Osteoporosis, a skeletal condition characterized by reduced bone mass, mineralization, and strength, is usually associated with aging and increases the risk of fractures. People who experience a bone fracture have a substantially increased risk of subsequent fractures, long-term disability, and premature death.⁶ Therefore, the primary goal of osteoporosis prevention and treatment is to prevent fractures.^1,7

In the United States, around 44 million people are living with osteoporosis, and 2 million osteoporosis-related bone fractures occur every year.² Osteoporosis is most often diagnosed in women, although men have a higher risk of osteoporosis than previously appreciated.⁸ In fact, studies show that 33–50% of women and 20% of men over 50 years of age will experience an osteoporosis-related fracture, known as a fragility fracture, at some point in their lifetime.^6,7,9 Although more osteoporotic fractures in people aged 50 and older occur in women, mortality following a fracture is higher in men than in women.^6,7

Virtually everyone will lose bone strength as they age, generally without symptoms. In fact, a fracture is often the first sign of bone loss. This is why screening is so important.¹⁰

Although osteoporosis cannot be reversed, steps can be taken to prevent further bone loss. Diet and lifestyle exert considerable influence over bone health. Important risk factors for osteoporosis include advancing age, smoking, drinking too much alcohol, not exercising enough, eating an unhealthy diet, having gone through menopause, and deficiencies in key nutrients like calcium and vitamin D, vitamin K2, boron, and magnesium.⁵

Medical treatments can also help preserve bone mass. There are several types of pharmaceuticals that may be used to treat or prevent osteoporosis. In general, these either prevent bone breakdown or promote bone formation.^4,5

In this protocol, you will learn about how osteoporosis develops, how it is diagnosed, and what treatments are available. These treatments include nutrients and lifestyle modifications to support bone health, as well as medical approaches.

Osteoporosis is a complex condition characterized by reduced bone mass and strength, leading to a higher risk of fractures. Osteoporosis may arise without a specific cause other than aging, in which case it is called “primary osteoporosis.” If bone loss is due to a clearly identifiable cause, such as another medical condition or treatment side effect, it is called “secondary osteoporosis.” In general, the development of osteoporosis can be understood as an interplay of several factors, including hormonal changes, nutritional deficiencies, genetic predisposition, and lifestyle choices.^11,12

Bone mass is the total amount of bone tissue in the body, whereas bone mineral density (BMD), or simply bone density, refers to the mineral (mainly calcium and phosphorus) content of the bone relative to the overall size of the bone. Though somewhat different, these terms are often used interchangeably.¹³

Peak bone mass generally occurs in the third or fourth decade of life, but timing can differ due to genetic, hormonal, and environmental factors and may be different for different anatomical sites.¹¹ Gradual age-related bone loss typically begins shortly after peak bone mass and occurs at an average rate of about 1–1.5% annually. By 80 years of age, 30–50% of peak bone mass may be lost simply due to aging.¹⁴

Dual-energy X-ray absorptiometry (DEXA or DXA) is a test that measures BMD and is used to identify osteopenia and osteoporosis. In older adults, a diagnosis of osteopenia or osteoporosis is made based on a decrease in BMD relative to normal peak BMD levels, whereas in younger people, these diagnoses are made based on comparisons to normal BMDs for age.^9,15

Bones are dynamic tissues, constantly undergoing remodeling through the action of osteoblasts (cells that build bone) and osteoclasts (cells that break down bone).⁵ (It may be helpful to think of the b in “osteoblasts” as meaning “build” and the c in “osteoclasts” as meaning “chew,” as in chew up or break down.) As people age, osteoclast activity usually outweighs osteoblast activity, leading to net bone loss. Osteoporosis is a result of long-term imbalance in bone remodeling favoring bone breakdown.⁵

Osteoblasts build bone by secreting proteins that help create and maintain the bone matrix. For example, receptor activator of nuclear factor-kappa B ligand (RANKL) is a protein produced by osteoblasts with a key role in regulating bone remodeling. RANKL interacts with RANK receptors on osteoclasts and osteoclast precursor cells to stimulate osteoclast activity, generation, and survival. RANKL can also interact with osteoprotegerin (OPG), another protein released from osteoblasts. OPG acts as a “decoy receptor” for RANKL, thereby inhibiting its signaling and slowing bone breakdown. The RANK-RANKL-OPG system is now known to have other functions, including regulation of immune cells and formation of cells that line breast ducts, and represents a link between cancer and bone loss.¹⁶

Osteoblasts also contribute to bone-building through their ability to transform into osteocytes, which are the most abundant bone cells and reside deep in the bone matrix.¹⁷ Osteocytes are critical to regulating bone remodeling and mineralization.⁵

Osteocytes are specialized in mechanosensation, the ability to sense mechanical stressors on bone. Osteocytes integrate and respond to mechanical, hormonal, and inflammatory signals by secreting molecules that regulate osteoblast and osteoclast activity.¹⁴ These include sclerostin, which suppresses osteoblast-induced bone formation, and fibroblast growth factor (FGF) 23, which regulates bone matrix mineralization. In addition, molecules from osteocytes can exert hormone-like effects on distant tissues.¹⁷ Osteocytes also produce RANKL, but its function when released in the bone matrix is not yet fully understood, although it can clearly lead to induction of more osteoclasts.¹⁶

Aging is associated with reduced transformation of mesenchymal stem cells (stem cells in the bone marrow that can differentiate into multiple different types of tissue cells) into osteoblasts. Instead, these stem cells are more likely to transform into fat cells.⁵ Osteocyte function is also disrupted by aging, especially in the context of factors such as estrogen or androgen deficiency, dysregulation of parathyroid hormone (PTH), excess inflammatory signaling, lack of mechanical load-bearing, and low nutrient availability. The result is imbalanced bone remodeling favoring bone breakdown and increased risk of osteoporosis.^14,17

The main characteristic of osteoporosis is loss of bone structure and strength, which increases the risk of fracture. A range of factors can contribute to bone loss and raise osteoporosis risk, including advancing age, family history, female gender, hormonal disturbances, white or Asian racial background, being underweight, nutrient deficiencies, a number of lifestyle characteristics, some medical conditions, and use of certain medications.¹⁸

Age

Advancing age is a primary risk factor for osteoporosis. Bone mass generally peaks in ones 20s or 30s, depending on anatomical site, and begins gradually declining at around 40 years of age.^14,19 Aging is associated with increased fat tissue accumulation in bone marrow due to changes in hormone status and metabolism. This reduces bone density and strength, particularly in long bones.²⁰ In addition, aging is accompanied by loss of osteoblasts and osteocytes and accumulation of senescent (persistent and dysfunctional) cells, resulting in imbalanced bone resorption relative to formation.^14,21 Epidemiological evidence has indicated 54% of U.S. adults over age 50 years may have osteopenia, putting them at increased risk of osteoporosis.²¹ Advancing age also leads to sarcopenia, the degenerative loss of skeletal muscle mass and strength. Decreased measures of muscle strength and function have been found to be independently linked to fracture risk in the elderly, due in part to increased risk of falling.²²

Family History & Genetics

Having a family history of osteoporosis increases the risk of developing the condition. One observational study compared 100 postmenopausal women diagnosed with osteoporosis against 100 age-matched women without evidence of osteoporosis and found those with a close relative (usually a mother) with osteoporosis were almost five times as likely to also have osteoporosis.²³ Heritable genes related to vitamin D receptors, estrogen receptors, collagen type I, bone morphogenetic protein, and other factors influence the achievement of peak bone density, bone architecture, and bone mechanics, contributing to osteoporosis risk in women and men.^23-25

Hormonal Factors in Women

Estrogen plays a crucial role in maintaining bone density by promoting the activity of osteoblasts, the cells responsible for forming new bone, and inhibiting osteoclasts, which break down bone tissue.²⁶ As women reach menopause (typically around the age of 50 years), estrogen levels drop sharply, leading to an increase in bone resorption over formation and raising the risk of osteoporosis and fracture.²⁷ Estrogen also plays a role in modulating the gut microbiome, and emerging evidence suggests menopause-induced changes to microbiome composition may contribute to bone loss.²⁶

Early menopause, generally defined as occurring between 40 and 45 years of age, has been found to significantly increase fracture risk.²⁷ The most common sites of osteoporotic fracture in postmenopausal women are the hip, spine, and wrist. These fractures impair quality of life and are associated with increased mortality.²⁷

A woman’s rate of bone loss and risk of osteoporosis later in life are influenced by the peak bone density she achieved decades prior. In the longest study to date, 686 postmenopausal women were monitored with DXA scans and risk factor questionnaires every five years for 25 years. The average total bone loss over 25 years was 10.1% (0.4% per year) and ranged from about 7.4–11.1%. Having a higher baseline BMD was associated with a lower rate of bone loss. A lower body mass index (BMI) at baseline, greater increase in BMI during the study, and using hormone therapy were the only other factors significantly associated with reduced rate of bone loss.²⁸

Thyroid hormones are also a factor in women’s bone health. Excess thyroid hormone, the hallmark of hyperthyroidism, enhances bone breakdown and is a risk factor for osteoporosis, especially in postmenopausal women.^29,30 Women with frank hyperthyroidism have a three- to four-fold increased risk of hip or spine fracture. Even subclinical hyperthyroidism, a condition in which thyroid levels are normal but thyroid stimulating hormone (TSH) levels are low, has been linked to lower bone density and higher fracture risks in both women and men.³⁰ Although low TSH levels have been reported to affect as many as 10% of women in their 50s and 60s, normal aging is associated with modestly rising TSH and declining thyroid hormone levels, which may have a protective effect on bones. Overcorrection of hypothyroidism in older women is common and may contribute to osteoporosis risk.^29,31

Hormonal Factors in Men

Although the effects of androgens (mainly testosterone and dihydrotestosterone [DHT]) on bone are not as well studied as estrogens, androgens appear to contribute directly and indirectly (through conversion to estrogen) to bone quality.^32,33 For example, testosterone directly increases bone growth and indirectly inhibits bone breakdown.³⁴ As a result, men generally achieve larger bone size and higher peak BMD than women.^33,35,36

Whereas women experience a sharp decline in estrogen levels during menopause, men experience a more gradual decline in testosterone over time. This is why aging men do not experience rapid bone loss to the same extent as women. Nevertheless, men with testosterone deficiency (hypogonadism)—due to factors such as aging or prostate cancer treatment—have accelerated bone loss and increased risk of osteoporosis and fractures that improve with testosterone therapy.^32,33,36

Adequate estrogen is also required for bone maintenance in aging men. In fact, testosterone’s protective effect on bone density in older men appears to be exerted mainly through its conversion to estrogen.^33,34 Increased bone turnover and loss of BMD occur when serum testosterone levels fall below 200 ng/dL and serum estradiol (a form of estrogen) levels drop to 10–15 pg/mL.³² In addition, thyroid diseases, though less common in men than women, have similar effects on osteoporosis risk in both genders.³⁷

Underweight

Low body weight is a risk factor for osteoporosis and fractures. This may be due in part to decreased muscle mass and function and lower mechanical load on bone, leading to reduced bone growth and strength.⁴² A meta-analysis of data from 172,059 participants from 51 studies conducted in 20 countries around the world found women with underweight had a 1.3-fold increased risk and men with underweight had a 2.5-fold increased risk of hip fracture over an average of about eight years of monitoring. Interestingly, the analysis also noted an increased fracture risk in men with overweight and obesity after adjusting for bone density.⁴³ One study examined data from 561,779 adults over 40 years of age and found being underweight was associated with a 17% increased rate of total fractures and 21% increased rate of vertebral fractures during three years of follow up, and fracture risk remained higher even in those who reached normal-weight status during the study.^44,45

Dietary Factors

Eating an unhealthy diet is associated with an increased risk of bone loss and fractures.⁴⁶ Ultra-processed foods contain high amounts of simple sugars, saturated fats, and phosphorus that can impair bone metabolism, and are low in nutrients that support bone maintenance like calcium, magnesium, vitamins D and K, omega-3 polyunsaturated fats, and antioxidants.⁴⁷

Inadequate intake of vitamin D, calcium, and protein are all associated with reduced BMD and estimated bone strength.⁴⁶ Calcium is needed for bone mineralization, and vitamin D helps regulate calcium levels by enhancing its absorption in the intestines and reducing its clearance by the kidneys.^47,48 The amino acids obtained from dietary protein are used to build bone matrix and maintain muscle mass.⁴⁷ Dietary protein also promotes secretion of insulin-like growth factor 1 (IGF-1), which is involved in vitamin D activation and stimulates osteoblasts to build new bone tissue.^47,48

