Osteoporosis is one of the chronic health conditions for which many women seek input and recommendations from natural medicine practitioners. This is a challenging area for practitioners who have a priority for natural medicines. While natural medicine and lifestyle issues are fundamental to prevention of osteoporosis and osteoporotic related fractures, natural medicine-only treatment interventions can be naïve and insufficient for statistical and meaningful fracture prevention in what might be years from the present. On the other hand, conventional medications come with risks along with benefits, and some of the risks are not an acceptable risk for many patients. It is important to educate patients on the risks of inadequate treatment, while also weighing the benefits and the risks of treatment options.   

The focus of this article is to point out some key aspects of osteoporosis, the prevalence, risk factors and assessment and indications for bone density testing. Unfortunately, too many practitioners of all disciplines jump to exercise, vitamin D, and other supplements and/or pharmacologic agents and do not do their due diligence of evaluating the condition itself.  

Identifying and Understanding Osteoporosis 

Osteoporosis is the most common bone disorder in humans. It is a general skeletal disorder characterized by a decrease in bone strength that then predisposes an individual to an increased risk of fracture, with the most important sites being the spine and hip. Osteoporosis-related serious fractures occur most often in older postmenopausal women and can be life-altering. Bone loss during the menopause transition and the early part of menopause is what results in osteoporosis. Fractures that are less serious than the spine or hip are those in the wrist in postmenopausal women (often in their 50s and 60s) and can be early warning signs of osteoporosis. 

Fortunately, we can identify osteoporosis and identify those women who are at high risk of fracture. Evaluating skeletal health should be a skill set of all primary health care providers, especially those who offer primary care to postmenopausal women. 

Osteoporosis is determined by bone densitometry and, according to the World Health Organization (WHO), is defined by a bone mineral density (BMD) T-score less than or equal to -2.5 at the total hip, femoral neck, or lumbar spine (with at least two vertebral levels in the posteroanterior position) in a postmenopausal woman or a man over age 50.^1,2 Most other organizations support this description. The presence of a fragility fracture also justifies a clinical diagnosis of osteoporosis. 

There has been a shift in the thinking about the term osteopenia. The diagnosis of osteopenia or low BMD does not necessarily mean that she has experienced bone loss.  The term is now thought to have limited clinical value because it includes young postmenopausal women without other risk factors who are actually at low risk of fracture while also including older women with other risk factors who are at very high risk of fracture.  

In addition to BMD, a clinical diagnosis of osteoporosis can be made in postmenopausal women who have a fracture in their spine or hip or who have other risk factors that results in a high risk of fracture.  

Osteoporosis is also categorized as either primary or secondary. Primary osteoporosis is related to bone loss that occurs after menopause as women age. Secondary osteoporosis is diagnosed when it is secondary to issues such as glucocorticoids, vitamin D deficiency, hyperthyroidism, hyperparathyroidism, renal calcium leak, or other diseases that contribute to bone loss. It is important that clinicians learn to evaluate secondary causes of bone loss to rule out these other causes.   

Prevalence, Morbidity, and Mortality 

In the National Health and Nutrition Examination Survey of 2013-2014, 16.5 % of American women aged 50 years or older had osteoporosis at either the femoral neck or lumbar spine.³  The prevalence of osteoporosis of the femoral neck increases with age from 6.8% in women aged 50-59 to a striking 34.9% in women aged 80 years and older.⁴ African American women have the highest BMD and Asian American women have the lowest.⁵ Most osteoporosis fractures occur in postmenopausal women, with two-thirds of them after age 75.⁶ In Caucasian American women aged 50 years, the risk of having an osteoporotic fracture in the remaining years is about 40%, and if you break it down, it’s 17.5% for the hip, 16.0% forearm and 15.6% for a symptomatic vertebral fracture.⁷ 

Hip fractures after age 82 are the most life-altering and can lead to up to a 25% increase in mortality within 1 year of the fracture.⁸  And it’s not just mortality -- up to 25% of women require long term care after a hip fracture and 50% will have some long-term loss of their mobility.⁹ 

