—Kevin M. Connolly, Ph.D. Coauthor
Bone health is one of the most widely written about topics in the United States and most of us, no doubt, feel we have a grasp of how to protect ourselves. Sadly, most of us would be wrong in judging our own risk of suffering from osteoporosis or related conditions and most of us would be wrong in evaluating which nutrients are most important for protecting bone health.
Let’s start with the basics. Osteoporosis can be a silent disease that may not be revealed until a fracture is experienced. Only perhaps one half of individuals suffering from osteoporosis are aware of their condition. On the National Health and Nutrition Examination Survey (NHANES) only one percent of men and 11 percent of women over 65 reported they had osteoporosis. However, bone mineral density (BMD) testing revealed that four percent of male and 26 percent of female survey takers actually had the disease. The mismatch between perception and reality with regard to bone health gains importance from the fact that the number of individuals involved is huge.
Over 10 million Americans suffer from osteoporosis, a number that is expected to grow to 14 million in the next decade. About 20 percent of these cases are men. Another 34 million have thinning bones and low BMD that puts them at risk for osteoporosis. It is estimated that 50 percent of women (and 25 percent of men) will suffer an osteoporotic fracture in their lifetimes; amounting to approximately two million fractures per year in the U.S. Although women are significantly more likely to experience an osteoporotic fracture (up to 90 percent of all hip and spine fractures in women 65 – 84 years can be attributed to the disease), men account for about 29 percent of fractures annually. Studies have also indicated that 30 percent to 50 percent of patients on glucocorticoid therapy sustain fractures due to secondary osteoporosis.
The common wisdom regarding osteoporosis risk is rather wide of the mark. To make matters worse, our usual supplement choices may not reflect any better aim. To improve bone health and reduce fracture risk, Americans have been taught to focus on calcium supplements and bone mineral density. Many experts, however, look elsewhere. They draw a distinction between bone quality (which concerns reduced risks of fracture) and bone quantity (which is concerned exclusively with bone mineral density). One reason for this distinction is that for the vast majority of women, BMD is not statistically significantly related to fracture risk. Bone quality, not merely quantity, is important. Moreover, calcium, the major component of BMD measurements, does not add greatly to bone’s resistance against the most dangerous types of mechanical stresses. Calcium alone does not greatly improve bone quality. It is the other 28 percent of the bone, the collagen and other components found in the bone matrix, that are active in bone formation, and give a degree of flexibility to bone — hence primarily help to reduce fracture risk. Likewise, it is factors other than calcium in the diet and supplements that primarily determine what the body does with calcium and whether supplemental calcium actually improves bone health.
Calcium and vitamin D are familiar to most people; indeed, usually they are considered to be synonymous with bone health supplements. The uptake, transport, and incorporation of calcium into the skeleton is a complex process that is critically dependent on the endogenous hormone calcitriol (activated vitamin D), which in turn is reliant on a set of regulatory reactions that carefully maintain the overall calcium balance. Calcium bioavailability involves a highly regulated intestinal absorption system as well as the regulated incorporation of calcium into the bones themselves.
Calcium is absorbed primarily in the small intestine both actively (by a transport system) and passively (by diffusion). “Passive” absorption accounts only for a small amount of total calcium assimilation. “Active” transport is a regulated transport that responds to levels of calcium in the body and only allows absorption if more calcium is needed. Thus, if calcium levels are sufficient in the body, the active transport system becomes inactive. Similarly, the faster and the greater the amount of calcium presented to the body at any one time, the greater the likelihood that calcium absorption will be regulated downward.
Does the form of calcium matter? If all that is involved is absorption from the gut, apparently not very much. For example, mean apparent calcium absorptions have been calculated based on three to eight studies (for each of four calcium salts) and 12 to 14 studies (for carbonate and milk calcium). Here are the results based on either fasting (between meal) or meal-based ingestion:
Although these numbers must be interpreted cautiously inasmuch as the studies were performed using different test groups and study parameters, it is clear that when averaged over several studies, calcium absorption is limited to about one quarter to one third of ingested dose with the greatest documented differences between calcium forms amounting to only a few percent. One should be aware of the fact that carbonate is the calcium storage form for several of the “food-matrix” commercial calcium supplements: eggshell, algal and shellfish calcium are all calcium carbonate. The absorption of calcium generally declines with age and the use of certain medications. Likewise, taking large amounts at any one time diminishes uptake. Contrarily, dividing calcium doses significantly increases fractional absorption by preventing the saturation and shutdown of the active transport system. In one particularly illustrative (and extreme) example, dividing a 1000 mg dose into 17 evenly-spaced doses over an eight-hour period increased its fractional absorption by almost 100 percent!
