Osteoporosis Prevention and Treatment -
Beyond Calcium By Michael T. Murray, N.D.

Introduction

Osteoporosis literally means porous bone. Normally there is a decline in bone mass after the age of 40 in both sexes (about 2% loss per year), but women are at a much greater risk for osteoporosis because of lower bone density prior to age 40. Many factors can result in excessive bone loss and different variants of osteoporosis exist, but postmenopausal osteoporosis is the most common form of osteoporosis. Approximately one in four postmenopausal women have osteoporosis. Osteoporosis affects more than 20 million people in the United States.

Although the entire skeleton may be involved in postmenopausal osteoporosis, bone loss is usually greatest in the spine, hips, and ribs. Since these bones bear a great deal of weight, they are then susceptible to pain, deformity or fracture. At least 1.5 million fractures occur each year as a direct result of osteoporosis inducing 250,000 hip fractures, the most catastrophic of fractures. Hip fracture is fatal in 12-20% of cases and precipitates long-term nursing home care for half of those who survive. Nearly one-third of all women and one-sixth of all men will fracture their hips in their Iifetime.


Diagnostic Summary

• Usually asymptomatic until severe backache
  
• Most common in postmenopausal white women
  
• Spontaneous fractures of the hip and vertebra
  
• Decrease in height
  
• Demineralization of spine and pelvis as confirmed by x-ray techniques

Etiology

Osteoporosis involves both the mineral (inorganic) and the non-mineral (organic matrix composed primarily of protein) components of bone. This basic physiology clearly indicates that there is more to osteoporosis than simply a lack of dietary calcium. In fact, lack of dietary calcium in the adult results in a separate condition known as osteomalacia or Òsoftening of the bone.Ó The two conditions, osteomalacia and osteoporosis, are different in that in osteomalacia there is only a deficiency of calcium in the bone. In contrast, in osteoporosis there is a lack of calcium and other minerals as well as a decrease in the non-mineral framework (organic matrix) of bone. little attention has been given to the important role that this organic matrix plays in maintaining bone structure.

Table 1. Major risk factors for osteoporosis in women

• Postmenopausal
  
• White or Asian
  
• Premature menopause
  
• Positive family history
  
• Short stature and small bones
  
• Leanness
  
• Low calcium intake
  
• Inactivity
  
• Nulliparity
  
• Gastric or small-bowel resection
  
• Long-term glucocorticosteroid therapy
  
• Long-term use of anticonvulsants
  
• Hyperparathyroidism
  
• Hyperthyroidism
  
• Smoking
  
• Heavy alcohol use

Bone is dynamic living tissue that is constantly being broken down and rebuilt, even in adults. Normal bone metabolism is dependent on an intricate interplay of many nutritional and hormonal factors, with the liver and kidney having a regulatory effect as well. Although over two dozen nutrients are necessary for optimal bone health, it is generally thought that calcium along with vitamin D are the most important nutritional ~factors. However, hormones are also critical, as the incorporation of calcium into bone is dependent upon estrogen.


Gastric Acid

The absorption of calcium is dependent on becoming ionized in the intestines. The poor ionization of calcium has been the major problem with the most widely utilized form of calcium used for nutritional supplementation, calcium carbonate. In order for calcium carbonate to be absorbed it must first be solubilized and ionized by stomach acid.

In studies with postmenopausal women, it has been shown that about 40% are severely deficient in stomach acid.3 It has been shown that patients with insufficient stomach acid output can only absorb about 4% of an oral dose of calcium as calcium carbonate while a person with normal stomach acid can typically absorb about 22%. Patients with low stomach acid secretion need forms of calcium already in a soluble and ionized state, such as calcium citrate, calcium lactate, or calcium gluconate. About 45% of the calcium is absorbed from calcium citrate in patients with reduced stomach acid compared to 4% absorption for calcium carbonate.

This difference in absorption clearly demonstrates that ionized soluble calcium is much more beneficial than insoluble calcium salts like calcium carbonate in patients with reduced stomach acid secretion. It has also been demonstrated that calcium is more bioavailable from calcium citrate than from calcium carbonate in normal subjects as well.


