Penn Herb Wellness Guide
Risk Factors for Osteoporosis
AgePeople of advanced age have a higher risk of osteoporosis, resulting from cumulative years of gradual bone loss starting before middle age. They also have an increased risk of falling, due to changes in vision, strength, and balance. Together, these factors contribute to the large number of fractures experienced by older people.1 People with long life expectancy should adopt dietary and lifestyle habits that will maximize peak bone mass early in life and minimize the bone loss that occurs naturally with aging.
AlcoholChronic alcohol abuse appears to increase bone loss and contributes to osteoporotic fractures. However, mild to moderate drinking may result in greater bone density than no alcohol intake at all,2,3,4 possibly due to increases in estrogen. Of course, alcohol consumption is associated with other health hazards, such as breast and other cancers, liver disease, alcoholism, and accidents, so its use may not be appropriate in many people, despite the potential lowering of osteoporosis risk.
Higher body weight reduces the risk of osteoporosis and related fractures, primarily because more weight on bones causes them to increase their density to support that weight.5,6 Moreover, researchers have shown that people who successfully lose weight have greater loss of bone compared with those who do not lose weight.7 Therefore, people who lose weight need to be more vigilant about preventing osteoporosis.
Due to health consequences associated with being overweight, healthcare professionals do not recommend weight gain for most people in order to reduce the risk of osteoporosis. However, very underweight people, such as those with anorexia nervosa, not only produce less weight-bearing pressure, but also produce less bone-protecting hormones, and may have many nutritional deficiencies that contribute to an increased risk of bone loss.8,9 Weight gain in underweight people may reduce the risk of osteoporosis.
CaffeineCaffeine has been linked to fracture of the hip in a large study following American women for six years.10 Caffeine increases urinary loss of calcium.11 In one trial, caffeine was linked with lower bone mass but only in women who consumed relatively little calcium.12 The authors of this report concluded that two to three cups of coffee per day might speed bone loss in women with calcium intakes of less than 800 mg per day. Most nutritionally oriented doctors recommend decreasing caffeine intake from caffeinated coffee, black tea, and some soft drinks as a way to improve bone mass.
In a group of 980 postmenopausal women, lifetime caffeine intake equal to two cups of coffee per day associated with decreased bone density in those who did not drink at least one glass of milk daily during most of their life.13 However, in 138 postmenopausal women, long-term dietary caffeine (coffee) intake was not associated with bone density.14 Until more is known, postmenopausal women should limit caffeine consumption and consume a total of approximately 1,500 mg of calcium per day (from a combination of diet and supplements).
Good calcium nutrition throughout life is essential for achieving peak bone mass and preventing deficiency-related bone loss.15 Many trials have investigated the effects of calcium supplements on bone mass. Although insufficient when used as the only intervention, calcium supplements have helped to prevent osteoporosis.16 Though some of the research remains controversial, the protective effect of calcium on bone mass is one of very few health claims permitted by the U.S. Food and Drug Administration.
In several studies, calcium intake has not correlated with protection—for example in men17 or in women who have just started menopause.18 Moreover, even most positive studies focusing on the effects of isolated calcium supplementation on bone mass show only minor effects. Nonetheless, a review of the research shows that calcium supplementation plus hormone replacement therapy is much more effective than hormone replacement therapy without calcium.19 Double-blind research has found that increasing calcium intakes results in greater bone mass in girls.20 An analysis of many studies investigating the effects of calcium supplementation in premenopausal women has also shown a significant positive effect.21 Studies in elderly people also confirm the value of calcium supplementation to prevent bone loss and fractures in older individuals.22,23 Most doctors, recommend calcium supplementation as a way to partially reduce the risk of osteoporosis. In order to achieve the 1,500 mg per day calcium intake deemed optimal by many researchers, 8001,000 mg of supplemental calcium are generally added to diets that commonly contain between 500700 mg calcium.
