Approximately 44 million American women and men aged 50 and older have osteoporosis (severe bone loss) or osteopenia (mild bone loss), with women being affected about twice as often as men.1 At least 1.5 million fractures of the hip, vertebra (back or neck), or wrist occur each year in the United States as a result of osteoporosis, and the annual cost of treating this disorder is nearly $14 billion and rising. And the toll in human suffering and loss of independence is even greater.
Q. What are the risk factors for osteoporosis?
A. Small body frame, underweight, Caucasian or Asian race, a sedentary lifestyle, cigarette smoking, excessive alcohol or caffeine intake, high intake of carbonated beverages (especially colas), and having other family members with osteoporosis all increase personal risk of developing the disease. Certain medical conditions, including diabetes, celiac disease, hyperthyroidism, rheumatoid arthritis, chronic obstructive lung disease, hyperadrenalism, and hyperparathyroidism, are all associated with an increased risk of osteoporosis. Some medications increase the rate at which bone is lost; these include drugs prescribed for the treatment of seizures, drugs used for blood thinning, steroids such as prednisone, aluminum-containing antacids, and loop diuretics (furosemide [Lasix]).
Q. Isn't bone loss just a normal consequence of aging?
A. Although bone mass normally declines after the age of 35, bone loss severe enough to cause fractures after just minor trauma (such as a bump or fall) seems to be a relatively new phenomenon. Osteoporosis was rare in the late 19th century, and it was not until around 1920 that the condition began to attract attention among doctors. Since that time, the percentage of people who develop osteoporosis has continued to increase. For example, the age-adjusted prevalence of osteoporosis in England and Sweden doubled between 1950 and 1 980.2-4
In addition, the percent of elderly people with osteoporosis in some developing countries is lower than that of elderly Americans, despite lower calcium intakes in the developing countries, further suggesting that osteoporosis is a disease of modern civilization.5
Q. Can osteoporosis be prevented?
A. Engaging in regular weight bearing exercise, avoiding excessive consumption of alcohol and caffeine, and quitting smoking will slow the rate of bone loss. Eating adequate, but not excessive, amounts of protein also enhances bone health. In addition, a growing body of research has shown that supplementing with various vitamins and minerals may not only help prevent, but in some cases actually reverse, bone loss. At least 15 different nutrients have been found to play a role in bone health.
Q. What type of calcium is best?
A. For most people, the different types of calcium salts are absorbed about the same, between 30% and 40% of the administered dose. People who have low stomach acid (hypochlorhydria) should not use plain calcium carbonate, because that form of calcium is absorbed poorly in the absence of stomach acid. Calcium phosphate may be preferable for many older people, because phosphorus is necessary for normal bone formation, the phosphorus intake of older people is often low, and calcium supplements inhibit the absorption of phosphorus.6
Also, calcium bound to phosphorus is the form in which calcium in the bone is stored, and it has a much greater bone activity than other forms.7 A combination of a highly concentrated calcium (calcium carbonate), with a proven most effective calcium (calcium triphosphate), and a calcium shown to increase absorption of magnesium (calcium gluconate) is the best combination.
Q. How much vitamin D is needed to promote strong bones?
A. Because vitamin D is produced when ultraviolet rays from the sun come in contact with skin, people who stay out of the sun, who wear sunscreen, or who live in a northern latitude (such as Boston or Seattle) where less ultraviolet light reaches the skin are at increased risk of vitamin D deficiency. In addition, aging decreases a person's ability to synthesize vitamin D in the skin. Results from five research trials on vitamin D found that supplementation with 700-800 IU of vitamin D per day decreased the number of hip fractures by 26%, but 400 IU per day was ineffective.8 In addition to enhancing bone health, vitamin D improves nerve and muscle function in older people, thereby reducing their chances of falling down.
Supplementation of elderly women with 800 IU of vitamin D per day has been shown to decrease the number of falls by about 50%.9,10
Q. Is that much vitamin D safe?
A. The Food and Nutrition Board of the Institute of Medicine established a "safe upper limit" of 2,000 IU per day in 1997. More recent research suggests that up to 4,000 IU of vitamin D per day is safe for the average person.11 However, this amount is more than generally regarded necessary to address most bone issues.
