Decreased bone mineral density (BMD) leads to increased risk of cardiovascular (CV) disease

A study to optimise bone strength and reducing risk of fracture, while at the same time decreasing risk of cardiovascular disease was done by the following team:

1Saint Luke’s Mid America Heart Institute, Kansas City, Missouri, USA
2Cleveland Clinic Foundation, Center for Functional Medicine, Cleveland, Ohio, USA
3Center for Primary Health Care Research, Department of Clinical Sciences, Faculty of Medicine at Lund University, Malmö, Sweden
4Emeritus Professor of Nutritional Science, Colorado State University, Fort Collins, Colorado, USA
Correspondence to Dr James H O’Keefe; gro.sekul-tnias@efeekoj

The majority of Americans do not consume the current recommended dietary allowance for calcium, and the lifetime risk of osteoporosis is about 50%. However, traditional mononutrient calcium supplements may not be ideal. We comprehensively and systematically reviewed the scientific literature in order to determine the optimal dietary strategies and nutritional supplements for long-term skeletal health and cardiovascular health. To summarise, the following steps may be helpful for building strong bones while maintaining soft and supple arteries: (1) calcium is best obtained from dietary sources rather than supplements; (2) ensure that adequate animal protein intake is coupled with calcium intake of 1000 mg/day; (3) maintain vitamin D levels in the normal range; (4) increase intake of fruits and vegetables to alkalinise the system and promote bone health; (5) concomitantly increase potassium consumption while reducing sodium intake; (6) consider increasing the intake of foods rich in vitamins K1 and K2; (7) consider including bones in the diet; they are a rich source of calcium-hydroxyapatite and many other nutrients needed for building bone.


Key questions

What is already known about this subject?

  • The lifetime risk of osteoporosis is approximately 50%. Most people do not consume the Recommended Daily Allowance of calcium. Traditional mononutrient calcium supplements may not be ideal for promoting long-term cardiovascular and skeletal health.

What does this study add?

  • Calcium is ideally obtained from dietary sources. The form of calcium in bones and bone meal is calcium-hydroxyapatite, which may be particularly effective for building bone.

How might this impact on clinical practice?

  • Increased consumption of calcium-rich foods such as bones, fermented dairy products (e.g. yogurt, kefir, cheese), leafy greens, almonds, and chia seeds may be effective for improving both skeletal and cardiovascular health.


Calcium: general physiology and epidemiology

Calcium is the most ubiquitous mineral in the human body. An average-sized adult body contains approximately 1000 to 1200 g of calcium, which is predominately incorporated into bones and teeth in the form of calcium-hydroxyapatite (Ca10(PO4)6(OH)2) crystals. The remainder circulates throughout the blood and soft tissues, and plays fundamental roles in cell conduction, muscle function, hormone regulation, vitamin (Vit) K-dependent pathways, and cardiac and blood vessel function.1

Some studies indicate only 30% of the US population consumes the Recommended Dietary Allowance of calcium, which is 1000–1200 mg daily.1 Furthermore, humans absorb only about 30% of calcium from foods depending on the specific source.1 The body will demineralise its own skeletal system to maintain serum calcium levels in situations where dietary calcium is insufficient and/or absorption is decreased, and/or excretion is increased.2

Osteopenia/osteoporosis: an epidemic

Starting at about age 50 years, postmenopausal women lose about 0.7–2% of their bone mass each year, while men over age 50 years lose 0.5–0.7% yearly. Between ages 45 and 75 years, women, on average, lose 30% of their bone mass, whereas men lose 15%.

According to the US Surgeon General’s Report, 1 in 2 Americans over age 50 years is expected to have or to be at risk of developing osteoporosis.3 Osteoporosis causes 8.9 million fractures annually, with an estimated cumulative cost of incident fractures predicted at US$474 billion over the next 20 years in the USA.3–6 Among adult women over age 45 years, osteoporosis accounts for more days spent in hospital than many other diseases such as diabetes, myocardial infarction (MI), chronic obstructive airway disease and breast cancer.3 Fragility fractures are the primary cause of hospitalisation and/or death for US adults ≥ age 65 years and older; and 44% of nursing home admissions are due to fractures.3

A Mayo Clinic study reported that compared to 30 years ago, forearm fractures have risen more than 32% in boys and 56% in girls. The authors concluded that dietary changes, including insufficient calcium and excess phosphate, were significantly associated with increased fractures.7 Public health approaches are crucial to prevent symptomatic bone disease, but widespread pharmacological prophylaxis is prohibitively expensive and carries potential serious adverse effects.

Cardiovascular disease and bone mineral disease: a calcium nexus

Strong epidemiological associations exist between decreased bone mineral density (BMD) and increased risk of both cardiovascular (CV) disease and CV death.8 For example, individuals with osteoporosis have a higher risk of coronary artery disease, and vice versa. This problem will be magnified if the therapies for osteoporosis (eg, calcium supplements) independently increase risk of MI.


Maintaining replete magnesium status may reduce risk for the metabolic syndrome, diabetes, hypertension and MI.30 Circumstantial and experimental evidence has also implicated magnesium deficiency in osteoporosis.31–34 Optimal dietary magnesium intake is about 7–10 mg/kg/day, preferably in the context of a net base-yielding diet, since a net acid-yielding diet increases excretion of both magnesium and calcium (table 2).