Studies that have evaluated the effect of protein intake above the recommended daily allowance (>0.8 grams/kg body weight daily) on bone turnover have produced inconsistent results. Some evidence has indicated protein intake above the RDA may be associated with bone loss, particularly in sedentary individuals, whereas other studies suggest it is beneficial, particularly in older adults.^47,49 A systematic review and meta-analysis that included 127 observational studies and clinical trials found increasing protein consumption had neither a positive nor a negative effect on bone health or fracture risk for individuals consuming 0.8–1.3 grams/kg of body weight daily.⁵⁰ Nevertheless, protein deficiency is common in elderly people and contributes to fracture risk. In a randomized controlled trial that included 7,195 elderly residents in 60 elder-care facilities, a two-year dietary intervention that bolstered calcium and protein intake led to a 33% reduction in fractures, 46% reduction specifically in hip fractures, and an 11% reduction in falls. The dietary intervention consisted of additional milk yogurt, and cheese, which boosted calcium intake from about 600 mg to 1,142 mg/day and protein from less than 1 gram/kg of body weight to 1.1 grams/kg of body weight daily.⁵¹

Vegetarian and vegan diets have been linked to increased fracture risk: in a meta-analysis of findings from 20 observational studies involving a total of 37,134 participants, vegetarians and vegans had lower BMD and a substantially higher fracture rate than omnivores.⁵² One study that followed 54,898 individuals for 9–17.6 years found fracture risk was 25% higher in vegetarians and 26% higher in those who ate fish, but not meat, compared with meat eaters. In vegans, the fracture risk was more than two-fold higher than in those who ate meat. Data analysis indicated these differences were modified slightly, but still significant, after adjusting for dietary calcium or protein intake.⁵³ Another study followed 34,542 non-Hispanic White peri- and postmenopausal women and men aged 45 years and older for a median of 8.4 years. The study found vegan women, but not men, had a 55% higher risk of hip fracture than non-vegetarians; however, further analysis showed vegan women who supplemented with both vitamin D and calcium did not have an increased fracture risk.⁵⁴

Diet is also closely linked to body-wide (systemic) inflammation. In a meta-analysis of findings from 11 correlational studies with a total of 127,769 participants, increasing dietary inflammatory index (DII) scores, which reflect the inflammatory potential of a diet, were associated with decreasing BMD in the lumbar spine. In addition, those with the highest scores had increased risks of osteoporosis and fractures.⁵⁵

Lifestyle-Related Factors

While osteoporosis risk is mainly determined by advancing age and diminishing hormone levels, certain lifestyle factors also contribute to the likelihood of this condition. Lifestyle-related risk factors are modifiable, meaning people can make healthy changes to alter their risk of osteoporosis.

Smoking

Smoking decreases circulation to the bones and other tissues.¹⁰ In addition, toxic substances found in tobacco, such as nicotine, interfere with the body’s absorption and use of nutrients, including calcium and protein. These substances can also make the blood more acidic, promoting bone resorption and reducing BMD.⁴⁸ Studies have consistently shown that smokers have significantly lower BMD compared with nonsmokers.^10,58,59 Research has indicated smoking one pack of cigarettes daily throughout adulthood is associated with an up to 10% lower BMD.¹⁰ Early findings from studies examining the effects of e-cigarette use, or vaping, on bone health suggest it may also impair bone cell function.^60,61 One observational study with 5,569 participants found users of e-cigarettes were 46% more likely to report having experienced an osteoporotic fracture compared with never users.⁶²

Excessive Alcohol Consumption

Excessive alcohol consumption is detrimental to bone health. It is not entirely clear how alcohol affects bone metabolism, but it is thought that alcohol may negatively affect osteoblasts.⁴⁸ A meta-analysis of data from eight observational studies comparing alcohol consumption to fracture risk indicated people who consumed three or more standard alcoholic drinks daily had an increased risk of hip fracture compared with non-drinkers. In a meta-analysis that included data from six studies, people who consumed one to two alcoholic drinks per day were found to have a 34% higher risk of developing osteoporosis compared with non-drinkers, and those who consumed two or more alcoholic drinks per day had a 64% higher risk.⁶³ On the other hand, a more recent meta-analysis of findings from 11 studies examined the effect of alcohol consumption on BMD and found those who regularly consumed one to two alcoholic drinks per day had higher bone density than non-drinkers.⁶⁴

Excessive Caffeine Intake

Caffeine is a natural compound found in widely consumed beverages including coffee, tea, colas, energy drinks, and some other soft drinks. While moderate caffeine intake (about 400 mg, or four cups of brewed coffee, daily) may actually support healthy bone metabolism, excess caffeine (≥800 mg daily) appears to interfere with osteoblast and osteoclast function.^65,66 Caffeine may also affect bone loss by increasing calcium excretion by the kidneys and modifying vitamin D function.^65,67 Observational studies examining the relationship between caffeine intake and osteoporosis risk have had mixed findings. One study in 8,789 subjects aged 50 years and older found moderate coffee intake (≤ two cups per day) was associated with lower risk of osteopenia or osteoporosis in the spine and femoral neck (a location in the hip).⁶⁸ Another study in 4,286 postmenopausal women found caffeine intake was unrelated to BMD, but higher urine levels of certain caffeine metabolites were associated with lower BMD.⁶⁹

Lack of Physical Activity/Exercise

A sedentary lifestyle is linked to more fragile bones as well as balance and coordination issues, leading to higher risk of falls and fractures.⁵ In contrast, regular physical activity positively influences BMD, bone strength, and balance, all of which reduce the risk of falling and fractures.^70,71 The combination of high-intensity resistance training, impact training, and aerobic exercises is key to preventing bone loss, fractures, and osteoporosis. Examples include walking, weight training, gymnastics, and jogging.^48,70,72

Medications

A number of classes of medications impair bone remodeling and increase osteoporosis risk. Examples include⁷³:

• Glucocorticoids: steroidal anti-inflammatory drugs like prednisone, hydrocortisone (Cortef), and dexamethasone
• Proton pump inhibitors (PPIs): stomach acid reducers like omeprazole (Prilosec), pantoprazole (Protonix), and esomeprazole (Nexium)
• Anticonvulsants: drugs used to treat seizures, like phenytoin (Dilantin), phenobarbital (Luminal), and carbamazepine (Tegretol)
• Aromatase inhibitors: drugs that suppress conversion of testosterone to estrogen and are used in breast cancer treatment, like letrozole (Femara), exemestane (Aromasin), and anastrozole (Arimidex)
• Gonadotropin releasing hormone (GnRH) analogues: drugs that, when taken long term, inhibit ovarian or testicular function and are used to treat hormone sensitive conditions like endometriosis, uterine fibroids, and prostate cancer; they include leuprolide (Lupron), goserelin (Zoladex), and triptorelin (Trelstar)
• Selective serotonin reuptake inhibitors (SSRIs): a class of antidepressants that includes paroxetine (Paxil), citalopram (Celexa), and sertraline (Zoloft)
• Medroxyprogesterone acetate (Provera), a synthetic progesterone-like drug
• Tenofovir (Viread), an antiretroviral medication
• Some chemotherapy agents

Glucocorticoids (also known as corticosteroids or steroids) are commonly prescribed anti-inflammatory medications. Although these medications are highly effective in the treatment of acute inflammatory conditions and autoimmune diseases, long-term use substantially increases fracture risk.⁵ In fact, as many as 50% of people who take glucocorticoids for an extended period develop fractures. This is because glucocorticoid use is associated with decreased bone formation due to osteoblast inhibition, increased bone resorption, and larger areas of dead tissue due to decreased bone blood supply.⁷⁴

Proton pump inhibitors (PPIs), which are used to treat peptic ulcer disease and gastroesophageal reflux disease (GERD or acid reflux), are among the most commonly prescribed drugs in the United States. Research suggests that PPIs disrupt calcium metabolism by impeding intestinal absorption of calcium, magnesium, and other nutrients due to reduced stomach acid production.^75,76 This leads to increased bone resorption and higher risks of osteoporosis and fractures.⁷⁷ A meta-analysis of 24 observational studies with a combined total of more than 2 million participants found taking PPIs for more than one year was associated with increased hip fracture risk, and the risk increased with dosage and duration of use.⁷⁸

Chronic Conditions

A range of chronic conditions are associated with bone loss and may contribute to osteoporosis and fracture risks. These include autoimmune, parathyroid, and digestive diseases.

Autoimmune Disorders

Autoimmune disorders are chronic inflammatory conditions, and many have been associated with reduced bone mass. Inflammation and inflammatory autoimmune signaling can disrupt the balance of osteoblast and osteoclast activities in favor of osteoclastic bone breakdown.^79,80 For example, rheumatoid arthritis is a common autoimmune condition affecting the joints and has been shown to trigger increased osteoclast activity and bone resorption.^81,82 Other autoimmune diseases linked to higher osteoporosis and fracture risk include ankylosing spondylitis, inflammatory bowel disease, and systemic lupus erythematosus.⁸³

Parathyroid Disorders

The parathyroid gland is responsible for producing parathyroid hormone (PTH), which maintains normal blood calcium levels through several mechanisms, including stimulating calcium release from bones. Hyperparathyroidism, a condition marked by high calcium levels and high or inappropriately normal (in the context of high calcium) PTH levels,⁸⁴ can be due to dysfunction of the parathyroid gland (primary) or other conditions such as vitamin D deficiency (secondary). Hyperparathyroidism often manifests in osteoporosis, fractures, kidney stones, and cardiovascular problems.⁸⁵ One meta-analysis of 12 studies found people with primary hyperparathyroidism had an increased risk of forearm and spine fractures.⁸⁶ Individuals with hypoparathyroidism have also been paradoxically found to have an increased risk of vertebral fractures, despite having higher BMD than age- and sex-matched people with normal PTH levels.⁸⁷ The reason for this finding is not clear, but it is known that hypoparathyroidism is associated with increased loss of calcium in the urine.

Gastrointestinal Diseases

Some gastrointestinal diseases can compromise bone health due to nutrient malabsorption, inflammatory signaling, medication side effects, and possibly imbalanced gut microbiome (dysbiosis).^88,89 Celiac disease and inflammatory bowel disease—including Crohn’s disease and ulcerative colitis—compromise gut health and interfere with nutrient absorption.^90,91 Malabsorption deprives bones of minerals, vitamin D, and other nutrients that support normal bone remodeling. Furthermore, it is increasingly clear that signaling from beneficial gut bacteria is an important factor in maintaining healthy BMD, whereas patterns of dysbiosis have been associated with low BMD.⁹² Although a gluten-free diet may alleviate symptoms and reverse bone loss in some patients with celiac disease, others may continue to experience gradual bone loss despite gluten avoidance. People with celiac disease should therefore be screened regularly for changes in BMD.⁹³

A systematic review of 25 studies with more than 5 million participants found peptic ulcer disease (PUD), Helicobacter pylori infection (the cause of 85–95% of PUD cases), and use of PPIs (drugs used to treat PUD) were associated with an increased risk of osteoporosis.⁹⁴ In addition to PUD, H. pylori is a contributing factor in gastritis, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer.⁸⁹ Research shows that PUD caused by H. pylori infection inhibits calcium and other nutrient absorption, reduces estrogen levels, increases inflammatory signaling, and alters levels of other signaling molecules from the stomach leading to increased bone loss and risk of osteoporosis.^89,94

Other Associated Conditions

Osteoporosis has been associated with a number of other health conditions, many of which are related to aging.

