Osteoporosis is a major public health issue affecting more than 10 million Americans. It is usually diagnosed in later life, but the most important time to focus on building healthy bones is during the first 3 decades of life. Providing sufficient bone-building nutrients, along with weight bearing exercise, may be the best protection against this disease.
Pharmaceutical agents can be effective in treating osteoporosis, but there is an increased interest in non-pharmacological prevention and treatment for the condition.
Pharmaceutical agents can be effective in treating osteoporosis, but there is an increased interest in non-pharmacological prevention and treatment for the condition. Healthcare providers can help prevent and treat osteoporosis by supporting the improvement of nutritional status through diet and nutritional supplementation, along with suggestion for an increase in exercise training.
Osteoporosis is a disease of the skeletal system that is characterized by deterioration of bone tissue, along with a decrease in bone mass. It can strike anyone at any age, although it is most prevalent in Caucasian and Asian, small-boned women over 50. Osteoporosis is recognized as a major public health issue. More than 10 million Americans are afflicted, and 34 million more may already be exhibiting signs of low bone mass, which increases the risk of developing osteoporosis. Bone mass can be determined by a bone mineral density test (BMD), such as a dual-energy x-ray absorptiometry (DXA). Low bone mass increases the risk of developing osteoporosis and fractures. Osteoporosis can affect any bone in the body, although the most common sites are the wrist, spine, and hips. It increases fracture risk, causing a huge amount of personal suffering and loss of quality of life.1 Osteoporosis also has a high cost to society. The cumulative economic burden of care for fractures due to osteoporosis from 2008 to 2028 is estimated at $474 billion dollars in the United States alone.2
The term osteoporosis describes a condition inside the bones in which large porous areas develop, weakening the bone structure. Bone is a living tissue that maintains a balance through the bone-building activity of osteoblasts, with the reabsorptive activity of osteoclasts. When factors such as advancing age cause a change in this balance toward reabsorption, bone mass decreases. After reaching a fracture threshold, bone that was normally able to withstand a minor stress, such as a fall or blow, becomes subject to break or fracture more easily. Osteoporosis is most often diagnosed in the senior years. However, the most important time to focus on building healthy bones is during the first 3 decades of life. Providing sufficient bone-building nutrients, along with weight bearing exercise, may be the best protection against this disease.3
Several risk factors increase the chance of developing osteoporosis: family history, gender (women are 6 to 8 times more likely than men), being postmenopausal, advanced age, race (Caucasians are the most likely), low calcium intake, smoking, alcohol consumption, a sedentary lifestyle,4 and soft drink consumption.5,6
Since many of these contributing factors are self-regulated, healthcare providers can have a direct impact on this health issue by diligently educating clients. Risk of osteoporosis is also directly linked to the use of many prescription and over-the-counter drugs: corticosteroids/steroids, thyroid hormones, anticonvulsants, aluminum containing antacids (ironically, often recommended as a calcium source by mainstream physicians), loop diuretics, gonadotropin-releasing hormones, and many others.7 Wherever possible, healthcare providers can instruct clients about natural therapies that may be equally effective for specific health conditions, but present a substantially lower risk for interfering with bone density.
Drug therapies for osteoporosis include bisphosphonates, such as alendronate and risedronate. These drugs are associated with a growing list of concerns, including research that suggests a link between the use of bisphosphonates and esophageal cancer.8 A once-per-month tablet, ibandronate sodium, claims the advantage of greater convenience but still has a host of possible adverse effects, such as esophageal irritation, heartburn, and ulcers. In addition, it is not recommended that women with hypocalcemia take these drugs.
Hormone replacement therapy was previously touted as a treatment for osteoporosis, and may, in fact, be quite useful for decreasing bone loss. However, this benefit decreases if hormone therapy is discontinued. In addition, many women refuse hormone therapy due to other known or perceived adverse effects.9,10 Although pharmaceutical agents can be effective, there is an increased interest in non-pharmacological prevention and treatment of osteoporosis.11
Healthcare providers can be proactive on this front by supporting the improvement of nutritional status through diet and nutritional supplementation, along with suggestion for an increase in exercise training.
