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 Osteoporosis: Protecting And
 Strengthening Bones Naturally

It should come as no surprise that as the population gets increasingly older and life expectancy continues to increase, age-related diseases such as osteoporosis will impact more individuals. Reduced bone mineral density and resulting fractures is not inevitable, however. Diet and lifestyle factors, as well as numerous specific natural agents have tremendous impacts on preserving bone mass, preventing fractures, and even building bone mass. This review will outline strategies for preventing and treating osteoporosis using these factors.

Osteoporosis is a systemic skeletal disease involving decreased bone mass, weakened bone tissue and eventually leads to increased risk of bone fractures. Disease severity is defined by the World Health Organization (WHO) by an individual's bone mineral density (BMD) compared to mean peak young-adult BMD. Bone mass which is less than 1 standard deviation (SD) from the mean is considered osteopenia, while BMD less than 2.5 SD from the mean is diagnostic for osteoporosis. It should be noted that this diagnosis implies the bone is normal in every other respect, unlike osteomalacia, a metabolic disorder resulting in faulty mineral deposition in bone.

Osteoporosis Risk Factors

Osteoporosis is more than simply a disease of aging. While it is true that the prevalence of this condition is age-dependent, other factors such as peak bone mass while young (see below), nutrition, exercise and hormonal status (for women) play a significant role in determining an individual's risk for osteoporosis.

Genetic factors also play a role and it is known that Caucasian women have an increased risk compared to African American (typically higher BMD) and Asian women (typically lower BMD). Endogenous hormone profile, as well as age of menopause will affect risk for osteoporosis in all women. In some studies oral contraceptive use had slight adverse effects on bone mineral density.  Certain other drugs, especially the use of glucocorticoids, often lead to a reduction in BMD and increased risk of fractures. Additionally, high alcohol intake, smoking and "thin body type" are all linked to increased risk for osteoporosis (16,17).

The onset of menopause is typically seen as leading factor in a rapid decline of bone mineral density (see Figure 1). This is seen in nearly all women and magnifies the importance of peak bone mass prior to this decline. For a complete discussion of menopause and natural treatments please see The Standard Volume 4 No. 1.

Peak Bone Mass

"Osteoporosis is a paediatric disease" - so said Charles Dent over thirty years ago, and to a great extent he was right (1,2). A high peak bone mass (PBM) may be one of the most important factors in maintaining strong bones in ones elderly years (See Figure 1). Reaching sufficient peak bone mass is accomplished in the first few decades of life and is influenced by genetics (some say 75%) and by many modifiable factors; the two most studied are diet (especially calcium and protein intake) and weight- bearing activities. Only in recent decades have these factors been analyzed critically; and it seems that while calcium intake is an important contributor, especially when woefully inadequate, weight-bearing activities during and just after the onset of puberty seems to be more important- even compensating for less than adequate calcium intake (3-7). Other factors that also influence PBM are age of puberty (esp. menarche in girls)(8), subsequent amenorrhea and eating disorders like anorexia nervosa (9).

The role of soft drink consumption by young women and subsequent osteoporosis risk has been controversial. It seems to be true that increased carbonated soft drink consumption by young girls reduces BMD and dramatically increases fractures, although the causative nature may be an indirect relationship with reduced calcium intake (from milk) or from a depletion of nutrients related to consuming sugar sweetened soft drinks (6,10-13). The impact this has on future osteoporotic risk is unknown, but is unlikely to be insignificant. Since there are numerous reasons to recommend reduction (or elimination) of soft drink consumption by young girls- this serves only to add to the growing list (nutrient depletion, obesity and diabetes risk (14)). Calcium supplementation in young girls, conversely, is known to improve bone mineral content and improve bone health (15).


Measuring Bone Density and Turnover

Measuring bone density and bone turnover is important in the assessing of an individual's risk for fractures and in determining the effectiveness of various therapies. Perhaps the most common analysis is the Dual Energy X-ray absorption (DEXA) scan. This method is considered more reliable and consistent than simple x-ray and is now considered the best validated method for determining bone mineral density. Typically these are done at the femur/hip and various lumbar vertebrae and computer analyzed for comparisons to mean peak bone mass (T score) and age adjusted mean bone mass (Z score). Most clinical trials that seek to measure therapies for osteoporosis risk will include DEXA scan data.

Several other markers are also used to measure bone turnover and therapy function. Various serum and urine tests can be used to measure bone specific alkaline phosphatase, osteocalcin, collagen and other proteins and peptides related to bone resorption and formation. Often these biochemical markers will be used to confirm DEXA scan data or follow the patients for more frequent intervals between the much more expensive DEXA scans.

