Osteoporosis
Updated: 07/17/2006

It is common knowledge that calcium and vitamin D work together to help prevent osteoporosis. But what about the many other essential minerals and nutrients needed for bone health? And which kind of calcium is really the best? Many people are surprised to learn it is probably not the kind they are taking on a regular basis.

The human skeleton is the single largest organ system in the body. Composed of a complex mix of organic proteins and inorganic mineral crystals, bones are much more than just structural supports. They are the body’s only reservoir of minerals such as calcium and phosphorus, which are critical for virtually every other organ system. The bones are also highly sensitive to hormonal changes. During puberty, when hormone levels surge in both boys and girls, bones are stimulated to grow rapidly as teenagers become full-sized adults. Thus, it is not really surprising that in later years, as hormone levels decline, the bones become vulnerable.

Maintaining healthy bones goes far beyond calcium and vitamin D, although these are vital. A healthy bone matrix also relies on vitamins and minerals that are rarely mentioned in the context of osteoporosis, including zinc, boron, copper, magnesium, vitamin K, silicon, folic acid, and others. This information is vital to the 10 million people, including 2 million men, who are known to suffer from osteoporosis in the United States.

Causes of Osteoporosis: Bone Remodeling

Osteoporosis is defined as a reduction of bone mass, or bone density, which causes the bones to become brittle and fragile. People afflicted with osteoporosis are at increased risk of a range of fractures, including fractures of the hip, spine, and wrist. Fractures associated with osteoporosis are debilitating and costly (Melton LJ 2003; Woolf AD et al 2003). Mortality rates one year after hip and spine fractures have been reported to be as high as 30 percent (Rossell PA et al 2003; Kanis JA et al 2004). Many studies report high rates of institutionalization, loss of function, and death after hip and spine fractures.

Bone is living tissue comprising both organic protein matrix (30 percent) and various minerals (70 percent). Throughout life, cells known as osteoblasts construct bone matrix and fill it with calcium. At the same time, cells called osteoclasts work just as busily to tear down and resorb the bone. This fine balance is regulated by many factors, including systemic hormones and cytokines. Bone mass reaches its peak by the middle of the third decade of life and plateaus for about 10 years. During this time bone turnover is constant, meaning bone formation approximately equals bone resorption.

As our bodies age, this fine balance is lost. As the relative hormone levels shift in midlife—more drastically in women than in men—the osteoclasts gain the upper hand, and bone mass begins dwindling. Some bone is already being lost by the time women reach menopause, but the rate of loss can increase as much as tenfold during the first six years after menopause. This is the essence of primary osteoporosis, or osteoporosis that occurs as a natural part of aging.

From midlife onward, bone health is threatened by overactive osteoclasts. To add to the problem, the osteoblasts may become less active from age 60 onward, causing type II osteoporosis. Whereas trabecular (spongy looking) bone in the vertebrae and elsewhere was formerly at risk from excess osteoclast activity, now the cortical (dense) bone of the hip, shin, pelvis, and other sites becomes more prone to fracturing because osteoblasts do not make enough of it.

Osteoporosis can also be caused by medications, especially glucocorticoids and corticosteroids, testosterone-deprivation therapy in prostate cancer patients, and any condition that impairs calcium metabolism, including kidney disease, organ transplants, smoking, and others.

Recent research suggests that advanced glycation end products, or AGEs, are implicated in bone loss. AGEs are formed when proteins interact with glucose molecules to form damaged structures in the body. One study examined the proteins in osteoporotic bones to determine if there was damage by AGEs. More AGEs present resulted in fewer bone-building osteoblasts (Hein G et al 2006).

Nutritional Therapies: Calcium and Beyond

Calcium and vitamin D are the cornerstone of osteoporosis prevention, yet they are not the whole story. Other minerals and nutrients that are vital to a healthy bone matrix include magnesium, potassium, vitamin C, vitamin K, vitamin B12, and others, including zinc, manganese, boron, copper, and silicon (Nieves JW 2005; Hirota T et al 2005).

