about 0.7 – 2.0 mSv. Next, widely accepted reference ranges are lacking for QCT results, potentially making osteoporosis diagnosis based upon QCT somewhat inconsistent. However, regardless of the chosen methodology for assessing BMD, experienced physicians are usually able to make sound judgments as to bone health and the best path forward for the patient (Adams 2009; Mettler 2008).

The results of bone density testing are given in T-scores. These scores are developed by comparing the person being tested to a young adult of the same gender between 25 and 45 years of age. A T-score of -2.5 or lower indicates high fracture risk, or a 60% chance of fracturing a hip. For every decrease of 1 in T-score, there is a twofold increase in risk of fracture. Individuals with a T-score of -1.1 to -2.5 are diagnosed with osteopenia, or mild bone loss. Results are also given as Z scores, which measures individual results against people of the same age, gender, and race (National Osteoporosis Foundation 2013).

DXA and QCT scans require specialized equipment, keeping them from more widespread use in rural areas. As a result, a variety of predictive scales and scores are being developed that have similar predictive accuracy at substantially less cost. Ultrasonometric scanner (Gueldner 2008), Osteoporosis Prescreening Risk Assessment (OPERA) tool (Salaffi 2005), and Osteoporosis Self-Assessment Tool (OST) (Perez-Castrillon 2007) are a few examples.

The problem, however, with using any of these modalities is that they are useless until substantial bone mineral loss has already occurred (because they rely on measuring that loss). In most people these findings occur only after years of progressive exposure to the chronic, underlying causes of osteoporosis such as oxidant stress, inflammation, insulin resistance, and insufficiency or deficiency of vitamins D and K.

5 Conventional Treatments and Associated Risks

Hormone Replacement Therapy (HRT)

For many years, while osteoporosis was thought of as primarily a disease of post-menopausal women, treatment included conventional hormone replacement therapy (HRT) using conjugated equine estrogen (CEE) and the synthetic progestogen - medroxyprogesterone acetate (MPA). Early termination of the large Women’s Health Initiative trial in 2002 revealed the dramatic faults in that approach, demonstrating increased rates of breast cancer and heart attack risk in women using conventional HRT (Sveinsdóttir 2006, Archer 2010). As a result, conventional HRT fell out of favor, because of risks associated with stroke, heart disease, and some types of cancer.

In an effort to recoup some of the beneficial effects of conventional HRT, drug companies have brought out a new class of single-targeted drugs called selective estrogen receptor modifiers, or SERMs. These drugs mimic the beneficial effects of estrogen on bone density in postmenopausal women (Silverman 2010, Ko 2011). Raloxifene is an example of this drug class, approved for women with osteoporosis, not men. SERMs theoretically should reduce both osteoporosis and breast cancer. While they show some promise, these drugs remain expensive and associated with side effects such as blood clots, hot flashes, and leg cramps (Ohta 2011).

Life Extension suggests that women talk to their doctor about bioidentical hormone replacement instead, for details please read our Female Hormone Restoration protocol.


When a man has osteoporosis because of low testosterone production, testosterone treatment may be recommended. The positive effects of testosterone on lumbar bone density in men were consistent (Tracz 2006, Isidori 2005). A common misconception is that testosterone administration necessarily increases the risk of prostate cancer, in a causal fashion similar to the risk of HRT and breast cancer in women. However, a careful review of the medical literature reveals otherwise. For example, in a landmark review article published in the New England Journal of Medicine, the authors report “there appears to be no compelling evidence at present to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadism [low testosterone] with exogenous androgens increases this risk” (Rhoden 2004). However, since testosterone stimulates cell growth in androgen-responsive tissues, it may accelerate the growth of existing prostate cancer. Cancer-screening tests such as a PSA test are necessary before replacement therapy. Testosterone-replacement therapy is contraindicated in men with active prostate cancer (Morgentaler 2011).


Bisphosphonate drugs, such as risedronate (Actonel) and alendronate (Fosamax), are chemical mimetics of a naturally occurring molecule, inorganic pyrophosphate, which regulates mineral metabolism. Bisphosphonates are used to help prevent loss of bone density (Hinshaw 2016). What many do not know is bisphosphonates work by limiting additional bone loss rather than building more bone. When taken up by osteoclasts, bisphosphonates impair those cells’ ability to resorb bone minerals (Drake 2010). The result is an increase in bone mineral density, but since the remodeling process is reduced, the bone may accumulate microdamage after prolonged use, which may contribute to atypical fractures (Abrahamsen 2010, Seeman 2009; Ma 2017). Bisphosphonate drugs were found, in a laboratory and an animal study, to increase oxidative stress and inflammatory processes (Enjuanes 2010, Karabulut 2010).