Q. Why would nutrients besides calcium and vitamin D be important?
A. Bone is living tissue, constantly remodeling itself and engaging in numerous biological functions. Like other tissues in the body, bone has a wide range of nutritional needs. The typical refined and processed American diet has been depleted of many different vitamins and minerals, some of which play a key role in promoting bone health.12 Not getting enough of one or more of these micronutrients may be an important contributing factor to the modern epidemic of osteoporosis. In addition, supplementing with calcium may cause a loss of magnesium, zinc, silicon, manganese, and phosphorus, unless these nutrients are also provided.13-20
Q. What nutrients besides calcium and vitamin D promote healthy bones?
A. Magnesium, zinc, copper, manganese, vitamin K, boron, strontium, silicon, folic acid, vitamin B6, vitamin B12, phosphorus, and vitamin C have all been shown to play a role in bone health. Following is a brief description of the role that each of these 15 nutrients play in building healthy bones.
Calcium: A component of the mineral crystals that make up bone
Vitamin D: Enhances calcium absorption, prevents falls by improving nerve and muscle function.
Magnesium: Important for bone mineralization (accumulation of minerals which form bones). Magnesium deficiency is associated with abnormal bone mineral crystals in humans.21 In an open clinical trial in postmenopausal women, magnesium supplementation increased bone mineral density up to 8% in some participants after 1-2 years.22
Copper: Laboratory research has found that copper promotes bone mineralization and decreases bone loss, and that osteoporosis can develop if the diet is deficient in copper.23,24 Western diets often contain less copper than the amount recommended by the National Academy of Sciences.25 In a 2-year double-blind trial, copper supplementation reduced bone loss by 90% in middle-aged women, compared with a placebo.26
Zinc: Like magnesium, zinc is important for bone mineralization, and also has been shown to decrease bone loss.27-28 Low dietary zinc intake was associated with increased fracture risk in a study of middle-aged and elderly men.29 The zinc content of the diet is frequently low; a study of elderly low-income people found they were consuming only half the Recommended Dietary Allowance for this mineral.30
Manganese: Plays a role in the synthesis of the connective-tissue components of bone. Manganese deficiency in laboratory tests resulted in low bone mineral density and weak bones.31,32 Manganese deficiency may be associated with the development of osteoporosis.33,34
Boron: Supports creation of bone-protecting hormones such as estrogen, testosterone, and DHEA. Boron supplementation prevented bone loss in experimental studies.35 In human volunteers consuming a low-boron diet, boron supplementation decreased urinary calcium excretion by 25-33%, a change that may indicate reduced bone loss.36
Silicon: Plays a role in the synthesis of the connective-tissue components of bone. Silicon deficiency has been associated with bone abnormalities. In an observational study, higher dietary silicon intake correlated with higher bone mineral density.37 In a clinical trial, administration of an organic silicon compound increased bone mineral density of the femur (thigh bone) in postmenopausal women.38
B vitamins (folic acid, vitamin B6, and vitamin B12): These three B vitamins have been shown to lower blood levels of homocysteine, a breakdown product of the amino acid methionine.
An elevated homocysteine concentration is a strong and independent risk factor for fractures in older men and women.39,40 Homocysteine levels increase around the time of menopause, which may explain in part why bone loss accelerates at that time.41 In a 2-year double-blind trial, supplementation of elderly stroke patients with folic acid and vitamin B12 reduced the number of hip fractures by 78%, compared with a placebo.42
Strontium: This trace mineral is incorporated into bone and appears to increase bone strength. It also stimulates bone formation and inhibits bone breakdown. Controlled trials have demonstrated that strontium supplementation of postmenopausal women increases bone mineral density and decreases fracture risk.43,44
Vitamin K: Best known for its effect on blood clotting, vitamin K is also required for the creation of osteocalcin, a unique protein found in bone that participates in the mineralization process. The amount of vitamin K needed for optimal bone health appears to be greater than the amount needed to prevent bleeding.45,46 Vitamin K levels tend to be low in people with osteoporosis.47 In randomized clinical trials, supplementation of postmenopausal women with vitamin K prevented bone loss and reduced the incidence of fractures.48,49
