Medical Conditions Disclaimer
Statements on this website have not been evaluated by the Food and Drug Administration. Our products are not intended to diagnose, treat, cure or prevent any disease. The information on this website is designed for educational purposes only. It is not intended as, nor should it be construed as, a substitute for informed medical advice. Please consult a doctor with any questions or concerns you might have regarding your health.
THE FOLLOWING MEDICAL AND SCIENTIFIC MATERIAL IS FOR CONSUMER INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY UNDER SECTION 5 OF DSHEA.
Osteoporosis is a disease in which there is low bone mass and structural deterioration of bone tissue. Osteoporosis develops when the body fails to form enough new bone (the function of cells called osteoblasts), or when too much old bone is broken down and resorbed by the body (the function of cells called osteoclasts). As a result, the bones can become weak and brittle and are more susceptible to fractures, most commonly of the hip, spine and wrist.
Severely low bone mass (osteoporosis) and moderately low bone mass (osteopenia) are more common than is often realized, affecting an estimated 44 million women and men aged fifty or older in North America. Of these, 10 million have full-blown osteoporosis, and 34 million have the osteopenia. This equates to more than 50% of people in that age group. Although it is often thought to be solely a disease of older women, approximately one-fifth of people with osteoporosis are men. Although osteoporosis risk increases with advancing years, it can occur at any age. Osteoporosis has also been found to occur at an increased frequency in people with HIV infection, both women and men.
Contrary to common myth, loss of bone affects all races. It is estimated that one in two women and one in four men over the age of 50 will have an osteoporosis-related fracture at some point during their lives. These can cause significant pain and disability, a lower quality of life, and can even result in life-threatening complications. It is estimated that 20 percent of people who experience a hip fracture will die in the year after the fracture. Deaths most commonly occur from complications such as pneumonia or blood clots in the lung related to the fracture or the surgery needed to repair the hip. In people with advanced osteoporosis, a fall or trauma to the bone is not required for a fracture. Just bending over or lifting a suitcase or even coughing might result in a bone break.
Osteoporosis has been called a "silent disease" since many people are unaware of the disease until a fracture occurs. In some people with osteoporosis, the spinal vertebrae can spontaneously collapse, causing back pain, stooped posture, and height loss. A commonly held myth is that the gradual loss of height is just a part of normal aging when, in fact it may be an important warning that osteoporosis is developing.
The silent nature of this disease makes proper diagnosis and screening very important. The best screening test is a DEXA (dual energy X-ray absorptiometry) scan. It can measure bone density in the spine, hip, and wrist, predicting the likelihood of future fractures and detecting osteoporosis before a fracture occurs. Serial tests can be done to measure disease progression and to assess the effectiveness of a treatment program.
The risk of osteoporosis can be greatly reduced if health-promoting lifestyle choices are made. Ideally, a prevention program would begin early in life since by the early twenties much of the structure of the bones has already been created, and by the mid-30's peak bone mass has been achieved. However, at any age, a combination of healthy lifestyle choices can help prevent or reverse the disease.
Bone is a living tissue in which new bone is constantly being made and old bone is constantly being broken down and resorbed. This process is called remodeling and it helps keep the bones strong and healthy. Providing a steady supply of the building blocks for creating bone tissue through diet and supplements while promoting the bone building process with weight-bearing exercise can help maintain bone strength. The strength of the bones depends on their size and density; and bone density depends largely on the amount of minerals they contain.
A healthy diet that is rich in bone-building nutrients such as calcium, magnesium, phosphorus, vitamin D, manganese, molybdenum, selenium, boron, and vitamin K provides an important foundation for bone health. In general, a rich supply of these and other micronutrients are found in a diet that is loaded with nutrient-rich fruits, vegetables, and whole grains, along with healthy fats, especially monounsaturated fats like olive oil and the omega-3 fatty acids found in fish. Healthy food sources of protein, including low-fat meat, poultry, eggs, fish, nuts, seeds, and beans, also provide the nutrients required for building strong, healthy bones.
Getting plenty of vitamin D (found in fatty fish, egg yolks, and dairy products) and calcium (found not only in dairy products but in foods such as almonds, broccoli, cooked kale and other dark leafy greens, and canned salmon with the bones) are particularly important. A plentiful intake of fruits and vegetables is also very important to support bone rebuilding since they contain phytochemicals, minerals, and the vitamin K which bones need. In addition, fruits and vegetables have an alkalizing effect that can help to neutralize excess acid in the body and prevent the leaching of minerals from the bones (as occurs with high intake of soft drinks - see below). Many studies have shown a strong tie between higher intake of fruits and vegetables and increased bone mineral density in both younger and older people.1,2,3,4,5 A healthy skeleton is best built by consuming a nutrient-rich diet from childhood through young adulthood. Continuing to consume a healthy diet throughout the adult years supports the maintenance of bone health.