While bisphosphonates are a leading therapy for osteoporosis and bone loss, they are associated with a number of serious though rare side effects. These include osteonecrosis of the jaw, atypical fractures, low blood calcium, kidney toxicity, and musculoskeletal pain; reflux, esophagitis, and ulcers with oral treatment; and flu-like symptoms with intravenous administration (Whitaker 2012; Diab 2010). Some studies have concluded that longer treatment with bisphosphonates increases the risk of fractures and some adverse effects (Drieling 2016; Jung 2018). Since bisphosphonates remain in bone for years after treatment, and can continue to have therapeutic efficacy after being discontinued, “drug holidays” lasting up to several years have been proposed in those who are candidates for long-term bisphosphonate therapy (Brown 2014; Lee 2015; Adler 2016).

Reports of osteonecrosis of the jaw secondary to bisphosphonate therapy indicated patients receiving bisphosphonates orally were at a negligible risk of developing osteonecrosis of the jaw compared with patients receiving bisphosphonates intravenously. In a study of 208 patients who had taken alendronate, 70 mg once weekly for 1‒10 years, nine (4%) developed jaw bone osteonecrosis. None of more than 13,500 dental patients who had not taken alendronate developed jaw bone osteonecrosis (Sedghizadeh 2009). In patients taking bisphosphonates, 3‒5% developed atrial fibrillation and 1‒2% developed serious atrial fibrillation, with complications including hospitalization or death (Miranda 2008).

Another rare (up to 1% of users) side effect of some bisphosphonates is orbital inflammation, a painful condition that affects the eye and eye socket. Orbital inflammation affects up to 1% of bisphosphonate users, and requires prompt evaluation and management (Chehade 2019; Altundag 2017; Lee 2018). Numerous case reports have described instances of bisphosphonate-associated orbital inflammation, and it is believed that as more individuals are treated with bisphosphonates, cases will increase (Chehade 2019; Tan 2018; Lefebvre 2016; Boni 2013; Pirbhai 2015; Vora 2014). Bisphosphonate-induced orbital inflammation tends to affect individuals in their mid-60s, and can usually be resolved with a course of corticosteroid anti-inflammatory medication. Once the inflammation is resolved, a retrial of another bisphosphonate is often tolerated without problems (Chehade 2019). This complication has only been associated with the newer class of aminobisphosphonates, such as alendronate and zoledronate (Reclast), and not with the older class of non-aminobisphosphonates that includes edidronate (Didronel) and clodronic acid (Chehade 2019; Marcus 2013).

There is some evidence that prolonged bisphosphonate treatment (more than five years) is associated with increased risk for esophageal cancer (Green 2010). Experts generally advise a critical reassessment of fracture risk, a risk versus benefit evaluation, and consideration of a drug holiday after 3‒5 years of bisphosphonate therapy (Abrahamsen 2010; Brown 2014).


In 2010, the human monoclonal antibody denosumab (Prolia, Xgeva) was approved for the treatment of osteoporosis. Denosumab prevents bone resorption by binding to receptor activator of nuclear factor kappa-B ligand (RANKL), thereby blocking RANKL from binding to RANK on the surface of osteoclasts and their precursor cells. This inhibition of the RANKL/RANK interaction causes apoptosis of mature osteoclasts, and prevents pre-osteoclasts from maturing, thereby reducing the number and function of osteoclasts. These effects lead to a decrease in osteoclast activity (bone resorption) and promote osteoblast activity (bone formation), resulting in increased bone density (Rosen 2021; Kendler 2022).

In the initial 3-year placebo-controlled FREEDOM trial, 7,868 women between ages 60 and 90 years with lumbar spine or hip osteoporosis received denosumab (60 mg) administered via subcutaneous injection every six months. This treatment was shown to reduce the risk of vertebral fracture by 68%, hip fracture by 40%, and nonvertebral fractures by 20%. Importantly, there were no serious adverse reactions or increases in risk of osteonecrosis of the jaw (Cummings 2009). After the initial study, participants were able to enroll in an open-label continuation of treatment for an additional seven years. After 10 years of treatment, 2,626 women completed the long-term extension. Denosumab treatment led to low fracture incidence and continued increases in BMD (without a plateau, compared to bisphosphonates which generally plateau after 3-4 years) (Kendler 2022). In contrast to FREEDOM, serious adverse events did occur in the extension trial, including osteonecrosis of the jaw, though the rates were low. And despite the study population’s increasing age, fracture rates remained steady through both the initial three-year FREEDOM trial and seven-year extension (Bone 2017).

