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ProView - The technical publication for Infinity2 health professionals. Volume 7 • Number 1
Osteroporosis
By: J.Ferniza, MS, CCN, CSCS
INTRODUCTION
Osteoporosis is a progressive disease in which the bones gradually become weaker and weaker, causing changes in posture and making the individual very susceptible to bone fractures. Osteoporosis affects more than 28 million Americans and leads to more than 1.5 million fractures each year. By age 60 to 70, more than 30% of women have osteoporosis, and the incidence increases to 70% by age 80 (46). Because you may not notice any symptoms until a bone breaks, osteoporosis is called the “silent disease.”

Many people have the impression that osteoporosis is caused solely by a dietary calcium deficiency and therefore can be remedied by taking calcium supplements. But that is not entirely true. While calcium supplementation is important in dealing with osteoporosis, there are other considerations as well. Factors such as exercise, hormonal status, genetics, smoking, caffeine, salt intake, and deficiencies of other vitamins and minerals can all influence bone density, calcium status and risk for osteoporosis (1).

Bone is a living, continuously self-renewing tissue (20). It is actually made up of several types of specialized cells that perform this self-renewing process. Special cells called osteoclasts (bone-resorbing cells) break down old bone as other cells called osteoblasts (bone-forming or remodeling cells) replace it with new tissue (20;33). The loss of bone mass and bone architecture is a result of an imbalance between the normal resorption and remodeling processes that occur in the skeleton to rebuild and renew bone tissue.

The inside of bone normally looks like a honeycomb. In osteoporosis, the spaces in this honeycomb grow larger because much more bone is destroyed than is replaced (Figure 1). This makes the bones weaker and more prone to fractures.

Vertebral fractures are the most frequent of the fractures associated with osteoporosis, followed by femoral or hip fractures, and fractures of the wrist (40). Hip fractures are a major problem resulting in severe loss of function and often require hip replacement surgery, which can be very expensive. Unlike hip and wrist fractures, vertebral fractures often do not come to clinical attention at the time of fracture (46). In fact, because vertebral fractures often occur without causing pain, only about 1/3 are ever diagnosed (46).

Unfortunately, vertebral fractures can significantly impair an individual’s functional capacity because they commonly cause kyphosis or Dowager’s hump making it difficult for individuals to reach and perform heavy housework (40).

DIAGNOSIS, PREVENTION AND TREATMENT
In individuals with osteoporosis, low trauma fractures can occur even when performing routine activities (19). Thus, preventing fractures and promoting functional independence should be the goals for the treatment and prevention of osteoporosis. Identifying those at risk for osteoporosis is often the first step. Risk factors for developing osteoporosis are summarized in Table 1.

Table 1:
Risk Factors for Developing Osteoporosis
Family history of osteoporosis
Female
White or Asian
Slight body build
Estrogen depletion
Menopause
Early oophorectomy in women
Hypogonadism in men
Hypogonadism in women with excessive exercise
Age: especially after age 60
Lack of exercise
Prolonged use of certain medications
Aluminum-containing antacids
Steroids
Tetracycline
Anticonvulsants
Exogenous thyroid
Underweight or underfat
Cigarette smoking
Excessive alcohol consumption
Excessive fiber consumption
Excessive caffeine consumption
Inadequate calcium or vitamin D intake

Although fractures are the true functional endpoint of osteoporosis, bone density is the most common measure used in determining the presence or absence of osteoporosis. The bone density at which a fracture is likely to occur is called the fracture threshold. As long as the bone density and bone strength is above the fracture threshold, fractures are not as likely to occur. The theory follows that, the greater the peak bone mass attained, the longer it will take to reach the osteoporotic state (47).

Peak bone density or peak bone mass (PBM) is the maximum amount of bone tissue an individual attains (46). Ninety-five percent (95%) of bone mass is attained by the end of linear growth, but an additional 5-10% of bone mass can be accrued after maximum height has been achieved (36). The major final phase of PBM development in white women is 20 to 25 years of age (8); however, the exact timing seems to differ for different types of bone (36). Optimal development of PBM in adolescents or young adulthood may be the most effective preventive strategy against late-life osteopenia and potential osteoporotic fracture(8).