Cardiovascular Disease

Cardiovascular disease and osteoporosis commonly co-occur, especially in older age.Observational studies have shown that patients with low BMD and/or the presence of osteoporotic fractures have increased risks of heart attack, stroke, and cardiovascular mortality. Likewise, individuals with arterial calcifications have been noted to have decreased BMD.⁹⁵

Similarities between the processes of bone loss and the buildup of calcium along the artery walls (arterial or vascular calcification) are striking. In the late 20^th century, researchers found that bone matrix vesicles (mineral-laden particles involved in bone, cartilage, and tooth mineralization), bone morphogenic protein (a growth factor that promotes bone formation), and hydroxyapatite (an inorganic crystalline material composed mainly of calcium and phosphorus) were present in atherosclerotic plaques lining human arteries. This discovery led to the hypothesis that arterial calcification is upregulated by factors that drive bone demineralization.⁹⁶ The interplay between bone and artery mineralization is sometimes referred to as the “bone–vascular axis.”⁹⁷

Specialized vitamin K-dependent proteins in bone, such as osteocalcin and matrix Gla protein, are involved in tissue calcification. In addition to bone, matrix Gla protein is found in arterial, heart, kidney, lung, and a range of other tissues. These proteins are activated through a process involving vitamin K, which leads to calcium deposition in thebones and prevents arterial calcification.^97,98 Furthermore, vitamin K has anti-inflammatory effects that may help limit arterial calcification.⁹⁸ As a result, vitamin K deficiency can be linked to both osteoporosis and vascular calcification.⁹⁹

Other factors that could underlie the relationship between osteoporosis and cardiovascular disease include estrogen deficiency, vitamin D deficiency, inflammatory signaling, and dysbiosis.⁹⁵

Kidney Disease and Kidney Stones

Patients with chronic kidney disease (CKD) have an increased risk of osteoporosis and fracture. In fact, in those with CKD, hip fracture risk is 2–4 times higher, occurs at a younger age, and results in longer hospital stays and higher mortality risk than in those with normal kidney function. Notably, a significant proportion of CKD-related fractures occur in individuals without a DXA-based diagnosis of osteoporosis, suggesting kidney dysfunction impacts aspects of bone quality not reflected in BMD measurement.¹⁰⁰

Chronic kidney disease patients frequently experience metabolic acidosis due to the kidney’s compromised ability to excrete acid byproducts of metabolism. Metabolic acidosis triggers increased osteoclast activity and suppresses osteoblast activity, increasing bone breakdown and raising the availability of calcium in the blood, which helps buffer high acidity.¹⁰¹ Kidney dysfunction also results in mineral imbalance, with increased phosphorus retention and calcium loss, partly due to the kidney’s compromised ability to activate vitamin D. This leads to greater secretion of PTH, which stimulates calcium release from bone.¹⁰²

Kidney stones are hard deposits made of calcium and other minerals that form in the urinary tract. A meta-analysis of data from nine correlational studies with a total of 454,464 participants found that osteoporosis was more prevalent in people with kidney stones compared to those without kidney stones. The analysis also showed participants with osteoporosis had an increased risk of kidney stones compared to those without osteoporosis, suggesting these conditions have a reciprocal, or bidirectional, relationship.¹⁰³ Osteoporosis and kidney stones may be linked by shared pathways leading to high blood calcium levels, such as hyperparathyroidism.¹⁰⁴ Importantly, excess calcium and vitamin D levels may contribute to kidney stone risk in some individuals. Since virtually all patients with osteoporosis take calcium and vitamin D, periodic blood testing is prudent to ensure appropriate vitamin D and calcium status, especially in those with a history of kidney stones or who are otherwise at risk of kidney stones. Also, ensuring that calcium supplements are taken with meals, as opposed to apart from meals on an empty stomach, may mitigate kidney stone risk. This is because calcium that is part of a meal can bind dietary oxalate in the intestine, preventing its absorption and thereby reducing availability of this component of kidney stones.¹⁰⁵

Obesity and Type 2 Diabetes

Contrary to traditional beliefs about the protective effects of increased body weight on bone growth, obesity—especially visceral obesity—is now known to have damaging effects on bone quality. In fact, people with obesity have been found to have an increased fracture risk, often despite having normal BMD.^106,107 Some research indicates people with obesity have increased osteoporotic fracture risk at atypical sites such as the ankle, upper leg, and upper arm.¹⁰⁸ Factors linked to increased fracture risk in older subjects with obesity include chronic inflammatory status, altered secretion of adipokines (immune-regulating molecules [cytokines] produced by fat cells), vitamin D deficiency, insulin resistance, and reduced mobility.¹⁰⁷

In a meta-analysis of eight observational studies involving 671,532 postmenopausal women, those with obesity had an 18% increase in fracture risk overall, a 15% increase in vertebral fracture risk, no difference in hip and shoulder fracture risks, and a 42% lower risk of pelvic fracture (an uncommon site for osteoporotic fractures).¹⁰⁹ Furthermore, type 2 diabetes, a condition closely related to obesity, compromises bone remodeling, increasing bone fragility.¹¹⁰ Metabolic changes related to type 2 diabetes and obesity lead to increased intramuscular fat, which reduces stability and increases fall risk, and bone marrow fat, which impairs bone strength and increases fracture risk.^106,107

Cancer

Cancer-associated bone loss is driven by the disease itself and treatments used to manage it. Bone is a common site of cancer metastasis, resulting in bone destruction or pathological bone growth.¹¹¹ In addition, some cancers increase expression of RANKL, leading to increased osteoclast activity and bone resorption.¹⁶

Studies have found that cancer treatment is a leading cause of secondary osteoporosis, resulting in bone fragility, higher risk of fracture, and lower quality of life. Examples of cancer therapies known to negatively affect bone health include glucocorticoids, chemotherapies, androgen deprivation therapy (for treating prostate cancer), and aromatase inhibitors (for breast cancer).^112,113 Some observational data indicate that certain newer antitumor agents in the class of programmed death-ligand 1 (or PD-L1) inhibitors mayhave a neutral effect on BMD, but this needs to be studied further.¹¹⁴

Periodontal Disease

Good oral health has been correlated with higher bone density and lower risk of osteoporosis and fractures in older individuals.¹¹⁵ Periodontal disease is a serious inflammatory condition that affects the gums (gingivitis) and deeper tissues that support the teeth (periodontitis), including the alveolar bone. Bone destruction is part of osteoporosis and periodontal disease, and the two conditions share a number of risk factors, including aging, hormone imbalance, metabolic disorders, and lifestyle factors.¹¹⁶ A meta-analysis of 28 observational studies involving 19,611 participants found postmenopausal osteoporosis was strongly associated with periodontitis risk and severity.¹¹⁷ One reason may be that mandibular (jaw) bone loss, a common manifestation of osteoporosis, increases susceptibility to periodontitis.¹¹⁸

Osteoporosis is a “silent disease,” meaning there are typically no symptoms until a fracture occurs. In fact, many people are unaware they have osteoporosis prior to a fracture.¹⁸

Fragility Fractures

The most common symptom of osteoporosis is a skeletal fracture. People with osteoporosis may fracture a bone during a normal activity such as lifting a heavy object, bending over, opening windows, or even coughing. Minor falls that would not normally result in a broken bone can also cause a fracture for those with osteoporosis.¹⁸ Osteoporotic fractures due to mild traumas are known as fragility fractures.¹¹⁹

Loss of Height and Rounded Shoulders/Hunched Posture (Kyphosis)

Aging is associated with loss of height in part due to degeneration and flattening of the discs between spinal vertebrae, as well as weakening of core abdominal and back muscles.¹²⁰ Osteoporosis can cause vertebrae to slowly collapse and take on a wedge shape, adding to height loss and creating an exaggerated forward curvature in the upper spine known as kyphosis.¹¹⁹

Height loss and kyphosis are aggravated by osteoporosis-related vertebral compression fractures. While some vertebral fractures cause back pain, microfractures can occur with no symptoms. An osteoporotic compression fracture in one vertebra increases the risk of fracture in the adjacent vertebrae and may trigger an event called vertebral fracture cascade, which dramatically worsens kyphosis. Eventually, a rounded hump, called a hunchback or a dowager’s hump, may form on the upper back.¹¹⁹ This spinal deformity can be accompanied by increased instability and risk of falling, difficulty walking, neurological problems, and increased mortality risk.^119,121

Back Pain

Osteoporosis can cause acute or chronic back pain. Compression fractures in the spine can cause back pain ranging from generalized chronic pain to severe sudden pain near the fracture site.¹¹⁹ The most common location of vertebral compression fractures is at the junction of the thoracic and lumbar spinal regions (roughly near the waistline), but can occur anywhere in the spinal column. Back pain from a compression fracture characteristically worsens while sitting, standing, or changing positions, as well as sneezing or coughing, and is relieved from lying down.¹¹⁹

Tooth Loss

Osteoporosis has been linked to an increased risk of tooth loss. Bone loss in the jaw makes teeth more susceptible to detachment and loss.¹²² One observational study involving 74 women over 65 years of age found those with high fracture risk scores were 25% more likely to experience tooth loss during five years of monitoring. In addition, those with untreated or recently treated osteoporosis were four times more likely to have a higher number of lost teeth due to periodontal disease compared with those who had normal bone density or had been treated for osteoporosis for three years or longer.¹²³ Another study in 655 older women found vertebral fractures, but not other types of fractures, were associated with increased tooth loss at baseline and after an average of four years of follow-up.¹²⁴

The diagnosis of osteoporosis and assessment of future osteoporosis risk currently relies on BMD measurement.⁹ Guidelines from the Endocrine Society, U.S. Preventive Services Task Force (USPSTF), and others recommend BMD testing in women aged 65 years and older, as well as postmenopausal women under the age of 65 years with osteoporosis risk factors, to aid in osteoporosis diagnosis, fracture risk assessment, and osteoporosis treatment monitoring.^125-127 Guidelines for men are less consistent. For example, the Endocrine Society and the National Osteoporosis Foundation recommend BMD testing in men aged 70 years and older, as well as men aged 50–69 years with risk factors; however, the USPSTF does not offer recommendations for men due to lack of sufficient evidence of potential benefits outweighing potential harms.^125,128

However, most fragility fractures (which are definitively diagnostic for osteoporosis) occur in individuals with BMD scores that do not indicate osteoporosis.^129,130 Experts generally recommend a more comprehensive fracture risk assessment be performed for men and postmenopausal women aged 50 years and older to help identify those who might benefit from further investigation or preventive therapies.^125,128,131 Furthermore, evaluation for undiagnosed vertebral fractures using X-ray or DXA technology may be useful in patients with very low BMD, back pain, height decrease of 4 cm (about 1.5 inches) or more in a lifetime or 2 cm (about ¾ inch) or more during medical observation, glucocorticoid use, and/or advanced age.^6,129 Once osteoporosis has been diagnosed, biomarkers of bone turnover can be useful for monitoring progression and treatment response.¹³²

Tests for Measuring BMD

Dual-energy X-ray Absorptiometry

The most commonly used BMD test is dual-energy X-ray absorptiometry (DEXA or DXA). This technique uses X-rays to measure the calcium content in specific areas of bone in the hip, spine, and sometimes the wrist.⁹

In postmenopausal women and men aged 50 years and older, DXA measurements are used to derive a T-score. This score is a comparison of a person’s BMD to that of a healthy young adult. The lower the T-score, the higher the osteoporosis and fracture risk. A T-score is interpreted as follows^9,127:

• +1 to -1 indicates healthy bone
• -1 to -2.5 indicates the presence of osteopenia
• -2.5 or lower indicates an osteoporosis diagnosis
• -2.5 or lower plus a fragility fracture indicates established osteoporosis

Each 1-point drop in T-score is associated with a 1.5- to 2-fold increase in fracture risk.¹²⁷

Premenopausal women and men below the age of 50 years receive Z-scores instead of T-scores. A Z-score compares your BMD to the average BMD in people of the same age, sex, and ethnicity. A Z-score of -2.0 or less indicates low BMD and osteoporosis, likely caused by a medication or underlying condition.¹²⁷

Repeat DXA assessments are generally recommended at the following intervals for individuals with or at high risk for osteopenia or osteoporosis^6,131:

• One to two years after starting or changing medical therapy for osteoporosis
• Every two years for those with T-scores of -2.00 to -2.49 or for those at risk of ongoing bone loss due to hyperparathyroidism or glucocorticoid use
• Every three to five years for those with T-scores of -1.50 to -1.99 who are not at risk for accelerated bone loss
• Every five to 10 years for those with T-scores of -1.01 to -1.49 who are not at risk for accelerated bone loss and with a moderate absolute fracture risk
• Every 10 to 15 years for those with T-scores greater than -1.0 who are not at risk for accelerated bone loss and with a low absolute fracture risk

An earlier follow-up DXA may be advised if an individual’s fracture risk increases. The fracture risk assessment tool (or FRAX, described below) may be helpful in assessing the 10-year probability of fracture.¹³¹

Computed Tomography

Emerging evidence suggests BMD measurements from computed tomography (CT) are as accurate as DXA and can be used to detect osteopenia and osteoporosis.^133-135 CT scans are routinely performed as part of colorectal cancer screening (showing the bones of the hip) and evaluation of musculoskeletal problems such as shoulder and wrist fractures. BMD measurements from these scans could help identify individuals with osteoporosis who have not undergone DXA evaluation, potentially resulting in earlier diagnosis and treatment.^134,135

Heel Ultrasound

Quantitative ultrasound of the heel bone (calcaneus) is an alternative method of assessing bone density. A systematic review of 15 studies in postmenopausal women found heel ultrasound was well correlated with DXA.¹³⁶ Another systematic review that included studies in elderly subjects also found heel ultrasound to be a reliable measure of BMD and fracture risk.¹³⁷ However, more research is needed to fully validate heel ultrasound as a bone assessment tool and establish standards for osteoporosis diagnosis and fracture risk prediction.^136,137