It is important to avoid foods that may contribute to unhealthy bones. In particular, the consumption of soft drinks may cause harm. The phosphoric acid in sodas can change the acid balance in the blood in a way that can directly cause bone loss,6 making the intake of sodas a risk factor for osteoporosis. Caffeine may also interfere with calcium absorption while its diuretic effect increases bone mineral loss. Studies have shown increased hip fracture risk with higher caffeine intake.7,8 However, it appears that most of the caffeine risk is seen in populations where coffee is the main source. Tea may actually be beneficial. In one study of 1256 older women (65-76 years old), those who drank tea had higher bone mineral density measurements than did those who did not drink tea.9 The researchers hypothesized that nutrients found in tea, such as flavonoids, may positively influence bone mineral density and that tea drinking may actually protect against osteoporosis in older women.
Avoiding excessive salt intake is also important for bone health. Studies have shown that a high sodium intake is associated with increased urinary calcium excretion,10,11 and when combined with low calcium intake, may lead to bone loss.12,13 In one study of 186 adults of all ages (23-76 years old), a reduced sodium intake reduced calcium excretion and those who also followed the DASH diet had reduced bone loss.14 The DASH diet (Dietary Approaches to Stop Hypertension) emphasizes an optimal intake of fruits, vegetables, low fat dairy foods, whole grains, poultry, fish and nuts, and is very low in fats, red meat, sweets and sugar-containing beverages. The DASH diet and reduced sodium intake may have complementary beneficial effects on supporting bone health.
Adequate protein is also important for the proper building of bone, but elevated protein consumption may be detrimental to bone health. People who eat large amounts of meat without a plentiful intake of fiber, especially from fruits and vegetables may create an excess of phosphates and uric acid in the body when dietary animal proteins are metabolized. This can alter the acid balance in the body in a way that contributes to loss of bone.
The other crucial component of a bone health program is weight-bearing exercise (walking, jogging, stair climbing, skipping rope, trampoline, and any other impact-producing sport) combined with resistance-training exercise (lifting weights, strength training). As with a healthy diet, beginning these habits early in life and continuing them throughout adulthood is ideal. However, even if one starts exercising late in life, it can still greatly contribute to restoring the health and structure of bones. Exercise is what sends the message "grow and strengthen" to the bones. Any type of weight-bearing exercise can help, but activities or exercises that include jumping and hopping are particularly good promoters of bone growth.
Strength training is also an important component of a program aimed at bone fitness. In one year-long study, women who did high-intensity strength training exercises two days per week had significant gains in bone mineral density in the hip and spine, while women who were inactive during that year lost bone mineral density in both places.15 Osteoporosis can be site specific so exercise that strenghtens only the legs might keep those bones strong but could allow problems to occur in the upper body. Utilizing a program that exercises all parts of the body will help maintain healthy bones from top to bottom. You should always discuss your current health status with your physician before instituting an exercise program. When you're given the go-ahead, make regular exercise part of your life and you'll gain countless benefits, including improved bone health.
Avoiding smoking or excessive alcohol intake can also contribute to improved bone health. Researchers have found that tobacco use is tied to weak bones in both men and women,16,17 possibly because it reduces calcium absorption in the intestines as well as decreasing estrogen production in women. Although modest alcohol intake is associated with improved bone mineral density,18,19,20 excessive alcohol intake is tied to bone loss.21 In fact, for men, alcoholism is one of the leading risk factors for osteoporosis. Excessive alcohol consumption (more than the equivalent of one or two glasses of wine daily), in both men and women, reduces bone formation and interferes with the proper absorption of calcium.
Standard Medical Therapies
When lifestyle changes are unable to control osteoporosis, there are a number of medications approved by the FDA for the prevention or treatment of osteoporosis.
Biphosphonates (Fosfamax®, Boniva®, Actonel®) inhibit the breakdown of bone by suppressing the activity of the osteoclasts (cells that are responsible for resorbing old bone tissue). The result is an increase in bone mass and bone density. Side effects of these drugs can sometimes be severe and include nausea, abdominal pain, inflamed esophagus, and esophageal ulcers. There have also been reports of osteonecrosis (bone death) ofthe jaw inpeople taking biphosphonates. Because these drugs will remain in bones for years, even after they are discontinued, it is not known how long the risk of osteonecrosis can last. Various biphosphonate medications are approved for specific populations:
Alendronate (Fosamax®) and alendronate plus vitamin D (Fosamax® plus D) are approved for the treatment of osteoporosis in men and for the treatment of glucocorticoid (steroid)-induced osteoporosis in men and women.