Optimal bone mass depends on three essential supports: hormones, building materials (via nutrition) and mechanics (physical load) (50). If any of the three is deficient, optimal bone mass cannot be achieved. Each of these three supports will be discussed as they relate to optimal bone mass, but it is important to remember that low bone density is only one factor contributing to osteoporotic fractures (19). There are actually a variety of elements that contribute to fractures including falls, bone strength, padding and postural reflexes (27).

EXERCISE IN PREVENTION
AND TREATMENT OF OSTEOPOROSIS
The mechanics or physical load required for optimal bone mass is achieved through physical activity. The mechanical stimulation created by exercise supports bone formation and is one of the most potent anabolic influences on the skeleton. Mechanical loading can stimulate a cascade of intra and intercellular events that culminate directly in inhibition of bone resorption (breakdown) and/or stimulation of new bone formation (35).

Exercise therapy in the prevention and treatment of osteoporosis has three main goals(50):
1- Optimizing peak bone mass in young adults, especially pre-menopausal women.
2- Preventing the decline in bone mass associated with age and menopause.
3- Improving other factors that contribute to fractures including muscle strength, proprioception, gait, postural stability and functional ability (39). The majority of osteoporotic fractures occur as a result of a fall and many of the factors that predispose a person to falls can be modified by exercise (39).

Long-term physical activity is the most significant determinant of PBM(8) and when combined with appropriate nutrition and good health during the growth period, PBM is optimized. Exercise prescriptions for healthy young men and pre-menopausal women should include high intensity weight training and weight bearing endurance training in order to provide maximal mechanical loading to stimulate increases in bone mineralization and bone architecture, and maximize peak bone mass.

Normal mechanical utilization through daily activities conserves the existing bone in healthy men and pre-menopausal women. After menopause, however, the set points of the minimum effective mechanical load on the bone increase, in part, from decreased estrogen (21;27).

This change in minimum stimulation requirements results in a disuse message being transmitted to the bone, causing breakdown, even though normal mechanical utilization continues. Therefore, women need more mechanical force for conserving existing bone after menopause.

Exercises not involving any loading are less effective, because they do not activate the mechanical loading mechanisms that stimulate modeling. Weight bearing activities or exercise at an intensity of at least 60 to 80% of the 1RM (1 repetition max) is required to produce stimuli adequate to elicit any effects on bone density (25). Studies using exercise protocols based on these concepts have shown that exercise at these intensities is effective in preserving and/or increasing bone mass (21;23;25;32;37;39;42) and a minimum of 20 minutes of low impact exercise 3 days/week is effective at maintaining BMD (23). Exercise has positive effects not merely on bone density, but also on symptoms and complaints related to osteoporosis (21). The optimal exercise regimen for older adults and postmenopausal women should thus avoid further bone loss, reduce the risks of injury, relieve or prevent back pain, correct inappropriate posture and retain mobility (16;21). It should also be enjoyable in order to increase compliance (21;38).

HORMONES IN OSTEOPOROSIS
Estrogen is the hormone most often considered in treating osteoporosis, but the other, often forgotten hormones play an even more critical role in calcium balance and the onset or progression of osteoporosis. Three of the most important hormones are calcitriol, parathyroid hormone (PTH) and calcitonin. These three hormones are critical to maintaining and regulating plasma (blood) calcium levels.

Plasma calcium is very tightly controlled in a narrow range. If plasma calcium changes out of range, the body’s physiologic systems will react to return calcium to normal (48). Bone is the only real storage site for calcium, so if plasma calcium drops, calcium must be removed from the bone (resorption). Calcitriol (active vitamin D) in combination with parathyroid hormone (PTH) act to increase calcium resorption from bone in order to
stabilize plasma calcium (22;24). Calcitriol (active vitamin D) is also the most significant factor controlling ionic calcium absorption (48).

Calcitriol acts on the intestinal mucosal cells to increase the synthesis of calcium binding protein (CBP), which increases the absorption of ionic calcium from the intestine (22). A summary of these physiologic controls can be found in Table 2.

Secondary hormonal controls for calcium balance and bone metabolism include: insulin, cortisol, thyroxine, epinephrine, growth hormone, estrogen, and testosterone(22;33). The sex hormones, estrogen and testosterone, play key roles in bone metabolism and regulate other hormones. Estrogen in women is very important in bone growth and remodeling. It potentiates the bone modeling/remodeling responses to a given loading force (31) and acts to stimulate the osteoblastic activity in the remodeling process and during growth (22;24). Estrogen receptors have been found in both osteoblasts and osteoclasts (49) and estrogen depletion is directly related to bone loss in post-menopausal women (4;22;24).