Denosumab is not an appropriate initial therapy for most patients. However, initial therapy with denosumab may be appropriate in some patients such as those who are intolerant of or unresponsive to other therapies, such as bisphosphonates, or those with highly compromised kidney function. Denosumab is indicated only in postmenopausal women when used for osteoporosis treatment. Treatment of men with denosumab is more controversial and is generally restricted to men with bone loss due to androgen deprivation therapy for prostate cancer (Rosen 2021).

It is important to note that discontinuation of denosumab therapy can lead to a loss of the BMD gained during treatment and therefore an increased risk of fracture, particularly multiple vertebral fractures. Anyone discontinuing denosumab should transition to an alternative osteoporosis medication (eg, bisphosphonates) (Kendler 2022).

Stem Cell Therapy

Mesenchymal stem cells are easily obtainable from bone marrow by means of minimally invasive approach and can be expanded in culture and permitted to differentiate into the desired lineage. Experimental investigations of the clinical application of the adult bone marrow derived mesenchymal stem cells with bioactive molecules, growth factors have become promising (Chanda 2010). A case report of mesenchymal stem cells, when percutaneously injected into knees, resulted in significant cartilage growth, decreased pain and increased joint mobility in the patient (Centeno 2008).

Another study investigated the effects of systemic transplantation of human adipose-derived stem cells (hASCs) in ovariectomized mice. hASCs induced an increased number of both osteoblasts and osteoclasts in bone tissue and thereby prevented bone loss (Lee 2011).

Scientists believe that stem cells could halt osteoporosis, promote bone growth - and new pathways that controls bone remodeling (zur Nieden 2011).

Calcium and Vitamin D

Calcium and vitamin D supplements may help older patients lower their risk of hip fractures (details in prevention protocol). Most people in North America, however, lack sufficient sunlight exposure to produce adequate amounts of vitamin D, so vitamin D insufficiency is widespread (Drake 2010).

What You Need To Know

  • Osteoporosis is a condition in which healthy bone is lost through decreased new bone formation and increased resorption of existing bone
  • Osteoporosis was long thought to result simply from age-related reductions in sex hormones, primarily estrogen. As a result osteoporosis was only considered a disease of postmenopausal women.
  • Life Extension recognizes that osteoporosis is in fact the ultimate consequence of a host of modifiable factors that accumulate over time, including chronic oxidant stress, inflammation, insulin resistance and obesity, chronic life stress that increases cortisol secretion, and nutritional deficiencies or insufficiencies of a host of vitamins, minerals and other compounds
  • As a result, Life Extension recommends a multi-targeted approach to osteoporosis prevention, one that includes regular resistance exercise, weight loss, stress reduction, hormone restoration, and strategic use of nutritional supplements to restore or maintain a more youthful body milieu.
  • Life Extension’s supplement regimen goes beyond the simple recommendations for calcium and vitamin D provided by conventional medicine, adding supplements that promote healthy bone protein formation, and those that reduce inflammation, protect against oxidant stress, and supply adequate amounts of trace and ultra-trace minerals.

6 Osteoporosis Prevention and Treatment Protocol

In contrast with conventional medicine’s reactive, after-the-fact approach to osteoporosis, Life Extension recommends a comprehensive, integrative strategy to address all of the underlying causes and exacerbating factors involved in osteoporosis. Like most chronic conditions, prevention of osteoporosis is a much better choice than treatment.

Bioidential Hormone Replacement Therapy

Considering the importance of estrogen, progesterone and testosterone on bone health, Life Extension urges its customers to regularly obtain a complete hormone profile. Conventional hormone replacement therapy (Premarin® and Provera®) provides hormones that are unnatural to the human body. Bioidentical hormones, on the other hand, have the same exact molecular structure as the hormones produced naturally within the body. As a result, bio-identical hormones are properly utilized, and are then able to be naturally metabolized and excreted from the body. The use of bioidentical HRT has increased during the last several years as women have sought out a more natural approach to restoring hormonal balance. Generally overlooked by mainstream medicine are research findings suggesting that women may more safely benefit from individualized doses of natural estrogens and progesterone.

Estriol (a type of bioidentical estrogen), has been documented for increasing bone mineral density. A Japanese study involving 75 postmenopausal women found that after 50 weeks of treatment with 2 mg/day of estriol cyclically and 800 mg/day of calcium lactate, women had an increase in bone mineral density with no increased risk of endometrial hyperplasia (uterine tissue overgrowth that may precede cancer) (Minaguchi, 1996). In a second study emanating from Japan, researchers treated postmenopausal and elderly women with 2 mg/day of estriol and 1,000 mg/day of calcium lactate versus 1,000 mg/day calcium lactate alone. Bone mineral density significantly increased in women who received estriol, while the women who did not take estriol experienced a decrease in bone mineral density (Nishibe A, 1996).