Q. Which form of vitamin K is best?
A. Two forms of vitamin k compounds are present in food: vitamin K1 and vitamin K2. Vitamin K1 (also called phylloquinone) is present in leafy green vegetables and some vegetable oils, and vitamin K2 is found in much smaller amounts in meat, cheese, eggs, and natto (fermented soybeans).
To make things a little more complicated, Vitamin K2 itself can occur in more than one form. The two most important to this discussion are menaquinone-4 (MK-4, also called menatetrenone), which is licensed as a prescription drug in Japan, and menaquinone-7 (MK-7), which is extracted from natto.
Research suggests that MK-7 from natto may be an ideal form of vitamin K. The biological activity of MK-7 in laboratory studies was 17 times higher than that of vitamin K1 and 130 times higher than that of MK-4.50 After oral administration, MK-7 was better absorbed and persisted in the body longer, compared with MK-4 and vitamin K1.51,52
Although both have shown ability to prevent osteoporosis in laboratory research, a much lower dosage (600 times lower) of MK-7 is required,compared with MK-4, to obtain beneficial effects.53,54
Thus, MK-7 has greater biological activity, greater bioavailability, and possibly more potent effects on bone, compared with other forms of vitamin K. The potential value of MK-7 for bone health is supported by an observational study from Japan, in which increasing natto consumption was associated with a lower risk of hip fracture.55 While additional research needs to be done, the available evidence suggests that the best forms of vitamin K for long-term use at physiological doses are MK-7 and vitamin K1.
Q. What is the optimal dose of strontium for bone health?
A. The safest and most effective dose may turn out to be substantially less than what researchers are currently investigating. Strontium doses in recent clinical trials ranged from 170 to 680 mg per day, or up to 300 times as much as the 2-3 mg present in a typical daily diet.
Interestingly, the lowest strontium dose (170 mg per day) produced the greatest reduction in fracture risk, which raises the possibility that further lowering the dose might produce even better results.56
In fact, high-dose strontium causes rickets in animals under certain conditions, and in an observational study in Turkey, high soil strontium concentrations were associated with an increased prevalence of rickets in children.57,58 Thus, adverse effects counterbalance the beneficial effects of strontium on bone tissue, if the dose is too high. Strontium supplementation also increased thyroid-gland weight and decreased pituitary weight in rats, with a "no-observed-adverse¬effect-level" roughly equivalent to 41 mg per day for humans.59
In one of the clinical trials, bone biopsies performed after 3 years of strontium supplementation did not reveal any mineralization defects.60 However, only mature bone was biopsied, whereas the earliest evidence of a mineralization defect would likely be found in newly formed bone. Of note, the degree of protection against fractures decreased as the study progressed, even though bone mineral density continued to increase. That finding raises the possibility that the new bone formed under the influence of high-dose strontium therapy may not have been of high quality. Additional studies are therefore needed before long-term supplementation with high-dose strontium can be considered safe.
Q. So, physiological doses of strontium may be safer, but are they effective?
A. Even in the small amounts present in a normal diet, strontium accumulates in bone and persists there for decades. Consequently, strontium supplementation at physiological (as opposed to pharmacological) doses would be expected to have effects on bone. While low-dose strontium has not been studied as a treatment for osteoporosis, clues are provided from the effect of strontium on teeth, the other major calcified tissue in the body. In observational studies, the prevalence of dental caries (cavities) was lowest in geographical regions where the strontium content of drinking water was 5-6 mg per liter. Caries prevalence was higher when water contained substantially more or substantially less than 5- 6 mg of strontium per liter.61Thus, the optimal dose of supplemental strontium may turn out to be fairly low, perhaps in the range of 6 mg per day or less.