The sex hormone receptors that are found in the bone cells also mediate the effects of the gonadal and adrenal steroids (50). Although the exact mechanisms are unclear at this time, it is possible that these receptors are responsible for the alteration in the “setpoint” of bone mass(27). When women lose ovarian hormones (especially estrogen), the skeleton seems to “sense” that it has more bone than it needs and hence allows resorption to take away more bone than formation replaces (27). In addition to adjusting the bone mass setpoint, estrogen also influences the efficiency of intestinal calcium absorption and renal calcium conservation, through its effects on serum calcium and PTH (27;50).

Phytoestrogens
Because estrogen plays such a key role in the loss of bone during and following menopause, hormone replacement therapy (HRT) is a common treatment used by allopathic physicians. However, possible contraindications of HRT such as breast cancer, endometrial adenocarcinoma, and undesirable side effects (41) have created an interest in alternative and natural hormone therapies. These alternative therapies include natural estrogen and progesterone creams, as well as increasing dietary intake of soy. While there is only limited research currently available on natural hormone creams, there is a significant body of research supporting isoflavone-containing soy as a potential alternative for preventing bone loss during the menopausal transition.

Isoflavones, found predominantly in soy products, are estrogen-like substances structurally and functionally similar to the primary human estrogen (17 B-estradiol) (30). These phytoestrogens can bind to estrogen receptors in the body and are unique in that they can produce both estrogenic and antiestrogenic effects, depending on the tissue in which they act (34). In breast tissues, phytoestrogens appear to have an antiestrogenic effect by binding to the estrogen receptors and blocking the effects of estrogen, thereby preventing the adverse effects on breast tissue associated with elevated estrogen levels. In bone, these phytoestrogens have an estrogenic effect, helping to attenuate bone loss (3).

The dietary supplement, ipriflavone, is a synthetic derivative of isoflavones. This is a popular dietary supplement ingredient in the United States and Europe, but the positive results of past research on ipriflavone have recently been challenged by a large, randomized, double-blind, placebo-controlled study published in the March 21, 2001 issue of JAMA (7). This study concluded that in postmenopausal women, ipriflavone neither prevents bone loss, nor reduces fracture risk. It also cautions that the compound can lower the level of lymphocytes (white blood cells) - an effect that could make individuals more vulnerable to infection.

These adverse effects have not been reported in any of the studies using soy protein, which contains natural isoflavones; yet, soy protein has been shown in numerous studies to have a positive effect on bone density(3;9;10). Soy protein has also been reported to provide cardiovascular health benefits (2;5). These studies have found that consuming 25 grams of soy protein per day may reduce the risk of heart disease (2;5). Until the safety and appropriate dosage of isolated and synthetic isoflavones can be examined further, it may be better to consume soy protein rich in natural isoflavones rather than supplements containing isolated or synthetic isoflavones.

NUTRITION FOR BONE HEALTH
Even when hormone levels are optimal for increasing or preserving bone density, bone cannot effectively renew itself without the proper building materials. These building materials are supplied through the diet and include calcium, magnesium, vitamin D, zinc, copper and manganese.

Calcium
The largest component of bone is calcium. Therefore, calcium metabolism is directly linked to bone metabolism. Calcium intake is most important during adolescence in helping to achieve PBM (8;33). A few studies have found that calcium supplementation in elderly women reduced the incidence of fractures and reduced bone loss (27). However, calcium supplementation alone was not effective at increasing bone density in elderly women (27).

While adequate calcium intake is important in dealing with osteoporosis, there are other considerations as well. Dr. James Balch, author of Prescription for Nutritional Healing (15), reports “People in the Unites States consume more dairy products and other foods high in calcium per capita than the citizens of any other two nations on earth put together. We even have orange juice and antacids that are fortified with calcium. Yet, we also have the world’s highest rates of osteoporosis and bone fractures among elderly people.” Some of the possible reasons for this apparent discrepancy are related to our other habits that increase bone loss. For example, we get less exercise to stimulate bone growth than our grandparents did. At the same time, we consume high amounts of salt, caffeine, animal protein and phosphate-containing foods such as soft drinks. All of these factors can deplete calcium(1;15). These factors and their effects on calcium are summarized in Table 3.