Calcium. Many studies have shown that calcium can reduce bone loss and suppress bone turnover. Calcium intake is a foundation of osteoporosis prevention (Kasper DL et al 2005). Calcium requires the presence of vitamin D for maximum absorption.

Although calcium is readily available in dairy products and other dietary sources, many Americans are calcium deficient. There are a few possible explanations for calcium deficiencies:

• Decreased vitamin D availability, possibly due to kidney or liver problems or insufficient exposure to sunshine (ultraviolet radiation)
• Decreased gastrointestinal tract absorption due to stomach or intestinal problems
• Increased loss of calcium from the kidneys
• Increased loss of calcium from the colon and bowels
• Low dietary calcium intake
• Medications that inhibit calcium absorption

There are many forms of calcium on the market, including the common calcium carbonate, calcium gluconate, and calcium citrate. Of these, calcium citrate is the most easily absorbed and a good way to receive supplemental calcium.

It may also turn out that not only is supplementation vital to preventing and treating osteoporosis but that the timing of the supplementation is important. For example, in a study of healthy volunteers, two doses of 500 mg calcium and 400 IU vitamin D taken six hours apart produced a more prolonged decrease in serum parathyroid hormone levels (low levels of which indicate adequate calcium levels) than a single dose with the same total amounts of calcium and vitamin D.

Magnesium. Magnesium plays essential roles in bone formation and helps with calcium absorption. Studies have found that magnesium deficiency is associated with osteoporosis and bone fragility (Sasaki S 2006; Saito N et al 2005) and that adequate magnesium intake is associated with increased bone mineral density among white men and women (Ryder KM et al 2005).

Unfortunately, many people have magnesium deficiency, which may be caused by alcohol abuse or malabsorption (Takami S et al 2005). Dietary magnesium deficiency in North Americans often occurs because people do not consume enough dark green, leafy vegetables, which are rich in magnesium. If not provided in the diet, magnesium should be taken as a supplement.

Recommendations for postmenopausal women to increase calcium intake can lead to an unfavorable calcium-to-magnesium ratio unless magnesium intake is increased accordingly; the optimum ratio of calcium to magnesium is believed to be 2:1, though extra magnesium may be needed to protect against atherosclerosis.

Phosphorus. Phosphorus regulates bone formation, inhibits bone resorption, and also affects the regulation of calcium metabolism. Although there are few studies on the direct effect of phosphorus on bone mineral density, it is important to maintain a proper phosphorus-to-calcium intake because of the effect phosphorus has on calcium metabolism (Kawaura A et al 2005). One researcher recommended a daily intake of 1000 mg calcium, with three-quarters as much (750 mg) phosphorus, as this intake was associated with higher bone mineral density among young women (Kawaura A et al 2005). It is also a good idea to reduce the consumption of soft drinks since they are high in phosphorus and can unfavorably alter the calcium/phosphorus balance.

Other minerals and trace elements. Few people are aware of the importance of balanced intake of minerals and trace elements, including copper, zinc (Yamada S et al 2004), silicon, and boron. Recent research suggests that it is important to ensure adequate intake of these minerals (Miggiano GA et al 2005).

Copper plays an essential role in bone metabolism and turnover. It modulates the differentiation and proliferation of osteoblast precursors, namely the mesenchymal stem cells (Rodriguez JP et al 2002). Women taking copper supplementation have shown improved bone density, while copper deficiency can produce osteoporosis in animal models of the disease (Klevay LM et al 2002).

Boron assists with calcium absorption and bone formation. It maximizes the body’s utilization of calcium, vitamin D, and magnesium and has shown antiosteoporotic activity (Burnham BS 2005). It is especially effective in the presence of deficiencies in vitamin D, magnesium, and potassium (Schaafsma A et al 2001).