Other MineralsLow intake of minerals other than calcium may play a role in bone loss.24,25,26 One study reported that a daily combination of 1,000 mg calcium, 15 mg zinc, 2.5 mg copper, and 5 mg manganese was superior to calcium alone in preventing bone loss in postmenopausal women.27 Another study found that magnesium supplementation of at least 250 mg per day for two years arrested bone loss in most postmenopausal women.28
ExerciseExercise is known to help protect against bone loss29 and osteoporotic fracture, even in older people.30,31 Most types of weight-bearing exercise done by men and postmenopausal women, including walking, dancing, running, and some weight-training activities, increase bone mass in the spine and hip and lower the risk of osteoporosis at these sites.32,33,34 While more frequent and intense exercises have the greatest effect, these activities may increase the likelihood of injury. Non-weight-bearing exercises, such as arm exercises with weights, have greater benefit for the wrist and forearm.35 For premenopausal women, exercise is also important, but can be overdone if taken to extreme. Exercise so excessive that it leads to cessation of the menstrual cycle actually contributes to osteoporosis.36,37
Family HistoryMuch of the risk of osteoporosis depends upon genetics, which seems to greatly influence how much bone a person is able to build during their lifetime and how fast they will lose it. Therefore, people who have a parent (or possibly another close relative) who has been diagnosed with osteoporosis are at greater risk for developing the condition than someone with no family history of osteoporosis.38 People with higher genetic risk should adopt dietary and lifestyle habits that will maximize peak bone mass early in life and minimize the bone loss that naturally occurs with aging.
Gastrointestinal DiseaseSome diseases and conditions of the gastrointestinal tract make it difficult to absorb calcium and other nutrients essential to maintaining healthy bone. Due to this malabsorption problem, conditions such Crohn’s disease39 and surgical removal of part of the stomach (gastrectomy)40,41 increase the risk of osteoporosis. People with conditions that cause malabsorption should consult a healthcare practitioner to discuss the use of supplements that will help protect them from osteoporosis.
GenderOsteoporosis is most common in postmenopausal Oriental and white women. Premenopausal women are partially protected against bone loss by the hormone estrogen. Black women often have slightly greater bone mass in early adulthood compared with other women, which helps protect against bone fractures even though postmenopausal black women lose bone mass just as other women do. In men, testosterone partially protects against bone loss even after middle age. However, significant numbers of older men also develop osteoporosis severe enough to cause fractures.42 Women, because of their higher gender-related risk, should adopt dietary and lifestyle habits, such as increasing calcium intake and engaging in weight-bearing exercise, that will maximize peak bone mass early in life and minimize the bone loss that occurs naturally with aging.
Hormone DeficiencyWhenever women stop producing estrogen—due to natural menopause, intense athletic training, or anorexia nervosa—and they do not take replacement hormones, some bone loss is inevitable.43,44 Similar losses occur if men stop producing testosterone, though this is much less common.45,46 The best defense against this type of bone loss is to avoid athletic training intense enough to stop menses; seek treatment for anorexia nervosa and other conditions that reduce hormone production; and to develop above-average bone density early in life through optimum diet and lifestyle habits.
MedicationsCorticosteroid medication, even at low doses, increases risk of osteoporosis.47 Steroidal anti-inflammatory drugs reduce the body’s ability to activate vitamin D,48,49 increasing the risk of bone loss. Doctors can measure levels of activated vitamin D (called 1,25 dihydroxycholecalciferol) to determine whether a deficiency exists; if so, activated vitamin D is available by prescription. A study of rheumatoid arthritis patients treated with low doses of prednisone found that those who received 1,000 mg of calcium plus 500 IU of vitamin D per day maintained bone density.50 It makes sense for people taking corticosteroids for longer than two weeks to ask their doctor or pharmacist about calcium and vitamin D supplementation.
Taking thyroid hormones has been reported to increase urinary loss of calcium,51 although recent research suggests that under most circumstances bone density may not be reduced.52,53,54 However, when doses of thyroid medication are higher than necessary and result in suppression of thyroid-stimulating hormone (TSH), adverse effects on bone appear to be more common.55,56 People taking thyroid hormone should have TSH levels measured regularly by their doctor. If TSH levels are low, thyroid hormone dose should be reduced to protect against osteoporosis. Some doctors also suggest that people who supplement thyroid medication for more than a few months consider having 24-hour urinary calcium levels measured. Whether calcium supplementation for people taking long-term thyroid medication is helpful or necessary remains unclear.
ProteinThe risks of bone loss associated with high protein intake are somewhat unclear. In studies comparing different cultural diets, higher protein intake correlates with increased hip fracture.57 When dietary protein increases, so does the loss of calcium in urine58,59 (though this extra calcium loss is not always statistically significant).60 One study that followed over 85,000 American women for twelve years found that those who ate the most animal protein (meat, poultry, and dairy) had a significantly higher risk of developing osteoporotic fractures.61 In contrast, animal protein intake associated with fewer fractures in another trial.62 Nevertheless, many healthcare practitioners recommend a move toward vegetarian diets for people wishing to avoid osteoporosis or who have already diagnosed with it.