Fracture Risk Assessment Tool

The Fracture Risk Assessment Tool (FRAX) is a scoring tool used to estimate a person’s 10-year fracture risk and inform treatment decisions. This score takes into account demographics (age, sex, and country), health information (BMI, smoking status, and alcohol use), medical risk factors (personal and family fracture history, causes of secondary osteoporosis, and glucocorticoid use), and BMD.⁹ The FRAX has been validated in numerous clinical studies and incorporated into guidelines worldwide.¹³⁰ Some studies have found FRAX scores calculated without BMD may still provide relevant information about fracture risk, although the importance of including BMD appears to increase with aging.^138,139

Bone Turnover Markers

Bone turnover markers are proteins produced during the bone remodeling process. Whereas changes in BMD occur over long periods of time, blood levels of bone turnover markers provide immediate information about bone activity and can be used to assess osteoporosis progression and monitor treatment.^132,140,141

Examples of bone turnover markers used to measure osteoblast activity (bone formation) include procollagen type 1 N-terminal propeptide (P1NP), bone-specific alkaline phosphatase (ALP), and osteocalcin. Markers of osteoclast activity (bone resorption) include tartrate-resistant acid phosphatase 5b (TRACP 5b), C- and N-terminal telopeptides of type I collagen (CTX and NTX), beta-CrossLaps (beta-CTX), pyridinoline, and deoxy-pyridinoline.^9,132

The primary goal of osteoporosis treatment is to prevent fractures.^12,142 In addition to diet and lifestyle interventions plus calcium and vitamin D supplements when appropriate, medications that limit bone breakdown or promote bone formation are recommended. These include bisphosphonates, monoclonal antibodies, parathyroid hormone-related drugs, and hormone and hormone-modulating therapies.^12,143

Bisphosphonates

Bisphosphonates inhibit bone resorption and are generally recommended as first-line treatment for primary osteoporosis in women and men.¹² Research shows bisphosphonate therapy increases BMD, reduces bone turnover marker levels, and can reduce vertebral fractures by 50–70%, non-vertebral fractures by 20–30%, and hip fractures by 40%.¹⁴²

Bisphosphonates used to treat osteoporosis include^12,144:

• Alendronate (Fosamax). Taken orally once daily or once weekly, alendronate reduces the risk of vertebral and hip fractures and decreases height loss due to vertebral fractures.
• Risedronate (Actonel). Taken orally once a day, once a week, or once a month, risedronate reduces the risk of vertebral and hip fractures.
• Ibandronate (Boniva). Taken orally once a day or once a month, or given as an intravenous injection every three months, ibandronate reduces the risk of vertebral fractures but has not been shown to reduce hip fractures.
• Zoledronic acid (Reclast). Given intravenously once a year over 15 minutes, zolendronic acid reduces the risk of vertebral and hip fractures. Extended dosing frequencies have also been explored. In a 10-year, double-blind, placebo-controlled trial of 1,054 women aged 50–60 years with lumbar-spine, femoral-neck, or total-hip T-scores between 0 and −2.5, intravenous zoledronic acid (5 mg) was given either at baseline and again at year five, only at baseline, or not at all. A new vertebral fracture occurred in 22/352 (6.3 %) women who received two doses and 23/351 (6.6 %) who received one dose, versus 39/351 (11.1 %) with placebo; the two-dose regimen reduced risk by 44 %, while the single dose showed a non-significant 41% reduction. The authors concluded that administering zoledronic acid at baseline and again five years later effectively prevented vertebral fractures in early postmenopausal women for at least a decade.¹⁴⁵
• Neridronate (Nerixia). This newer drug is a bisphosphonate derivative administered intravenously or intramuscularly every one to three months. Emerging research shows it can improve BMD and bone turnover marker levels in patients with osteoporosis from any cause, especially due to menopause.¹⁴⁶ However, its long-term effect on fracture risk has not been established.

Oral bisphosphonates are poorly absorbed and can cause gastrointestinal side effects like esophageal irritation and heartburn. Taking them first thing in the morning on an empty stomach with 8 ounces of plain non-carbonated water while in an upright position, and waiting 30–60 minutes before eating, taking other medications, or lying down, generally improves absorption and reduces side effects.¹⁴⁴

Research shows long-term use of bisphosphonates can suppress bone remodeling, leading to atypical femur fractures and, rarely, osteonecrosis (bone tissue death) of the jaw.¹⁴⁷ Therefore, their use is generally limited to three to five years. Further treatment may not be needed; however, if BMD deteriorates or a fracture occurs, returning to drug therapy may be recommended after a one- to five-year break.^142,144

Monoclonal Antibodies

Monoclonal antibodies that target protein regulators of bone remodeling are used in osteoporosis treatment.

Denosumab (Prolia) targets a protein called receptor activator of nuclear factor kappa B ligand, or RANKL. Because RANKL stimulates osteoclast activity, its inhibition by denosumab blocks bone resorption. It is recommended as second-line treatment for women and men who have contraindications to or experienced adverse side effects from bisphosphonates. Whether or not denosumab increases the incidence of osteonecrosis of the jaw is uncertain.¹²

Denosumab is administered as a subcutaneous injection once every six months. Its use has been associated with adverse side effect such as skin infection, eczema, and low blood calcium levels. In addition, bone loss, and the potential risk of a vertebral osteoporotic fracture, occurs rapidly after stopping denosumab; therefore, it should be replaced by another drug upon discontinuation.¹⁴⁴

Romosozumab (Evenity) is an anabolic agent that promotes bone formation by targeting the protein sclerostin. Because sclerostin suppresses osteoblast activity, blocking sclerostin leads to increased bone formation.¹⁴³ As of mid-2025, evidence shows romosozumab can benefit women with primary osteoporosis and a very high fracture risk.¹² Meta-analyses of randomized controlled trials have found treatment with romosozumab reduced fractures, particularly vertebral fractures, as well as or better than bisphosphonates.^12,148,149

Romosozumab is administered as a subcutaneous injection once per month for up to one year before switching to a bisphosphonate. Its use is limited to one year due to its association with increased incidence of cardiovascular and cerebrovascular events (eg, heart attack and stroke), as well as atypical femur fractures and osteonecrosis of the jaw.^12,143 Because rapid bone loss and a rebound increase in fracture risk may occur after stopping romosozumab, it is generally replaced with a bisphosphonate upon discontinuation.¹²

Parathyroid Hormone-Related Drugs

Parathyroid hormone-related drugs are anabolic agents, meaning they promote bone growth rather than inhibit resorption. They are administered as daily subcutaneous injections for up to two years prior to bisphosphonate therapy.¹⁴⁴

Teriparatide (Forteo), a recombinant human parathyroid hormone (PTH), activates osteoblasts, leading to increased bone growth.¹⁵⁰ Teriparatide has been found to benefit postmenopausal women with primary osteoporosis who have a very high fracture risk.¹² Meta-analyses of randomized controlled trials have shown teriparatide treatment reduces fracture risk and increases BMD more in the femoral neck, lumbar spine, and total hip compared with bisphosphonates.^151-153 Rapid bone loss can occur after stopping teriparatide; therefore, it is usually replaced with a bisphosphonate.¹²

Abaloparatide (Tymlos), a human PTH-related protein analog, stimulates bone formation through activating osteoblasts and their precursors.¹⁴³ A meta-analysis of eight randomized controlled trials found abaloparatide increased BMD and reduced vertebral fracture risk.¹⁵⁴ Another meta-analysis included four randomized controlled trials comparing abaloparatide to teriparatide. The analysis found abaloparatide increased BMD more than teriparatide and placebo and caused fewer adverse effects, but it was unclear whether it prevented fractures more effectively than teriparatide.¹⁵⁵

PTH-related drugs have been reported to cause adverse side effects such as nausea, dizziness, vomiting, headache, palpitations, and leg cramps.¹² Their use is restricted to a maximum of two years, partly due to evidence from animal studies showing a possible increased incidence of a bone cancer called osteosarcoma.¹⁴³

Women—Menopausal Hormone Therapy

Estrogen has both antiresorptive and anabolic effects on bone.^33,156 Estrogen therapy is important for preventing osteoporosis and other chronic health problems in women who have lost ovarian function before age 40 years and is generally prescribed until the average age of natural menopause.¹⁵⁷ Postmenopausal women using estrogen therapy to manage symptoms such as hot flashes and vaginal dryness also have reduced bone loss and decreased fracture risk, and these bone benefits may be greater when therapy is initiated before the age of 60 years or within 10 years of menopause and combined with calcium and vitamin D supplementation.^156,158,159 Because long-term postmenopausal estrogen therapy is associated with increased cardiovascular and breast cancer risks, it is not recommended solely for osteoporosis prevention; however, it remains an option for osteoporosis prevention (but not treatment) in postmenopausal women who cannot use other bone-specific drugs.^143,144,159

Low- and ultra-low-dose transdermal (topical) and vaginal estrogen formulations are frequently prescribed for managing menopausal symptoms and are safer than standard-dose oral estrogens.¹⁵⁸ Clinical trials have indicated low-dose transdermal (25 mcg per day) and oral (0.5 mg per day) estradiol (a bioidentical type of estrogen) can provide sufficient bone loss prevention. While 14 mcg per day (considered an ultra-low dose) of transdermal estradiol has also demonstrated positive effects on bone, it is unclear whether this dose provides sufficient protection against bone loss.¹⁶⁰

It is important to note that women with an intact uterus (who have not had a hysterectomy) should use progesterone or a progesterone-like drug in conjunction with estrogen therapy to prevent endometrial cancer.¹⁵⁸ Women who have undergone a hysterectomy may elect to use progesterone for symptom relief. For more information about menopausal hormone therapy, please see the Menopause & Perimenopause protocol.

Men—Testosterone

Testosterone plays an important role in maintaining bone health in men through direct effects and indirectly through its conversion to estrogen.³⁴ Testosterone levels diminish gradually with aging and many older men develop testosterone deficiency, a condition referred to as age-related hypogonadism.¹⁶¹ Hypogonadism can also be a side effect of a number of medications, including drugs used to treat prostate diseases and glucocorticoids.¹⁶² Chronically low testosterone levels result in decreased BMD and increased fracture risk, and have detrimental impacts on muscle and other tissues in the body.¹⁶¹

Testosterone replacement therapy (TRT) is generally used to treat symptoms of hypogonadism and may have bone-protective effects in men with this condition. The potential benefits of TRT in aging men without frank hypogonadism are less certain.³⁶ Although evidence is mixed, some clinical trials investigating the effects of TRT on bone density in men have shown benefits, but the effects are stronger in men with low baseline testosterone levels and osteopenia or osteoporosis.³⁴ Testosterone replacement therapy has so far not been conclusively shown to prevent falling or fractures.^34,161 First-line osteoporosis therapies are therefore recommended for men with a high fracture risk and may be used in conjunction with TRT in those who also have symptomatic hypogonadism.³⁶ For more information about testosterone replacement therapy, please see the Male Hormone Restoration protocol.

Novel and Emerging Interventions

Pyridoxamine

Advanced glycation end products (AGEs), which can accumulate in bone tissue with aging and in those with diabetes, are a risk factor for osteoporosis. AGEs have been shown to exert proinflammatory effects and negatively affect bone microarchitecture, induce cell death in osteoblasts, and alter bone resorption and formation.^163-166

Pyridoxamine is a form of vitamin B6 that is known to inhibit AGE formation.^167,168 A double-blind controlled trial enrolled 55 older women with type 2 diabetes and randomized them to receive either 200 mg pyridoxamine twice daily or placebo for one year. BMD at the femoral neck increased and hemoglobin A1c (HbA1c) (a marker of long-term blood glucose control) decreased in the pyridoxamine group compared with the placebo group. In addition, treatment with pyridoxamine increased levels of a bone formation marker (P1NP) by 18.9% compared with placebo, a difference that was near statistical significance. However, there was no change in bone resorption markers or skin autofluorescence (a measure of AGEs in the skin).¹⁶⁹ Additional studies are required to further characterize the benefits of pyridoxamine on bone health.