Table 3

Factor or Nutrient Effect on Calcium Mechanism

Oxalic Acid

Decreases absorption

Binds Ca in intestine

Maldigested saturated fat

Decreases absorption

Binds Ca in intestine

Lactose

Increases absorption

Facilitates transport into mucosal cell

Protein and amino acids

Increases absorption

Facilitates transport into mucosal cell

High Protein (100-150g/day)

Increased excretion

Increased nitrogen levels increases urine output

Sodium

Increased excretion

Lost in urine with fluid

Caffeine

Increased urinary loss short term

Diuretic effect

High phosphate or phosphorus

Decreases plasma free calcium levels making it unavailable

Binds plasma calcium

Magnesium and Other Minerals
There are other minerals, such as magnesium, zinc, copper and manganese that are also important for achieving and maintaining proper bone mass(1). In a study published in the Journal of Nutrition (45), the effects of calcium supplementation with and without the addition of trace minerals (zinc 15 mg/day, manganese 5 mg/day, and copper 2.5 mg/day) on spinal bone loss was evaluated in healthy postmenopausal women in a two year, double blinded, placebo controlled trial. Bone loss relative to base line value continued in the placebo group. The group receiving calcium alone showed some slowing of the bone loss process, while the group receiving calcium plus trace minerals had its bone loss arrested.

More recent research has also focused on the effects of magnesium on bone metabolism and osteoporosis (43). There is growing evidence that magnesium may be an important factor in the qualitative changes of bone matrix that determine bone fragility (43). The fact is magnesium influences both matrix and mineral metabolism in bone, and magnesium depletion causes cessation of bone growth, decreased osteoblastic and osteoclastic activity, osteopenia, and bone fragility (43). Several reports indicate that osteoporotic trabecular bone has decreased magnesium content compared with healthy bone (43). In addition to its role in bone structure, serum magnesium is necessary for proper calcium metabolism. If magnesium status is abnormal, adequate calcium intake may not ensure proper bone health. Studies examining the effects of magnesium supplementation in postmenopausal women suggest that magnesium supplementation may be beneficial in the treatment and prevention of osteoporosis (43;44).

CHOOSING A SUPPLEMENT
FOR BONE HEALTH
As more people become aware of the importance of nutrition in osteoporosis, many people have turned to supplementation to provide the nutrients needed for bone health. Unfortunately, most of the media and advertisements have focused solely on calcium and treat all calcium supplements as equal. What few people realize is that some forms of calcium are more effective than others. A current television commercial states that a particular brand of antacid not only relieves upset stomach, but also delivers something else that a body needs: Calcium! On the surface, this product seems to be a good value for the consumer, but the success of this ad may have come at the expense of the consumer’s health. The active ingredient in this antacid/calcium supplement is calcium carbonate. It is the most commonly used source of calcium in supplements on the market today because it is inexpensive and has a high calcium content. This is an easy solution....but is it effective?

The answer is no. Research has shown that effective calcium supplementation should include a source of calcium that is safe, bioavailable, retained in the tissues, contains the correct dosage and be balanced with other nutrients.

Safety
All non-chelated calcium salts, such as calcium carbonate, have the potential to cause constipation, and have been shown to cause diarrhea in the elderly (29). Other side effects of calcium salts include flatulence, nausea, and bloating. One of the reasons for these side effects is the chemical reaction that calcium salts and/or ionic minerals undergo in the digestive tract. As illustrated by the chemical reaction for calcium carbonate below, all calcium salts are converted to calcium chloride in the stomach.

CaCO3 + 2HCl = CaCl2 + H2O + CO2
(The acid neutralization reaction which occurs in the stomach and creates calcium chloride)

It is the calcium chloride that produces gastrointestinal irritation. Therefore, all salt forms of calcium will produce some gastric irritation. The acid neutralization reaction shown previously forms the basis for calcium carbonate’s effectiveness as an antacid. This same chemical reaction is also the key to calcium carbonate’s ability to cause a greater danger than just gastrointestinal distress. Continued use of calcium carbonate has been associated with milk-alkali syndrome(6;29). Milk-alkali syndrome presents with three problems: hypercalcemia, metabolic alkalosis, and renal failure. Different forms of this syndrome have been described in medical literature. In 1995, researchers reported that increased consumption of calcium carbonate for prevention and treatment of osteoporosis may be causing the problem of milk-alkali syndrome to become prominent once again(18). These researchers documented cases where calcium carbonate products were the cause of an observed increased incidence of milk-alkali syndrome. The risk of milk-alkali syndrome with calcium carbonate is increased by high dosage, prolonged use, or the concomitant use of sodium bicarbonate and/or homogenized milk and vitamin D (6).