Q. Can people taking osteoporosis medications also take bone-building nutrients?
A. Because nutrients work by a different mechanism than osteoporosis drugs, nutritional supplements are likely to enhance the beneficial effect of these medications. Calcium or other minerals may interfere with the absorption of biphosphonates such as alendronate (Fosamax) or etidronate (Didronel). For that reason, calcium and other minerals should be taken at least two hours before or two hours after these medications. Also, it is always best to discuss the supplements you are using with your healthcare practitioner to create an integrated health plan.
Osteoporosis is a common and potentially serious condition. Fortunately, a great deal can be done to help prevent, and in many cases reverse, bone loss. Important components of a bone loss prevention program include diet, lifestyle changes, regular exercise, and taking a broad-spectrum nutritional supplement that contains all of the nutrients that play a role in bone health.
1. America's Bone Health: The State of Osteoporosis and Low Bone Mass. National Osteoporosis Foundation. Available at: http://www.nof.org/advocacy/prevalence/. Accessed on November 15, 2005.
2. Boyce WJ, Vessey MP. Rising incidence of fracture of the proximal femur. Lancet. 1 985;1 :150- 151.
3. Johnell O, Nilsson B, Obrant K, Sernbo I. Age and sex patterns of hip fracture - changes in 30 years. Acta Orthop Scand. 1984 ;55:290-292.
4. Bengner U, Johnell O. Increasing incidence of forearm fractures. A comparison of epidemiologic patterns 25 years apart. Acta Orthop Scand. 1 985;56:1 58-160.
5. Zeegelaar FJ, Sanchez H, Luyken R, Luyken-Koning FWM, van Staveren WA. Studies on physiology of nutrition in Surinam. XI. The skeleton of aged people in Surinam. Am J Clin Nutr. 1 967;20:43-45.
6. Heaney RP, Nordin BEC. Calcium effects on phosphorus absorption: implications for the prevention and co-therapy of osteoporosis. J Am Coll Nutr. 2002;21 :239-244.
7. Shapiro R, Heaney RP. Co-dependence of calcium and phosphorus for growth and bone development under conditions of varying deficiency. Bone. 2003 May;32(5):532-40.
8. Bischoff-Ferrari HA, Willett WC, Wong JB, Giovannucci E, Dietrich T, Dawson-Hughes B. Fracture prevention with vitamin D supplementation: a meta-analysis of randomized controlled trials. JAMA. 2005;293:2257-2264.
9. Bischoff HA, Stahelin HB, Dick W, Akos R, Knecht M, Salis C, et al. Effects of vitamin D and calcium supplementation on falls: a randomized controlled trial. J Bone Miner Res. 2003;18:343- 351.
10. Harwood RH, Sahota O, Gaynor K, Masud T, Hosking DJ. A randomised, controlled comparison of different calcium and vitamin D supplementation regimens in elderly women after hip fracture: The Nottingham Neck of Femur (NONOF) Study. Age Ageing. 2004;33:45-51.
11. Vieth R, Chan PCR, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr. 2001 ;73:288-294.
12. Schroeder HA. Losses of vitamins and trace minerals resulting from processing and preservation of foods. Am J Clin Nutr. 1971 ;24:562-573.
13. Smith KT, Luhrsen KR. Trace mineral interactions during elevated calcium consumption. Fed Proc. 1 986;45:374.
14. O'Dell BL, Morris ER, Regan WO. Magnesium requirement of guinea pigs and rats. Effect of calcium and phosphorus and symptoms of magnesium deficiency. J Nutr. 1960;70:103-1 11.
15. Wood RJ, Zheng JJ. High dietary calcium intakes reduce zinc absorption and balance in humans. Am J Clin Nutr. 1 997;65:1803-1809.
16. Argiratos V, Samman S. The effect of calcium carbonate and calcium citrate on the absorption of zinc in healthy female subjects. Eur J Clin Nutr 1 994;48:198-204.