Several natural interventions promote increased bone health. These include sufficient consumption of bone-supportive nutrients through healthy eating and nutritional supplements, including calcium, magnesium, vitamin D, boron, strontium, soy isoflavones, and vitamin K. Novel supplements such as bone morphogenic proteins are also under investigation.12 In addition, exercise aids in strengthening bones.
The Importance of Exercise
Exercise has an important impact on bone health. Several studies have increased awareness on how exercise can most constructively be used to prevent the development of osteoporosis.13
Starting to exercise at a young age is best to achieve long-term positive effects, since maximum bone mass is usually achieved during the first third of the life cycle. However, exercise at any age can improve bone health. Weight-bearing exercises, including weight training, hiking, climbing stairs, and walking, force the bones to work against gravity and are effective at increasing bone mass.14 Researchers from the Bone & Joint Injury Prevention & Rehabilitation Center at the University of Michigan investigated a host of exercise studies from 1961 to 2009 to determine the kind of exercise that had the greatest impact on bone health and density. They concluded that 3 factors were most important in predicting the best exercise outcome: strain magnitude (how much impact the exercise has on the bones and muscles), strain rate (how often maximum vs. minimum strain is applied), and strain frequency (how often strain occurs in a given amount of time).15
A combination of these 3 factors determines how helpful a given exercise regime is in helping increase bone density. However, there is no consensus about the exact combination of these factors that is most likely to maximize osteogenic activity.16 For most individuals, practicing weight-bearing exercise 3 times per week for 12 to 20 minutes is sufficient to increase bone density. Since each joint will respond to the strain load individually, its best to rotate exercise on sites and focus on each one for a limited time period. Continuing to exercise throughout life helps to reduce bone loss and the risk of falls.17
Effective Dietary Interventions
The best approach to getting sufficient nutrients to build and maintain strong bones is to consistently make healthy food choices. As we discuss each nutrient below, food sources will be included, along with suggestions for possible supplementation, which is secondary to whole-food ingestion.
Calcium is the most abundant mineral in the human body. It is well recognized for its importance in the development of bones and teeth and has many other functions as well. The ability of calcium supplements to “maintain good bone health and reduce the high risk of osteoporosis later in life” is one of the few health label claims allowed by the U.S. Food and Drug Administration. The best food sources of calcium, other than dairy, include whole grains, beans, almonds and other nuts, and dark green leafy vegetables like kale.18 Milk and dairy products contain a substantial amount of calcium; however, it is interesting to note that individuals who avoid dairy due to lactose intolerance do not experience a corresponding increase in osteoporosis.19 Calcium supplements have been shown in several studies to be effective at slowing bone loss in both perimenopausal and postmenopausal women.20 A 2004 Cochrane Database Review Article states that “calcium supplements … at 500 to 2,000 mg per day, are the simplest and least expensive way to prevent bone loss.”21 A comprehensive literature review published in the British Medical Journal (2010) questioned the commonly held belief in the benefits of using calcium supplements. In this meta-analysis the reviewers concluded that subjects who took a 500 mg/day calcium supplement (without vitamin D) experienced an increased risk of myocardial infarction when compared to those who did not take calcium supplements. These results will likely lead to further investigation of current recommendations.22