Ibandronate (Boniva®) is approved for the prevention and treatment of osteoporosis in postmenopausal women.
Risedronate (Actonel®) and risedronate with calcium (Actonel® with Calcium) are approved for the prevention and treatment of glucocorticoid-induced osteoporosis in men and women.
Zoledronic Acid (Reclast®), given intravenously once annually, is approved for the treatment of osteoporosis in postmenopausal women.
Calcitonin is a naturally occurring thyroid hormone that helps regulate calcium levels in the body and is involved in the process of bone formation. When given as a medication, it can reduce bone resorption and therefore slow bone loss in the spine, hip, and pelvis, as well as help prevent spinal compression fractures. It is usually given as a nasal spray but can also be injected. Calcitonin medications (Fortical® and Miacalcin®) are approved for the treatment of osteoporosis in postmenopausal women who are at least five years past menopause. Side effects of the nasal spray may include nasal irritation, runny nose, nausea, and skin flushing (redness). Side effects of the calcitonin injections may include nausea and/or vomiting, diarrhea, inflammation at the site of the injection, skin flushing (redness), increased urination, and increased number of bowel movements.
Hormone therapy with estrogen or estrogen with progesterone is approved for prevention of osteoporosis in postmenopausal women. Although estrogen replacement therapy was once the most common form of osteoporosis treatment, side effects and concerns about safety, including risks of cancer, blood clots, gallbladder disease, and other health concerns, and the current availability of other treatments, have eliminated it as the preferred therapy. According to the FDA, estrogen replacement should not be prescribed for the prevention of postmenopausal osteoporosis unless a woman is at significant risk of osteoporosis and cannot take non-estrogen medications, in which case the FDA recommends prescribing the lowest possible dose of hormone therapy for the shortest period of time.
Physicians who specialize in using natural hormone replacement therapy generally recommend against the use of conventional estrogen therapy (Premarin®, derived from horse urine and containing horse estrogens). Instead, they recommend that any woman in need of estrogen therapy use a natural triple estrogen formula containing 80% estriol, 10% estrone, and 10% estradiol. These are the three estrogen compounds which naturally occur in the human body. They also recommend accompanying such natural estrogen therapy with natural progesterone which has also been reported to increase bone density when used in conjunction with nutritional supplements and exercise.22
Two other hormones that work to stimulate the formation of new bone are testosterone and DHEA (dehydroepiandrosterone). In women, testosterone and DHEA are normally secreted by from a healthy adrenal gland. The levels of these hormones tend to decrease with advancing age and the progressive adrenal exhaustion that accompanies aging. DHEA therapy that restores DHEA-S levels to those seen in healthy young adults are well tolerated and may increase bone mineral density in women, particularly those with low pretreatment DHEA-S levels. This increase in bone mineral density occurs most likely through a combination of decreased bone resorption and increased bone formation.23 A review of clinical studies which have evaluated DHEA therapy as a treatment for age-related conditions and diseases concluded that DHEA supplementation, when used to counteract the gradual decrease in this important hormone as one ages, is highly beneficial and may have positive effects on many important bodily functions including bone mineral density, cardiovascular function, skin vitality, as well as on the nervous and immune systems.24
Research also shows that testosterone replacement therapy in older men helps to support increased bone growth. In one double-blind, placebo-controlled study, hypogonadal older men (men who were low in testosterone and 65 years of age or older) were given testosterone therapy for three years, either alone or in combination with finasteride (Proscar®). There were clear improvements in bone mineral density in both the spine and the hip in the men receiving testosterone, whether or not it was accompanied by finasteride,25 along with decreased fat, increased lean body mass, increased handgrip strength, and improved overall physical performance.26 In another study, six months of testosterone replacement therapy increased bone mineral density of the lumbar spine in men being treated with glucocorticoids, while also increasing muscle strength and mass.27 In a study of hypogonadal men, those given testosterone replacement therapy for 18 months experienced a 5% increase in bone mineral density at the lumbar spine.28
In addition to the direct effects of testosterone that promote increased bone density, testosterone replacement may help decrease bone fracture risk by a second mechanism. Research has shown that lower testosterone levels in older men are tied to an increased risk of falls, a major cause of fractures and disability.29 It is estimated that every year, falls occur in 30% of people who are 65 years or older and 40% to 50% of those who are 80 years or older.30,31 Thus, testosterone replacement therapy may help build bones while also lessening the risk of the falls that are a common cause of fractures in older men. Physicians who specialize in using natural hormone replacement therapy generally recommend a transdermal (applied to the skin) cream or gel to provide replacement testosterone for men (and sometimes women as well) who are deficient. Doses are adjusted in order to reach optimal blood levels.