Similar research has confirmed these findings. In this investigation, 25 postmenopausal women were given either 2 mg/day of estriol plus 2 gram/day of calcium lactate, or 2 grams/day of calcium lactate alone for one year. Bone mineral density was significantly reduced in the group that received calcium alone (without estriol). In contrast, the group that received estriol plus calcium experienced a 1.66% increase in bone mineral density after one year. Furthermore, biochemical markers of bone resorption were significantly decreased in the estriol group. “These data indicate that the acceleration of bone turnover usually observed after menopause was prevented by treatment with E3 [estriol],” the authors of this study noted (Nozaki, 1996).

A 2009 study compared the effects of conventional hormone replacement (conjugated equine estrogens and medroxyprogesterone) to that of estriol in 34 postmenopausal women. After one year of treatment, bone mineral density as well as lipids were measured. In both groups bone mineral density showed improvement however, women taking conventional HRT had an increase in triglycerides that was not seen in the women taking bioidentical estriol. The authors concluded that estriol might be an efficacious alternative to conventional HRT (Kika, 2009).

Given the degree of evidence, maturing women should understand that bioidentical hormone replacement, when appropriately prescribed, offers an alternative to conventional hormone replacement to help relieve menopausal symptoms and optimize bone density, and that accumulating evidence suggests that bioidentical hormone replacement appears to offer advantages over conventional hormone replacement therapy.

Hormonal balance is critical for maintaining optimal bone metabolism and overall health. In addition to restoring estrogen, testosterone, and progesterone levels to youthful ranges, DHEA levels should also be maintained. DHEA is a hormone that is active throughout the body; it also serves as a precursor to testosterone and estrogen. Indeed, some evidence suggests that DHEA supplementation may support bone health in aging women (Weiss 2009; von Muhlen 2008).

Note: For more information on bioidentical hormone replacement, please see the Female Hormone Restoration protocol.


Isoflavones, chiefly derived from soybeans, chemically resemble estrogen; as a result they are often referred to as phytoestrogens – literally, plant estrogens (Morabito 2002). Following the worrisome safety issues associated with the Women’s Health Initiative showing increased cancer risk in women on synthetic hormone replacement therapy (HRT), there has been dramatically increased interest in phytoestrogens as an alternative.

The primary soy isoflavones (in order of abundance) are genistein, daidzein, and glycitein; all three have confirmed phytoestrogenic effects (Anderson 1999). Genistein and daidzein have been shown in animal and human studies to contribute to increased bone mineralization and bone strength, while reducing bone resorption (Harkness 2004, Newton 2006, Weaver 2009, Sehmisch 2010). A 2002 study showed that genistein supplementation (54 mg/day) reduced urinary markers of bone turnover in a fashion similar to conventional HRT (Morabito 2002). The same study demonstrated increased serum markers of bone protein formation in genistein recipients; HRT recipients actually showed decreased levels of those proteins. And animal studies show that genistein reduces bone resorption by a mechanism different from the bisphosphonate drugs and estrogen (Lee 2004). Finally, the phytoestrogen isoflavones have substantial anti-inflammatory effect, adding to their ability to break the chain of events that contribute to osteoporosis (Ji 2011).

Concerns have been raised about the possible effects of phytoestrogens on breast cancer risk, given their biochemical similarity to estrogen (Marini 2008). Long-term studies, however, have demonstrated no increased risk of cancer or precancerous changes in women taking 54 mg/day of genistein (Marini 2008). In fact, “consumption of genistein in the diet has been linked to decreased rates of metastatic cancer in a number of population-based studies. Extensive investigations have been performed to determine the molecular mechanisms underlying genistein's antimetastatic activity, with results indicating that this small molecule has significant inhibitory activity at nearly every step of the metastatic cascade” (Pavese 2010).

A total daily isoflavone dose of about 54-110 mg for preventing loss of bone mineral content and reducing markers of bone resorption appears reasonable based upon the literature (Uesugi 2002, Harkness 2004, Atteritano 2009).

Vitamin K

Vitamin K regulates several biochemical processes that require exquisite balance to function normally, including blood coagulation, bone mineralization and vascular health. Through the diverse actions vitamin K holds promise in helping to prevent and manage some of the most crippling conditions associated with advancing age, including osteoporosis, coronary artery disease, and blood clots.