To maintain bone health, 1,000–1,500 mg/day of calcium (including food sources and supplements) is recommended (varies with age, weight, sex, etc.) by the National Academy of Sciences.23 Sufficient calcium intake is important in preventing osteoporosis, because if the body’s stores of calcium is low, calcium will be leached from bones, which can lead to decreased bone mass and the initiation or worsening of osteoporosis. While diet is the ideal source for all nutrients, calcium supplementation is often recommended to ensure that adequate amounts of this important mineral are ingested daily. This can be confusing due to the many forms of calcium on the market, the differences in dosage levels, absorption rates, delivery forms (i.e., tablets vs. liquids), cost, and other variables. Several studies have shown that calcium citrate is absorbed better than tricalcium phosphate, calcium lactate, and calcium carbonate (the kind of calcium in antacid tablets).24 Calcium citrate does not tend to cause gastric distress and has a pleasant taste. One study surmised that calcium formate is better absorbed than either calcium citrate or calcium carbonate.25 Microcrystalline hydroxyapetite (MH) is a form of calcium that was demonstrated to be more effective at slowing bone loss than calcium carbonate.26 MH was also shown to support bone density in a randomized, double-blind 2007 control study.27 Since calcium is so intimately involved in an array of metabolic reactions, it is not surprising that there is a long list of possible interactions with pharmaceutical drugs. For example, calcium decreases the absorption of bisphosphonates,28 levothyroxine,29 tetracycline, and quinolone antibiotics30; and thiazide can reduce calcium excretion, leading to hypercalcemia, metabolic alkalosis, and renal failure.31
Magnesium is the second most common mineral in the body, after calcium. Magnesium is important for many metabolic processes, including building bone, forming adenosine triphosphate, and absorbing calcium. Dietary sources of magnesium include nuts, whole grains, dark green vegetables, fish, meat, and legumes. Magnesium is often deficient in the standard American diet, due to low consumption of foods containing this nutrient, as well as soil depletion from commercial farming practices such as overcropping.32 Low levels of blood magnesium correlates with low bone density,33 and several studies have supported the use of oral magnesium supplementation to increase bone density.34,35,36,37 Even a moderate magnesium deficiency has been documented to cause bone loss in rats.38 Magnesium deficiency may impair the production of parathyroid hormone and 1,25-dihydroxyvitamin D, which negatively affects bone mineralization.39 Supplementing with 250–400 mg a day of magnesium is usually recommended. Magnesium glycinate and magnesium gluconate are preferable to magnesium oxide and are less likely to cause loose stools. Adverse effects of magnesium usually occur at higher dosages and are most often associated with intravenous magnesium. Drug interactions include neuromuscular weakness and possible paralysis when combined with aminoglycoside antibiotics, decreased absorption of biphosphates, tetracycline antibiotics, and calcium channel blockers. Conversely, many drugs cause hypomagnesemia, including aldesleukin, aminoglycosides, and amphotericin-B (common).40 Magnesium supplementation helps to balance a number of health issues in addition to osteoporosis, such as insomnia, headaches, chronic constipation, restless leg syndrome, anxiety, and irritability. It is often the first supplement we recommend in our clinical practice, after implementing a whole-foods based diet.