Bone formation requires protein, but people concerned with preservation of bone mass can eat too little protein as well as too much. In one trial of older women (average age 82) who had suffered an osteoporotic fracture, those given a 20 gram per day protein supplement had fewer complications, were less likely to die, and had much shorter hospital stays compared with women not assigned to receive extra protein.63 Similarly, in a three-year study of American women aged 50 to 69 funded by the National Dairy Council, those eating more animal protein had a lower risk of osteoporotic hip fracture compared with those eating less.64 A related double-blind trial in older women who had recently suffered an osteoporotic hip fracture found that a 20 gram per day protein supplement reduced bone loss compared with those not receiving protein.65
Pending further research, these conflicting reports show that drawing the line between too much protein and too little remains elusive. Nonetheless, most studies currently suggest that a life-long intake of high animal protein correlates with an increased risk of developing osteoporosis. Protein supplementation following an osteoporotic fracture in elderly people has improved bone health, but less is known about the effects of protein supplementation in the prevention of osteoporosis. People who wish to protect themselves against osteoporosis and who are concerned about protein intake should have a qualified healthcare practitioner analyze their dietary protein intake. (Most Americans eat levels of protein far above recommended levels.)
RaceMost researchers have reported that Caucasian and Asian women have higher risk for osteoporosis and associated fractures compared to black and Hispanic women.66,67,68 However, preliminary results of a large U.S. study suggest that Native American, Hispanic, and black women have a much greater risk of low bone mass after menopause than was previously believed.69 Some of the effect of race may be due to differences in body composition; for example, black women have greater muscle and bone mass compared to Caucasians.70 People with risk factors for osteoporosis that can not be changed should adopt dietary and lifestyle habits, such as increasing calcium intake and engaging in weight-bearing exercise, that will maximize peak bone mass early in life and minimize the bone loss that occurs naturally with aging.
SaltShort-term increases in dietary salt result in increased urinary calcium loss, which suggests that over time, salt intake may cause significant bone loss.71 Most researchers have shown that increasing dietary salt increases markers of bone loss in post- (though not pre-) menopausal women,72,73,74 though not all studies have found this relationship.75 Although a definitive link between salt intake and osteoporosis has yet to be proven, many healthcare practitioners recommend that people wishing to protect themselves against bone loss use less salt and eat less highly salted processed and restaurant foods.
SmokingSmoking leads to both increased bone loss76,77,78 and increased risk of osteoporotic fracture.79 For this and many other health reasons, smoking should be avoided.
Soy foods such as tofu, soy milk, roasted soybeans, and soy extract powders may be beneficial in preventing osteoporosis. Isoflavones from soy protect animals from bone loss.80 In women, taking 40 grams of soy protein powder containing 90 mg isoflavones increased bone mineral density of the spine in a double-blind trial.81 However, lower intakes (providing 56 mg isoflavones) did not improve bone density in this report. A synthetic isoflavone, ipriflavone, has reduced osteoporotic bone fractures in several reports.82 Although the use of soy in the prevention of osteoporosis looks hopeful, knowing to what extent soy reduces bone loss will require further research.
One study found that increasing intake of vitamin A in the diet was associated with bone loss and risk for hip fracture, possibly due to a vitamin A-induced stimulation of cells that break down bone.83 Vitamin A is found in high amounts in liver, cod liver oil, fortified dairy products and breakfast cereals, some fish, and vitamin A supplements. Beta-carotene (which can be used by the body to make vitamin A) has not been linked to reduced bone mass. Until more is known, people concerned about osteoporosis and wishing to supplement with vitamin A may consider taking beta-carotene supplements instead.