Vitamin K is an essential co-factor for building the protein matrix that traps calcium crystals in bone (Sogabe 2011, Rejnmark 2006). Like vitamin D, vitamin K is also essential for preventing calcium accumulation in arterial walls (Okura 2010). People with lower levels of vitamin K are at increased risk for calcification of major arteries (Okura 2010). Vitamin K also reduces activity of bone-resorbing cells by decreasing levels of inflammation regulating complexes (Morishita 2008). Low vitamin K status and use of warfarin-like anticoagulants (which antagonize the action of vitamin K by undermining a process called carboxylation) are associated with low bone mineral density and increased fracture risk (Rezaieyazdi 2009, Binkley 2009). Vitamin K2 supplementation (1,500 mcg/day) has been shown to accelerate proper bone protein formation (Koitaya 2009).

Vitamin K comes in two main forms, K1 (phylloquinone), and K2 (menatetrenone, or M4). Vitamin K2 has been shown to support bone health when used as a supplement in humans (Binkley 2009, Bunyaratavej 2009, Sato 2002).

Vitamin K2 supplementation reduces the amount of circulating bone protein, a measure of inadequate bone formation (Yasui 2006, Shiraki 2009). Supplementation also increases bone mineral content and bone strength at many different body sites, although DEXA scans may or may not show improvement in bone mineral density (Knapen 2007). K2 supplementation added to bisphosphonate drug therapy brings further benefit to both bone mineral density and bone protein (Hirao 2008).

Some individuals with osteoporosis who may benefit from supplementation with vitamin K are also taking warfarin, and so avoid vitamin K because they are concerned that it might interfere with their anticoagulant therapy. However, low-dose vitamin K (100 mcg daily) has been shown to help stabilize the INR (clotting time) of patients on anticoagulant therapy in a small trial (Reese 2005). In fact, emergent research suggests that some the beneficial effects of vitamin K2 for promoting bone mineral density may be entirely unrelated to vitamin K-dependent carboxylation, and resistant to the antagonistic effects of warfarin (Atkins 2009; Rubinacci 2009). Individuals on anticoagulant therapy who are interested in supplementing with vitamin K should discuss low-dose vitamin K with their physicians.

Vitamin D

Along with calcium, vitamin D is the nutrient that most people recognize as important for bone health (Holick 2007). But, even today, few people understand the powerful and complex ways that vitamin D acts to promote not only bone health, but the way the entire body handles calcium, both in healthy and in undesirable ways (Holick 2007). Vitamin D triggers absorption of calcium from the intestine and deposition of calcium in bone — and also removal of calcium from blood vessel walls. Conversely, insufficient vitamin D intake results in depletion of calcium from bones — and increased deposition of calcium in arterial walls, contributing to atherosclerosis (Celik 2010, Tremollieres 2010).

Vitamin D deficiency (or insufficiency) also causes muscle weakness and neurological deficits, increasing the risk of falling, which of course makes fractures still more likely (Bischoff-Ferrari 2009, Pfeifer 2009, Janssen 2010). The dose of vitamin D required to achieve the neuroprotective and other non-bone related effects are substantially higher than those required simply to achieve good calcium absorption (Bischoff-Ferrari 2007).

A validated measure of total body vitamin D status in blood is serum 25-hydroxy vitamin D (also known as 25(OH)D, or calcidiol). Note that this measure is reported in two different units, nmol/L and ng/mL, so it is vital to check which set of units a lab is using. Vitamin D deficiency is defined as a serum 25(OH)D level of less than 50 nmol/L, or less than 20 ng/mL. Experts recommend a higher level of 75 nmol/L, or 30 ng/mL (Bischoff-Ferrari 2007, 2009). To obtain the many health benefits of Vitamin D, current scientific evidence suggests a minimum target threshold for optimal health is over 50 ng/ mL or 125 nmol/L (Aloia 2008, Dawson-Hughes 2005, Heaney 2008).

The optimal dose of vitamin D has been hotly debated in recent years. More than 13,000 Life Extension customers have had their vitamin D level checked. The results from these tests provides important information about achieved vitamin D blood levels in a large group of dedicated, health-focused individuals. Vitamin D dosage as high as 5000 to 8000 IU per day may be required to achieve a minimum target level for optimal health in aging individuals (Faloon 2010).

A new study in the journal Anticancer Research echoed Life Extension’s recommendation, noting that traditional intakes of the essential vitamin just aren't enough (Garland 2011), “We found that daily intakes of vitamin D by adults in the range of 4,000 to 8,000 IU [international units] are needed to maintain blood levels of vitamin D metabolites in the range needed to reduce by about half the risk of several diseases -- breast cancer, colon cancer, multiple sclerosis and type 1 diabetes," said the author in a news release about their findings.