Risk Factors and Risk Assessment 

Risk factors for low BMD include advanced age, weight (< 127 lb), genetics, and smoking.  Numerous diseases and medications have negative impact on bone, including eating disorders, rheumatoid arthritis, celiac disease, hyperparathyroidism, Cushing’s Syndrome, aromatase inhibitors, glucocorticoids and gastric bypass surgery. Proton pump inhibitors are associated with increased fracture risk without causing bone loss. In addition, disorders and drugs that affect muscle strength, balance, and eyesight increase the risks of falls and fracture. Counterintuitive to many, it turns out lifetime intake of calcium or vitamin D, alcohol, caffeine, or current or past physical activity are not predictors of low BMD.  

The tools to evaluate risk include a comprehensive history and physical exam with an eye towards yellow and red flags. These flags include:  

• Surgical menopause and not on extended menopause hormone therapy 
• Premature ovarian insufficiency and not on menopausal hormone therapy until at least age 52 
• Early menopause (onset between 40-45) and not on menopausal hormone therapy until at least age 52   

Other key historical findings are a parent with a history of hip fracture, being a current smoker, consuming more than three servings of alcohol daily, and the diseases and medications mentioned earlier. Other known risk factors for fracture include dementia, low physical activity, thoracic kyphosis, rates of bone loss, weight loss, and loss of height.¹⁰ 

The primary objective tool for assessing bone density is a DXA scan, but ultrasound and quantitative computed tomography (CT) can be adjunct, although they should not be substitutes for DXA and the T-scores of the hip or spine obtained with DXA scans.  

The most important risk factors for fracture in postmenopausal women are a history of a previous fracture or falls, older age, and low BMD. Combining these and other independent risk factors improves the clinician’s ability to identify women at high fracture risk. The computer-based algorithm FRAX is a tool that can easily be learned to determine risk and is available online. The FRAX calculation is now often reported in DXA reports.   

Indications for Bone Density Testing 

Bone density testing should be done in postmenopausal women with risk factors for low bone density and where knowing that will influence the clinical management: 

• Women with a history of postmenopausal fracture 
• Women with known medical causes of bone loss or fracture 
• Women 65 and older 
• Women 50 and older and with one or more additional risk factors of: 
• Weight less than 127 lb 
• Family history of hip fracture in a mother or father 
• Currently a smoker 
• Discontinuing her systemic menopausal hormone therapy with additional risk factors for fracture. 

For postmenopausal women aged 50 to 64 years with baseline T-scores greater than -1.5, retesting can wait until age 65. Age 65 is the age at which routine BMD screening is recommended for all women. Retesting earlier can be considered in women within 5 years of menopause whose initial BMD T score was worse than -1.5 or in those with other risk factures such as a prior postmenopausal fracture or if they have medical problems or medications associated with bone loss. 

A comprehensive physical exam for osteoporosis evaluation should include an assessment of kyphosis, muscle strength, balance, height, weight, oral health (gum disease, tooth loss, tooth fractures), bone tenderness of thoracic vertebrae and anterior tibia and joint laxity.   

Laboratory testing should be done prior to any intervention for women with osteoporosis, to evaluate for secondary causes of bone loss. Routine tests include CBC, general serum chemistry (especially serum calcium, creatinine, alkaline phosphatase, albumin, serum phosphate and serum vitamin D). A 24-hour urinary calcium excretion test is used to test for poor calcium absorption and hypercalciuria. An intact parathyroid hormone test is also important in determining if there is hyperparathyroidism.  

Other special tests can be considered based on abnormal values of any of the above, other special cases of osteoporosis, or clinical indications of other diseases that affect bone loss. Serum markers of bone turnover, while popular amongst integrative, functional medicine, and alternative-minded practitioners, cannot diagnose osteoporosis and have unpredictable ability in assessing fracture risk. Their primary value has been in clinical trials where large groups of women are studied and group responses to treatment are assessed.  For individual patient evaluation of women with osteoporosis, it is not recommended. 