17. Carlisle EM. A relationship between silicon and calcium in bone formation. Fed Proc. 1 970;29:565.
18. Morris ER, Ellis R, Hill AD, McCarron PB, Moser-Veillon PB, Anderson HL. Effect of three dietary calcium intakes on trace element balance of men consuming a constant amount of phytate. Am J Clin Nutr. 1 988;47:780.
19. Freeland-Graves JH, Lin PH. Plasma uptake of manganese as affected by oral loads of manganese, calcium, milk, phosphorus, copper, and zinc. J Am Coll Nutr. 1991 ;10:38-43.
20. Heaney RP, Nordin BEC. Calcium effects on phosphorus absorption: implications for the prevention and co-therapy of osteoporosis. J Am Coll Nutr. 2002;21 :239-244.
21. Cohen L, Kitzes R. Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Isr J Med Sci. 1981 ;1 7:1123-1125.
22. Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two year controlled trial of peroralmagnesium in osteoporosis. Magnes Res. 1993;6:155-1 63.
23. Follis RH Jr, Bush JA, Cartwright GE, Wintrobe MM. Studies on copper metabolism. XVIII. Skeletal changes associated with copper deficiency in swine. Bull Johns Hopkins Hosp. 1 955;97:405-409.
24. Wilson T, Katz JM, Gray DH. Inhibition of active bone resorption by copper. Calcif Tissue Int. 1981 ;33:35-39.
25. Baker DH. Cupric oxide should not be used as a copper supplement for either animals or humans. J Nutr. 1999;129:2278-2279.
26. Eaton-Evans J, McIlrath EM, Jackson WE, McCartney H, Strain JJ. Copper supplementation and the maintenance of bone mineral density in middle-aged women. J Trace Elem Exp Med. 1 996;9:87-94.
27. Leek JC, Keen CL, Vogler JB, et al. Long-term marginal zinc deprivation in rhesus monkeys. IV. Effects on skeletal growth and mineralization. Am J Clin Nutr. 1 988;47:889-895.
28. Moonga BS, Dempster DW. Zinc is a potent inhibitor of osteoclastic bone resorption in vitro. J Bone Miner Res 1 995;1 0:453-457.
29. Elmstahl S, Gullberg B, Janzon L, Johnell O, Elmstahl B. Increased incidence of fractures in middle-aged and elderly men with low intakes of phosphorus and zinc. Osteoporos Int. 1 998;8:333-340.
30. Hutton CW, Hayes-Davis RB. Assessment of the zinc nutritional status of selected elderly subjects. J Am Diet Assoc. 1 983;82: 148-152.
31. Strause L, Saltman P. Biochemical changes in rat skeleton following long-term dietary manganese and copper deficiencies. Fed Proc. 1 985;44:752.
32. Amdur MO, Norris LC, Heuser GF. The need for manganese in bone development by the rat. Proc Soc Exp Biol Med 1 945;59:254-255.
33. Science News 1986(Sept. 27);130:199.
34. Science 80 1980(May/June):101-102.
35. Rico H, Crespo E, Hernandez ER, Seco C, Crespo R. Influence of boron supplementation on vertebral and femoral bone mass in rats on strenuous treadmill exercise. A morphometric, densitometric, and histomorphometric study. J Clin Densitom. 2002;5:1 87-192.
36. Nielsen FH, Hunt CD, Mullen LM, Hunt JR. Effect of dietary boron on mineral, estrogen, and testosterone metabolism in postmenopausal women. FASEB J. 1 987;1 :394-397.
37. Jugdaohsingh R, Tucker KL, Qiao N, Cupples LA, Kiel DP, Powell JJ. Dietary silicon intake is positively associated with bone mineral density in men and premenopausal women of the Framingham Offspring cohort. J Bone Miner Res. 2004;1 9:297-307.
38. Eisinger J, Clairet D. Effects of silicon, fluoride, etidronate and magnesium on bone mineral density: a retrospective study. Magnes Res. 1 993;6:247-249.
39. Van Meurs JBJ, Dhonukshe-Rutten RAM, Pluijm SMF, van der Klift M. de Jonge R, Lindemans J, et al. Homocysteine levels and the risk of osteoporotic fracture. N Engl J Med. 2004;350:2033-2041.