Calcium is the predominant mineral in bone, and crystals of calcium compounds give bone its hardness and strength. Most Americans do not meet the daily adequate intake for calcium, so supplementation is generally recommended (Straub 2007). Calcium supplementation also suppresses bone resorption, further fighting osteoporotic changes (Ortolani 2003). Large trials of calcium supplementation, with and without vitamin D, have shown mixed results at preventing osteoporosis, but closer examination of those studies has revealed that many of the patients who got no benefit did not take the supplements regularly (Lips 2009, Nordin 2009, Spangler 2011).

Individuals that are at high risk or that have been diagnosed with osteoporosis may need to consume up to 1,200 mg/day. Calcium supplements are available in many forms. For optimal absorption and convenience of dosing, use a combination of dicalcium malate (DimaCal®), calcium glycinate chelate (TRAACS®), and calcium fructoborate. Calcium citrate is also a water soluble form, and can be taken at any time; it is the supplement of choice for people with suppressed gastric acid secretion, such as those taking antacids and proton pump inhibitors (Straub 2007).


Magnesium is an important micronutrient that regulates active calcium transport in humans, and is therefore important in bone health (Aydin 2010). Older adults tend to be magnesium deficient because of diminished dietary intake and absorption coupled with increased urinary losses (Barbagallo 2009). Chronically elevated stress hormone levels also contribute to depressed magnesium levels (Barbagallo 2009). Together these effects conspire to damage bone health.

Magnesium supplementation in both animal and human studies reduces bone turnover, tending to favor bone formation over bone resorption (Aydin 2010, Aydin 2010).  The resulting improved bone mineralization contributes to a reduction in fracture frequency (Sojka 1995).


Boron is an ultra-trace element that has been discovered to be essential for bone health (Volpe 1993). Its primary effect seems to be its interactions with more prevalent minerals such as calcium and magnesium, but it also has independent anti-inflammatory effects that may contribute to its usefulness (Scorei 2011).

In human studies boron deficiency caused changes in calcium metabolism that resemble those seen in osteoporosis, and which were exacerbated by low magnesium levels (Nielsen 1990). Animal studies show that boron supplementation stimulates bone formation and inhibits bone resorption (Xu 2006).

A daily dose of 3-9 mg of boron from calcium fructoborate, a boron-based supplement which also has antioxidant and anti-inflammatory actions, is reasonable for bone health based upon the scientific literature (Scorei 2005, Scorei 2011).


Silicon is one of the most abundant elements in the Earth’s crust. It has few known biological functions, but recently silica (silicon dioxide) has been discovered to play an important role in bone formation and health (Li 2010). Silicon deficiency in animals results in bone defects (Calomme 2006).

Supplementation with organic silicon compounds, on the other hand, improves bone mineral density and prevents bone loss (Kim 2009, Calomme 2006). A human study demonstrated that the addition of organic silicon to a calcium and vitamin D3 regimen improved production of bone proteins (Spector 2008).


Researchers are now discovering the vital importance of collagen for achieving optimal bone tensile strength. Collagen, a resilient type of protein molecule, makes up most of the structure of bone (Ailinger 2005). The spongy matrix of collagen fibers and crystalline salts within bone is crucial to absorbing compression forces to resist stress fractures, much as the tensile supports of steel bridges provide flexibility so that the bridge can withstand gale force winds and heavy traffic.

Scientists developed a new form of calcium that molecularly binds collagen. This unique form of collagen calcium chelate is designed to enhance collagen support and turnover while increasing bone mineral density and bone strength (AIDP data on file).

Scientists at Tokyo University found that supplementation with collagen calcium chelate improved bone strength to a greater extent than the same amounts of calcium and collagen either given separately or together but in a non-chelated form. Specific improvements with collagen calcium chelate were seen not only in bone mineral density but just as importantly in femur (thigh bone) weight, bone collagen production, and bone flexibility and strength.

In an experimental model of osteoporosis, the test group received a low-calcium diet for one week. In addition to their low-calcium diet, some of the test group consumed a high-dose collagen calcium chelate. The cohort receiving high-dose collagen calcium chelate had an increase in femur bone weight by an impressive 9.6%, compared with the group given the same amount of calcium in non-chelated form. The test group receiving the collagen calcium chelate had dose-dependent increases in bone mineral density, which were 3.5% to 11.1% higher than those seen in the group receiving the same amount of non-chelated calcium. The investigators concluded that collagen calcium chelate had an additive effect on bone mineral density, better than that of calcium alone or of a simple calcium and collagen mixture (AIDP data on file).