- carbonate, from 26.4 percent (fasting) to 29 percent (meal)
- citrate/malate from 32 percent (fasting) to 37 percent (meal)
- citrate 23.5 percent (fasting)
- lactate/gluconate 24.5 percent (fasting)
- chloride 30.6 percent (fasting)
- milk 32.4 percent, cheese 32.8 percent
- mineral waters 32.3 percent
Are Some Forms of Calcium More Beneficial? Yes, but It’s Not the Calcium!
Active absorption is the major source of calcium uptake, yet if the primary influence on active absorption — the amount of acid released in the stomach — is reduced, then passive absorption takes on greater importance as a fallback. Calcium chelates are complexes of calcium and other organic molecules, such as organic acids (citrate, malate, threonate, ascorbate) or amino acids (aspartate). Like salts, they can dissociate into ionized calcium for the active transport mechanism, but they are more resistant to this process. Unlike salts, however, they are soluble in their unionized, intact form; this may allow them to be directly absorbed by passive diffusion. The advantages to chelates appears to be that in situations in which calcium digestion is sub-optimal, they exhibit less of an absorption penalty. Hence, if calcium is taken between meals or individuals exhibit achlorhydria or are taking proton-pump inhibitors or histamine blockers, chelated calcium, such calcium citrate or calcium malate, may be preferable forms.
Matrix-bound calciums are complexes of calcium or calcium salts with an organic matrix. In most cases, matrix-bound calciums are inorganic salts of calcium, with a protein and polysaccharide component extracted from a natural source. Matrix-bound calciums are often marketed as “food-based” or “recognized by the body as food,” but these statements should be interpreted with caution. For the most part, the calcium in these matrices is a calcium salt, usually calcium carbonate. Algal, eggshell, and shellfish calciums all predominately consist of crystals of calcium carbonate. In contrast, calciums from milk and bone are different — they are tricalcium phosphate and hydroxyapatite (different types of calcium phosphates).
Often it is claimed that matrix-bound calcium products — algal, eggshell, milk, bone, etc. — provide superior benefits. Perhaps they do, but it is not because of the nature of the calcium present. The benefits of matrix-bound calcium over other forms has more to do with the nature of the matrix than with the calcium:
- Algal and eggshell calciums contain additional trace elements
- Bone-specific growth factors are found in eggshell and ossein (bone) matrices
- Milk calcium (if it uses the milk matrix and is not simply purified tricalcium phosphate) has a significant portion of colloidal phosphocaseinate that may prevent calcium precipitation and may prolong calcium residence time in the gut. Providing a sustained calcium dose has a stimulatory effect on passive diffusion.
To clarify the impact of matrix components other than calcium on bone health benefits, let’s take a closer look at the effects of bone-derived calcium on bone growth. Bone-derived calcium is ossein-hydroxyapatite complex (OHC) also sometimes referred to as microcrystalline hydroxyapatite. This complex of hydroxyapatite calcium and protein (ossein) is isolated from bovine bone. Ossein is rich in proteins that stimulate bone growth: collagens, osteocalcin, and growth factors (IGF-I,II, TGF-B, bone morphogenic protein). This calcium source has been the subject of numerous studies (for a summary of 18 comparative OHC studies. When compared to calcium alone in the form of calcium carbonate, the ossein matrix provided an additional increase in BMD of at least one percent for total BMD and increases of up to five percent in vertebrae.
Clinical studies thus have uncovered an important clue about the relation between calcium absorption and BMD, especially with regard to certain sites, such as the spine. If taken with meals, most forms of calcium yield similar absorption data and the differences between the best and the poorest performing sources can generally be overcome by taking just a bit more calcium. The 5 percent additional calcium found in the spinal vertebrae of women taking bone-derived calcium rather than calcium carbonate represents the actions of the other components found in the calcium source and not the impact of the calcium itself.
Non-calcium Nutrients Benefits for Both Bone Quantity and Quality
Non-calcium nutrients play many roles in bone health. The trace mineral boron, for instance, has a part in estrogen metabolism. Potassium has been shown to reduce calcium loss from the body. Magnesium helps to keep calcium in the bones, where it belongs, rather than in the lining of the arteries, where it does not. Zinc stimulates bone formation and reduces bone resorption.