Calcium & Vitamin D

Reported Dosage: 800–4,000 IU (10–100 mcg) vitamin D and 1,000–1,200 mg calcium daily

Adequate calcium is needed for normal bone mineralization, and vitamin D is a key regulator of calcium metabolism. Deficient calcium intake can result in bone demineralization, increasing osteoporosis and fracture risk.¹⁸ Vitamin D deficiency is also a risk factor for osteoporosis and fractures.^18,170 The Endocrine Society Guidelines recommend maintaining 25-hydroxyvitamin D levels of ≥20 ng/mL for maximum bone health.¹⁷⁰ Other researchers have concluded that 20–30 ng/mL may be optimal.¹⁷¹ While much higher levels may be safe, it is possible that levels ≥50 ng/mL may cause harm by elevating blood calcium levels.¹⁷¹

Although maintaining healthy calcium intake and avoiding vitamin D deficiency are important for bone health, clinical trials examining the usefulness of supplementing with these nutrients have yielded mixed results. In a meta-analysis of data from 19 randomized controlled trials involving a total of 69,234 elderly participants with osteoporosis, the combination of calcium plus vitamin D increased BMD and reduced the rate of fractures by 6%, but had no effect on mortality.¹⁷² Another meta-analysis that included data from seven randomized controlled trials with a total of 12,620 subjects over 65 years of age found 800 IU (20 mcg) vitamin D3 plus 1,200 mg calcium daily reduced hip fractures by 31% and non-vertebral fractures by 20%, but the same amount of vitamin D3 with only 1,000 mg of calcium had no effect on hip fractures.¹⁷³ On the other hand, a meta-analysis of 18 trials with a total of 39,759 elderly subjects who had experienced an osteoporotic fracture found treatment with calcium, vitamin D, or both had no effect on fracture risk compared with placebo or no treatment.¹⁷⁴ Furthermore, a secondary analysis of data from a randomized controlled trial involving 25,871 American adults (men aged 50 years and older and women aged 55 years and older) found 2,000 IU (50 mcg) vitamin D3 daily had no effect on risk of total, nonvertebral, or hip fractures after a median of 5.3 years of monitoring. The analysis also showed that neither having low baseline vitamin D levels nor taking calcium supplements in addition to vitamin D changed the lack of effect from supplementation.¹⁷⁵

Future research may help clarify whether the inconsistencies in findings from clinical trials are due to differences in vitamin D and calcium doses, baseline vitamin D levels, genetic factors affecting vitamin D receptors, or other factors affecting bone health.^176-178

Vitamin K

Reportage Dosage: K1: 30 – 5,000 mcg daily, MK-4: 45 mg daily, and MK-7: 100–375 mcg daily

Vitamin K is a fat-soluble nutrient that has a critical role in bone health through its ability to activate osteocalcin and matrix Gla protein, which help mineralize the bone matrix. When activated by vitamin K-dependent enzymes, osteocalcin efficiently deposits calcium in bone and matrix Gla protein helps keep calcium from building up in the arteries. Thus, adequate levels of vitamin K are essential for keeping calcium in the bones and out of the arteries where it can cause harm. Vitamin K also decreases bone resorption by inhibiting RANKL signaling.^99,179-181

There are two forms of vitamin K: vitamin K1, known as phylloquinone, and vitamin K2, called menaquinone (MK). Vitamin K1 is mainly found in leafy greens and algae, while K2 is made by bacteria and is found in meat, cheese, and certain fermented foods. Vitamin K2 is also made by gut bacteria.^182,183 Some clinical trials have indicated vitamin K2 plays a larger role in bone health than K1, and vitamin K requirements may vary based on age, gender, diet, and the presence of chronic health conditions.¹⁸² A form of vitamin K2 called menaquinone-7 (MK-7) is thought to be the most bioavailable form of vitamin K in humans.^184,185 Dosages of vitamin K1 used in studies that have evaluated outcomes or biomarkers related to bone health range from about 30 mcg to 5,000 mcg daily, whereas dosages for vitamin K2 range from about 90 mcg to 45,000 mcg (45 mg).¹⁸⁶

In an observational study in 71 patients who underwent spinal surgery due to vertebral osteoporosis and degenerative disease, the addition of 45 mg of vitamin K2 per day to calcium (1,200 mg daily) plus vitamin D3 (250 IU [6.25 mcg] daily) therapy for six months was associated with higher levels of P1NP (a marker of bone formation) at three months and better surgical outcomes at six months than calcium plus vitamin D3 alone. Those who received vitamin K2 also had higher BMD at six months than those who did not receive K2; however, this difference was not statistically significant, partly due to the short timeline.¹⁸⁷

Evidence from clinical trials has been mixed. Some studies have shown that vitamin K supplementation reduces fracture risk, whereas others have not.¹⁸⁸ A meta-analysis of data from nine randomized controlled trials involving a total of 6,853 postmenopausal women found vitamin K2 supplementation increased spine and wrist BMD and raised levels of activated osteocalcin.¹⁸⁹ Another meta-analysis pooled findings from 16 randomized controlled trials that included a total of 6,425 postmenopausal women with osteoporosis. The analysis found vitamin K2, alone or in conjunction with other therapies (calcium and/or vitamin D or a bisphosphonate) and usually as menaquinone-4 (MK-4) at a dose of 45 mg daily, improved BMD in the lumbar spine, but not in the hip, femoral neck, or forearm. The analysis also found a 57% reduction in fracture risk when vitamin K2 was included in treatment, but the study authors cautioned against drawing conclusions because only five trials had data to contribute to this finding.¹⁹⁰

MK-7 has been studied for its potential role in bone loss prevention. In a randomized controlled trial involving 244 healthy postmenopausal women, 180 mcg of MK-7 per day for three years reduced the age-related decline in bone density in the spine and femoral neck, though not in the hip overall.¹⁹¹ Another trial in 148 postmenopausal women with osteopenia found the addition of 375 mcg of MK-7 daily decreased age-related changes in bone microarchitecture compared with placebo after one year.¹⁹² However, in another trial conducted by the same research team that included 142 women with osteopenia receiving 800 mg calcium and 1,520 IU (38 mcg) vitamin D daily, the addition of 375 mcg MK-7 daily did not improve bone microarchitecture, BMD, or levels of markers of bone turnover compared with placebo after three years.¹⁹³ In a retrospective cohort of 77 adults (94% women, 81% postmenopausal; 38% had failed or stopped bisphosphonates), daily supplementation for 12 months with 2,000 IU (50 mcg) vitamin D3, 100 mcg vitamin K2 (as MK-7), 680 mg strontium citrate, 25 mg elemental magnesium (form not specified), and 250 mg DHA was evaluated. Dietary advice regarding sources of calcium and encouragement to engage in impact exercise was provided as well. Mean BMD rose significantly at several sites including the femoral neck, hip, and spine; the improvements matched or exceeded those reported for bisphosphonates or strontium ranelate. Interestingly, although this study included only five men, improvements in BMD were greater in the men than in the women. No fragility fractures occurred during the study. This study was limited by its lack of a control group and relatively short follow-up duration.¹⁹⁴

Because vitamin K and calcium work together, a meta-analysis examined the effect of co-supplementation with these nutrients. The analysis included 10 randomized controlled trials with 1,346 participants and found vitamin K plus calcium improved BMD at the lumbar spine, but not other sites, compared with either nutrient alone or placebo. In addition, stronger effects were seen in trials using K2 versus K1 and those using >1,000 mg versus ≤1,000 mg of calcium per day.¹⁸⁶

Isoflavones

Reported Dosage: 40–300 mg daily

Isoflavones are compounds found mostly in soybeans that belong to the family of phytoestrogens—plant chemicals that weakly activate estrogen receptors.¹⁹⁵ In an observational study that followed 48,584 postmenopausal women (average age 61.4 years) for a median of 10.1 years, higher intake of soy isoflavones (>42 mg vs. <18.7 mg daily) was associated with a 28% lower risk of fracture among participants with a history of a prior fracture, and the effect was stronger in women who were less than 10 years past menopause.¹⁹⁶ An observational study that followed 61,025 men, aged 40 years and older, for a median of 9.5 years found those with the highest intake of soy isoflavones (>45.2 mg daily) had a 27% lower risk of fracture compared to those with the lowest intake (<21.7 mg daily).¹⁹⁷

A systematic review and meta-analysis of 63 randomized controlled trials involving 9,026 postmenopausal women showed that isoflavones have a positive impact on BMD in the lumbar spine, femoral neck, and distal radius (wrist). The analysis further showed isoflavones were effective for raising BMD when used at doses providing at least 50 mg per day of the soy isoflavone genistein and for a duration of at least one year.¹⁹⁸ In a meta-analysis of 18 randomized controlled trials involving a total of 2,350 postmenopausal women, treatment with isoflavones (40–300 mg daily for six to 24 months) was found to moderately improve lumbar spine, femoral neck, and total hip BMD measurements. Overall, the effects appeared to be enhanced with longer duration of treatment.¹⁹⁹ However, a meta-analysis of data from 20 randomized placebo-controlled trials with more than 2,000 participants found soy isoflavones, at doses ranging from 30.9 mg to 300 mg daily for a duration of three to 24 months, improved levels of bone turnover markers in postmenopausal women, but the effects were not statistically significant.²⁰⁰

Magnesium

Reported Dosage: 105–315 mg daily

Magnesium is a cofactor in more than 600 enzymatic systems throughout the body.²⁰¹ Circulating magnesium also helps regulate calcium levels by supporting normal function of the parathyroid gland as well as vitamin D.²⁰¹ Roughly 50–60% of the body’s magnesium is found in the bones.²⁰²

A systematic review and meta-analysis of 11 observational studies involving a total of 92,170 participants aged 60 years and older found higher magnesium intake was associated with increased BMD in the femoral neck and total hip.²⁰³ Another systematic review and meta-analysis included data from four large studies with 119,755 participants and found individuals with the lowest blood magnesium levels had a 58% higher fracture risk than those with the highest levels.²⁰⁴

One study considered the magnesium intake and magnesium depletion scores—a number based on the use of medications that deplete magnesium (PPIs and diuretics), heavy alcohol consumption, and impaired kidney function—of 14,566 U.S. adults who were followed for 13 years as part of the National Health and Nutrition Examination Survey. The study found, among individuals aged 55 years and older, increasing magnesium intake was associated with reduced risk of osteoporosis. However, in women, this relationship was only seen in those with low magnesium intake (below approximately 332.5 mg per day); whereas in men, the relationship persisted at magnesium intakes well above recommended levels. In addition, higher magnesium depletion scores were associated with higher risk of osteoporosis in older participants, especially in those with low magnesium intake. The study authors concluded that magnesium intake and depletion scores should be considered for the most accurate assessment of risk.²⁰⁵

A large study that followed 73,684 postmenopausal women from the Women’s Health Initiative Study for an average of 7.6 years found, while increased magnesium intake was correlated with higher BMD, it was not associated with reduced fracture risk. In fact, women with higher magnesium intake had more falls and wrist or lower arm fractures, possibly due to being more physically active.²⁰⁶

It is worth noting that many Americans do not get the recommended daily amount of magnesium (320 mg for women and 420 mg for men) from diet alone. A report published by the U.S. Department of Agriculture estimated daily magnesium intake to be around 250–350 mg in adults who did not take magnesium supplements.²⁰⁷

Evidence from randomized trials of magnesium supplementation for bone health have been somewhat mixed but seem generally promising. In a controlled trial that included 20 postmenopausal women, 1,830 mg of magnesium citrate (about 293 mg elemental magnesium) per day for 30 days effectively suppressed bone turnover markers.²⁰⁸ In contrast, in a short-term study involving young women, aged 20–28 years, supplementation with about 583 mg of magnesium hydroxide (245 mg elemental magnesium) daily for 28 days did not affect markers of bone turnover.²⁰⁹ Interestingly, a similar study in young men aged 27 to 36 years found that 30 days of magnesium supplementation decreased markers of bone turnover.²¹⁰ In an open controlled trial in 54 postmenopausal women, those who received 250–750 mg of magnesium hydroxide (105–315 mg elemental magnesium) per day for six months followed by 250 mg of magnesium hydroxide (105 mg elemental magnesium) per day for another 18 months had increased BMD after one year that stabilized in the second year, while those who did not receive magnesium experienced bone loss during the two-year trial.²¹¹ However, in a randomized placebo-controlled trial involving 78 men and women with overweight or obesity, the combination of 360 mg of magnesium glycinate (about 51 mg elemental magnesium) plus 1,000 IU (25 mcg) vitamin D3 daily for 12 weeks did not alter levels of bone turnover markers.²¹²

Zinc

Reported Dosage: 15–50 mg daily

Zinc is an essential trace mineral that is well known for its role in bone growth, development, and maintenance. More than 85% of the body’s zinc is found in bone and skeletal muscle tissue, where it has been shown to promote osteoblast formation and inhibit osteoclast activity—possibly in part by influencing key signaling pathways involving RANKL.^213,214