Nutritional Factors (18,19)

Bone turnover is a life-long process (see Figure 2). The need for proper nutritional factors in the form of vitamins and minerals has been recognized as an important area of study. The population most susceptible to osteoporosis, the elderly, is also the most likely to be deficient in many key nutrients. Below is an outline of many of the key nutrients, their mechanism for improving bone health and data supporting their use in the prevention or treatment of osteoporosis.


Minerals

Calcium and Phosphorus
Nearly 99% of the 1-1.5 kilograms of calcium in the adult is located within the skeletal system as a complex with phosphorus called hydroxyapetite. The obvious importance of these minerals for bone strength often overshadows the importance the bone minerals play as repositories for total body calcium and phosphorus and maintaining homeostasis of these important biochemical minerals. The sheer volume of calcium found within bone tissue and its importance in building bone in adolescents has made it the most studied nutritional component related to bone health and osteoporosis (22). It is commonly advised that individuals past early adolescence should consume 1,000 to 1,500 mg/day of calcium from dietary or supplement sources to prevent inadequate bone formation.

While there seems to be a consensus that calcium intake seems to be one of the more important factors leading to peak bone mass development, there is much less consensus on the use of calcium alone to prevent or treat osteoporosis in peri and postmenopausal women. One recent meta-analysis suggests that calcium alone generally favors bone density improvements but rarely has shown a decreased risk of fractures after 2 years in well controlled trials (20). That said, nearly every trial comparing agents (drugs or supplements) intended to prevent or treat osteoporosis includes calcium supplementation as part of the regimen. Because the forms of calcium used in these trials was not consistent (or often not reported) it makes it quite difficult to assess the true benefit of calcium in this population.

Few well designed studies have compared clinical outcomes derived from different forms or sources of calcium. Calcium carbonate, one of the least expensive forms of calcium, is often used in the published trials leading many to believe it is superior to other forms. However, in 1990 the USDA published a trial comparing calcium carbonate with calcium citrate-malate with respect to improved bone mineral density in postmenopausal women. They found that the citrate-malate form was significantly better at preventing bone-loss in this trial than was the carbonate form (21).  Another recent report showed calcium citrate improved several biochemical markers of bone resorption when compared to equivalent amounts of calcium carbonate (23), perhaps owing to a greater bioavailability (24); although not all reports agree (25).

One important factor often omitted in selecting calcium supplement sources is its relationship with phosphorus. Calcium, like most minerals and vitamins should be consumed with a meal. However, when high doses of calcium are ingested with food phosphorus, nearly all the phosphorus is complexed by unabsorbed calcium and is non-available for bone formation. Consuming forms of calcium like dicalcium phosphate or tricalcium phosphate (hydroxyapatite) maintains available phosphorus for bone formation (26,27). At this time there does not seem to be one particular calcium form which meets every potential benefit (high absorption, phosphorus retention, cost effectiveness) and combinations of salt forms, hydroxyapatite forms and amino acid chelate forms should be considered as a balanced way to combine these benefits.

Magnesium
Unlike calcium and phosphorus, magnesium is not part of the hydroxyapatite crystals themselves but nearly 2/3 of the magnesium in the human body is located within the bones. Magnesium is a vital cofactor for nearly all the reactions involving calcium, including those involved in calcium absorption and bone formation. Magnesium deficiency is often associated with decreased bone density (28,29), although magnesium alone is rarely studied in clinical trials for improved BMD in osteoporotic women (30, 33). Medical conditions and poor dietary habits are often associated with hypomagnesemia leading to poor BMD and increased osteoporotic risk (31,32).

Strontium (34-37)
For many, the use of strontium to prevent and treat osteoporosis is rather new- following the recent publication of a large three year phase III clinical trial. However, others have known about strontium for some time. Strontium is a mineral which is closely related to calcium and is metabolized in the body in nearly identical ways. While the use of strontium for improved bone mineral strength in both animals and humans has been known for almost 50 years, the confusion between normal stable strontium with its radioactive isotopes has led many to shy away from using it. The unique benefit of strontium is its ability to incorporate into bone (to a maximum of 1 out of 10 calcium atoms), strengthening the bone matrix while also stimulating osteoblast formation and inhibiting osteoclast activity.

The most recent clinical trials have focused on one particular salt form, strontium ranelate, for both the prevention and treatment of osteoporosis in postmenopausal women. The Prevention of Early Postmenopausal Bone Loss by Strontium Ranelate (PREVOS) (38) trial was a two-year double-blind dose-response trial using either 125 mg, 500 mg or 1gram/day of strontium ranelate in postmenopausal women without osteoporosis (T-Scores -1.3 to -1.5). Each participant was also given 500 mg of calcium carbonate/day at lunch. Only in the 1 gram/day group did they see significant increase in BMD of the lumbar (L2-L4), femoral neck and total hip; increased bone specific alkaline phosphatase levels and decreased urinary cross-linked C-terminal telopeptide of type 1 collagen- all measures of improved bone strength and reduced risk for future fractures. The authors conclude that 1 gram/day was sufficient to prevent bone loss in early postmenopausal non-osteoporotic women (39).