Vitamin D

It is well known that vitamin D stimulates the absorption of calcium. Since vitamin D can be synthesized by the action of sunlight on 7-dehydrocholesterol in the skin, many experts consider it more of a hormone than a vitamin. The sunlight changes the 7dehydrocholesterol into vitamin D3 (cholecalciferol). It is then transported to the liver and converted into 25-hydroxycholcalciferol (25-(OH)D3) which is five tunes more potent than cholecalcilerol (D3). The 25 hydroxycholcalciferol is then converted by the kidneys to 1,25-dihydroxycholecalciferol (1,25(OH)2D3), which is ten times more potent than cholecalciferol and the most potent form of vitaain D3 (see Table 2).

Table 2. Relative Activities of Vitamin D Forms

• Vitamin D3= 1
  
• V itamin D2 = 1
  
• 25-(OH)D3 = 2-5
  
• 25-(OH)D2 = 2-5
  
• 1,25-(OH)2D3 = 10
  
• 1,25-(OH)2D2 = 10

Disorders of the liver or kidneys results in impaired conversion of cholecalcilerol to more potent vitamin D compounds. Many patients with osteoporosis have a high level of 25-OH-D3 but a quite low level of 1,25-(OH)2D3. This signifies an impairment of the conversion of 25-(OH)D3 to 1,25-(OH)2D3 within the kidneys in people with osteoporosis.6Õ7 Many theories have been proposed to account for this decreased conversion inducing relationships to estrogen and magnesium deficiency. Recently, the trace mineral boron has been theorized to play a role in this conversion. All of these theories are discussed below.


Hormonal Factors

The concentration of calcium in the blood is strictly maintained within very narrow limits. If levels start to decrease there is an increase in the secretion of parathyroid hormone by the parathyroid glands and a decrease in the secretion of calcitonin by the thyroid and parathyroids. The calcium levels in the blood start to increase there is a decrease in the secretion of parathyroid hormone and an increase in the secretion of calcitonin. An understanding of how these hormones increase (parathyroid hormone) and decrease (calcitonin) serum calcium levels is necessary in understanding osteoporosis.

Parathyroid hormone increases serum calcium levels primarily by increasing the activity of the osteoclast catabolism of bone, although it also decreases the excretion of calcium by the kidneys and increases the absorption of calcium in the intestines. In the kidneys, parathyroid hormone increases the conversion of25(OH)D3 to 1,25-(OH)2D3. One of the theories relating bone loss to estrogen deficiency is that an estrogen deficiency makes the osteoclasts more sensitive to parathyroid hormone resulting in increased bone breakdown, thereby raising blood calcium levels. This elevation in blood calcium leads to a decreased parathyroid hormone level that results in diminished levels of active vitamin D and increased calcium excretion as well. This theory appears to best explain the hormonal effects in osteoporosis.

Therapeutic Considerations

Recently, there has been considerable public advocation to increase dietary calcium to prevent osteoporosis. while this appears to be sound medical advice for many, osteoporosis is much more than simply a lack of dietary calcium. It is a complex condition involving hormonal, lifestyle, nutritional, and environmental factors. A comprehensive plan that addresses these factors offers the greatest protection against developing osteoporosis.

The primary goals in the treatment and prevention of osteoporosis are to. (1) preserve adequate mineral mass; (2) prevent loss of the protein matrix and other structural components of bone; and (3) assure optimal repair mechanisms to remodel damaged areas of bone.

Hormone Replacement Therapy (HRT)

One of the most publicized effects of hormone replacement therapy (combination of estrogen and progesterone) in menopause is its role in maintaining bone health and preventing osteoporosis. The research dearly demonstrates that the benefits of hormonal therapy significantly outweigh its risks in women who are susceptible to osteoporosis and women who have already experienced significant bone loss.

Since both estrogen and progesterone exert beneficial effects against bone loss and, in women with established bone loss, actually increase bone mass, estrogen-progesterone combinations are preferred to estrogen alone. The exception is in women at high risk for breast cancer or women with a disease aggravated by estrogen including breast cancer, active liver diseases, and certain cardiovascular diseases, in which case progesterone alone should be used.

Although women are often routinely placed on HRT for prevention of osteoporosis, screening women with bone density determination is recommended as the most cost effective as well as the safest measure.