Creams or gels containing natural hormones are available through compounding pharmacies with a prescription from a physician who will monitor their use. It is important to test hormone levels before and throughout treatment to help maintain optimal levels in anyone being treated with natural hormone replacement. For more information on hormone testing and natural hormone replacement therapy, see the paper titled 'Hormones for Immune Support' in the Medical Condition Information section of our website.
Raloxifene (Evista®) is a medication in a class of drugs called selective estrogen receptor modulators (SERMs). Raloxifene®is approved for the prevention and treatment of osteoporosis in postmenopausal women.
This drug mimics estrogen's beneficial effects on bone density in postmenopausal women without some of the risks such as increased cancer risks. However, hot flashes are a common side effect, and the drug should not be used in anyone with a history of blood clots.
Teriparatide (Forteo®) is approved for the prevention and treatment of osteoporosis in postmenopausal women. It is an analog of parathyroid hormone which is approved for the treatment of osteoporosis in postmenopausal women and in men who are at high risk for a fracture. Teriparatide stimulates new bone growth and is given as an injection under the skin of the thigh or stomach. Because long-term effects are not yet known, the FDA recommends limiting treatment with teriparatide to two years or less.
Ensuring the consumption of optimal doses of all the key nutrients used by the body to build and maintain strong bones is a very important component of a program aimed at optimizing bone health. Although most people think of only calcium (and perhaps vitamin D) in this regard, there are actually a number of other important nutrients the body must have to physically create the structure of bones and maintain their health.
Included on the list of important bone nutrients are calcium, vitamin D, vitamin K, magnesium, manganese, molybdenum, phosphorus, selenium, boron, and copper. Studies indicate that the plant estrogen-like compound ipriflavone may also support bone health. Recent research indicates that B-12 may also be very important.
• Calcium is the mineral that makes up the majority of bone tissue. Ingesting optimal amounts of calcium throughout your lifetime is important to reduce the risk of osteoporosis and to help prevent the bones from becoming weaker in those already diagnosed with osteoporosis. Research has shown that calcium supplementation has a positive effect on bone density.32 In combination with vitamin D and the other key bone micronutrients, calcium can help replace bone that has already been lost. The amount of calcium that is needed for optimal health varies at different life stages. The need for calcium is highest in childhood and adolescence because the skeleton is growing rapidly, as well as during pregnancy and breast-feeding, because of the demands placed on a woman's body by the baby. Higher amounts of calcium are also needed in postmenopausal women and older men because the body no longer absorbs calcium as well, and many older people take medications that interfere with calcium absorption.
The recommended intake of calcium for postmenopausal women not taking hormone replacement therapy, and all men and women older than 65, is 1,500 mg of elemental calcium daily. Premenopausal women and postmenopausal women on hormone replacement therapy are advised to consume at least 1,000 mg of elemental calcium daily. Steroid therapy (often prescribed for asthma and autoimmune diseases) greatly increases one's need for calcium and other bone building nutrients.
In general, research has made it clear that calcium replacement alone is not optimal for preventing osteoporosis. For example, in a two-year, double-blind, placebo-controlled trial of healthy postmenopausal women, the combination of calcium, vitamin D, and vitamin K resulted in better improvements in bone health than were seen in women given only calcium with D.33 Calcium should always be used in conjunction with other nutrients that are needed for optimal bone health.
• Magnesium is the fourth most abundant mineral in the body, with approximately 50% of total body magnesium found in bone. Among its many beneficial effects, magnesium helps to regulate calcium transport in the body. Increased magnesium intake has been associated with increased bone mineral density in elderly men and women.34 Postmenopausal women with osteoporosis have been shown to commonly have reduced intake of magnesium.35 Premenopausal women with higher intakes of magnesium were shown to have increased bone mineral density in the lumbar spine.36 Both premenopausal and postmenopausal women with higher dietary intakes of magnesium were shown to have increased bone mineral content in the forearm.37 Cancellous bone (bone that has a lattice-like or spongy structure) in women with osteoporosis has been shown to have a low magnesium content which is associated with bone crystals that are more brittle than those seen in bone with sufficient magnesium.38,39
According to the Institute of Medicine, a number of studies have suggested that magnesium supplementation may improve bone mineral density.40 A two-year placebo-controlled trial of magnesium supplementation in postmenopausal women with osteoporosis showed that women taking magnesium supplements (two to six tablets daily of 125 mg each of magnesium hydroxide) showed significant increases in bone density, both at one and two years, compared to decreases in bone density in the un-supplemented women.41
Data from the 1999-2000 National Health and Nutrition Examination Survey suggests that a substantial percentage of adults in the United States fail to consume the recommended amount of magnesium, and that magnesium intake is even lower in older adults in every racial and ethnic group.42Older adults have a combination of factors that places them at risk for magnesium deficiency, including decreased magnesium absorption, increased renal excretion of magnesium, and a higher intake of medications that bind magnesium.43 For many people, dietary intake may not be high enough to promote optimal magnesium status, making magnesium supplementation very important for maintaining healthy bone density.