Non-pharmacologic Treatments and Lifestyle Modifications 

The whole point of management of bone health in postmenopausal women is to minimize bone loss and reduce the likelihood of fractures. All postmenopausal women, whether they have low bone density, osteoporosis, or already have had a postmenopausal osteoporosis related fractures should be educated and urged to make lifestyle modifications to support general health and bone health. Examples include a balanced, whole foods-oriented diet with adequate intakes of calcium, vitamin D, adequate physical activity and to avoid smoking and excess alcohol. Adequate physical activity in the case of bone health should be focused on weight bearing exercise. Weight-bearing exercises produce a force on bones that makes them work harder. Examples are: 

• Brisk walking (3 to 4 miles per hour) 
• Jogging or running 
• Tennis, badminton, ping pong, pickleball, and other racket sports 
• Climbing stairs 
• Dancing 

Resistance training exercises (weight lifting) puts stress on bones which then improves bone strength. Strength-training exercises can involve: 

• Weight machines 
• Free weights 
• Resistance bands 
• Use of your own body weight (such as pushups or pullups) 

Balance training is especially important for older adults to improve balance and help prevent falls. Examples are: 

• Walking on an unstable surface (e.g., a foam mat or wobble board) 
• Tai chi 
• Walking backwards 
• Step-ups 
• Lunges 
• Shifting your body weight backward and forward while standing with both feet together or on one foot 

According to the U.S. Department of Health and Human Services, adults of all ages should aim to get the following amounts of exercise: 

• At least 150 minutes (2.5 hours) a week of moderate-intensity exercise OR at least 75 minutes a week of vigorous-intensity exercise 
• For additional benefit, muscle-strengthening activities of at least moderate intensity at least twice a week 

However, it is important to appreciate that these efforts will not prevent bone loss in early menopause, will not significantly increase BMD in postmenopausal women, and are not adequate as solo treatment interventions for women with osteoporosis.   

Research on Non-pharmacologic Treatments 

Most of the research studies that have been done to evaluate non-pharmacologic treatments and lifestyle changes are small and short, and as such, recommendations are usually based on systematic reviews, meta-analysis, and opinions of expert committees. While it is true that intakes of calcium and vitamin D are required for normal skeletal growth in childhood, the data is less clear for healthy postmenopausal women. The Institute of Medicine (IOM) committee proposed daily intakes of calcium for postmenopausal women of 1,000-1,200 mg/day with an upper limit of 2,000 mg/day, but note that these recommendations are based on uncertain and even inconsistent data. It is important to note that the average daily dietary intake of calcium for women in the U.S. and Canada is 700 mg-800 mg daily. About one third of that comes from dairy products, which would mean if a woman consumed an average dairy-free diet, her diet would contain only amount 500 mg/day of calcium. That leaves us with women consuming daily dairy of about 250 mg, and assuming the other 500 mg comes from non-dairy sources, she would need to add 250 mg to 450 mg/daily of supplemental calcium. Most dairy-free women would need to add 500 to 700 mg daily. When reviewing a woman’s dietary calcium intake, use a simple list of calcium content foods to estimate her dietary daily calcium. The National Institute of Health Osteoporosis and Related Bone Diseases National Resource Center has a simple list.   

To highlight the importance of estimating dietary calcium and then recommending women supplement the difference to get up to the total of 1,000-1,200 mg/day, in the Women’s Health Initiative (WHI) Calcium and Vitamin D study, the average calcium intake was about 1,100 mg daily. In the group that added another 1,000 mg of daily calcium supplement, the risk of kidney stones was increased by 17%.¹¹ There have been reports of the possibility that a calcium supplement of 1,000 mg/day with a total diet plus supplement of 2,000 mg/day is associated with increased cardiovascular risk.^{12, 13}  Any association of total calcium intake with cardiovascular risk was not seen in the WHI.¹⁴ An analysis published in 2016 found that a calcium intake of 2,000 mg-2,500 mg/day was not associated with cardiovascular risk in healthy adults.¹⁵ Due to any lack of benefit for a total of more than 1,200 mg/day of dietary plus supplemental calcium, the recommendation of about 1,200 mg/day total (diet plus supplementation) is still given for postmenopausal women with or without osteoporosis and for women of any age with osteoporosis.   