Lifestyle Factors

Certain lifestyle factors significantly impact bone health. For example, coffee, alcohol, and smoking cause a negative calcium balance and are associated with an increased risk of developing osteoporosis while regular exercise reduces the risk. In fact, as important as hormonal and dietary factors are, exercise is more critical for maintaining health bones.

Numerous studies have demonstrated that physical fitness is the major determinant of bone density Physical exercise consisting of one hour of moderate activity three times a week has been shown to prevent bone loss and actually increase bone mass in postmenopausal women. In contrast to exercise, immobilization doubles the rate of urinary and fecal calcium excretion resulting in a significant negative calcium balance. Although nutritional factors are important, the most effective practice for strengthening bones appears to be physical activity.

General dietary factors

Many dietary factors have been suggested as a cause of osteoporosis including: low calcium-high phosphorus intake, a high protein diet, a high acid-ash diet, high salt intake, and trace mineral deficiencies. A vegetarian diet (both lacto-ovo and vegan) is associated with a lower risk of osteoporosis. Although bone mass in vegetarians does not differ significantly from omnivores in the third, fourth, and fifth decades, there are significant differences in the later decades. These findings indicate the decreased incidence of osteoporosis in vegetarians is not due to increased initial bone mass, but rather decreased bone loss.

Several factors are probably responsible for the decrease in bone loss observed in vegetarians. Most important is probably a lowered intake of protein. A high-protein diet or a diet high in phosphates is associated with increased excretion of calcium in the urine. Raising dally protein from 47 to 142 grams doubles the excretion of calcium in the urine . A diet this high in protein is common in the United States and may be a significant factor in the increased number of people suffering from osteoporosis in this country. Another dietary factor that increases the loss of calcium from the body is refined sugar. Following sugar intake, there is an increase in the urinary excretion of calcium. Considering that the average American consumes in one day 125 grams of sucrose, 50 grams of corn syrup plus other refined simple sugars, and a glass of a carbonated beverage loaded with phosphates along with the high-protein, it is little wonder that there are so many people suffering from osteoporosis in this country.


Soft Drinks

Soft drink consumption may be a major factor for osteoporosis as these beverages are high in phosphates but contain virtually no calcium. This leads to lower calcium levels and higher phosphate levels in the blood. The United States ranks first among countries for soft drink consumption. The per capita consumption is approximately 15 ounces per day The link between soft drink consumption and bone loss is going to be even more significant as children practically weaned on soft drinks reach adulthood. Soft drink consumption in children poses a significant risk factor for impaired calcification of growing bones. Since there is such a strong correlation between maximum bone mineral density and the risk of osteoporosis, the rate of osteoporosis may reach even greater epidemic proportions.

The severe negative impact that soft drinks exert on bone formation in children was dearly demonstrated in a study that compared 57 children aged 18 months to 14 years with low blood calcium to 171 matched controls of children with normal calcium levels. The goal of the study was to assess whether the intake of at least 1.5 quarts per week of soft drinks containing phosphates is a risk for the development of low blood calcium levels. Of the 57 children with low blood calcium levels, 38 (66.7%) drink more than 4 bottles (12-16 ounce) per week, but only 48 (28%) of the 171 children with normal serum calcium levels drink as much of the soft drinks. For all 228 children, a significant inverse correlation between serum calcium level and the number of bottles of soft drink consumed each week was found.

Green Leafy Vegetables

Consumption of green leafy vegetables (kale, collard greens, parsley, lettuce, etc.) offers significant protection against osteoporosis. These foods are a rich source of a broad range of vitamins and minerals important to maintaining healthy bones including calcium, vitamin K1 and boron.

Vitamin K1 is the form of vitamin K that is found in plants. A function of vitamin K1 that is often overlooked is its role in converting inactive osteocalcin to its active form. Osteocalcin, the major non-collagen protein in bone, anchors calcium molecules to the protein matrix.