A second dose response clinical trial was performed to determine the optimal dose for postmenopausal women with established osteoporosis (40). In this two-year trial, while 1 gram/day was statistically better than placebo, 2 grams/day was better in most categories and was set as the optimal dose for treating these women. This dose was then used in a larger, phase III clinical trial published in early 2004 in the New England Journal of Medicine with dramatic results (41). A total of 1649 postmenopausal women with osteoporosis and at least 1 vertebral fracture were randomly assigned 2/grams per day of strontium ranelate or placebo (calcium and vitamin D were also supplemented to both groups). After three years, the difference in BMD between the groups was significantly different in the lumbar spine (+14.4%), femoral neck (+8.3%) and total hip (+9.8%). Participants taking strontium also had 41% fewer new vertebral fractures over the three year study. These results are similar to some of the most powerful drugs which thwart bone loss by preventing bone turnover- a mechanism which eventually prevents new bone growth. Strontium, on the other hand, stimulates new bone growth by improving bone-turnover rather than inhibiting it.

It should be noted that the close relationship between calcium and strontium means that they compete for absorption and should be taken at separate occasions. Each of these clinical trials gave strontium either in a single dose (evening) or in divided doses (morning and evening) and instructed participants to consume their calcium supplements at lunchtime.

Many forms of strontium are available as dietary supplements: carbonate, citrate, chloride etc. Previous human, animal and in vitro research shows that each of these forms acts similarly with respect to bone metabolism, but no clinical trial has been conducted to compare their relative effectiveness.

Other Minerals
Other trace minerals/metals which are necessary nutrients for proper bone strength include boron, zinc, copper, manganese and molybdenum. In animal studies and a few human observational studies, boron was able to modify calcium, phosphorus and vitamin D interactions which has beneficial outcomes for bone mineralization (42-46). Deficiencies in boron, like copper, results in weakened bone strength. Supplemental copper and manganese are able to slow the progressive bone-loss of ovariectomized rats- a model for menopausal bone loss (47,48). Low copper status can result in serious health consequences, while as little as 1 mg/day of supplemental copper is sufficient to prevent these concerns (49).

In one particular study (53), postmenopausal women were supplemented with calcium alone (1000 mg/day as calcium citrate malate) or given additional zinc (15 mg/day), copper (2.5 mg/day) and manganese (5 mg/day). Those given the trace mineral blend along with the calcium had significantly higher bone mineral density that those given only calcium. The role of each trace mineral, their interaction with one another and the levels which are necessary to prevent deficiency-related animal and human bone-loss is far from agreement in the scientific community. Many studies, however, have addressed various aspects of trace mineral bone metabolism (50-52).

Vitamins

B-Vitamins
The vitamins often considered to be the most important for bone health are the fat-soluble vitamins D and K. Two recent articles published in the New England Journal of Medicine (NEJM), however, have given us reason to consider the role of B-vitamins in the prevention of osteoporotic risk. Both of these articles linked increasing levels of the blood chemical homocysteine with elevated risk for osteoporotic fractures (54,55). Elevated homocysteine levels, more commonly known as a risk factor for cardiovascular disease (56), is commonly linked with low intake of folic acid, vitamin B6 and B12. Some studies suggest that the homocysteine relationship is merely a measure of folate deficiency, the true culprit of poor bone metabolism and increased risk of osteoporotic fractures in menopausal women (57,58). In younger women, vitamin B12 deficiency, common in vegetarians, is known to decrease bone mineral density (59).

Vitamin D (60,63)
The use and understanding of vitamin D in maintaining proper bone health is fairly ubiquitous. The active metabolite, 1,25 (OH) vitamin D3 (calcitriol) functions to facilitate calcium absorption in the intestines by stimulating calbindin synthesis. Its hormone-like activity, related to parathyroid hormone, modulates bone turnover and improves bone strength. Deficiencies of vitamin D manifest as the bone disease rickets. Most supplements use cholecalciferol (D3) or ergocalciferol (D2); while several vitamin D analogs have approved drug status.

It is now common practice to recommend high levels of vitamin D (800 IU or more orally per day or up to 300,000 IU injections once per year), with calcium for prevention and treatment of osteoporosis (65-67). Of course, proper exposure to sunlight which allows for natural conversion of pre-vitamin D within the skin is highly recommended in those for whom sunlight is not contraindicated. Large numbers of the elderly, already at risk for other reasons, are deficient in vitamin D because of diet and low sunlight exposure (61). In fact, vitamin D intake by most Americans, especially adolescent and adult women is below recommended levels (64).