The role of zinc in osteoporosis is less well understood, but it is increasingly apparent that zinc deficiency is a risk factor for osteoporosis. It has been theorized that zinc deficiency may lead to the increase of natural anticoagulants in the blood (Atik OS et al 2006). In alcoholics, zinc has also been shown to limit the damaging effects of alcohol on bone (Gonzalez-Reimers E et al 2005).

Silicon is also important to bone health. A study of both men and women in the large Framingham Heart Study found that silicon intake was positively related to increases in bone mineral density in the hip and spine (Jugdaosingh R et al 2004).

Vitamins to Support Healthy Bones

Vitamin D. Vitamin D, a hormone-like substance, promotes the absorption of calcium. Vitamin D is made by the skin after exposure to sunlight or ultraviolet radiation, and vitamin D deficiency is widespread throughout the United States. People with light skin synthesize vitamin D in their skin easier than dark-skinned people. In the winter when people spend more time indoors and have less exposure to sunlight, their vitamin D levels plummet. Of special concern, vitamin D deficiency is a very important winter-time risk for people with dark-skin, who must have more exposure to sunlight than light-skinned people in order to generate similar amounts of vitamin D. Some people must avoid exposure to sunlight for various reasons, such as incompatibility of sunlight with certain medications. Recent studies have suggested that the recommended US RDA for vitamin D (600 IU daily) is actually too low and that people would benefit from 800 to 1000 IU and more daily (Nieves JW 2005).

Vitamin C and vitamin E. Vitamin C, also known as ascorbic acid, is essential for the formation of collagen and the stimulation of proteins derived from osteoclasts (Schaafsma A et al 2001). Studies show that vitamin C contributes to increased bone mineral density by improving markers of bone turnover (Hall SL et al 1998; Katsuyama H et al 2005) and that increased antioxidant intake, especially vitamin E, is associated with reduced risk of hip fracture, especially among smokers. It is also necessary for the synthesis of steroid hormones and neurotransmitters, which are vital to bone formation. In addition, this vitamin makes iron more available. Vitamin C is a powerful antioxidant and helps protect the body from cytokines that are produced during bone breakdown. Studies demonstrate a significant decrease in antioxidant defenses in older women (Maggio D et al 2003).

Bioflavonoids. Bioflavonoids include rutin, quercetin, hesperidin, and eriodictyol. They are found in onions, peppers, garlic, black currants, blueberries, red berries, buckwheat, and green tea. These nutrients have been shown to stimulate bone morphogenetic proteins, which are known to increase bone formation (Mundy GR 2006).

Vitamin B12. Recent evidence has implicated elevated homocysteine as a possible risk factor for osteoporosis, especially in women (Gjesdal CG et al 2006; Herrmann M et al 2005). Vitamin B12, together with folic acid and vitamin B6, can help lower homocysteine. Before the evidence connecting elevated homocysteine to osteoporosis emerged, vitamin B12 had already been identified as a possible strategy to reduce the risk of osteoporotic fracture, primarily because vitamin B12 deficiency has been associated with decreased bone-mineral density in the hip (Stone KL et al 2004). Vitamin B12 and folate have been shown to reduce the risk of hip fracture in elderly Japanese people who have suffered stroke (Uebelhart B et al 2006).

Vitamin K. Vitamin K facilitates the activity of calcium in bone building. Vitamin K is necessary for the activation of osteocalcin, a protein found in relatively high amounts in the bone, which allows calcium to bind to bone matrix. Osteocalcin that is not appropriately synthesized with vitamin K may lead to low bone mineral density and an increased risk of osteoporosis (Schaafsma A et al 2001; Okano T 2005).

