OSTEOPOROSIS

By Ellen Kamhi PhD, RN, AHG, AHN-BC www.naturalnurse.com

and  Eugene Zampieron, ND, AHG www.drznaturally.com

Osteoporosis is a disease of the skeletal system, which 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 woman over 50 years old. Osteoporosis is recognized as a major public health issue. Over 10 million Americans are afflicted, with 34 million more who 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 effect any bone in the body, although the most common sites are the wrist, spine and hips. It is credited with more than 1.5 million fractures in both the United States and Canada per year, causing a huge amount of personal suffering and loss of quality of life. (3) (4) This disease also has a high cost to society. The cumulative economic burden of care for fractures due to osteoporosis from 2008-2028 is estimated at $474 billion dollars in the United States alone. (5) 

The term, ‘osteoporosis’, describes the condition of the inside of the bones in people who have this disease, where large porous areas develop, weakening the bone structure. Throughout life, 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 towards 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 bone 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. (6)   

There are several risk factors that increase the chance for an individual to develop osteoporosis: family history, female (six to eight times more likely than male) especially post-menopausal, due to decreased estrogen levels, advancing age, Caucasian , low calcium intake, smoking, alcohol consumption, a sedentary lifestyle , (7)  and soft drink consumption. (8)  (9)

Since many of these contributing factors are self regulated, health care 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 OTC 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. (10)   Wherever possible, health care 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. A growing list of concerns is linked to the use of these drugs, including research that suggests a link between the use of these agents and esophageal cancer. (11)   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, 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. (12)  (13) Although pharmaceutical agents can be effective, there is an increased interest in non pharmacological prevention and treatment of osteoporosis. (14) 

Health care 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.

There are several natural interventions that promote increased bone health. These include sufficient consumption of bone supportive nutrients through healthy eating, regular exercise, 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.   (15)  

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. (16)  

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, and other exercises that force the bones to work against gravity, are effective at increasing bone mass. (17)   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 three 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).  (18) 

A combination of these three 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 three factors that is most likely to maximize osteogenic activity. (19)  For most individuals, practicing weight bearing exercise three 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 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. (20)  

Dietary Interventions

The best approach to getting sufficient nutrients to build and maintain strong bones is by consistently making 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

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 United States FDA.   The best food sources of calcium, other than dairy, include whole grains, beans, almonds and other nuts, and dark green leafy vegetables, such as kale. (21) 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. (22) Calcium supplements have been shown in several studies to be effective at slowing bone loss in both peri-menopausal and post menopausal women. (23)   A Cochrane Database Review Article (2004), states that “calcium supplements ….. at 500 to 2000 mg per day, are the simplest and least expensive way to prevent bone loss.”  (24) 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. (25) 

To maintain bone health, 1000- 1500mg/day of calcium (including food sources and supplements) is recommended (varies with age, weight, sex, etc.) by the National Academy of Sciences. (26)  Sufficient  calcium intake  is important in preventing osteoporosis, because if thebody’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 (ie tablets, vs. liquids), cost, etc.  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). (27)   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. (28) Microcrystalline hydroxyapetite (MH) is a form of calcium that was demonstrated to be more effective at slowing bone loss than calcium carbonate. (29)   MH was also shown to support bone density in a randomized double blind 2007 control study.   (30)   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. Examples follow: Calcium decreases the absorption of bisphosphonates, (31) levothyroxine (32)  , tetracycline and quinolone antibiotics (33) Thiazide can reduce calcium excretion, leading to hypercalcemia, metabolic alkalosis and renal failure. (34) Health care practitioners can assist customers to choose a calcium supplement that best meets their needs.

Magnesium

Magnesium is the second most common mineral in the body (after calcium). Magnesium is important for many metabolic processes, including building bone, formation of ATP, and promoting calcium absorption. 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 eating a diet low in this nutrient, and soil depletion due to commercial farming practices such as overcroping. (35)  Low levels of blood magnesium correlates with low bone density, (36) and several studies have supported the use of oral magnesium supplementation  to increase bone density. (37) (38) (39) (40)  Even a moderate magnesium deficiency has been documented to cause bone loss in rats. (41) Magnesium deficiency may impair the production of parathyroid hormone and 1,25-dihydroxyvitamin D, which negatively effects bone mineralization. (42)  Supplementing with 250-400 mg a day of magnesium is usually recommended. Magnesium glycinate or 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. These may include: diarrhea, drowsiness, loss of tendon reflexes, thirst, hypotension,  muscle weakness and respiratory and cardiac irregularities. (43)   Drug interactions include neuromuscular weakness and possible paralysis when combined  with aminoglycoside antibiotics, decreased absorption of biphosphates, tetracycline antibiotics and calcium channel blockers(take at different times). Conversely, many drugs cause hypomagnesemia, including aldesleukin, aminoglycosides and amphotericin-B(common). (44)   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, and is often the first supplement we recommend in our clinical practice, after implementing a whole food based diet.