An observational study that included data from 2,895 subjects aged 40 years and older participating in the ongoing National Health and Nutritional Examination Survey found higher blood levels of zinc were correlated with greater BMD at the spine and femur and higher zinc intake levels were correlated with higher femoral BMD. The study also found those who had higher levels of three zinc parameters (zinc levels, zinc intake from food, and total zinc intake [from food and supplements]) were less likely to have experienced a fracture.²¹⁵

A meta-analysis of 40 observational studies evaluated the relationships between zinc intake and blood levels with BMD and bone turnover markers in older individuals. Overall, the data showed people with osteoporosis had lower blood zinc levels than those without osteoporosis; low dietary zinc intake was associated with increased fracture risk; and zinc supplementation was linked to improved osteocalcin and ALP levels as well as increased femoral neck BMD.²¹⁶ Furthermore, a review of 16 observational studies and clinical trials found insufficient zinc intake (< 3 mg daily) may be a risk factor for osteoporosis and fracture, while supplementing with 40–50 mg per day may help maintain BMD, suppress bone loss, and improve healing of fractures, particularly in those with low dietary zinc intake.²¹³

An uncontrolled trial in 122 zinc-deficient patients aged 65 years or older being treated for osteoporosis found 25 mg of zinc twice daily for one year raised blood zinc levels, improved bone turnover marker levels, and increased BMD.²¹⁷ In a controlled trial in 59 postmenopausal women with an average age of 66 years, daily supplementation with 1,000 mg of elemental calcium plus a combination of 15 mg of zinc, 2.5 mg of copper, and 5 mg of manganese for two years prevented loss of bone density in the lumbar spine compared with placebo, while neither calcium plus placebo nor the micronutrient combination plus placebo had a significant effect relative to placebo alone.²¹⁸ However, a placebo-controlled trial in 224 postmenopausal women receiving 600 mg of calcium daily found adding 12 mg of zinc plus 2 mg of copper daily for two years increased BMD only in women whose daily dietary zinc intake was < 8 mg. In fact, women whose daily zinc intake from food was ≥ 8 mg experienced a decrease in BMD compared with placebo.²¹⁹

Omega-3 Fatty Acids

Reported Dosage: 1,000 mg daily (EPA: 333–465 mg, DHA: 375–667 mg)

Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are found in high amounts in fish oil, and alpha-linolenic acid (ALA), which is found in high amounts in flaxseed oil, can reduce inflammation and may protect against disease-related calcification in blood vessels and tumors. At the same time, omega-3 fatty acids appear to promote bone mineralization and may help reduce osteoporosis and fracture risks.²²⁰ In fact, higher fish or omega-3 fatty acid consumption and higher blood omega-3 fatty acid levels have been associated with higher BMD and lower risk of osteoporosis in observational studies.^221-223 In a study based on data from 441,756 subjects who had never had a fracture at baseline, those who reported regularly using fish oil supplements had a 15% reduced risk of vertebral fracture, 25% reduced risk of hip fracture, and 7% reduced risk of any type of fracture than those who did not use fish oil during a median of 8.1 years of monitoring.²²⁴ Furthermore, a meta-analysis of findings from nine observational studies with a total of 292,657 participants found higher blood levels of omega-3 fatty acids were linked to a 12% reduction in hip fracture risk.²²⁵

Clinical trials investigating the effects of omega-3 fatty acid supplementation on markers of bone health have yielded mixed results. A meta-analysis that included 12 randomized controlled trials with a total of 780 participants found omega-3 fatty acid supplementation significantly reduced levels of type 1 collagen crossed-linked C-terminal peptide (CTX), a marker of bone resorption, and increased BMD. The effects were more pronounced in studies wherein the participants were postmenopausal women, the duration was less than six months, and treatment was with ALA. Postmenopausal women who received omega-3 fatty acids also displayed a significant decrease in levels of type 1 collagen crossed-linked N-terminal peptide (NTX), another marker of bone resorption.²²⁶ A systematic review and meta-analysis that included findings from 19 randomized controlled trials in a total of 2,546 subjects found treatment with omega-3 fatty acids had no effect overall on lumbar or femoral BMD or on levels of markers of bone turnover, calcium metabolism, and inflammation. Nevertheless, certain subgroups appeared to benefit: in women, people under the age of 60, and subjects in studies performed in Eastern countries, femoral neck BMD was increased after omega-3 fatty acid therapy.²²⁷

Large trials have found that relatively modest dosages of omega-3 supplementation do not reduce fracture risk. For example, in the DO-HEALTH trial, 1 gram of omega 3 fatty acids (333 mg EPA and 667 mg DHA) alone or in combination with 2,000 IU (50 mcg) of vitamin D per day had no effect on vertebral fracture risk over a three-year period in generally healthy European adults.²²⁸ This same trial found that omega-3 fatty acids had no effect on hip or spine BMD compared with placebo.²²⁹ In the VITAL trial, which randomized over 25,000 adults to receive 1 gram/day of marine omega-3 fatty acids (Omacor) alone or in combination with 2,000 IU (50 mcg) of vitamin D, or placebo, fish oil supplementation did not reduce the risk of incident fractures over a median follow-up of 5.3 years compared with placebo.¹⁷⁵

Specialized pro-resolving mediators (SPMs) are compounds made in the body from omega-3 fatty acids. SPMs play a key role in resolving inflammation and clearing away cellular debris following the acute inflammatory response.²³⁰ Resolvin E1 (RvE1) from EPA and maresin 1 (MaR1) from DHA are examples of SPMs that have been studied for their potential role in bone preservation. Preclinical studies suggest MaR1 can stimulate osteoblast proliferation and RvE1 can inhibit osteoclast formation and maturation by reducing RANKL release.^231-233 Clinical trials involving human subjects are needed to clarify SPMs’ possible role in preserving bone health.²³⁴

Vitamin E

Reported Dosage: 400 IU mixed tocopherols daily; 300–600 mg tocotrienols daily

Vitamin E is a fat-soluble vitamin found mainly in nuts, seeds, and oils. There are eight forms of vitamin E—four tocopherols and four tocotrienols—but alpha-tocopherol is the most active form in the body and is required to prevent deficiency.²³⁵ Many vitamin E supplements contain exclusively alpha-tocopherol; however, tocotrienols have emerged as potential anti-osteoporosis agents, with bone supportive effects related to their strong antioxidant and anti-inflammatory properties.^236-238 Preclinical research has shown tocotrienols increase osteoblast numbers and suppress osteoclast formation.^237,239 Rich sources of tocotrienols include annatto beans, palm oil, rice bran, coconut oil, and barley.²³⁶

Observational studies have correlated low vitamin E intake and low blood alpha-tocopherol levels with low BMD in older people.^240-242 In addition, a meta-analysis of observational studies that evaluated the effects of vitamins A, C, and E on fracture risk found higher vitamin E intake was associated with a 34% reduced risk of fractures.²⁴³

In a randomized controlled trial in 52 postmenopausal women with osteopenia, those who received 400 IU of mixed tocopherols daily for 12 weeks had stable blood levels of the bone resorption marker C-terminal telopeptides of type I collagen (CTX), while CTX levels increased by 35.5% in the placebo group.²⁴⁴ A randomized placebo-controlled trial in 87 postmenopausal women with osteopenia found supplementing with annatto seed oil, providing either 300 mg or 600 mg of tocotrienols daily for 12 weeks, improved urine and blood levels of bone turnover markers, as well as blood levels of the regulatory proteins RANKL and OPG. There were no significant differences in the effects of the two doses.²⁴⁵

Vitamin C

Reported Dosage: 100–1,000 mg daily

Vitamin C (ascorbic acid) has anti-inflammatory and antioxidant properties and is needed for collagen formation. Furthermore, vitamin C alters epigenetic programming leading to increased osteoblast formation and function, greater bone formation, and enhanced mineralization.²⁴⁶

A number of observational studies have indicated lower dietary intake and blood levels of vitamin C were correlated with lower BMD.²⁴⁷ One study included 994 postmenopausal women, 277 of whom reported regularly supplementing with vitamin C at daily doses ranging from 100 mg to 5,000 mg (average daily dose 745 mg). The study found BMD levels overall were about 3% higher in vitamin C users than non-users. The relationship was stronger in women who also used estrogen therapy, and strongest in those who used vitamin C, estrogen therapy, and calcium supplements.²⁴⁸

Most clinical trials investigating the effect of vitamin C supplementation on bone health have had positive results. In one randomized controlled trial in 90 elderly men and women, 400 IU of vitamin E plus 1,000 mg of vitamin C for 12 months reduced hip, but not lumbar spine, BMD loss compared with placebo; however, 400 IU of vitamin E plus 500 mg of vitamin C did not show a protective effect.²⁴⁹ Another trial that included 34 postmenopausal women found those assigned to either an exercise program, supplementation with 280 mg of synthetic alpha-tocopherol plus 1,000 mg of vitamin C daily, or both had no change in BMD while those assigned to no exercise and a placebo had diminished BMD after six months.²⁵⁰

Vitamin C has also been studied as part of a more comprehensive supplement program in people with osteopenia. In one trial, 40 women with osteopenia who had never been treated with estrogen therapy were assigned to receive either 1,000 mg calcium plus 250 IU (6.25 mcg) vitamin D daily or the same calcium plus vitamin D plus collagen-supportive nutrients (500 mg vitamin C, 75 mg vitamin B6, and 500 mg proline) daily. Those who received calcium plus vitamin D alone continued to lose bone at the lumbar spine and hip, but those who received calcium, vitamin D, and collagen-supportive nutrients had no further BMD loss.²⁵¹ In another trial in 44 postmenopausal women with osteopenia being treated with 500 mg calcium plus 400 IU (10 mcg) vitamin D twice daily, those who received an antioxidant combination with 30 mg vitamin C, 5 mg vitamin E, 2.75 mg selenium, and 300 mg lipoic acid daily for one year had increased BMD as measured by heel ultrasound compared with those who did not.²⁵²

Curcumin

Reported Dosage: 80-1,000 mg daily

Curcumin is a well-studied carotenoid extracted from turmeric. Through its antioxidant and anti-inflammatory effects, curcumin may also influence bone remodeling by increasing bone formation by osteoblasts and suppressing bone resorption by osteoclasts.^253,254

In a randomized controlled trial, 60 postmenopausal women with osteoporosis taking 1,000–1,500 mg of calcium carbonate daily received either alendronate plus 110 mg of curcumin per day, alendronate alone, or no additional treatment for 12 months. Those who received alendronate plus curcumin had more improvement in levels of bone turnover markers and BMD measurements compared with those who received alendronate alone or no treatment.²⁵⁵ In a small controlled clinical trial, 57 women with low bone density receiving standard care were given 1,000 mg curcumin daily for 24 weeks or no additional treatment. Ultrasound measures of bone density increased 21% in the heel, 7.1% in the finger, and 4.8% in the upper jaw in the group receiving standard care plus curcumin, while these measures were unchanged in the group receiving standard care alone.²⁵⁶ A randomized controlled trial enrolled 120 postmenopausal women, aged 50–65 years, with osteopenia or osteoporosis being treated with alendronate, 500 mg calcium per day, and 400 IU (10 mcg) vitamin D per day. In addition, they received either 80 mg per day of nanomicelle curcumin (a highly absorbable form), 1,000 mg per day of black cumin (Nigella sativa) seed oil, curcumin plus black cumin seed oil, or placebo for six months. The curcumin plus black cumin seed oil group had a greater decrease in levels of a marker of bone breakdown compared with the other groups.²⁵⁷

Resveratrol

Reported Dosage: 150–500 mg daily

Resveratrol is an antioxidant compound in the polyphenol family and is found in peanuts, berries, red grape skins, and red wine.²⁵⁸ It may be best known for its antiaging and cardioprotective properties, but has also demonstrated bone-protective effects in a number of studies using animal models of aging, estrogen depletion, and various causes of secondary osteoporosis.^258-260 Multiple mechanisms may contribute to resveratrol’s ability to mitigate bone resorption, including reducing inflammatory signaling, decreasing oxidative stress, suppressing the RANKL pathway and osteoclast formation, stimulating osteoblast formation, and modulating estrogen receptor activity.²⁶¹ Furthermore, resveratrol has been shown to enhance the growth and diversity of beneficial bacteria in the gut microbiome.²⁶²