• Vitamin D is just as important as calcium for bone health since it is required for calcium absorption and for day-to-day maintenance of calcium and mineral homeostasis in the body. Research has made it abundantly clear that optimal amounts of vitamin D are crucial for supporting healthy bone density. Several studies have shown that supplementation with 700 to 800 IU per day of vitamin D results in significant reductions in fractures.44,45,46 However, studies in which only 400 IU per day of vitamin D were given did not find any significant reduction in fractures.47,48 In a review of a dozen randomized controlled trials that assessed the effectiveness of vitamin D supplementation for preventing either hip fracture (five trials involving 9294 people) or non-vertebral fracture (seven trials involving 9820 people), it was shown that supplementation with at least 700-800 IU of vitamin D daily provided significant protection.49 Supplementation at this level reduced the risk of hip fracture by 26% and the risk other non-vertebral fractures by 23 %. However, supplementation with a lower dose of only 400 IU did not provide significant protection.
In addition to the bone-building usefulness of vitamin D, it may also help to reduce fractures by improving muscle strength and function in a way that helps prevent falling. It is estimated that every year, falls occur in 30% of people who are 65 years or older and 40% to 50% of those who are 80 years or older.50,51 Research has shown that vitamin D supplementation in elderly people may reduce the risk of falling by 22 percent, a hugely significant decrease since falls can lead to serious injury and even death, and are often the precipitating factor which eventually cause an older person to be sent to a nursing home.52
Experts in the field point to an unrecognized epidemic of vitamin D deficiency among older Americans which may contribute substantially to an increase in falls as well as the development of osteoporosis and the fractures that result from it.53 Daily consumption of 800 IU of vitamin D is the minimum recommendation, and many scientists now believe that substantially higher doses may be optimal. Research makes it clear that it is the combination of vitamin D with calcium supplementation that achieves the best results.54
• Ipriflavone is a â€œplant estrogen-like compoundâ€ that has been studied in both animal and human trials. Research has shown that ipriflavone increases absorption of calcium from the intestines.55 Ipriflavone is also believed to slow the rate of bone loss while also increasing the rate of bone formation.56 In two double-blind, placebo-controlled studies, women with osteoporosis given 600 mg per day of ipriflavone combined with 1,000 mg of calcium had a significant increase in bone density and a significant reduction in vertebral fractures, along with significant improvements in bone pain and mobility.57 Several other studies have shown that supplementing ipriflavone (generally in doses of 200 mg, three times daily) can prevent bone loss in postmenopausal women.58,59,60
• Vitamin K is required for the synthesis of osteocalcin, a bone protein important for bone formation. Osteocalcin provides structure and order to bone tissue. Without osteocalcin, bones would be fragile and easily broken. In humans, vitamin K levels fall during recovery from a fracture providing evidence that this nutrient is actually drawn from the rest of the body to the site of the fracture. Vitamin K deficiency has been shown to be common in people diagnosed with osteoporosis.61 In a very large study of 72,327 women, low intake of vitamin K was shown to be associated with a significantly increased risk of hip fracture.62 In another study, low dietary vitamin K intake was clearly associated with low bone density in women.63 In one large study of postmenopausal women that compared the results of those receiving placebo to those given supplementation with either a combination of the nutrients calcium, magnesium, zinc, and vitamin D or those same nutrients with the addition of vitamin K, there was significantly less bone loss in the women given the nutrient combination that included vitamin K.64 In a two-year, double-blinded, placebo-controlled trial of healthy postmenopausal women, the combination of calcium, vitamin D, and vitamin K resulted in better improvements in bone health than were seen in women given only calcium with vitamin D.65 Ensuring adequate supplies of vitamin K may be one of the most important steps for maintaining healthy bones.