A deficiency of vitamin K leads to impaired mineralization of bone due to inadequate osteocalcin levels. Very low blood levels of vitamin K1 have been found m patients with fractures due to osteoporosis. The severity of fracture strongly correlated with the level of circulating vitamin K. Other studies have shown that the lower the level of circulating vitamin K, the lower the bone density. This evidence clearly indicates the importance of vitamin K1. The richest sources of vitamin K1 are dark green leafy vegetables, broccoli, lettuce, cabbage, spinach, and green tea. Good sources are asparagus, oats, whole wheat, and fresh green peas. In addition to vitamin K1, the high levels of many minerals like calcium and boron in green leafy vegetables, may also be responsible for this protective effect. Boron is a trace mineral gaining recent attention as a protective factor against osteoporosis.30 Supplementing the diet of postmenopausal women with 3 mg of boron per day reduced urinary calcium excretion by 44% and dramatically increased the levels of 17 beta-estradiol, the most biologically active estrogen. It appears boron is required to activate certain hormones including estrogen and vitamin D. Boron is also apparently required for the conversion of vitamin D to its most active form (1,25-(OH)2D3) within the kidney A boron deficiency may contribute greatly to osteoporosis as well as menopausal symptoms.

As fruits and vegetables are the main dietary sources of boron, diets low in these foods may be deficient in boron. Typically, the standard American diet is severely deficient in these foods. According to several large surveys including the U.S. Second National Health and Nutrition Examination fewer than 10% of Americans met the minimum recommendation of two fruit servings and three vegetable servings per day, and only 51% ate one serving of vegetables per day.

In order to guarantee adequate boron levels, supplementing the diet with a daily dose of 3 to 5 mg of boron is indicated. Boron has been shown to mimic some of the effects of estrogen therapy in postmenopausal women.


Milk Consumption and Osteoporosis

Numerous clinical studies have demonstrated that calcium supplementation can retard bone loss. However, the data is inconclusive in regards to a high dietary calcium intake and prevention of osteoporosis and bone fractures. Particularly debatable is the effect of milk on bone health. It is interesting to note that countries with the highest dairy intake have the highest rate of hip fractures per capita.

In analyzing data from the Nurses' Health Study, 77,761 women, aged 34 through 59 years in 1980 who had never used calcium supplement, researchers found no evidence that higher intakes of milk or calcium from food sources actually reduced fracture incidence. In fact, women who drink two or more glasses of milk per day had a 45% increased risk for hip fracture compared to women consuming one glass or less per week. The data simply does not support the idea that Òevery body needs milk.”

Nutritional Supplements

It is worth repeating that osteoporosis involves much more than calcium. Bone is dependent on a constant supply of many nutrients. A deficiency of any one of these nutrients will adversely affect bone health. In addition to vitamin K and boron discussed above, following is a brief discussion on other key nutrients critical to bone health.

Calcium

Supplementation of calcium has been shown to be effective in reducing bone loss in postmenopausal women. Although by itself, calcium supplementation does not completely halt calcium loss, it does slow the rate by at least 30 to 50% and offers significant protection against hip fractures. Combined with exercise and the dietary recommendations given above, calcium is dearly part of an effective treatment plan for most women. while menopausal and postmenopausal women are often told that without hormone replacement therapy they will most definitely get osteoporosis, several studies provide strong evidence of the in acurracy of this commonly held view.

In one study, 118 healthy, white women who had experienced the onset of menopause three to six years previously were randomly allocated to receive either 1,700 mg of calcium as calcium carbonate, a placebo, or Premarin with 1,700 mg of calcium. The nearly three-year long study indicated that calcium supplementation alone significantly prevented bone loss. Using a more absorbable form of calcium like calcium citrate or calcium bound to other Krebs cycle intermediates may have provided greater benefit compared to calcium carbonate due to enhanced absorption (discussed below). Although calcium alone was less effective than the Premarin-calcium combination, calcium supplementation carries with it no significant health risks. This study thus reinforces the opinion that hormone replacement therapy should definitely be reserved for women at significant risk for osteoporosis.

In another study, 86 postmenopausal women received either 1 gram of elemental calcium in an effervescent form containing 5.24 g calcium-lactate gluconate and 0.8 g calcium carbonate or a placebo of an identical effervescent tablet containing no calcium for four years. Clinical status, calcium intake, physical activity, and bone mineral density was assessed at baseline and every 6 months. The study found that continued calcium supplementation produces a sustained reduction in the rate of loss of total bone mineral density in healthy postmenopausal women. As a result, the incidence of bone fractures was far lower in the group taking calcium (2 out of 38) compared to the placebo (9 out of 40).