The IOM also recommends 600 IU /day of vitamin D for women between 50 and 70 years of age and 800 IU daily for women older than 70. However, the recommendations were based on the fact that these doses were sufficient to achieve a serum 25-OHD level of at least 20ng/mL in most postmenopausal women. Not all are happy with this threshold and cite that it should be at least 30 ng/mL. While surprising, most studies report no benefit of calcium and/or vitamin D on fracture risk. Meta-analyses of the effects of calcium and/or vitamin D on the risk of fracture provide inconsistent conclusions, with most of the studies reporting no benefit on fracture risk.^{16, 17} This inconsistency in benefits might be related to calcium and vitamin D being threshold nutrients, with severe deficiencies being harmful, but intakes more than the threshold to avoid deficiency does not really provide additional benefit. The effects of vitamin D with calcium on fracture risk have been mostly observed in women who are institutionalized or in older women with vitamin D deficiency.¹⁸ Even the US Preventive Services Task Force (USPSTF) has chimed in, concluding that there was insufficient evidence to assess the balance of the benefits and harms of a daily supplementation of vitamin D 400 IU or more and calcium of 1,000 mg or more for primary prevention of osteoporosis in non-institutionalized postmenopausal women.¹⁹ From these data, it seems that even women with osteoporosis do not require more calcium or vitamin D than women with normal BMD unless they have what is defined as a deficiency. But, to make matters more confusing, a meta-analysis published in 2016 evaluated randomized controlled trials of calcium plus vitamin D supplementation and fracture prevention.²⁰ After a PubMed search spanning 14 years up through July 2015, summary relative risk estimates were given for total fractures and hip fractures. A total of only 8 studies met the inclusion criteria, but in the end, the meta-analysis showed that calcium plus vitamin D supplementation produced a statistically significant 15 % reduced risk of total fractures and a 30 % reduced risk of hip fractures. A limitation is that this study utilized data from subgroup analysis of the Women's Health Initiative but it does support the use of calcium plus vitamin D as an intervention for fracture risk reduction, whether community dwelling or institutionalized adults. 

Other Supplements of Note 

Strontium has received some attention, but it is important to realize that the drug, strontium ranelate (a strontium salt) was never approved in the U.S. or Canada and even now is not available in other countries due to concerns about increased cardiovascular risk. There is no evidence for other strontium salts sold as dietary supplements when it comes to support for bone health. Magnesium, manganese, copper, zinc, folic acid, boron, vitamin C and more have scant data but are often included in multi-ingredient bone health supplements to support the potential benefits on bone metabolism, bone strength, and bone architecture, but doubtful for bone density.   

Vitamin K is more interesting and does have individual study data of some compelling importance. I’ll go into some detail here, as it is the one supplement I feel may have some hope for my patients who have osteoporosis and decline drug therapy. Vitamin K is required for the production of the bone protein osteocalcin. Osteocalcin draws calcium to bone tissue, enabling calcium crystal formation. Osteocalcin provides the protein matrix for mineralization and is thought to act as a regulator of bone mineralization.²¹ Vitamin K plays a key role in the formation, remodeling, and repair of bone by attracting calcium to the site of this protein matrix.²² A low dietary intake of vitamin K seems to increase the risk of osteoporotic hip fractures in women, according to data from the Nurses’ Health Study.²³ 

There are various forms of vitamin K, but human trials have been done on vitamin K₁ (phylloquinone), MK4, (MK4, a form of vitamin K₂) and menaquinone-7 (longer-chain MK7). 