Vitamin D increases calcium absorption, and older people with hip fractures are often low in vitamin D.84,85 Vitamin D supplements or injections have reduced bone loss or fractures in some,86,87,88 but not all,89,90,91 studies. Commonly, trials reporting reduced risk of fracture have used the combination of vitamin D and calcium compared with placebo, making it impossible to assess the specific benefit of vitamin D.92 Nonetheless, vitamin D does appear partially protective, at least in certain circumstances. Double-blind research indicates that vitamin D supplementation reduces bone loss in women who consume insufficient amounts of vitamin D from food.93 A double-blind trial also supports the use of higher (700 IU per day) supplemental intakes of vitamin D, particularly as a way to reduce bone loss in women during winter and spring, when vitamin D levels are typically at their lowest.94
While people who get outdoors regularly and live in sunny climates are unlikely to need vitamin D supplementation (particularly during the summer), healthcare practitioners often recommend vitamin D to most other people as a way to help protect bone mass despite remaining inconsistencies in the research. Typical supplemental amounts are between 400 and 800 IU per day, depending on dietary intake and exposure to sunlight.
1. Silver JJ, Einhorn TA. Osteoporosis and aging. Clin Orthop 1995;316:1020 [review].
2. Feskanich D, Korrick SA, Greenspan SL, et al. Moderate alcohol consumption and bone density among postmenopausal women. J Womens Health 1999;8:6573.
3. Felson DT, Zhang Y, Hannan MT, et al. Alcohol intake and bone mineral density in elderly men and women. The Framingham Study. Am J Epidemiol 1995;142:48592.
4. Holbrook TL, Barrett-Connor E. A prospective study of alcohol consumption and bone mineral density. BMJ 1993;306:15069.
5. Wardlaw GM. Putting body weight and osteoporosis into perspective. Am J Clin Nutr 1996;63:433S6S [review].
6. Nguyen TV, Eisman JA, Kelly PJ, et al. Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 1996;144:25563 [review].
7. Salamone LM, Cauley JA, Black DM, et al. Effect of a lifestyle intervention on bone mineral density in premenopausal women: a randomized trial. Am J Clin Nutr 1999;70:97103.
8. Powers PS. Osteoporosis and eating disorders. J Pediatr Adolesc Gynecol 1999;12:517 [review].
9. Heaney RP. Bone mass, nutrition, and other lifestyle factors. Nutr Rev 1996;54:S3S10 [review].
10. Hernandez-Avila M, Colditz GA, Stampfer MJ, et al. Caffeine, moderate alcohol intake, and risk of fractures of the hip and forearm in middle-aged women. Am J Clin Nutr 1991;54:15763.
11. Kynast-Gales SA, Massey LK. Effect of caffeine on circadian excretion of urinary calcium and magnesium. J Am Coll Nutr 1994;13:46772.
12. Harris SS, Dawson-Hughes B. Caffeine and bone loss in healthy postmenopausal women. Am J Clin Nutr 1994;60:5738.
13. Barrett-Connor E, Chang JC, Edelstein SL. Coffee-associated osteoporosis offset by daily milk consumption. The Rancho Bernardo Study. JAMA 1994;271:2803.
14. Lloyd T, Rollings N, Eggli DF, et al. Dietary caffeine intake and bone status of postmenopausal women. Am J Clin Nutr 1997;65:182630.
15. Consensus Development Conference Panel. Optimal calcium intake: Consensus Development Conference statement. JAMA 1994;272:19428.
16. Reid IR, Ames RW, Evans MC, et al. Long-term effects of calcium supplementation on bone loss and fractures in postmenopausal women: a randomized controlled trial. Am J Med 1995;98:3315.
17. Owusu W, Willett WC, Feskanich D, et al. Calcium intake and the incidence of forearm and hip fractures among men. J Nutr 1997;127:17827.
18. Hosking DJ, Ross PD, Thompson DE, et al. Evidence that increased calcium intake does not prevent early postmenopausal bone loss. Clin Ther 1998;20:93344.
19. Nieves JW, Komar L, Cosman F, Lindsay R. Calcium potentiates the effect of estrogen and calcitonin on bone mass: review and analysis. Am J Clin Nutr 1998;67:1824.
20. Bonjour J-P, Carrie A-L, Ferrari S, et al. Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial. J Clin Invest 1997;99:128794.
21. Welten DC, Kemper HCG, Post GB, van Stavberen WA. A meta-analysis of the effect of calcium intake on bone mass in young and middle aged females and males. J Nutr 1995;125:280213.
22. O’Connell MB. Prevention and treatment of osteoporosis in the elderly. Pharmacotherapy 1999;19:7S20S [review].
23. Dargent-Molina P. Risk factors and prevention of fractures in the elderly. Curr Opin Rheumatol 1998;10:35761 [review].