Diets with more vegetables and less meat are higher in vitamin K. One study examined the relationship between vitamin K intake and hip fracture. Using 10 years of data on 72,000 participants in the Nurses’ Health Study, researchers found that study participants who received the most vitamin K were about a third less likely to get a hip fracture. Those who ate lettuce every day slashed their risk of hip fracture in half compared to those who ate it less than once a day (lettuce is a source of vitamin K) (Feskanich D et al 1999). The effect of taking vitamin K was greater than the effect of taking synthetic estrogen, which did not protect the participants’ bone density in this study, nor did vitamin D. In fact, women who took a lot of vitamin D but had low intakes of vitamin K had a doubled risk of hip fracture. Although vitamin D increases the amount of bone-friendly osteocalcin, only vitamin K can make it work properly.

Vitamin K shows remarkable results against bone loss in postmenopausal women. A study of 1 mg vitamin K daily for two weeks demonstrated it increased the bone-building protein gamma-carboxyglutamic acid in women (Knapen MH et al 1989). Another study showed that vitamin K slowed calcium loss by one-third in people who have a tendency to lose it (Knapen MH et al 1993). Drugs containing vitamins K1 and K2 are being used to treat osteoporosis (Hodges SJ et al 1991). The dosage used in Japan is 45 mg daily (Shiraki M et al 2000).

The Best Test for Osteoporosis

Around perimenopause, which begins near age 40 in women, many physicians begin talking to their female patients about risk factors for osteoporosis and regular screening to detect the disease. Osteoporosis is an insidious condition because it usually has no symptoms until the bones become so thin and brittle that they cannot withstand the pressures exerted on them, and they break.

Two tests are used to measure bone mineral density. The dual energy X-ray absorptiometry (DEXA) test is most commonly used because there are more DEXA testing devices in doctors’ offices than the more advanced quantitative computed tomography (QCT) equipment. However, studies suggest that the QCT test is much more sensitive.

In one clinical study, osteoporosis was present in 63 percent of men at the time of diagnosis of prostate cancer, prior to any therapy. In this landmark paper, the investigators evaluated DEXA bone mineral density testing and compared it to QCT bone mineral density testing in the same patients. A significantly greater percentage of men were found to have osteoporosis by the QCT methodology than by means of the DEXA approach. DEXA bone mineral density evaluation detected osteoporosis in only 5 percent of men, whereas with QCT technology, 63 percent of men were diagnosed with osteoporosis. Using QCT technology, bone density abnormalities (osteopenia and osteoporosis) were found in 95 percent of men, compared to 34 percent of men evaluated with DEXA (Smith MR et al 2001).

Although QCT testing exposes patients to more radiation than DEXA does, the amount of radiation associated with QCT for determining bone density is roughly equivalent to that of a dental series and is approximately 50 percent that of a mammogram (depending on the technique used). Most important, QCT generates far less radiation exposure—orders of magnitude is less than a contrast-enhanced abdominal CT scan.

The results of bone density testing are given in T-scores. These scores are developed by comparing the person being tested to a young adult of the same gender between 25 and 45 years of age. A T-score of -2.5 or lower indicates high fracture risk, or a 60 percent chance of fracturing a hip. For every decrease of 1 in T-score, there is a twofold increase in risk of fracture. Individuals with a T-score of -1.1 to -2.5 are diagnosed with osteopenia, or mild bone loss.

Results are also given as Z scores, which measures individual results against people of the same age, gender, and race.

In addition to measuring bone density directly, physicians might recommend a number of tests to measure calcium levels, such as the level of calcium in the urine, as well as the levels of various hormones such as parathyroid hormone and calcitonin. Lab tests can also indicate absorption problems in the gut. The effectiveness of therapy may be monitored by tests that measure bone formation and bone turnover.

Conventional Treatment of Osteoporosis

In many cases, the first exposure someone with osteoporosis has to treatment is emergency medical treatment to repair a fractured bone. Hip fractures almost always require surgery, ranging from pins and plates to support of the hip to total hip replacements. For painful spinal fractures, painkillers may be recommended, along with anti-inflammatory medications. Other fractures, such as wrist or ankle fractures, are often treated with supportive care.