Table 2

Magnesium dietary sources

Potassium/sodium ratio affects calcium metabolism

A potassium/sodium ratio of 1.0 or higher is associated with a 50% lower risk of CVD and total mortality compared with a ratio under 1.0.35 Reducing excessive sodium intake is also associated with resultant decreased urinary calcium excretion, which may help to prevent against bone demineralisation.36 The average potassium content (about 2600 mg/day) of the typical US diet is substantially lower than its sodium content (about 3300 mg/day).35 Approximately 77% of dietary sodium chloride is consumed in the form of processed foods. By contrast, potassium is naturally abundant in many unprocessed foods, especially vegetables, fruits, tubers, nuts, legumes, fish and seafood. In fact, a high potassium/sodium ratio is a reliable marker for high intake of plant foods and lower intake of processed foods.35 High dietary sodium intake has been associated with endothelial damage, arterial stiffness, decreased nitric oxide production and increased levels of transforming growth factor β; whereas, high potassium dietary intake can counteract these effects.35 36

Evidence indicates that the lowest CV event rates occur in the moderate sodium excretion and high potassium excretion groups.37 Thus, it appears that a moderate sodium diet (2800–3300 mg/day) in conjunction with a high potassium intake (>3000 mg/day) might confer the optimal CV benefits for the general population.37

Vit K and bone health

Emerging evidence suggests that Vit K may confer protective effects for both the skeletal and CV systems. Vit K operates in the context of other fat-soluble vitamins, such as A and D, all of which are involved in maintenance of serum calcium concentration, along with the manipulation of materials leading to bone morphogenesis and maintenance of bone tissue.38 Specifically, the oxidation of Vit K results in activation/carboxylation of matrix Gla protein (MGP) which is partially responsible for mineralising bone.39

Also, Vit K is required for the activation (γ-carboxylation) of osteocalcin; the inactivated form, or per cent of undercaboxylated-osteocalcin (%ucOC), has been found to be a sensitive indicator of Vit K nutrition status.38 In cross-sectional and prospective analyses, elevated %ucOC, which occurs when Vit K status is low, is a marker of increased risk for hip fracture in the elderly.38

Several large observational studies appear to support the benefits of Vit K on bone health.38 A meta-analysis concluded that while supplementation with phytonadione (Vit K1) improved bone health, Vit K2 was even more effective in this regard.40 This large and statistically rigorous meta-analysis concluded that high Vit K2 levels were associated with reduced vertebral fractures by approximately 60% (95% CI 0.25% to 0.65%), hip fractures by 77% (95% CI 0.12% to 0.47%), and all non-vertebral fractures by approximately 81% (95% CI 0.11% to 0.35%). Moreover, the benefit of Vit K on bone may not be due to its ability to increase BMD, but rather to its effects at increasing bone strength.41

Vit K benefits in CV health

Mounting evidence suggests vascular calcification whether in the coronary or peripheral arteries is a powerful predictor of CV morbidity and all-cause mortality.42 Prevention of vascular calcification is therefore important as an early intervention to potentially improve long-term CV prognosis.

A major calcification inhibitory factor, is a Vit K-dependent protein synthesised by vascular smooth muscle cells.42 Increased Vit K2 intake has been associated with decreased arterial calcium deposition and the ability to reverse vascular calcification in animal models. Vit K2 prevents pathological calcification in soft tissues via the carboxylation of protective MGP. The undercarboxylated (inactive) species of MGP is formed during inadequate Vit K status, or as a result of Vit K antagonists.42 Low Vit K status is associated with increased vascular calcifications, and can be improved by effective Vit K supplementation (table 3).4344 In two different randomised, double-blind controlled trials, supplemental Vit K has been shown to significantly delay both the development of coronary artery calcification and the deterioration of arterial elasticity.45 46

Table 3

Vitamin K1 dietary sources

Dietary Vit K exists as two major forms: phylloquinone (K1) and menaquinones (MK-n). K1, the predominant dietary form of Vit K, is abundant in dark-green leafy vegetables and seeds. The main dietary sources for MK-n in Western populations are fermented foods, especially natto, cheese and curds (mainly MK-8 and MK-9).47

Calcium supplementation and bone health

A recent large meta-analysis of 26 randomised controlled trials reported that calcium supplements lowered the risk of any fracture by a modest but statistically significant 11% (n=58 573; RR 0.89, 95% CI 0.81 to 0.96).48

Importantly, a low dietary calcium intake with or without calcium supplementation is also associated with higher CV morbidity and mortality rates.51

Figure 3

Relationship of daily calcium intake to risk of CV mortality during follow-up. Data were fully adjusted for confounding variables. The calcium intake for optimising CV longevity is about 1000 mg/day, with higher and lower calcium intakes associated

Elevated serum calcium concentrations are associated with carotid artery plaque thickness, arterial and aortic calcification, and incidence of MI.57 58 Transient elevations in serum calcium levels have been noted following ingestion of 500–1000 mg of calcium supplements.63 64 By contrast, calcium from dietary sources or bone (calcium hydroxyapatite) ingestion results in much smaller changes in circulating calcium levels.

A plant-rich, grain-free diet alters the acid–base status so as to be slightly alkaline, which is conducive for bone health. However, plants are relatively poor sources of calcium compared to animal sources such as dairy products and animal bones. We suspect that milk, though an excellent source of bioavailable calcium, has potential adverse health effects for some individuals. Additionally, 65% of the world’s population show some decrease in lactase activity during adulthood. Importantly, fermented dairy has been linked to favourable outcomes for bone health and mortality risk.

In a small placebo-controlled randomised trial, women who took 1000 mg of calcium in the form of hydroxyapatite in conjunction with oral Vit D showed a significant increase in bone thickness, whereas those who took 1000 mg of a standard calcium carbonate supplement did not (figure 4).

In theory, consuming calcium-rich foods such as bones, fermented dairy (eg, unsweetened yogurt, kefir, cheese), leafy greens, almonds, and chia seeds may be an effective strategy for improving both calcium intake and long-term health.

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