And finally, in another four year study the long-term effect of calcium supplementation on bone density was determined in 84 elderly women (54-74 years) more than 10 years past the menopause.35 A placebo group who did not take calcium supplements at all during the 4-year study served as a comparison. Changes in bone density at the lumbar spine, hip and ankle sites, current calcium intake and activity were monitored. Over the 4 years, the calcium supplement group (average calcium intake of nearly 2,000 mg/day) did not lose bone at the hip and ankle sires. The control group (average calcium intake mg/day) lost significantly more bone than the calcium supplement group at all sites of the hip and ankle. No overall bone loss was seen at the spine, in either group, over the 4 years of this study.

There is a strong correlation between premenopausal bone density and the risk of osteoporosis. That being the ease, building strong bones should be a lifelong goal beginning in childhood. However, most women probably are not concerned about osteoporosis until a few years before menopause. Fortunately, calcium supplementation does improve bone density in periomenopausal women.

In a two-year study, 214 petimenopausal women received either 1,000 or 2,000 mg of calcium provided in an effervescent mixture as described above. While the control group actually lost 3.2% of their bone density of their spine, the calcium-treated groups increased their density by 1.6% (there was no difference between the two calcium groups). These results highlight the importance of calcium supplementation prior to menopause in the battle against osteoporosis.


Forms of Calcium Supplements

The best form of calcium is certainly neither oyster shell nor bone meal. Studies have indicated that these calcium supplements may contain substantial amounts of lead. In 1981, the FDA cautioned the public to limit their intake of calcium supplements derived from either dolomite or bone meal because of the potentially high lead levels in these calcium supplements. More recent studies have shown that other calcium sources such as carbonate (from oyster shells) and various chelates may also contain high amounts of lead. One study measured the lead level in 70 brands of calcium supplements and found some forms and brands to have high levels.41 The 70 products were divided into five categories: refined calcium carbonate produced in a laboratory (number=17); unrefined calcium carbonate derived from limestone or oyster shells (number-25); calcium bound to various organic chelates like citrate, gluconate, lactate, etc. (number=13); dolomite (number=9); and bone meal (number=6). The results (lead content in micrograms per 800 mg calcium) are listed in Table 3.

Magnesium

Magnesium supplementation may turn out to be as important as calcium supplementation in the prevention and treatment of osteoporosis. Women with osteoporosis have lower bone magnesium content and other indicators of magnesium deficiency than people without osteoporosis. In human magnesium deficiency, there is a decrease in the serum concentration of the most active form of vitamin D (1,25-(OH)2D3) which has been observed in osteoporosis. This finding could be either due to the enzyme responsible for the conversion 0f25-(OH)D3 to 1,25-(OH)2D3 being dependent on adequate magnesium levels or magnesiumÕs ability to mediate parathyroid hormone and calcitonin secretion.

The benefits of magnesium supplementation were investigated in a small two-year trial in 31 postmenopausal women.50 The women received an initial daily dosage of either 250 mg of magnesium (as magnesium hydroxide) or a placebo. Dosages were increased to a maximum of 750 mg for the first six months followed by a maintenance dosage of250 mg for the remaining 18 months of the trial. After one year, the women in the magnesium-treated group showed a slight improvement in bone density In con trast, the placebo group showed a slight decrease in bone density. Hopefully there will be follow up studies to this preliminary study to better assess the benefits of magnesium in osteoporosis.

Vitamin B6, Folic Acid, and Vitamin B12

Low levels of these nutrients are quite common in the elderly population and may contribute to osteoporosis. These vitamins are important in the conversion of the amino acid methionine to cysteine. if deficient in these vitamins or if a defect exists in the enzymes responsible for this conversion, there will be an increase in homocysteine. This compound has been implicated in a variety of conditions including atherosclerosis and osteoporosis.