24. Saltman PD, Strause LG. The role of trace minerals in osteoporosis. J Am Coll Nutr 1993;12:3849 [review].
25. Cohen L, Kitzes R. Infrared spectroscopy and magnesium content of bone mineral in osteoporotic women. Isr J Med Sci 1981;17:11235.
26. Geinster JY, Strauss L, Deroisy R, et al. Preliminary report of decreased serum magnesium in postmenopausal osteoporosis. Magnesium 1989;8:1069.
27. Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal women supplemented with calcium and trace minerals. J Nutr 1994;124:10604.
28. Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two year controlled trial of peroral magnesium in osteoporosis. Magnesium Res 1993;6:15563.
29. Chow R, Harrison JE, Notarius C. Effect of two randomised exercise programmes on bone mass of healthy postmenopausal women. Br Med J 1987;295:14414.
30. Gregg EW, Cauley JA, Seeley DG, et al. Physical activity and osteoporotic fracture risk in older women. Ann Int Med 1998;129:818.
31. Silman AJ, O’Neill TW, Cooper C, et al. Influence of physical activity on vertebral deformity in men and women: results from the European Vertebral Osteoporosis Study. J BoneMineral Res 1997;12:8139.
32. Layne JE, Nelson ME. The effects of progressive resistance training on bone density: a review. Med Sci Sports Exerc 1999;31:2530 [review].
33. Marcus R, Drinkwater B, Dalsky G, et al. Osteoporosis and exercise in women. Med Sci Sports Exer 1992;24:S3017 [review].
34. Nguyen TV, Eisman JA, Kelly PJ, et al. Risk factors for osteoporotic fractures in elderly men. Am J Epidemiol 1996;144:25563 [review].
35. Ayalon J, Simkin A, Leichter I, et al. Dynamic bone loading exercises for postmenopausal women: effect on the density of the distal radius. Arch Phys Med Rehab 1987;68:2803.
36. Nattiv A, Agostini R, Drinkwater B, et al. The female athlete triad: the inter-relatedness of disordered eating, amenorrhea and osteoporosis. Clin Sports Med 1994;13:40518 [review].
37. Drinkwater BL, Bruemmer B, Chestnut III CH. Menstrual history as a determinant of current bone density in young athletes. JAMA 1990;263:5458.
38. Diaz MN, O’Neill TW, Silman AJ, et al. The influence of family history of hip fracture on the risk of vertebral deformity in men and women: the European Vertebral Osteoporosis Study. Bone 1997;20:1459.
39. Jahnsen J, Falch JA, Aadland E, et al. Bone mineral density is reduced in patients with Crohn’s disease but not in patients with ulcerative colitis: a population-based study. Gut 1997;40:3139.
40. Tovey FI, Hall ML, Ell PJ, et al. Postgastrectomy osteoporosis. Br J Surg 1991;78:13357.
41. Rao SD, Kleinkoper M, Rogers M, et al. Is gastrectomy a risk factor for osteoporosis? In Osteoporosis: Proceedings of the Copenhagen International Symposium on Osteoporosis, Christiansen C, Arnaud CD, Nordin BEC, et al., eds. 1984;2:7757[review].
42. Anderson FH. Osteoporosis in men. Int J Clin Pract 1998;52:17680 [review].
43. Heaney RP. Bone mass, nutrition, and other lifestyle factors. Nutr Rev 1996;54:S3S10 [review].
44. Heaney R. Estrogen-calcium interactions in the postmenopause: a quantitative description. Bone Miner 1990;11:6784.
45. Ohishi T, Koide Y, Takahashi M, et al. A case of femoral neck fracture in a patient with severe testosterone deficiency. J Bone Miner Metab 1999;17:514.
46. Daniell HW. Osteoporosis after orchiectomy for prostate cancer. J Urol 1997;157:43944.
47. Meunier PJ. Is steroid-induced osteoporosis preventable? New Engl J Med 1993;328:17812 [editorial].
48. Trovato A et al. Drug-nutrient interactions. Am Family Phys 1991;44:16518 [review].
49. Chesney RW et al. Reduction of serum-1,25-dihydroxyvitamin-D, in children receiving glucocorticoids. Lancet 1978;ii:11235.
50. Buckley LM, Leib ES, Cartularo KS, et al. Calcium and vitamin D3 supplementation prevents bone loss in the spine secondary to low-dose corticosteroids in patients with rheumatoid arthritis. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1996;125:9618.