40. McLean RR, Jacques PF, Selhub J, et al. Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med. 2004;350:2042-2049.
41. Brattstrom LE, Hultberg BL, Hardebo JE. Folic acid responsive postmenopausal homocysteinemia. Metabolism 1 985;34:1 073-1077.
42. Sato Y, Honda Y, Iwamoto J, Kanoko T, Satoh K. Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial. JAMA. 2005;293:1082-1 088.
43. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350:459-468.
44. Meunier PJ, Slosman DO, Delmas PD, et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis - a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab. 2002;87:2060-2066.
45. Sokoll LJ, et al. Changes in serum osteocalcin, plasma phylloquinone, and urinary gamma-carboxyglutamic acid in response to altered intakes of dietary phylloquinone in human subjects. Am J Clin Nutr. 1 997;65:779-784.
46. Binkley NC, Krueger DC, Kawahara TN, Engelke JA, Chappell RJ, Suttie JW. A high phylloquinone intake is required to achieve maximal osteocalcin gamma-carboxylation. Am J Clin Nutr. 2002;76:1 055-1060.
47. Kanai T, Takagi T, Masuhiro K, Nakamura M, Iwata M, Saji F. Serum vitamin K level and bone mineral density in post-menopausal women. Int J Gynecol Obstet. 1 997;56:25-30.
48. Braam LA, Knapen MHJ, Geusens P, et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int. 2003;73:21 -26.
49. Shiraki M, Shiraki Y, Aoki C, Miura M. Vitamin K2 (menatetrenone) effectively prevents fractures and sustains lumbar bone mineral density in osteoporosis. J Bone Miner Res. 2000;15:515-521.
50. Matschiner JT, Taggart WV. Bioassay of vitamin K by intracardial injection in deficient adult male rats. J Nutr. 1 968;94:57-59.
51. Schurgers LJ, Vermeer C. Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations. Haemostasis. 2000;30:298-307.
52. Sato T, Ohtani Y, Yamada Y, Saitoh S, Harada H. Difference in the metabolism of vitamin K between liver and bone in vitamin K-deficient rats. Br J Nutr. 2002;87:307-314.
53. Yamaguchi M, Kakuda H, Gao YH, Tsukamoto Y. Prolonged intake of fermented soybean (natto) diets containing vitamin K2 (menaquinone-7) prevents bone loss in ovariectomized rats. J Bone Miner Metab. 2000;1 8:71-76.
54. Yamaguchi M, Taguchi H, Gao YH, Igarashi A, Tsukamoto Y. Effect of vitamin K2 (menaquinone-7) in fermented soybean (natto) on bone loss in ovariectomized rats. J Bone Miner Metab. 1 999;1 7:23-29.
55. Kaneki M, Hedges SJ, Hosoi T, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition 2001 ;17:315-321.
56. Meunier PJ, Slosman DO, Delmas PD, et al. Strontium ranelate: dose-dependent effects in established postmenopausal vertebral osteoporosis - a 2-year randomized placebo controlled trial. J Clin Endocrinol Metab. 2002;87:2060-2066.
57. Kroes R, den Tonkelaar EM, Minderhoud A, et al. Short-term toxicity of strontium chloride in rats. Toxicology. 1977;7:11-21.
58. Ozgur S, Sumer H, Kocoglu G. Rickets and soil strontium. Arch Dis Child. 1996;75:524-526
59. Kroes R, den Tonkelaar EM, Minderhoud A, et al. Short-term toxicity of strontium chloride in rats. Toxicology. 1 977;7:1 1-21. This estimate was based on a human diet providing 2,000 kcal/day, with 30% wt/wt from fat (i.e. 416.6 g per day of food, dry weight).
60. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J Med. 2004;350:459-468.
61. Curzon MEJ, Spector PC, Iker HP. An association between strontium in drinking water supplies and low caries prevalence in man. Arch Oral Biol. 1 978;23:31 7-321.