• Vitamin B-12 may also play an important role in preventing osteoporosis. Researchers have reported that women with lower levels of vitamin B-12 are more likely to experience rapid bone loss. In one study of 83 women over the age of 64, researchers found that women with the lowest levels of B-12 experienced dramatic and rapid hip bone loss compared with women with higher levels of B-12.66 In a study of postmenopausal women, those diagnosed with pernicious anemia (caused by B-12 deficiency) had an almost 2-fold increase in the risk of hip and spine fractures and almost 3 times the risk of wrist fractures compared to healthy women.67 The Framingham osteoporosis study has also found that low B-12 levels are associated with lower bone mineral density.68
Deficiencies of B-12 are quite common among older men and women.69,70 It is important to note that recent Yale School of Medicine research has clearly shown that none of the currently available tests used to assess B-12 status (serum B-12 level, homocysteine level, and methylmalonic acid level) accurately show B-12 deficiency.71 The author of this study, Yale's Lawrence Solomon, M.D., reports that people with a clinical picture consistent with B-12 deficiency often benefit from B-12 therapy regardless of their serum vitamin B-12, methylmalonic acid, or homocysteine values. For people at risk of osteoporosis and especially those who show any of the typical symptoms related to B-12 deficiency (including memory loss, confusion, decreased reflexes, unsteady gait, weakness, fatigue, disorientation, impaired pain perception, neuropathy, and paresthesias), regular B-12 supplementation may be useful. Methylcobalamin is one of the best absorbed oral forms of vitamin B12.
1. Fruit and vegetable intakes and bone mineral status: a cross-sectional study in 5 age and sex cohorts. Am J Clin Nutr. 2006;83:1420—8. Prynne CJ, Mishra GD, O'Connell MA, et al.
2. Nutritional influences on mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997;65:1831-9. New SA,Bolton-Smith C, Grubb DA, Reid DM.
3. Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69:727—36. Tucker KL, Hannan MT, Chen H, Cupples LA, Wilson PW, Kiel DP.
4. Nutritional associations with bone loss during the menopausal transition: evidence for a beneficial effect of calcium, alcohol, and fruit and vegetable nutrients and of a detrimental effect of fatty acids. Am J Clin Nutr. 2004;79:155—65. Macdonald HM, New SA, Golden MHN, Campbell MK, Reid DM.
5. Associations between urinary potassium, urinary sodium, current diet and bone density in prepubertal children. Am J Clin Nutr. 2001;73:839—44. Jones G, Riley MD, Whiting SJ.
6. Consumption of soft drinks with phosphoric acid as a risk factor for the development of hypocalcemia in children: a case-control study. J Pediatr. 1995;126:940-2. Mazariegos-Ramos E, Guerro-Romero F, Rodriguez-Moran M, et al.
7. Caffeine, moderate alcohol intake, and risk of fractures of the hip and forearm in middle-aged women. Am J Clin Nutr. 1991;54:157-63. Hernandez-Avila M, Colditz GA, Stampfer MJ, et al.
8. Caffeine and the risk of hip fracture: the Framington study. Am J Epidemiol. 1990;132:675-84. Kiel DP, Felson DT, Hannan MT, et al.
9. Tea drinking and bone mineral density in older women. Am. J. Clinical Nutrition. 2000;71(4):1003-1007. Hegarty VM, May HM, Khaw K-T.
10. Sodium-calcium inter-relationships with specific reference to osteoporosis. Nutr. Res. Rev. 1990;3:101-115. Shortt C and Flynn A.
11. Dietary salt, urinary calcium and bone loss. J. Bone Miner Res. 1996;11:731-736. Massey L and Whiting S.
12. Urinary calcium excretion at extremes of sodium intake in normal man. Am. J. Nephrol. 1981;1:84-90. McCarron D, Rankin L, Bennet W et al.
13. The role of dietary sodium on renal excretion and intestinal absorption of calcium and on vitamin D metabolism. J. Clin. Endocrinol. Metab. 1982;55:369-373. Breslau N, McGuire J, Zerwekh J, Pak C.
14. The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. J. Nutr. 2003;133:3130-3136. Lin P-H, Ginty F, Appel LJ, et al.
15. Effects of high-intensity strength training on multiple factors for osteoporotic fractures: a randomized controlled trial. JAMA. 1994;272:1909—14. Nelson ME, Fiatarone MA, Morganti CM, et al.
16. Risk factors for spinal osteoporosis in men. Am J Med. 1983;75:977—83. Seeman E, Melton LJ III, O'Fallon WM, Riggs BL.
17. The effect of smoking at different life stages on bone mineral density in elderly men and women. Osteoporos Int. 1996;6:240—8. Kiel DP, Zhang Y, Hannan MT, et al.