Furthermore, a recent meta-analysis published in JAMA shows that elderly individuals are 20% less likely to fall if they are taking vitamin D supplements. This, the authors conclude, is due to the additional benefit vitamin D has on muscular strength (62). The benefit for proper vitamin D intake may then be even greater since falls combined with bone brittleness are the leading cause of fractures in the elderly.

Vitamin K (75)
Most people recognize vitamin K for its role in blood coagulation, although much more attention is now focused on its role in bone metabolism. The fat soluble vitamin is a coenzyme for specific carboxylating enzymes. Three proteins, the most important being osteocalcin, are responsible for enhancing calcium incorporation into hydroxyapatite crystals in the bone- only when carboxylated. Low vitamin K status will result in undercarboxylated osteocalcin (uOC), a marker for increased osteoporotic risk.

Two forms of vitamin K exist naturally; K1 (phylloquinone) produced primarily by plants and K2 (a family of menaquinones) produced by bacteria. Both forms seem to have similar functions. Vitamin K1 is the most commonly used in supplementation and foods although recent commercially available forms and research on vitamin K2 has piqued interest in this form.

It is fairly well documented that low levels of vitamin K intake (or serum levels) is directly related to reduced bone mineral density and increases the risk for osteoporotic fractures in women (68-72). Individuals with inflammatory bowel disorders like Crohn's disease may be particularly susceptible to vitamin K (as well as vitamin D) related BMD losses (73,74).

Intervention trials with vitamin K1 at 1 mg/day and K2 (typically at 45 mg/day) with or without vitamin D have been shown to increase carboxylation of osteocalcin and improve bone mineral density (76-80). Nearly all of the research on vitamin K2 comes from Japan where the K2-rich fermented soy product natto is consumed. More research needs to be conducted to determine how these two forms and doses compare and if either is more advantageous for certain populations.

Phytoestrogens (81)
Phytoestrogens are plant compounds that result in physiological changes characteristic of endogenous estrogens- regardless of their ability to bind to one or more type of estrogen receptor. As estrogen and its analogs are known to effect bone physiology, the question of whether phytoestrogens will have a positive impact on bone mineral density and osteoporosis requires investigation.

Soy Isoflavones
By far, the most commonly studied phytoestrogens are those derived from the soybean (Glycine max). The isoflavones genestein and daidzein are converted to active compounds by normal gut microflora before they enter the body to affect physiology.

For the most part, in vitro, animal and human epidemiological studies suggest that soy intake has a positive affect on bone mineral density and decreases incidence of postmenopausal fracture, but intervention trials using soy in postmenopausal women rarely show consistent positive results (82-87).

Ipriflavone
Ipriflavone is an isoflavone derivative studied for the past 20 years in humans for its ability to improve bone mineral density without affecting other estrogenic target tissues (88). Ipriflavone has been shown to improve calcium bioavailability and also improve bone formation while preserving bone biomechanics (89-91). Numerous positive clinical trials have shown 600 mg/day of ipriflavone to be an effective way to prevent bone mineral density loss in postmenopausal women (92-96). One study, however, questioned the role of ipriflavone in this population (97). This one negative study, while gaining prominence because it was published in JAMA, has several peculiarities. The greatest of which is the fact that in each of the previous trials the placebo group (calcium and vitamin D only) showed consistent decreases in bone mineral density and secondary markers for bone remodeling; while the JAMA publications placebo group showed no such changes and even improved in some of these categories. The overwhelming balance of the data suggests, however, that ipriflavone is both safe and effective at preventing BMD loss in postmenopausal women.

Summary

Decreased bone mineral density is not inevitable and certainly not irreversible. While the pharmaceutical companies continue to develop agents which unnaturally restrict the normal bone-turnover process in hopes of slowing bone loss, our bodies are designed to facilitate this necessary metabolic process with vitamins, minerals and other natural ingredients. Like many other chronic diseases, osteoporosis is exacerbated by our lifelong diet and lifestyle choices- making it difficult to rescue brittle bones in the sixth and seventh decade of life. Clinicians should encourage young women to eat a diet rich in calcium, magnesium, vitamins D and K and protein; while adding weight-bearing activities to their lifestyle. Improving peak bone mass into their middle-thirties is the greatest asset their bones will have during menopause. Supplementation of combination products, those including several of the nutrients described here, should be considered for all postmenopausal women as well as any pre-menopausal woman whose diet and lifestyle choices are likely to leave her vulnerable.

References