Vitamin D is essential for the formation and maintenance of bone tissue, due to its involvement in several complex mechanisms, including the regulation of calcium and phosphorous absorption. If vitamin D levels are low, parathyroid hormone (PTH) increases and triggers osteoclasts to release calcium into the blood via bone readsorption. If this process continues over time, it weakens bone and leads to osteoporosis. In addition, vitamin D stimulates intestinal epithelial cells to synthesize calcium-binding proteins that support the absorption of calcium in the blood.41
Vitamin D is synthesized when sunlight hits the skin and transforms 7-dehydrocholesterol into vitamin D3 (cholecalciferol). D3 is shuttled to the liver where it is converted to 25-hydroxycholecalciferol, which is then transformed into 1,25-dihydroxycholecalciferol (calcitriol). Calcitriol is 10 times more potent than vitamin D3. Magnesium and boron act as cofactors in this reaction. Food sources of vitamin D include fish and fish oils. Vitamin D deficiency is now recognized as an epidemic in the United States42 and is especially common in dark-skinned persons, the elderly, people living in northern areas, and anyone who has limited sun exposure. Deficiency can create secondary hyperparathyroidism, leading to a loss of collagen matrix and minerals, which increases the risk of osteoporosis and fractures. Poor bone remodeling due to higher osteoclast vs. osteoblast activity can occur with low levels of vitamin D, reduced synthesis of calcitriol in the kidneys, or a lack of calcitriol receptors in target organs.43
Vitamin D is available as a supplement in several forms. Vitamin D3 (cholecalciferol), vitamin D2 (ergocalciferol), and alfacalcidol are 3 common forms. Studies have demonstrated that alfacalcidol prevents osteoporosis in women on high-dose corticosteroids44 and increases muscle power and walking distance in the elderly.45 A study that compared results using alfacalcidol with vitamin D2 in elderly women with vertebral fractures showed that alfacalcidol has a greater effect than D2 at stimulating bones’ calcium absorption.46 Vitamin D3 is more effective than Vitamin D2 and is a better supplement choice for most individuals.47 An exception would be vegans, who prefer not to use animal-sourced products, since the starting material for D3 is fish or lanolin. Mechanisms of action of vitamin D’s role in building healthy bones includes increasing the number and activity of osteoblasts,48 reducing the activity of osteoclasts,49 and normalizing the turnover of bone in osteoporosis.50
Vitamin D appears to be most effective as a therapy for osteoporosis when combined with calcium.51 While 400 IUs of oral vitamin D (cholecalciferol) is the current recommended daily allowance (RDA), this level of supplementation appears to be insufficient to prevent fractures; while 700–800 IU/day appears to reduce the risk of hip and any nonvertebral fractures in both institutionalized and ambulatory elderly persons.52 Vitamin D is well tolerated at doses of 400–800 IU/day. Current studies are moving toward increasing the RDA of vitamin D, and many healthcare practitioners are already recommending much higher doses. Scandinavian countries are considering ways to increase levels of vitamin D through both supplementation and the use of UV lights.53 Vitamin D has a low incidence of adverse effects, although intoxication can result if higher doses are used long-term. Symptoms include weakness, nausea, vomiting, and poor appetite. Toxicity may be seen when serum 25(OH)D concentration is consistently >200 ng/mL (>500 nmol/L).54 More problematic are drugs that deplete vitamin D, including carbamazepine,55 cholestyramine, and colestipol.56
Boron is ubiquitous throughout the human body, with the highest concentrations found in the bones and dental enamel. Although there is currently no RDA for it, boron appears to be indispensable for healthy bone function, possibly because of its effects on reducing the excretion and absorption of calcium, magnesium, and phosphorus.57 It also affects signal transmissions across cell membranes by acting indirectly as a proton donor, which influences ion gradients that are involved with cell/cell communication.58,59 Boron may be involved in the synthesis of steroidal vitamins and hormones, such as vitamin D, 17 beta-estradiol, and testosterone. It inhibits a range of microsomal enzymes that catabolize these steroids, thus delivering a net up-regulatory effect, which could explain its bone-building properties.60 Boron clusters or carboranes have a high binding affinity for steroidal receptors61 and are being formulated into medications, such as specific protease enzyme inhibitors.62 Boron may be beneficial in the treatment of osteoporosis, especially in the case of vitamin D, magnesium, and potassium deficiency.63 One study found that boron supplementation as an isolated nutrient was not useful in terms of preventing bone loss.64 Fruits, vegetables, soybeans, and nuts can be rich sources of boron, but the level depends on the soil in which it is grown. A safe daily intake is estimated to be between 1 and 10 mg. Breast cancer patients are often cautioned not to use more than 3 mg a day due to references of boron’s ability to increase endogenous estrogen.65 Sodium borate and boron chelated with glycinate, aspartate, or citrate are the most common forms used in dietary supplements. Toxic effects appear at intakes of about 100 mg. A fatal dose in adults is 15 to 20 g and in children 3 to 6 g. Repeated intakes of small amounts can cause accumulative toxicity, so pulse dosing is recommended, rather than continuous use.