18. A prospective study of alcohol consumption and bone mineral density. BMJ. 1993;306:1506—9. Holbrook TL, Barrett-Connor E.
19. Effects of alcohol consumption on bone mineral metabolism in elderly women. Am J Clin Nutr. 2000;72:1073. Mukherjee S, Sorrell MF.
20. Alcohol intake and bone mineral density in elderly men and women. Am J Epidemiol. 1995;142:485—92. Felson DT, Zhang Y, Hannan MT, Kiel DP.
21. Alcohol abuse and osteoporosis.Semin Arthritis Rheum. 1990;19:371—6. Scharpira D
22. Is natural progesterone the missing link in osteoporosis prevention and treatment?Med Hypotheses. 1991;35:316-318. Lee JR.
23. DHEA in bone and joint diseases. Joint Bone Spine. 2001;68:588-594. Cormier C, Souberbielle J-C, Kahan A.
24. Dehydroepiandrosterone treatment in the aging male - what should the urologist know? European Urol. 2005;48(5):724-733.
25. Exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone. J Clin Endocrinol Metab. 2004;89:503-10. Amory JK, Watts NB, Easley KA et al.
26. Exogenous testosterone (T) alone or with finasteride increases physical performance, grip strength, and lean body mass in older men with low serum T. J Clin Endocrinol Metab. 2005;90:1502-10. Page ST, Amory JK, Bowman FD et al.
27. Randomized placebo-controlled trial of androgen effects on muscle and bone in men requiring long-term systemic glucocorticoid treatment. J Clin Endocrinol Metab. 2003;88:3167-76. Crawford BA, Liu PY, Kean MT, Bleasel JF, Handelsman DJ.
28. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996;81:4358-4365. Katznelson L, Finkelstein JS, Schoenfeld DA, et al.
29. Endogenous testosterone levels, physical performance, and fall risk in older men. Arch Intern Med. 2006;166:2124-2131. Orwoll E, Lambert LC, Marshall LM.
30. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701-1707. Tinetti ME, Speechley M, Ginter SF
31. Falls in old age: a study of frequency and related clinical factors. Age Ageing. 1981;10:264-270. Campbell AJ, Reinken J, Allan BC, Martinez GS.
32. Calcium supplementation on bone loss in postmenopausal women. Cochrane Database Syst Rev. 2004;1:CD004526. Shea B, Wells G, Cranney A, et al.
33. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007;22(4):509-19. Bolton-Smith C, McMurdo ME, Paterson CR, et al.
34. Potassium, magnesium and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr. 1999;69:727-36. Tucker KL, Hannan MT, Chen H, et al.
35. Calcium, phosphorus, and magnesium intakes correlate with bone mineral content in postmenopausal women.Gynecol Endocrinol. 1994;8:55—8. Tranquilli AL, Lucino E, Garzetti GG, Romanini C.
36. Nutritional influences on bone mineral density: a cross-sectional study in premenopausal women. Am J Clin Nutr. 1997;65:1831—9. New SA, Bolton-Smith C, Grubb DA, Reid DM.
37. Dietary intake and bone mineral density. Bone Miner. 1988;4:265—77. Angus RM, Sambrook PN, Pocock NA, Eisman JA.
38. Bone mineral content of the radius: correlations with physicochemical determinations in iliac crest trabecular bone of normal and osteoporotic subjects. Metabolism. 1981;30:57—62. Manicourt DH, Orloff S, Brauman J, Schoutens A.
39. Infrared spectrospcopy and magnesium content of bone mineral in osteoporotic women. Isr J Med Sci. 1981;17:1123—5. Cohen L, Kitzes R.
40. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. National Academy Press. Washington, DC, 1999. Institute of Medicine. Food and Nutrition Board.
41. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnes Res. 1993;6:155—63. Stendig-Lindberg G, Tepper R, Leichter I.
42. Dietary magnesium intake in a national sample of U.S. adults. J Nutr. 2003;133:2879-82. Ford ES and Mokdad AH.
43. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. National Academy Press. Washington, DC, 1999. Institute of Medicine. Food and Nutrition Board.
44. Effect of calcium and vitamin D supplementation on bone density in men and women 65 years of age or older. N Engl J Med. 1997;337:670-676. Dawson-Hughes B, Harris SS, Krall EA, Dallal GE.
45. Vitamin D3 and calcium to prevent hip fractures in the elderly women. N Engl J Med. 1992;327:1637-1642. Chapuy MC, Arlot ME, Duboeuf F, et al.
46. Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ. 2003;326:469. Trivedi DP, Doll R, Khaw KT.
47. Can vitamin D supplementation reduce the risk of fracture in the elderly? A randomized controlled trial. J Bone Miner Res. 2002;17:709-715. Meyer HE, Smedshaug GB, Kvaavik E, et al.
48. Vitamin D supplementation and fracture incidence in elderly persons: a randomized, placebo-controlled clinical trial. Ann Intern Med. 1996;124:400-406. Lips P, Graafmans WC, Ooms ME, Bezemer PD, Bouter LM.
49. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials.JAMA. 2005;293(18):2257-64. Bischoff-Ferrari HA, Willett WC, Wong JB, et al.
50. Risk factors for falls among elderly persons living in the community. N Engl J Med. 1988;319:1701-1707. Tinetti ME, Speechley M, Ginter SF.
51. Falls in old age: a study of frequency and related clinical factors. Age Ageing. 1981;10:264-270. Campbell AJ, Reinken J, Allan BC, Martinez GS.
52. Effect of vitamin D on falls.JAMA. 2004;291:1999-2006. Bischoff-Ferrari HA, Dawson-Hughes B, Willett WC, et al.
53. Vitamin D and calcium deficits predispose for multiple chronic diseases. European J Clin Invest. 2005;35:290-304. Peterlik M and Cross HS.
54. Need for additional calcium to reduce the risk of hip fracture with vitamin d supplementation: evidence from a comparative metaanalysis of randomized controlled trials. J. Clin Endocrinol Metab. 2007;92(4):1415-23. Boonen S, Lips P, Bouillon R, et al.
55. Ipriflavone, a synthetic phytoestrogen, enhances intestinal calcium transport in vitro. Calcif Tissue Int. 2000;67(3):225-229. Arjmandi BH, Khalil DA, Hollis BW.
56. In vitro and in vivo effects of ipriflavone on bone formation and bone biomechanics. Calcif Tissue Int. 1997;61 Suppl 1:S12-14. Civitelli R.
57. Efficacy of ipriflavone in established osteoporosis and long-term safety. Calcif Tissue Int. 1997;61 Suppl 1:S23-27. Agnusdei D, Bufalino L.
58. Bone density changes in postmenopausal women with the administration of ipriflavone alone or in association with low-dose ERT. Gynecol Endocrinol. 1997;11:289-293. de Aloysio D, Gambacciani M, Altieri P, et al.
59. Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years. Osteoporos Int. 1997;7(2):119-25. Adami S, Bufalino L, Cervetti R, et al.
60. Inhibitory effect of ipriflavone on vertebral bone mass loss in postmenopausal women with low bone mass. Osteoporos Int. 1996;6(1):93. Mazzuoli GF. Osteoporos Int. 1996;6(1):93. Mazzuoli GF.
61. Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab. 1985;60:1268-1269. Hart JP, Shearer MJ, Klenerman L, et al.
62. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr. 1999;69(1):74-79. Feskanich D, Weber P, Willett WC, et al.
63. Vitamin K Intake and bone mineral density in women and men. Am J Clin Nutr. 2003;77:512-516. Booth SL, Broe KE, Gagnon DR, et al.
64. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003;73(1):21-26. Braam LA, Knapen MH, Geusens P, et al.
65. Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res. 2007;22(4):509-19. Bolton-Smith C, McMurdo ME, Paterson CR, et al.
66. Low serum vitamin B-12 levels are associated with increased hip bone loss in older women: a prospective study. J Clin Endocrinol Metab. 2004;89(3):1217-21. Stone KL, Bauer DC, Sellmeyer D, Cummings SR
67. Risk of fractures in patients with pernicious anemia. J Bone Miner Res. 1992;7:573—579. Goerss JB, Kim CH, Atkinson EJ, et al.
68. Low plasma vitamin B12 is associated with lower BMD: the Framingham osteoporosis study. J Bone Miner Res. 2005;20:152-8. Tucker KL, Hannan MT, Qiao N, et al
69. Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate, and vitamin B-6 occur commonly in elderly people. Am J Clin Nutr. 1993;58:468—76. Joosten E, van den Berg A, Riezler R, et al.
70. Prevalence of cobalamin deficiency in the Framingham elderly population. Am J Clin Nutr. 1994;60:2—11. Lindenbaum J, Rosenberg IH, Wilson PW, Stabler SP, Allen RH.
71. Cobalamin-responsive disorders in the ambulatory care setting: unreliability of cobalamin, methylmalonic acid, and homocysteine testing. Blood. 2005;105(3):978-985. Solomon L.