In a double-blind study, 452 men and women (ages 60-80 years) received a multiple vitamin/multimineral supplement providing 600 mg/day of calcium and 400 IU/day of vitamin D, plus either 500 mcg/day of vitamin K₁ or no vitamin K₁.²⁴ BMD (determined by DEXA) and bone turnover were measured at 6, 12, 24, and 36 months. There were no differences in BMD at the femoral neck, lumbar spine, or total body between the two treatment groups, indicating that vitamin K₁ did not enhance the effects of calcium, vitamin D, or other nutrients in this patient population. In the double-blind ECKO trial,²⁵ a daily 5-mg supplement of vitamin K₁ for 2 to 4 years did not protect against an age-related decline in BMD in postmenopausal women with osteopenia, but significantly fewer women in the vitamin K₁ group than in the placebo group had fractures. 

Epidemiologic evidence has shown associations between low dietary intake of vitamin K and increased bone loss in elderly men and women. A 2006 meta-analysis of 13 randomized controlled trials²⁶ that gave vitamin K₁ or MK4 (a form of vitamin K₂) supplements for longer than 6 months reported data on bone loss and fracture rates. All but one study showed a reduction in bone loss with supplemental vitamin K. All 7 of the 13 studies that reported fracture data were in Japanese individuals and used MK4. Most of these trials used a high dose, 45 mg/day. 

Although the recommended dietary intake of vitamin K is 90 to 120 mcg/day, the optimal dose and form of vitamin K supplementation to achieve a protective effect on bone loss and fracture reduction is not known. The majority of studies used MK4 at doses approximately 400-fold higher than dietary recommendations for vitamin K₁. An additional issue is that these studies have been conducted almost exclusively in Japanese postmenopausal women. This population group may be influenced by unique dietary, environmental, and/or genetic factors, so it is not clear whether the findings from these studies can be generalized to other populations. In contrast to the seven positive Japanese studies, in a double-blind trial, 381 postmenopausal women received either phylloquinone 1 mg/day, MK4 45 mg/day, or placebo for 12 months.²⁷ No effect of phylloquinone or MK4 on the bone density of the lumbar spine or proximal femur was observed. 

Two long-term trials have previously been done evaluating the effect of vitamin K₁ supplementation on bone loss. In one study using 1 mg/day of vitamin K₁ plus calcium and vitamin D for 3 years in postmenopausal women aged 50 to 60 years,²⁸ bone loss was reduced at the femoral neck, but there was no beneficial effect on spinal bone density. In a second study,²⁹ 200 mcg/day of vitamin K₁ plus calcium and vitamin D given for 2 years to nonosteoporotic women aged 60 years or above resulted in a modest increase in BMD of the radius but not the femoral neck. 

Menaquinone-7, or MK-7 (a longer-chain form of vitamin K₂), is found in natto (highest concentration in fermented soybeans) and cheese and in lower concentrations in meat and other dairy products; a very small amount is produced by gut bacteria from dietary vitamin K₁.³⁰ MK-7 has been found in animal studies to be more potent and more bioavailable as well as to have a longer half-life than MK4. When taken as a daily supplement (0.22 μmol/day), MK-7 is more effective than K₁ in carboxylating osteocalcin. This is thought to be due to MK-7’s much longer residence time and the higher serum concentrations of MK-7 achieved during its prolonged intake.³¹ The longer-chain menaquinones such as MK-7 are much more hydrophobic, which contributes to their much longer half-lives (8 hours for K₁ and MK-4 vs. 96 hours for MK-7). ³² In a study of Japanese postmenopausal women, a significant inverse association was found between natto consumption and the incidence of hip fractures.³³ In a study of osteoporosis after organ transplantation, 1 year of MK-7 supplementation (180 mcg/day) resulted in increased bone mineralization compared with placebo.³⁴ However, a study of early menopausal women given 1 year of supplementation of 360 mcg/day of MK-7 in the form of natto capsules did not show a significant improvement in bone density despite a reduction in decarboxylated osteocalcin. ³⁵ A likely reason for these inconsistent results is the confounding effect of vitamin D status. The study in post-transplant patients noted a high incidence of vitamin D deficiency, which was found to affect the results. 