Collagen calcium chelate was also associated with increases in femur bone strength, by about 9.9% to 25%, compared with the group receiving the same amount of calcium (AIDP data on file). Remarkably, the benefits of collagen calcium chelate were evident after only eight weeks of supplementation. Given these encouraging results, a large clinical study is currently underway, in collaboration with the US Army, to look at the effect of collagen calcium chelate on bone fractures in hard-training recruits.

Antioxidant Vitamins

Oxidant stress, particularly that imposed by oxidized LDL-cholesterol, is a significant contributor to bone loss in osteoporosis (Zinnuroglu 2011, Mehat 2010). Some bisphosphonate drugs may themselves actually increase oxidant damage as well (Zinnuroglu 2011). Antioxidant vitamins and other supplements, therefore, have an important role in prevention (Chuin 2009, Sugiura 2011).

The antioxidant vitamins C and E play important roles in production of proteins, development of bone-forming cells, and bone mineralization (Zinnuroglu 2011, Hall 1998). Vitamin C also suppresses activity of bone-resorbing cells while promoting maturation of bone-forming cells (Gabbay 2010). Vitamin E improves bone structure, contributing to stronger bone (Shuid 2010).

Women with higher vitamin C intake have significantly better bone mineral density, so long as their calcium intake is also above 500 mg/day (Hall 1998). Postmenopausal women who took 600 mg vitamin E and 1000 mg vitamin C daily achieved stable bone mineral density compared with placebo recipients, whose density dropped over a 6-month period (Chuin 2009). Similar doses of both vitamins were useful in preventing bone loss in elderly men and women (Ruiz-Ramos 2010).

Daily doses of 1000 mg vitamin C, and 600 mg of vitamin E (as mixed tocopherols) are reasonable for osteoporosis prevention; alpha-tocopherol alone is likely to be ineffective (Ruiz-Ramos 2010, Mehat 2010, Chuin 2009, Ima-Nirwana 2004). Recent study investigated the bone anabolic effects of Vitamin E in rats and for the first time reported that gamma isomer improves all the parameters of bone biomechanical strength, while alpha tocopherols only improved some of the parameters (Shuid 2010).

Omega-3 Fatty Acids (Fish and Flax Oils)

The omega-3 fatty acids found in fish oil (EPA and DHA) and flax oil (ALA) have powerful anti-inflammatory and antioxidant effects (Trebble 2004, Fernandes 2008, Maggio 2009). That makes them ideal candidates for inclusion in an anti-osteoporosis regimen, given the role of inflammation in osteoporosis (Trebble 2004). EPA and DHA also reduce activity of bone-resorbing cells, increase that of bone-forming cells, and improve calcium balance (Maggio 2009).

Men and women who consume higher amounts of oily fish (tuna, mackerel, salmon, etc) have greater bone mineral density than do those with lower fish consumption (Farina 2011). Animal studies have shown increased bone mineral content and strength in animals supplemented with fish oils or the omega-3 fatty acids EPA and DHA, as well as the flax seed oil-derived ALA (Sun 2004, Ward 2007, Matsushita 2008, Salari 2008, Sacco 2009). Intriguingly, fish oil plus soy isoflavone supplementation resulted in a higher weight-bearing capacity of lumbar vertebra (Ward 2007).

EPA and DHA have specific anti-resorption effects on bone cells in culture, and also stimulate differentiation and activity of bone-forming cells (Rahman 2008, Rahman 2009). Increased dietary intake of omega-3’s in animals protects against bone loss by down-regulating the important NF-kappa-B inflammation-controlling complex (Fernandes 2008). In human studies, supplementation with EPA (omega-3)and GLA (gamma-linolenic acid-, a beneficial omega-6), along with 600 mg/day of calcium, maintained spine and hip bone mineral density over 18 months, while in placebo recipients bone density fell significantly (Kruger 1998). Fish oil supplements containing a total of 2.7 g/day of EPA and DHA reduced inflammatory cytokine production in humans (Trebble 2004). And daily 900 mg/day of mixed omega-3 fatty acids decreased bone resorption in postmenopausal women with osteoporosis (Salari 2010).


Curcumin is a bio-active component of the Indian spice turmeric (Shishodia 2005). It has powerful antioxidant and anti-inflammatory actions, particularly by reducing the gene expression of the master inflammation-regulatory complex NF-kappa-B (Shishodia 2005, Oh 2008).