In a randomized, placebo-controlled, crossover trial in 125 postmenopausal women, lumbar spine and femoral neck BMD increased and levels of the bone resorption marker CTX decreased more after 12 months of treatment with 75 mg of resveratrol twice daily than placebo. The degree of improvement with resveratrol was greater in women with lower markers of bone health at baseline and those who took vitamin D and calcium supplements.²⁶³ A randomized controlled trial that included 66 middle-aged men with obesity found 16 weeks of treatment with 1,000 mg per day of resveratrol increased blood levels of bone ALP, a measure of bone formation, and lumbar spine (but not hip) BMD significantly compared with placebo. While a lower dose of 150 mg resveratrol daily also led to improvements in bone ALP levels and lumbar spine BMD, the effects of this dose were not statistically significant compared with placebo.²⁶⁴ In a randomized controlled trial involving 192 people with type 2 diabetes, BMD and bone mineral content stabilized in those who received 500 mg of resveratrol daily for six months but diminished in those who received placebo. A subgroup analysis showed the effect was stronger in alcohol drinkers and those with lower baseline calcium and 25-hydroxyvitamin D levels.²⁶⁵

Quercetin

Reported Dosage: 500 mg daily

Emerging research suggests the flavonoid quercetin, abundant in several fruits and vegetables such as apples and onions, can promote bone health. A double-blind, randomized, controlled trial in 33 healthy postmenopausal women found that taking 500 mg quercetin once daily for 90 days raised levels of bone-formation markers: osteocalcin rose by 21% and P1NP rose by 29%. Quercetin also lowered the pro-resorptive cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha, indicating a shift in bone turnover despite unchanged BMD over the short study period. Interestingly, this trial also showed a 39% rise in CTX in the quercetin group that remained within optimal ranges, suggesting that quercetin may have promoted the overall bone remodeling process via increased resorption and rebuilding. Larger and longer trials are needed to determine whether quercetin supplementation can reliably increase BMD.²⁶⁶

Supporting these clinical signals, a 2020 systematic review of 19 animal studies showed that oral administration of quercetin or its derivatives (at widely varying dosages) for 4 12 weeks consistently improved trabecular BMD, bone strength, and serum osteocalcin while lowering CTX, with no toxicity observed.²⁶⁷ Several studies have demonstrated that quercetin can ameliorate bone loss in ovariectomized rats, a common model for postmenopausal osteoporosis. For instance, quercetin was shown to modulate the intestinal flora and reduce inflammatory signaling, leading to improved bone strength and prevention of ovariectomy-induced bone loss.²⁶⁸

At the molecular level, quercetin stimulates Wnt/beta-catenin and BMP/Smad pathways, upregulates RUNX2 and ALP in osteoblasts, and inhibits osteoclast differentiation through blockade of RANKL, MAPK and nuclear factor-kappa B signaling.²⁶⁹

Collectively, the concordance between short-term human biomarker improvements and robust preclinical gains in density, architecture, and strength suggests quercetin may hold some promise as an adjunct intervention for maintaining bone health.

Berberine and Hops

Reported Dosage: Berberine 200 mg daily; Hops 400 mg daily: 8-PN 100 mcg daily

Berberine is a phytochemical derived from herbs such as Chinese goldthread (Coptis chinesis), Oregon grape (Berberis aquifolium), and goldenseal (Hydrastis canadensis).²⁷⁰ Berberine has anti-inflammatory and antimicrobial effects and has been shown to improve digestive disorders and metabolic diseases.^271,272 Preclinical studies suggest berberine can enhance osteoblast proliferation and inhibit osteoclast production to promote bone regeneration. Furthermore, berberine can inhibit RANKL-induced osteoclast development by disrupting activity between the ligand and its receptor.²⁷¹

The hop plant (Humulus lupulus) has long been used by humans for medicinal purposes and as an ingredient in beer. Studies have investigated whether 8-prenylnaringenin (8-PN), a strong phytoestrogen extracted from hops, may help treat osteopenia and osteoporosis.^273,274 In preclinical research, 8-PN has been found to enhance osteoblast growth and maturation while inhibiting osteoclasts more than phytoestrogens from soy, and increase BMD in animal models of estrogen depletion.²⁷³

Two small, randomized, controlled trials were conducted in 33 and 45 postmenopausal women with metabolic syndrome who were instructed to eat a Mediterranean-style, low-glycemic load diet and engage in aerobic exercise. In addition, about half of the participants in each trial received a multi-nutrient intervention consisting of hops extract (rho iso-alpha acids, 200 mg), berberine (100 mg), vitamin D3 (500 IU [12.5 mcg]), and vitamin K1 (500 mcg) twice daily, while the rest received a placebo. Both trials found, after 14 weeks, the women who received hops, berberine, vitamin D, and vitamin K had greater improvements in bone biomarkers than those who received placebo.^275,276 Another randomized controlled trial examined the effect of hops alone in 100 postmenopausal women with osteopenia being treated with 1,000 mg calcium and 400 IU (10 mcg) vitamin D3 daily. The trial found those who received a hops extract providing 100 mcg of 8-PN per day had increased total body BMD compared with those who received placebo after 48 weeks.²⁷⁷ In a two-year trial, 31 postmenopausal women consumed 330 mL of hops-containing alcoholic beer per day, 660 mL of hops-containing non-alcoholic beer per day, or no hops-containing or alcoholic beverages. The trial found hops-containing beer, with or without alcohol, increased markers of bone formation but did not affect BMD.²⁷⁸

Melatonin

Reported Dosage: 1–5 mg daily

Melatonin is a hormone released primarily from the pineal gland in the brain. This hormone regulates sleep–wake patterns, modulates inflammatory pathways, and reduces oxidative stress.²⁷⁹ Melatonin has been shown to accelerate new osteoblast formation and function while inhibiting osteoclast development and activity in preclinical studies.^280,281 Furthermore, melatonin may support bone health by regulating the bone circadian system, improving gut microbiome composition, supporting healthy metabolism, and controlling nutrient absorption.²⁸² Declining levels of melatonin with aging may be a factor in age-related bone loss.²⁸³

Clinical trials have found that melatonin supplementation can have a positive effect on musculoskeletal diseases, including osteoporosis.²⁸⁴ In a small, randomized, placebo-controlled trial in 18 perimenopausal women, aged 45 to 54 years, 3 mg of melatonin nightly for six months decreased the ratio of NTX (a marker of bone breakdown) to osteocalcin (a marker of bone formation); however, compared with placebo, the change was not statistically significant, probably due in part to the small size of the trial.²⁸⁵ In another randomized placebo-controlled trial, 81 women, average age 63 years, received 1 mg of melatonin, 3 mg of melatonin, or placebo every day for one year. Melatonin increased femoral neck BMD compared with placebo, and the effect was stronger with 3 mg than 1 mg. Melatonin also decreased urinary calcium, increased volumetric BMD (a true measure of bone density that uses computed tomography) in the spine, and increased trabecular thickness (a measure of bone formation) in the tibia.²⁸⁶ A small, randomized, controlled trial in 22 women with osteopenia, aged 49 to 75 years, found a daily nutrient combination providing melatonin (5 mg), strontium citrate (450 mg), vitamin D3 (2,000 IU [50 mcg]), and vitamin K2 (60 mcg) significantly increased BMD in the hip and spine, increased bone formation marker levels, decreased bone resorption marker levels, and improved mood and sleep quality compared with placebo.²⁸⁷

Collagen Peptides

Reported Dosage: 5 grams daily

Collagen is a vital component of bone, and supplementing with collagen peptides may promote bone growth by improving calcium retention, stimulating the release of growth hormones, and increasing osteoblast function.²⁸⁸ Studies in animals have indicated collagen extracts from bovine or marine sources may counter age-related bone loss.^288,289

A randomized placebo-controlled trial in 131 postmenopausal women with osteopenia or osteoporosis found 5 grams of collagen peptides daily for one year increased spine and femoral neck BMD and improved levels of markers of bone turnover.²⁹⁰

Black Currant

Reported Dosage: 784 mg daily

Black currants are rich in phenolic compounds, including flavonoids, anthocyanins, and phenolic acids. They also contain vitamins C and E and the fatty acids gamma-linolenic acid (GLA) and alpha-linolenic acid (ALA).^291-293

Black currants may have positive effects on bone health, particularly in postmenopausal women. A small, double-blind, randomized, placebo-controlled trial involving 40 perimenopausal and early postmenopausal women demonstrated that black currant supplementation decreased the loss of whole-body BMD. Specifically, daily consumption of 784 mg of black currant extract powder for six months significantly mitigated bone loss and increased serum P1NP, a marker of bone formation.²⁹⁴ A follow-up study based on data from this trial found the bone-protective effects of black currant extract may have been mediated through changes in gut microbiota composition and suppression of cytokines that increase osteoclast formation.²⁹⁵

The trial reported in these publications also provided some evidence that the effects of black currant extract on measures or biomarkers of bone health might be dose-dependent—in some cases, the effects were more pronounced in the group of women who received 784 mg of black currant extract than in those who received half this dosage.

Whey Protein

Reported Dosage: 1.0–1.6 grams per kg body weight daily

Muscle tissue plays a key part in the development of bone growth and maintenance. Reduced physical activity can lead to a loss of muscle mass and increased bone breakdown.²⁹⁶ Dietary protein also influences skeletal muscle and bone.²⁹⁷ Data from the National Health and Nutrition Examination Survey showed nearly half of older adults did not get the minimum daily requirement for protein (0.8 grams per kg body weight) on a regular basis, and low protein intake was associated with poor physical function in elders.²⁹⁸ Moreover, clinical research in older adults indicates protein intake of approximately 1.2–1.6 grams per kg per day may be required to optimize muscle health, especially in those who are restricting calories for weight loss or engaging in strength training exercise.^299,300 Increasing intake of branched chain amino acids, in particular, may enhance muscle protein synthesis and help prevent sarcopenia.³⁰¹

Whey protein is rich in the branched chain amino acid leucine and has been shown to support muscle mass and physical function in older adults.³⁰² Whey proteins can also be digested by gut bacteria or enzymatic breakdown into bioactive peptides, some of which have been found to stimulate osteoblasts and promote bone regeneration in the laboratory.³⁰³ In one randomized controlled trial, 43 sedentary older men with osteopenia or osteoporosis plus sarcopenia (osteosarcopenia) receiving whey protein, calcium, and vitamin D supplements were assigned to either a high-intensity resistance training program twice weekly or no training for 18 months. The dose of whey protein was individualized to increase protein intake to 1.5–1.6 grams per kg body weight per day for exercisers and 1.2 grams per kg per day for non-trainers. After 12 months, the exercise/high-protein group had increased BMD at the lumbar spine and hip, and decreased osteosarcopenia symptoms.³⁰⁴ However, a randomized controlled trial in 208 older subjects found 45 grams of whey protein isolate for 18 months, with no exercise intervention, did not increase BMD in the lumbar spine, femoral neck, or total hip compared with placebo.³⁰⁵ Similarly, a randomized placebo-controlled trial in 219 healthy 70–80-year-old women found two years of supplementation with 30 grams of whey protein per day, with no exercise intervention, did not prevent hip and vertebral BMD from dropping.³⁰⁶

Silicon

Reported Dosage: 6–12 mg daily

Silicon is a mineral that affects the composition, strength, and mechanical properties of bone by improving bone matrix quality, stimulating osteoblast activity, contributing to bone mineralization, and increasing collagen synthesis.^307,308 Although silicon is found in some foods, only liquids such as beer and mineral water contain silicon as orthosilicic acid (OSA), the most bioavailable form. Liquid sources are responsible for up to 30% of dietary intake.³⁰⁸ Importantly, while adequate silicon appears to have positive effects on bone health, occupational exposure to excess silica has been linked to osteoporosis and diminished vitamin D levels.³⁰⁹

A large, cross-sectional, observational study that included food frequency questionnaire data from 2,847 adults in the United States found men and premenopausal women, but not postmenopausal women, with the highest dietary intake of silicon (> 40 mg per day) had higher hip BMD compared to those with the lowest intake (< 14 mg per day). Upon analyzing the participants categorically by overall silicon intake or energy-adjusted silicon intake, the researchers found that those in the highest quintile (one-fifth) of silicon intake had up to 10% greater BMD at four hip joint sites than those in the lowest quintile of silicon intake.³¹⁰ Interestingly, two other observational studies reported a relationship between silica and hormone status, finding its beneficial effects (define) on bone were greater in postmenopausal women using hormone replacement therapy.^311,312