Increased homocycteine concentrations in the blood have been demonstrated in postmenopausal women. Such concentrations are thought to play a role in osteoporosis by interfering with collagen cross-linking, leading to a defective bone matrix. Since osteoporosis is Known to be a loss of both the organic and inorganic phases of bone, the homocysteine theory has much validity as it is one of the few that addresses both factors.

Folic acid supplementation has been shown to reduce homocysteine levels in postmenopausal women even though none of the women were deficient in folic acid according to standard folic acid laboratory measurement criteria. Vitamin B6 and B12 are also necessary in the metabolism of homocysteine. Combinations of these vitamins will produce better results than any single one of them.

Silicon

Silicon is necessary for cross-linking collagen strands, thereby contributing greatly to the strength and integrity of the connective tissue matrix of bone. Since silicon concentrations are increased at calcification sites in growing bone, recalcification in bone remodeling may be dependent on adequate levels of silicon. It is not known whether the typical American diet provides adequate amounts of silicon. In patients with osteoporosis or where accelerated bone regeneration is desired, silicon requirements may be increased and therefore supplementation may be indicated.

Ipriflavone (Ostivone)

Ipriflavone (Ostivone)—a naturally-occurring flavonoid (plant pigment)—is an exciting natural approach to maintaining bone health. In fact, sixty-one clinical studies consisting of 2,835 patients treated with ipriflavone clearly show that longterm treatment with ipriflavone (along with 1,000 mg supplemental calcium) is safe and effective in halting bone loss. In addition, ipriflavone has been shown to actually increase bone density even in women with confirmed osteoporosis. The frequency of adverse reactions in ipriflavone-treated patients (14.5%) is actually less than that observed in subjects receiving the placebo (16.1%). Side effects were mainly stomach upset. Several double-blind studies have shown that this naturally-occuring flavonoid (plant pigment) can dramatically halt the progression of bone loss when used in combination with 1,000 mg of calcium.

In the most recent study, 56 early post-menopausal women with low bone density were randomly assigned to receive either ipriflavone (200 mg three times daily) or placebo for two years. Consistent with most other studies with iprillavone, all subjects also received 1,000 mg elemental calcium daily. Results indicated that while bone density declined by 4.9% after two years in women taking only calcium, there was no change in bone density with ipriflavone supplementation. Five patients taking ipriflavone and five taking placebo experienced gastrointestinal discomfort or other adverse reactions. The conclusion of the study was that ipriflavone prevents the rapid bone loss following early menopause by reducing the bone turnover rate.

In two double-blind studies of a total of 149 elderly, osteoporotic women with existing vertebral fractures (a common occurrence with osteoporosis) ipriflavone therapy not only stopped bone loss, but actually increased bone density and significantly eliminated or improved vertebral fractures and bone pain.

The results from these studies and others suggests that ipriflavone can provide the same sort of boneprotecting effects of estrogen without the risk of breast cancer (ipriflavone exerts no estrogenic effect). The typical dosage of ipriflavone is 200 mg three times daily.

Summary

Osteoporosis is a preventable illness if appropriate dietary and lifestyle measures are followed. Women of all ages, from the very young to the very old, should make building healthy and strong bones a lifelong priority This involves avoiding those dietary and lifestyle practices that leach calcium from the bone and choosing those factors which promote bone health.

Although calcium intake is important, strong bones require much more than this important mineral. Bone is a dynamic, living tissue that requires a constant supply of high quality nutrition and regular stimulation (exercise).

Diet:

Recommend that patients avoid those dietary factors that promote calcium excretion such as salt, sugar, protein, and soft drinks. Recommend that they increase their intake of green leafy vegetables and other foods with high vitamin K content.

Supplement Recommendations for Osteoporosis:

• High potency multiple vitamin and mineral formula Calcium:
  1,000-1,500 mg daily (including level in multiple)
  
• Vitamin D: 400 IU daily
  
• Magnesium: 400 to 800 mg daily
  
• Boron (as sodium tetrahydraborate): 3 to 5 mg daily
  
• Ipriflavone: 200 mg three times daily

Note: In severe cases intranasal calcitonin, hormone replacement therapy, or Fosamax may be appropriate. Although these measures have some side effects, the benefit (prevention of hip fracture) usually outweigh these side effects in cases where the patient's bone density is at the fracture threshold.