Vitamin D

Vitamin D is essential for the formation and maintenance of bone tissue, due to 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 readsorbtion. 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. (45) 

Vitamin D is called ‘the sunshine vitamin’ because the best source of vitamin D is from sensible sun exposure. 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 dihydrocholecalciferol (calcitriol); 10 times more potent than Vitamin D3.  Magnesium and boron act as co-factors 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 States (46), 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 be due to low levels of vitamin D, reduced synthesis of calcitriol in the kidneys or a lack of calcitrol receptors in target organs (47) Vitamin D is available as a supplement in several forms. Vitamin D 3 ( cholelcalciferol) Vitamin D 2( ergocalciferol) and Alfacalcidol are three common forms. Studies indicate that alfacaldidol  has been shown to prevent osteoporosis in women on high dose corticosteroids, (48)  as well as increasing muscle power and walking distance in the elderly. (49) A study which compared results using alfacalcidol with ergocalciferol (Vitamin D 2) in elderly women with vertebral fractures, discovered that alfacalcidol has a greater effect than D2 at stimulating calcium absorption by bones.  (50)  Vitamin D 3 is more effective than Vitamin D 2, and is a better supplement choice for most individuals. (51) An exception would be vegans, who prefer not to use any product that may have been animal sourced, since the starting material for D 3 is fish or lanolin. Mechanisms of action of Vitamin D’s role in building healthy bones includes increasing the number and activity of osteoblasts, (52) reducing the activity of osteoclasts, (53)  and normalizing the turnover of bone in osteoporosis. (54)  

Vitamin D appears to be most effective as a therapy for osteoporosis when combined with calcium. (55)     While 400 IU’s of oral vitamin D (cholecalciferol) is the current RDA, this level of supplementation appears to be insufficient to prevent fractures, while 700 to 800 IU/d appears to reduce the risk of hip and any nonvertebral fractures in both institutionalized and ambulatory elderly persons. (56)  Vitamin D is well tolerated at doses of 400 -800 IU. Current studies are moving towards increasing the RDA of Vitamin D, and many health 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. (57)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) (58) More problematic are drugs which deplete Vitamin D. These include carbamazepine, (59)  cholestyramine and colestipol. (60)

Boron

Boron is ubiquitous throughout the human body with the highest concentrations found in the bones and dental enamel. Although there is currently no RDA, boron appears to be indispensable for healthy bone function, possibly via effects on reducing the excretion and absorption of calcium, magnesium and phosphorus,

( 61)  and by affecting signal transmissions across cell membranes by acting indirectly as a proton donor, which influences ion gradients that are involved with cell/cell communication. (62)   (63)   Boron may be involved in the synthesis of steroidal vitamins and hormones, such as Vitamin D, 17 beta-estradiol and testosterone  and  inhibits a range of microsomal enzymes which catabolize  these steroids, thus delivering a net up-regulatory effect, which could explain its bone building properties. (64) Boron clusters or carboranes have a high binding affinity for steroidal receptors (65)  and are being formulated into medications such as specific protease enzyme inhibitors. (66) Boron may be beneficial in the treatment of osteoporosis, especially in the case of vitamin D, magnesium, and potassium deficiency. (67)  One study found that boron supplementation as an isolated nutrient was not useful in terms of preventing bone loss.  (68)   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. (69) 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.

Strontium

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, which compared two groups of postmenopausal women who already had a diagnosis of osteoporosis. One group was given two grams daily of non-radioactive 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. (70) Other promising studies showed reduced risks for non-vertebral fractures, including hip fractures following the use of strontium. (71)  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 two drug trials. The mechanism ofstrontium’s bone strengthening effect is believed to be decreased bone resorption and increased bone formation which increases bone mass, microarchitecture and strength. (72) 

In the US, 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. UC Davis is investigating the use of Sodium Citrate for the prevention of osteoporosis, but the results are not yet available. (73) 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 de-mineralize bone when calcium is deficient. (74)   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. (75)  For this reason, it is suggested that people on kidney dialysis should not use strontium supplements.