Lastly, a meta-analysis published in 2019 found no evidence that vitamin K affects bone density or vertebral fracture risk in postmenopausal women and the evidence confirming a reduction in clinical fractures was insufficient.³⁶ 

Too much dietary protein or protein deficiency can be problematic for bone. In older women who are prone to falling and losing weight, a higher protein intake has been associated with reduced frequency of falling.37   

Phytoestrogens, namely isoflavones, have moderately beneficial effects in slowing the bone loss associated with menopause in a systematic review.³⁸

We know that bone mass is impacted by impact loading exercise during childhood and that immobilization is associated with low bone mass. However, a Cochrane review and several meta-analyses are sobering in that they found relatively small, statistically significant effects of exercise on BMD in postmenopausal women.^{39, 40, 41}  

Any prevention strategies to reduce falls, especially in women aged 65 years and older as at least one third of these women experience one or more falls each year. This risk only increases with age, as does the risk of fracture. Most fractures occur as a result of a fall and exercise programs that emphasize balance, gait, and muscle strength are very effective ways to prevent falls and perhaps fractures. Assuring adequate vision, a safe home and attention to medications are important. Tapering the use of benzodiazepines, neuroleptic agents and antidepressants can reduce the risk of falling by more than 60%.  

Pharmacologic Therapy to Prevent Bone Loss and to Treat Osteoporosis in Postmenopausal Women 

This section will be brief and only key points summarized. Much data is available for your perusal should you be interested. Benefits and risks are specific to each agent, dose, and duration. 

Prevention of Bone Loss and Treatment of Osteoporosis 

The mechanisms of action of all osteoporosis pharmacologic agents are to either inhibit or to activate bone metabolism. The antiremodeling agents, also called antiresorptive drugs include systemic estrogen, estrogen agonists/antagonists, bisphosphonates, and denosumab. They all inhibit bone resorption and to a lesser extent, bone formation. These medications maintain or improve BMD and reduce the risk of fracture but do not improve or repair trabecular bone structure. The anabolic agents can actually increase bone density, and thus lower fracture risk. These currently include Tymlos, Forteo and Evenity.  

The prescribing of these prevention and treatment drugs are likely best done by osteoporosis experts, most often an endocrinologist with a subspecialty in osteoporosis or a rheumatologist. The role of the integrative, natural medicine, or functional medicine clinician is to know the benefits and risks of all treatment options, non-pharmacologic and pharmacologic, and then to integrate strategies the safest way possible.   

Conclusion 

At the forefront of our minds, it should be known that osteoporosis is a chronic, progressive condition and it affects a large percentage of postmenopausal women.  Women’s healthcare practitioners, and especially menopause practitioners, should be familiar with and comfortable with assessment and management, or refer to those that are. A naïve and uninformed clinician can miss the opportunity to accurately diagnose, individually assess fracture risk, individualize treatment approaches, and truly present women with options that include the whole spectrum of prevention and treatments. Under treatment is just as harmful – or perhaps more so – than over treatment. In the end, educating women with accurate studious information and the tools to make informed decisions that they feel the most comfortable with and realistically confident in is a critical aspect of offering good, respectful, medical care.  

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[36] Mott A, Bradley T, Wright K, et al.  Effect of vitamin K on bone mineral density and fractures in adults: an updated systematic review and meta-analysis of randomised controlled trials.  Osteoporos Int 2019;30:1543-1559.

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Other Resources: 

North American Menopause Society Position Statement: Management of osteoporosis in postmenopausal women: the 2021 position statement of the North American Menopause Society.  Menopause. 2021; 28(9): 973-997.

International Osteoporosis Foundation

National Osteoporosis Foundation (Now the Bone Health and Osteoporosis Foundation)

National Institute of Arthritis and Musculoskeletal  and Skin Diseases