The mineral strontium is a powerful agent in the treatment and prevention of osteoporosis. Strontium is a naturally occurring mineral present in water and food. Trace amounts of strontium are found in the human skeleton, where it is adsorbed at the matrix crystal surface of bones. The Spinal Osteoporosis Therapeutic Intervention study is a double-blind, randomized, placebo-controlled trial that compared 2 groups of postmenopausal women who already had a diagnosis of osteoporosis. One group was given 2 grams daily of nonradioactive strontium ranelate, while another group received a placebo. The strontium group illustrated a significant reduction (41%) in the relative risk of experiencing a new vertebral fracture.66 Other promising studies showed reduced risks for nonvertebral fractures, including hip fractures, following the use of strontium.67 In addition to reducing the risk of fracture, strontium ranelate increased bone mineral density throughout the study, peaking at 3 years, with augmented scores of 8.2% in the femoral neck and 9.8% in the hip. Japanese pharmaceutical researchers have trade named the strontium salt PROTELOS™ and are in phase 2 drug trials. The mechanism of strontium’s bone-strengthening effect is believed to be decreased bone resorption and increased bone formation, which increases bone mass, microarchitecture, and strength.68
In the United States, strontium is available as a dietary supplement in the form of strontium citrate. Theoretically, this form may have similar action to strontium ranelate, which has been used in most studies. University of California-Davis is investigating the use of strontium citrate for the prevention of osteoporosis, but the results are not yet available.69 Most practitioners recommend that strontium should be taken at bedtime, and not at the same time as calcium supplements, since they compete for adsorption into bone matrix. It is important to ensure calcium and vitamin D intakes are adequate when supplementing with strontium. This is underscored by earlier research on animals suggesting that increasing the intake of strontium via diet may demineralize bone when calcium is deficient.70 In rats with chronic kidney failure, strontium has been shown to cause osteomalacia, a condition in which bone is softened due to lack of mineral content.71 For this reason, people on kidney dialysis are advised against using strontium supplements.
Research supports the positive effects of soy isoflavones on reducing the risk of developing osteoporosis.72 Diets high in soy may decrease bone reabsorption in postmenopausal women.73 Although ipriflavone, a semi-synthetic flavone comparable to genistein and daidzein found in soy foods, was ineffective in restoring bone density in rats, it modulated IGF-I (insulin growth factor I),74 which is linked to bone mineral density, and increased bone remodeling through several mechanisms.75 Holistic health practitioners are currently measuring IGF-I (Somatomedin C) as one of the parameters to assess overall aging. In human trials, ipriflavone at doses of 200 mg per day yielded positive results on bone mass in elderly women with osteoporosis76 and seems particularly beneficial when combined with calcium.77 Moderate soy consumption (2–4 ounces per day) is likely a reasonable and prudent measure, due to scientific validation of its positive effects, combined with a low incidence of adverse reactions. Soy can cause allergic reactions in some individuals and may inhibit thyroid hormone synthesis.78 Fermented soy is less likely to cause these adverse effects.