Isoflavones

Research supports the positive effects of soy isoflavones for reducing the risk of developing osteoporosis. (76)  Diets high in soy may decrease bone re-absorption in postmenopausal women. (77)  Although ipriflavone, a semi synthetic flavone comparable to genistein and diadzein found in soy foods, was ineffective in restoring bone density in rats, it modulated IGF-I(insulin growth factor I), (78) which is linked to bone mineral density and increased bone remodeling through several mechanisms. (79) IGF-I (Somatomedin C) is currently being measured by holistic health practitioners as one of the parameters to assess overall aging. Ipriflavone yielded positive results on bone mass in elderly women with osteoporosis in human trials at doses of 200 mg per day, (80)  and seems particularly beneficial when combined with calcium.  (81)   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. (82)  Fermented soy is less likely to cause these adverse effects.

Vitamin K

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. (83) There are three known vitamin K dependent proteins that 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 two naturally occurring forms of vitamin K: Vitamin K 1 (phylloquinone), synthesized by plants, and Vitamin K 2 (Menaquinone-n) synthesized by bacteria. The ‘n’ signifies the number of 5 carbon chains that a specific kind of K 2 contains. Vitamin K 2 is available as both M-4 and M-7 as a dietary supplement. Research supports the use of both Vitamin K 1 and Vitamin K 2 in terms of benefits associated with osteoporosis. Vitamin K 1 supplementation has been shown to support a favorable bone biomarker profile. One study included vitamin K 1, along with Hop rho iso-alpha acids, berberine, vitamin D. The treatment group showed a significant decrease in  biomarkers that indicate bone turnover. (84) However, in a double blind study which followed patients who were given 500 mcg of Vitamin K 1 for three years their bone density scores were no better than the placebo group. (85)   Patients who undergo transplants have an increased risk for osteoporosis. A randomized, double blind, prospective longitudinal study investigated the effect of a dietary supplement which 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. (86)  Although Vitamin K 2 is currently gaining popularity as the preferred form to use in supplementation, Vitamin K 1 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 the 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 anti-coagulant pharmaceutical drugs, or who have difficulty with fat metabolism. People who develop osteoporosis have been documented to have a low dietary intake of vitamin K containing foods, (87) as well as low  blood levels of Vitamin K. (88)   Health practitioners can emphasize the importance of eating high quality (preferably organic) green vegetables as part of the diet. If supplementation with vitamin K is recommended, common doses include the RDA amount of 65-80 mcg/day.

Bone Morphogenic Proteins

In the early 1960’s, orthopedic surgeon Dr. Marshall Urist discovered a family of proteins that stimulates osteoblasts and cartilage chondrocytes, and named these proteins Bone Morphogenetic Proteins – or BMPs. The impact of Dr. Urist’s contribution to medicine and healthcare was first realized in the 1990’s when commercial bone-protein preparations containing BMP’s 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. BMP’s account for the major proportion of the osteoinductive potential of bone extracts. (89)  BMP’s bind to one of the two types of serine and threonine kinase membrane receptors, and upon binding, initiate an intracellular signaling cascade which modulate the activity of transforming growth factor beta ligands. (90) This in turn leads to the expression of the transcription factorCbfa1 (Runx2), which results in the expression of several proteinscritical for bone formation, ultimately leading to regulation of target genes involved in bone remodeling. (91)  BMPs are thought to be key regulators of embryonic skeletogenesis (92), endochondral ossification (93), bone remodeling (94) (95), fracture repair (96), and bone regeneration. (97)  Over 20 BMPs family members have been identified.  (98) It was once thought that BMP’s  could only be applied locally by orthopedic surgeons  for a procedure known as “screw and glue” as they attempt to mend a fracture, but recent research in animals suggest 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. (99) Somehealth practitioners are now recommending the use of oral BMP’s for osteroporosis and osteopenia at a dosage of 200-1000 mg/day with minimum adverse effects, except for occasional GI upset in some patients.

Health care practitioners can be instrumental in educating their patients to the fact that, with intelligent dietary and lifestyle choices, osteoporosis is largely preventable for most people.

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