In a 12-month trial involving 136 women with osteopenia, both 6 mg and 12 mg of choline-stabilized OSA per day, in addition to 1,000 mg calcium and 800 IU (20 mcg) vitamin D per day, improved levels of a bone turnover marker compared with placebo, and the effect was greater than that of calcium plus vitamin D alone. In addition, 6 mg OSA daily along with calcium plus vitamin D increased femoral neck (but not lumbar spine) BMD compared with placebo.³¹³ In an older clinical trial involving 53 osteoporotic women, silicon treatment for 14 to 22 months significantly increased femoral BMD, while treatment with etidronate (Didronel) and magnesium each had non-significant effects on lumbar BMD and no effect on femoral BMD, and treatment with fluoride increased vertebral BMD but slightly decreased femoral BMD.³¹⁴ On the other hand, a small controlled trial involving 17 postmenopausal women found drinking 1 liter of silica-rich water providing 86 mg of silica daily for 12 weeks increased urine silica concentrations but did not alter markers of bone turnover.³¹⁵

Iron

Reported Dosage: Does not have a true range

Iron is a critical trace mineral needed in adequate amounts for normal bone metabolism, but both deficiency and excess can have detrimental effects on bone regeneration. Iron overload increases oxidative stress, which stimulates osteoclasts and inhibits osteoblasts. Iron deficiency suppresses bone remodeling, impairing bone structure and mineralization by reducing cellular energy production, decreasing collagen synthesis, and possibly interfering with vitamin D activation.^316,317 An observational study that used data from 11,690 participants over 20 years of age in the National Health and Nutrition Examination Survey found iron intake had a U-shaped relationship with osteoporosis risk in women, but not men. Specifically, women in the third quartile for dietary iron intake had the lowest osteoporosis risk.³¹⁸ Based on this finding, moderate-dose oral iron supplements may be useful for preventing bone loss related to iron deficiency, but clinical trials are lacking.^316,317

Manganese

Reported Dosage: 5 mg daily

Manganese is an essential trace mineral that naturally occurs in drinking water and several foods, including whole grains, legumes, seafood, and tea. Very small amounts of manganese are needed by the body to support bone mineralization and the formation of collagen and cartilage. Manganese also plays a role in energy metabolism, antioxidant enzyme systems, reproductive hormone regulation, and neurotransmitter synthesis. It is poorly absorbed in the digestive tract, but excess manganese ingested in contaminated drinking water or inhaled due to industrial pollution can accumulate in the body leading to toxic overexposure. Manganese toxicity has been implicated in neurodegenerative diseases such as Alzheimer disease, Parkinson disease, Huntington disease, and amyotrophic lateral sclerosis (ALS).³¹⁹ Although the daily requirement for manganese has not been established, an upper limit of 11 mg per day is generally considered safe.^319,320

Manganese deficiency has been associated with bone loss leading to osteopenia and osteoporosis in animal studies.³¹⁹ An observational study in 627 adults in China, aged 50 years and older, found higher manganese levels, co-occurring with higher levels of iron, selenium, and copper, were associated with lower risk of osteoporosis.³²¹ On the other hand, in a study using data from 9,732 women aged 50–70 years in the United States participating in the National Health and Nutrition Examination Survey, high manganese levels were found to be correlated with low BMD.³²² Another study in 581 subjects found the rate of osteoporosis was higher in older women, but not men, with a history of chronic occupational exposure to manganese.³²³

There are currently no clinical trials evaluating the effects of manganese supplementation alone on osteoporosis or fracture risk. A two-year controlled trial in 59 postmenopausal women found daily supplementation with 1,000 mg of elemental calcium plus a trace mineral combination (5 mg of manganese, 15 mg of zinc, and 2.5 mg of copper) raised lumbar spine BMD more than placebo, but it is unclear how much manganese affected bone density from this result.²¹⁸

Multivitamins & Multi-Nutrient Formulations

Because bone health depends on adequate levels of a range of vitamins and minerals, multivitamin/mineral supplements are sometimes taken to boost intake of essential nutrients. A meta-analysis of data from eight observational studies lasting at least one year, with a combined total of 80,148 subjects, found multivitamin use was correlated with a 51% reduction in risk of osteoporotic hip fracture.³²⁴

Evidence from randomized trials regarding multivitamins and fracture risk is mixed. In a randomized controlled trial involving 3,318 subjects in China, a daily multivitamin with 26 nutrients, taken for six years, reduced fracture risk by 63% compared with placebo in men but had no effect in women. Post-intervention monitoring showed the fracture risk reduction in men was still significant 10 years after stopping the multivitamin, but not beyond 10 years.³²⁵ On the other hand, a large randomized controlled trial that included 21,442 elderly women and men found those given a standard, commercial, daily multivitamin supplement for a median of 3.6 years had the same fracture risk as those given placebo. However, the dosages of key nutrients, like vitamin D, calcium, and vitamin K, were insubstantial in this trial. For example, the multivitamin used contained 220 mg calcium, 30 mcg vitamin K (form not specified), and 1,000 IU (25 mcg) vitamin D.³²⁶

In one observational study, seven years of data from 172 women (average age 65.1 years) who used a multi-nutrient supplement providing 3 mg of boron daily, as well as plant-sourced calcium, magnesium, vitamin D3, vitamin K2 (as MK-7), vitamin C, and strontium citrate, for at least one of the seven years was analyzed; while BMD normally decreases by an average of 0.4% per year in older women, participants who used the multi-nutrient supplement experienced a 7.3% increase in BMD over seven years, or an average increase of 1.04% per year.³²⁷ In an open trial, a group of 158 adults engaged in a six-month program involving physical activity, lifestyle education, and supplementation with a multi-nutrient supplement containing plant-sourced calcium, magnesium, vitamin D3, vitamin K2, and strontium citrate. Then, another group of 58 participants engaged in the same six-month program with a more comprehensive multi-nutrient supplement that provided 3 mg of boron per day as well as vitamin C and vitamin K2 as MK-7 (instead of MK-4). Both groups experienced gains in BMD, but this change was only statistically significant in those who used the boron-containing multi-nutrient.³²⁸ In another open trial in 176 women over 40 years of age, a physical activity program plus the same comprehensive supplement led to a 2% increase in BMD over one year, while physical activity plus the multi-nutrient supplement without boron led to a 4.1% increase in BMD, and a calcium/magnesium/vitamin D3 supplement with no physical activity program led to a 1.30% increase in BMD.³²⁹

In summary, micro- and macro-nutrients and vitamins are important parts of a normal, healthy diet. Supplementation studies with certain nutrients, including vitamin K, have shown modest effects on bone mass and bone turnover markers such that the changes in BMD are slight and should not be expected to rival established treatments such as bisphosphonates. Moreover, BMD and bone turnover markers are only surrogates for fracture risk, and as of mid-2025 large scale randomized clinical trials of these nutrients have not been performed to show consistent risk reduction. Many thousands of participants would be required, and even then, it would require individuals at high risk for fracture to show any benefit. Nevertheless, these substances should be considered in the picture of a whole-body, health-conscious approach to supporting healthy bones.

Eating a healthy diet, getting regular exercise, not smoking, and limiting alcohol consumption are all recommended for preventing osteoporosis.⁵ For more information about how some diet and lifestyle factors contribute to osteoporosis risk, see the “Osteoporosis Risk Factors & Associated Conditions” section above.

Healthy Diet

Dietary recommendations for patients with or at risk for osteoporosis typically emphasize calcium and protein as key to supporting healthy bones. Addressing an underlying vitamin D deficiency through diet and supplements may also be appropriate.⁵¹ Dairy products are rich in high-quality protein and calcium and are typically fortified with vitamin D. Several meta-analyses have found higher intake of dairy products to be correlated with higher BMD and lower risk of falls and fractures, but others have not.⁴⁹ One meta-analysis of data from 20 observational studies found milk consumption was unrelated to fracture risk in women and men.³⁴³ Another meta-analysis that included data from 13 observational studies with a total of 486,950 participants found higher milk intake was associated with an increased risk of hip fracture, while higher yogurt and cheese intake were each associated with lower hip fracture risk.³⁴⁴ Other studies have also linked higher yogurt consumption, which may exert some of its effects through probiotic mechanisms, with higher BMD and lower hip fracture risk.^56,345

It is widely recognized that strict vegetarian and vegan diets have been associated with increased osteoporosis and fracture risk, but the important role of a variety of plant foods in preserving bone mass during aging is often underappreciated. Fruits and vegetables contain nutrients that are vital for healthy bone metabolism, and both higher vegetable intake and higher diversity of vegetables in the diet have been correlated with fewer falls and fractures.³⁴⁶ One meta-analysis that included findings from 13 observational studies and randomized controlled trials found adding one or more servings of fruits and vegetables per day led to a decreased fracture risk.³⁴⁷ A study that compared the dietary habits of 300 patients who had experienced a fall-related fracture to those of 590 matched healthy subjects found higher intake of fish, fruits, vegetables, and nuts were associated with lower risk of fall-related fracture.³⁴⁸

Berries and plums are especially rich in flavonoids called anthocyanins that have strong free radical scavenging effects. A meta-analysis of findings from 13 randomized controlled trials found increasing consumption of anthocyanin-rich foods significantly increased lumbar spine BMD and had other positive, though not statistically significant, effects on markers of bone metabolism.³⁴⁹ Randomized controlled trials in older men have shown adding 50 to 100 grams of dried plums (about five to 10 prunes) to a daily diet for up to one year can improve levels of some markers of bone turnover.^350,351 Clinical trials in older women have similarly reported finding improved bone turnover marker levels after six to 12 months of prune consumption. In addition, 50 grams of dried plums per day has been shown to prevent a drop in total body BMD after six months and decrease FRAX scores (a measure of fracture risk) after one year in postmenopausal women.^352-354

Measures of broadly healthy dietary patterns that emphasize fruits, vegetables, whole grains, legumes, and nuts and seeds, such as Dietary Approaches to Stop Hypertension (DASH), Mediterranean diet, Healthy Eating Index, and anti-inflammatory diet scores, have been associated with higher BMD and/or lower risk of osteoporosis in observational research.^355-358 In a randomized controlled trial involving 1,142 elderly participants, a one-year intervention that included adopting a Mediterranean-like diet and taking 400 IU (10 mcg) vitamin D3 daily reduced the rate of BMD loss in the femoral neck in subjects with osteoporosis—but not those with normal-for-age BMD.³⁵⁹

Weight-Bearing Exercise

Getting adequate daily physical activity can positively impact bone health, balance, and muscle strength—all of which can help reduce the risk of falling and fractures.⁵ Meta-analyses of data from numerous clinical trials have found various types of exercise interventions can increase BMD in postmenopausal women, although large scale studies for fracture risk are lacking.^360,361 Both strength (also known as resistance) training such as lifting weights and weight-bearing aerobic exercises like walking, jogging, and dancing are important for stimulating bone formation and preserving BMD.^70,362 Even for people with osteopenia and osteoporosis, a multicomponent exercise program that builds strength, balance, flexibility, and fitness has been shown to improve BMD, risk of falling, and quality of life.^70,363

Who is at risk for osteoporosis?

Anyone can develop osteoporosis, but certain factors can increase the chances. You may be more likely to develop osteoporosis if you are older, have a family history of osteoporosis, are female, are Asian or White, have low sex hormone levels, are underweight, use certain medications, eat a nutrient-deficient diet, are sedentary, smoke, or are a heavy alcohol drinker.¹⁸

Should men be concerned about osteoporosis?

Yes, men should be concerned about osteoporosis. Although their risk is lower than women’s, men are more likely to experience a life-threatening bone fracture compared with women.⁸

Is osteoporosis genetic?

Genetics play a role in your BMD, skeletal strength, and overall risk of osteoporosis. Having a family member with osteoporosis raises your risk of developing it yourself. There are some rare forms of osteoporosis caused by mutations in collagen genes such as COL1A1 and COL1A2 genes, which provide instructions for making and folding type 1 collagen proteins.³⁶⁴

Can osteoporosis be reversed?

Unfortunately, osteoporosis cannot be reversed—but steps can be taken to stop bone loss and support healthy bone tissue. Certainly, medications like bisphosphonates, denosumab, parathyroid hormone analogs, and romosozumab may halt bone loss.^6,12,365 You can help support bone health by exercising regularly, eating a nutrient-dense well-rounded diet, taking targeted supplements like calcium, vitamins D and K, magnesium, and trace minerals, and avoiding unhealthy habits such as drinking too much alcohol and smoking.

Does osteoporosis cause pain?

Osteoporosis does not generally cause pain, but osteoporosis-related fractures can be very painful. For example, osteoporotic compression fractures in the spinal vertebrae can cause substantial back pain that may be incorrectly diagnosed.¹¹⁹

Does osteoporosis make you tired?

Osteoporosis is also known as a “silent disease” because it does not cause recognizable symptoms until a bone breaks.^10,18 Fatigue accompanying osteoporosis may be due to other underlying health problems, nutrient deficiencies, medication side-effects, or pain from undiagnosed vertebral compression fractures.^18,119