Lab studies show that curcumin decreases activity of bone-resorbing cells by reducing NF-kappa-B expression (Oh 2008). Animal studies reveal multiple beneficial effects of curcumin on bone mineral content and structure (Yang 2011). Curcumin improves bone mineral density in rat models of postmenopausal osteoporosis, and increases bone strength (French 2008).


Resveratrol is a powerful phytoalexin molecule produced by plants, especially grape vines and Japanese knotweed, for protection against oxidant stress, and pathogens (Kupisiewicz 2010). As the chief health-promoting component of red wine, it has achieved prominence for its ability to mimic the beneficial effects of calorie restriction on many genes that contribute to longevity and health (Pearson 2008). Among the genes that resveratrol modulates are several that are crucial for bone health.

Certain stem cells can differentiate into either fat or bone tissue, depending on how their genes are regulated. Resveratrol activates genes that tip the cells to develop into bone forming cells, and suppresses those that would create fat cells (Kupisiewicz 2010, Song 2006, Backesjo 2009, Shakibaei 2011). Resveratrol also prevents inflammation-induced maturation of bone resorbing cells (He 2010). In animal studies, resveratrol supplementation results in increased bone mineral density and reduced bone resorption (Liu 2005).


Quercetin is a plant polyphenol found in a wide variety of fruits. It is a powerful antioxidant and a mild phytoestrogen as well (Boots 2008, Wattel 2004). Quercetin directly stimulates the differentiation and activity of bone-forming cells in laboratory studies (Yang 2006, Prouillet 2004). It also reduces activity of bone-resorbing cells through its down-regulation of inflammation (Wattel 2004).

Quercetin recently was shown to enhance activity of the vitamin D receptor in intestinal cells, which in turn helps in proper regulation of calcium metabolism (Inoue 2010). Together these effects provide support for the observation that quercetin supplementation in experimental models inhibits bone loss following induced menopause (Horcajada-Molteni 2000).


Berberine is a plant alkaloid used extensively in ancient Chinese and Japanese medicine for use in promoting bone health (Li 1999, Li 2008). Animal and laboratory studies reveal that berberine prevents decrease in bone mineral density by inhibiting the activities of bone-resorbing cells (Li 1999). Used as a dietary supplement in experimental models, berberine resulted in an increase in bone mineral density (Li 2003). Berberine also increases differentiation of bone-forming cells through activation of cellular signaling pathways (Lee 2008, Xu 2010).

Although berberine has been studied in human clinical trials and shown to have several metabolic benefits, concerns about long-term use of berberine have been raised on the basis of certain preclinical studies (Kysenius 2014; Mikes 1985; Mikes 1983). Some evidence suggests that long-term berberine use, especially at high doses, may impair particular aspects of cellular metabolism in specific types of cells. The implications of this preclinical research are yet to be determined by long-term human clinical trials, therefore Life Extension currently recommends short-term use of berberine.


Hops is an herb best known for producing the typical bitter flavor of beer, and has long been known to have health benefits (Kondo 2004). The active ingredients in hops have multiple biological effects, particularly in their ability to act as selective estrogen receptor modulators (SERMs). In this capacity, hops extracts may boost beneficial estrogen effects without triggering estrogen-related outcomes such as breast cancer (Effenberger 2005). Among their benefits are positive effects on bone mineral density and prevention of osteoporosis (Stevens 2004). Hops extracts increase gene expression and differentiation of bone-forming cells in laboratory studies (Effenberger 2005).


  • May: Added section on denosumab to Conventional Treatments and Associated Risks


  • May: Comprehensive update & review

Disclaimer and Safety Information

This information (and any accompanying material) is not intended to replace the attention or advice of a physician or other qualified health care professional. Anyone who wishes to embark on any dietary, drug, exercise, or other lifestyle change intended to prevent or treat a specific disease or condition should first consult with and seek clearance from a physician or other qualified health care professional. Pregnant women in particular should seek the advice of a physician before using any protocol listed on this website. The protocols described on this website are for adults only, unless otherwise specified. Product labels may contain important safety information and the most recent product information provided by the product manufacturers should be carefully reviewed prior to use to verify the dose, administration, and contraindications. National, state, and local laws may vary regarding the use and application of many of the therapies discussed. The reader assumes the risk of any injuries. The authors and publishers, their affiliates and assigns are not liable for any injury and/or damage to persons arising from this protocol and expressly disclaim responsibility for any adverse effects resulting from the use of the information contained herein.

The protocols raise many issues that are subject to change as new data emerge. None of our suggested protocol regimens can guarantee health benefits. Life Extension has not performed independent verification of the data contained in the referenced materials, and expressly disclaims responsibility for any error in the literature.


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