Vitamin K is a fat-soluble vitamin known for its effect in blood clotting, which it accomplishes by regulating the coagulation cascade via its ability to bind calcium ions (Ca2+), among other mechanisms.79 Three known vitamin K–dependent proteins have been isolated in bone: MGP (matrix Gla protein), protein S, and osteocalcin. One of vitamin K’s roles in helping to maintain healthy bone mass is linked to its importance in the formation of osteocalcin by osteoblasts. The synthesis of osteocalcin requires both vitamin D and vitamin K. There are 2 naturally occurring forms of vitamin K: vitamin K1 (phylloquinone), synthesized by plants, and vitamin K2 (menaquinone-n) synthesized by bacteria. The ‘n’ signifies the number of 5-carbon chains that a specific kind of K2 contains. Vitamin K2 is available as both M-4 and M-7 as a dietary supplement. Research supports the use of both vitamin K1 and vitamin K2 in terms of benefits associated with osteoporosis. Vitamin K1 supplementation has been shown to support a favorable bone biomarker profile. One study included vitamin K1 along with Hop rho iso-alpha acids, berberine, and vitamin D. The treatment group showed a significant decrease in biomarkers that indicate bone turnover.80 However, in a double blind study that followed patients who were given 500 mcg of vitamin K1 for 3 years, bone density scores were no better in the treatment group than in the placebo group.81 Patients who undergo transplants have an increased risk for osteoporosis. A randomized, double-blind, prospective longitudinal study investigated the effect of a dietary supplement that included vitamin K2 (180 mcg menakinon-7) on bone mass of 94 subjects who were followed for the first year after lung and heart transplantation. The outcome showed a favorable effect on bone mass density of the lumbar spine.82 Although vitamin K2 is currently gaining popularity as the preferred form to use in supplementation, vitamin K1 is more cost-effective, and therefore may be the better choice for some patients.
Vitamin K is a fat-soluble substance; however the body does not store a significant amount at any given time. The need to constantly replenish vitamin K through dietary intake is decreased due to the vitamin K cycle, which allows a small amount that is present to be used by the body several times. Vitamin K deficiency is rare, due to reuse via the vitamin K cycle and wide availability in the diet. Vitamin K is found in dark green vegetables such as kale, Swiss chard, parsley, and spinach, and to some extent in olive and soybean oils. Deficiency may occur in those taking anticoagulant pharmaceutical drugs, or in those who have difficulty with fat metabolism. People who develop osteoporosis have been documented to have low blood levels of Vitamin K83 as well as a low dietary intake of vitamin K–containing foods.84 Healthcare practitioners can emphasize the importance of eating high-quality (preferably organic) green vegetables. If supplementation with vitamin K is recommended, common doses reflect the RDA amount of 65–80 mcg/day.
Bone Morphogenic Proteins
In the early 1960s, orthopedic surgeon Marshall Urist discovered a family of proteins that stimulates osteoblasts and cartilage chondrocytes and named them bone morphogenetic proteins (BMPs). The impact of Dr. Urist’s contribution to medicine and healthcare was first realized in the 1990s when commercial bone-protein preparations containing BMPs and key growth factors were used by orthopedic surgeons for bone healing and spinal fusions. In 2002, the FDA approved select individual BMPs for use in surgical procedures as a more effective way to grow and heal bone. BMPs account for the major proportion of the osteoinductive potential of bone extracts.85 BMPs bind to 1 of the 2 types of serine and threonine kinase membrane receptors and, upon binding, initiate an intracellular signaling cascade that modulates the activity of transforming growth factor beta ligands.86 This in turn leads to the expression of the transcription factor Cbfa1 (Runx2), which results in the expression of several proteins critical for bone formation, ultimately leading to regulation of target genes involved in bone remodeling.87 BMPs are thought to be key regulators of embryonic skeletogenesis,88 endochondral ossification,89 bone remodeling,90,91 fracture repair,92 and bone regeneration.93 More than 20 BMP family members have been identified.94 It was once thought that BMPs could only be applied locally by orthopedic surgeons for a procedure known as “screw and glue” used to mend a fracture, but recent research in animals suggests that that systemically administered BMP-6 restores the bone inductive capacity, micro-architecture, and quality of the skeleton in osteoporotic rats. Human trials are needed.95 Some healthcare practitioners are now recommending the use of oral BMPs for osteoporosis and osteopenia at a dosage of 200–1,000 mg/day with minimum adverse effects, except for occasional GI upset in some patients.
Healthcare practitioners can be instrumental in educating their patients about the fact that, with intelligent dietary and lifestyle choices, osteoporosis is largely preventable for most people.