There are other factors, as well. Vitamin K maintains lumbar bone and reduces new fractures. Folic Acid reduces homocysteine levels because high levels have been linked to osteoporosis. Vitamin D, of course, is required for the regulation of absorption of calcium from the gut and then its use for maintaining bone calcium levels. Vitamin C, copper, manganese and glucosamine are all important for supporting the activities of the bone matrix, the most active site of bone repair.
Remember, the bone is approximately 28 percent collagen and other components found in the bone matrix and that are active in bone formation, give a degree of flexibility to bone, and primarily help to reduce fracture risk. Despite the media focus on BMD, preserving or even increasing BMD does not reduce fracture risks in the vast majority of women. This means that supplementing calcium alone does not reduce fracture risks in the vast majority of women. Bone is living tissue that must constantly be repaired. It is the quality of the repair, not just the amount, that matters.
Vitamin K’s role offers an illustration of the point. Vitamin K is a family of fat-soluble vitamins that are needed for the modification of certain proteins that are involved in blood coagulation as well as proteins that are involved in calcium chelation in bone and other tissues. Vitamin K1 (phylloquinone) can be found in leafy green and cruciferous vegetables and, to a lesser extent, in fruit. Vitamin K2 (menaquinone) is found in a number of fully fermented foods, including cheeses and soy products. Most of the activity of vitamin K in bone growth involves its function as a cofactor. For example, it is involved in the activation of Matrix Gla protein, which is thought to control the calcification process. Matrix Gla protein also has been shown to inhibit calcification in soft tissues (e.g., the cardiovascular system). Osteocalcin (sometimes called bone Gla protein) is the most abundant non-collagenous protein in bone. It is thought to directly bind to hydroxyapatite and possibly regulate calcium flux.
Low vitamin K status has been associated with reduced BMD and increased fracture risk in several reports. Short-term studies of vitamin K2 have shown it to be effective for maintaining BMD. Longer-term studies, typically requiring two years for benefits to manifest, have shown decreases in fracture incidence by up to 66 percent as well as increases in BMD, especially when combined with vitamin D3. Even in osteoporotic patients and without any significant impact on BMD, K1 supplementation for a period of four years reduced fracture risks. In short, Vitamin K supplementation for sustained periods of time, generally two years or more, benefits both BMD and fracture risk. The primary benefit likely is in the latter area and involves bone quality because fracture risks are reduced even in the absence of benefit to BMD.
And then there is silicon. Silicon (Si) is a semi-metallic element with important roles in plant and animal metabolism. It is distinct from, and often confused with silicone, a synthetic polymer. Silicon is found in nature as orthosilicic acid (OSA), Si(OH)4, a common component of mineral waters. OSA is taken up by plant roots. In animals and humans, silicon is involved in the synthesis of collagens, increasing the production of collagen mRNA, stimulating the production of the amino acid proline (the most abundant amino acid in the collagen), and serving as a cofactor for the collagen synthetic enzyme prolyl hydroxylase. Silicon may also have functions in the formation of glycosaminoglycans and in bone mineralization.
Silicon is required for proper bone formation in animals and has a positive correlation with BMD in humans. Analysis of data from the Framingham and Framingham Offspring studies for 1251 men and 1596 pre- and postmenopausal women (aged 30 – 87 years) revealed up to a 10 percent difference in BMD between individuals with the highest (>40 mg Si/day) and lowest (<14 mg Si/day) intakes of silicon. Combined therapy of silicon (as OSA) with calcium and vitamin D had profound effects on the preservation of BMD in humans. The addition six mg/day to a calcium/cholecalciferol regimen (1000 mg calcium carbonate and 800 IU vitamin D3) maintained baseline BMD levels in women with osteopenia over a period of 12 months, and displayed a significant increase (19 percent) in bone collagen formation, i.e., activation of the bone matrix. Women taking calcium and vitamin D alone experienced significant mineral loss. These data further implicate silicon as an effective, although often overlooked, addition to any strategy for maintaining skeletal health.
Bone health is a serious matter and it involves more than maintaining BMD or supplementing with calcium. The primary issue with calcium is not absorption, getting it into the body, but rather getting it to go where it is supposed to go and do what it is supposed to do. Most forms of calcium are similarly absorbed. Calcium forms are separated from one another in terms of benefits to a large extent by associated nutrients, including trace elements and activating factors. It is these factors that separate bone-derived or eggshell calcium from mere calcium carbonate. Similarly, nutrients such as silicon and vitamin K support calcium and vitamin D in part by influencing the factors associated with bone quality, not just bone quantity. Yes, calcium and BMD are important, but greater bone matrix health and reduced fracture risks are the true hallmarks of improved bone quality.