In addition, exercise is highly recommended. Weight-bearing exercise has been shown to reduce the rate of bone loss among postmenopausal women, although it does not seem to increase bone mass (Kasper DL et al 2005). Also, exercise promotes healthy joints, ligaments, and muscles, which make falling less likely.

If pharmacological treatment is necessary, a number of agents or drugs may be prescribed, including the following:

Hormone replacement therapy. Estrogen replacement therapy has long been prescribed to increase bone mineral density. Many studies have proved that estrogen replacement therapy can improve markers of bone turnover and reduce the risk of fracture (Prior JC 1990; Prior JC et al 1994; Zarcone R et al 1997; Castelo-Branco C 1998).

The benefits of estrogen replacement therapy, however, have to be weighed against recent evidence linking conventional estrogen replacement therapy to increased risk of breast cancer, stroke, heart attack, and blood clots. One study reported that women had a 20 percent to 70 percent increase in their risk of breast cancer while using estrogen alone or estrogen and a synthetic progestin. This study also showed that the carcinogenic risk of estrogen-progestin replacement therapy was more pronounced when it was used for 10 years or longer (Colditz GA et al 2000).

Perhaps more disturbing are the results of the large Women’s Health Initiative study. This study found that conventional hormone replacement therapy, with either estrogen alone or estrogen and synthetic progestin, was associated with an increased risk of stroke (Bushnell CD 2006). Additionally, in the first one to two years of therapy, women experience an increased risk of coronary heart disease, stroke, deep vein thrombosis, or pulmonary embolism. Moreover, the risk of fracture does not decline until the fifth year of treatment (LaCroix AZ 2005). These findings had a dramatic effect on the number of women taking conventional hormone replacement therapy: some studies report that as many as 80 percent discontinued their treatment after the results were made public (Bestul MB et al 2004).

It is important to understand, however, that the results from the Women’s Health Initiative detailed the risk of taking strong synthetic estrogens that are derived from horses’ urine. They were not looking at bio-identical hormone therapy using estrogens that are specially formulated to match a woman’s natural estrogen levels. Ultimately, the evidence that estrogen replacement therapy can protect bone loss is strong and must be balanced against the increased risk on an individual basis. Women who are at increased risk of breast cancer and cardiovascular disease may want to avoid estrogen replacement therapy, while women who are experiencing significant menopausal symptoms or are at high risk of osteoporosis may consider various natural estrogen options now available. For a more thorough discussion of the benefits and methods of bio-identical hormone replacement, see the chapter Female Hormone Restoration.

Bisphosphonates. Bisphosphonates are prescription drugs that interfere with osteoclast function and reduce the number of osteoclasts. The net result is an increase in bone mineral density and a reduced risk of fractures (Greenspan SL et al 2000; Fleisch HA 1997). They are also used to reduce the risk of fracture among people with glucocorticoid-induced osteoporosis (Kasper DL et al 2005). This class of drugs includes alendronate (Fosamax®), risedronate (Actonel®), pamidronate (Aredia®), etidronate, zolendronate (Zometa®), and ibandronate.

While studies have shown that bisphosphonates are effective at reducing bone turnover and increasing bone mass, these drugs have side effects. The most commonly reported side effects of oral bisphosphonates are gastrointestinal complications, such as esophagitis, gastritis, and diarrhea (Aki S et al 2003). They can also cause serious eye problems (Fraunfelder FW et al 2003), including acute glaucoma (Fraunfelder FW et al 2004).

More recently, bisphosphonates have been linked to osteonecrosis (death of the bone) in the jaw. In one study of women being treated with alendronate, pamidronate, or zolendronate, researchers reviewed records from a referral center. They identified 23 patients with osteonecrosis of the jaw who did not also have metastatic bone disease in that area. Of those 23, 100 percent had been treated within the previous 12 months with bisphosphonates (Farrugia MC et al 2006). Treatment for this condition includes stopping bisphosphonate treatment, as well as possible debridement and even radical surgery (Farrugia MC et al 2006).