Bioavailability
The second issue in choosing an appropriate calcium supplement is bioavailability. The calcium commonly found in supplements and products, such as the aforementioned antacid, are calcium carbonate and/or calcium citrate. Only about 20 to 25% of the calcium from these forms is absorbed (Figure 2 (28)). Calcium hydroxyapetite is another form of calcium, which is promoted by various supplement companies with statements such as, “calcium hydroxyapetite is a complex crystalline compound composed primarily of calcium, phosphorus, delicate organic factors and protein matrix, and a full spectrum of trace minerals that naturally comprise healthy bone.” What isn’t mentioned is that this popular form of calcium actually has the lowest absorption rate at only 17%.

Fortunately, there is a more absorbable and safer form of calcium available. Studies have shown that calcium amino acid chelate has approximately twice the absorption rate of other forms of calcium. The significant differences in bioavailability are in large part the result of the way that each type of mineral is absorbed and metabolized (11;12;14). For a mineral salt to be absorbed, the mineral must solubilize or ionize in the acid pH of the stomach after ingestion (13). Because the acid environment is essential for absorption of mineral salts, antacids have the potential to interfere with the absorption of numerous minerals. This illustrates another reason why antacids are not necessarily a good source of calcium. Once the mineral salt is in its ionic form (usually divalent), if it gets close enough, it can bind to the proteins on the mucosal cell membrane (that is, if it hasn’t bound to other food components in the digestive tract first, such as fiber and phytic acid). The mineral is then chelated to the membrane protein so that it can be transported into the mucosal cell, released intracellularly and rechelated to a smaller protein or amino acid for transport within the cell and the plasma (13).

The improved absorption of amino acid chelates compared to mineral salts is due to the way amino acid chelated minerals are absorbed (11;12;14). First, amino acid chelated minerals do not need to be solubilized and do not interact with other food components in the digestive tract (17). Second, the intestinal treatment of the chelate is as a peptide rather than an ion (11;12;14) and it is already in a form that can be absorbed and transported intracellularly. This allows it to potentially avoid the two-step absorption mechanism required for other mineral forms. The process of chelation with the membrane protein and the release of the ion for rechelation with an intracellular protein for transport to the basement membrane are not necessary (11;12). The result is absorption rates and retention rates that are much greater than mineral salts because the mineral is provided in a form that the body can use.

Retention
A third key to effective calcium supplementation is the ability of the calcium to be retained once it is absorbed. The data summarized in the figure below was constructed from data gathered by Professor D. Graff at Weber State University.
In this study, Professor Graff administered equal amounts of radio labeled calcium from chloride (which is the inorganic form of calcium formed in the stomach from calcium salts) and Albion Laboratories’ amino acid chelate. Seven days later, the absorbed calcium which was retained in the animals’ bodies was measured. The animals retained 54.4% more calcium from Albion’s calcium amino acid chelate. Significantly, 57% more calcium from Albion’s amino acid chelate found its way to the bone tissue than from calcium chloride (12).

Correct Dosage
The tendency for most supplement companies is to offer large amounts of calcium per tablet/capsule in dosage forms that permit a required daily intake in a single swallow. This may be an easy way to sell calcium supplements, but it is not in the consumer’s best interest. Based on absorption efficiency research, it would appear that the most effective calcium supplementation program would consist of smaller divided doses, as opposed to larger single doses. More per dose is not necessarily better(26).

Balanced with Other Nutrients
As discussed earlier, calcium is not the only mineral required for bone health (1;45). Studies have shown that magnesium must be balanced with calcium in order to optimize bone health (43;44). Supplementing with the other nutrients required for bone health provides greater benefits over calcium alone (45).

SUMMARY
In summary, osteoporosis is a multi-factorial disease that is influenced not only by dietary calcium intake, but also by other nutrients, exercise, genetics, hormonal status, and lifestyle factors such as smoking, alcohol consumption and caffeine intake. A successful program for the treatment and prevention of osteoporosis will examine hormonal status, increase physical activity, make appropriate alterations in lifestyle factors and include an effective calcium supplement that provides a safe, absorbable form of calcium combined with other important nutrients (magnesium, zinc, copper and manganese).

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