51. Kung AWC, Pun KK. Bone mineral density in premenopausal women receiving long-term physiological doses of levothyroxine. JAMA 1991;265:268891.
52. Schneider DL, Barrett-Connor EL, Morton DJ. Thyroid hormone use and bone mineral density in elderly men. Arch Intern Med 1995;155:20057.
53. Franklyn JA, Betteridge J, Daykin J, et al. Long-term thyroxine treatment and bone mineral density. Lancet 1992;340:913.
54. Lauwers A, Alexandre C. Impact on bone of thyroid hormone therapy. Rev Rhum Engl Ed 1997;64:1129 [review].
55. Greenspan SL, Greenspan FS. The effect of thyroid hormone on skeletal integrity. Ann Intern Med 1999;130:7508 [review].
56. Stall GM, Harris S, Sokoll LJ, et al. Accelerated bone loss in hypothyroid patients overtreated with L-thyroxine. Ann Intern Med 1990;113:2659.
57. Abelow BJ, Holford TR, Insogna KL. Cross-cultural associations between dietary animal protein and hip fracture: a hypothesis. Calcif Tissue Int 1992;50:148.
58. Heaney RP. Nutrient interactions and the calcium requirement. J Lab Clin Med 1994;124:156 [editorial/review].
59. Kerstetter JE, Allen LH. Dietary protein increases urinary calcium. J Nutr 1990;120:1346.
60. Draper HH, Pich LA, Gibson RS. Effects of a high protein intake from common foods on calcium metabolism in a cohort of postmenopausal women. Nutr Res 1991;11:27381.
61. Feskanich D, Willett WC, Stampfer MJ, Colditz GA. Protein consumption and bone fractures in women. Am J Epidemiol 1996;143:4729.
62. Munger RG, Cerhan JR, Chiu BC. Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women. Am J Clin Nutr 1999;69:14752.
63. Tkatch L, Rapin C-H, Rizzoli R, et al. Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. J Am Coll Nutr 1992;11:51925.
64. Munger RG, Cerhan JR, Chiu BC-H. Prospective study of dietary protein intake and risk of hip fracture in postmenopausal women. Am J Clin Nutr 1999;69:14752.
65. Schrch M-A, Rizzoli R, Slosman D, et al. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double blind, placebo-controlled trial. Ann Intern Med 1998;128:8019.
66. Bohannon AD, Hanlon JT, Landerman R, et al. Association of race and other potential risk factors with nonvertebral fractures in community-dwelling elderly women. Am J Epidemiol 1999;149:10029.
67. Turner LW, Wang MQ, Fu Q. Risk factors for hip fracture among southern older women. South Med J 1998;91:53340.
68. Lau EM, Cooper C. The epidemiology of osteoporosis. The oriental perspective in a world context. Clin Orthop 1996;323:6574 [review].
69. Anonymous. Minority women face higher-than-expected risk of osteoporosis. J Am Dietet Assoc 1999;99:848 [news item].
70. Gasperino J. Ethnic differences in body composition and their relation to health and disease in women. Ethn Health 1996;1:33747 [review].
71. Zarkadas M, Geougeon-Reyburn R, Marliss EB, et al. Sodium chloride supplementation and urinary calcium excretion in postmenopausal women. Am J Clin Nutr 1989;50:108894.
72. Evans CEL, Chughtai AY, Blumsohn A, et al. The effect of dietary sodium on calcium metabolism in premenopausal and postmenopausal women. Eur J Clin Nutr 1997;51:3949.
73. McParland BE, Boulding A, Campbell AJ. Dietary salt affects biochemical markers of resorption and formation of bone in elderly women. Br Med J 1989;299:8345.
74. Devine A, Criddle RA, Dick IM, et al. A longitudinal study of the effect of sodium and calcium intakes on regional bone density in postmenopausal women. Am J Clin Nutr 1995;62:7405.
75. Greendale GA, Barrett-Connor E, Edelstein S. Dietary sodium and bone mineral density: results of a 16-year follow-up study. J Am Geriatr Soc 1994;42:10505.
76. Hopper JL, Seeman E. The bone density of female twins discordant for tobacco use. N Engl J Med 1994;330:38792.
77. Egger P, Duggleby S, Hobbs R, et al. Cigarette smoking and bone mineral density in the elderly. J Epidemiol Community Health 1996;50:4750.
78. Kiel DP, Zhang Y, Hannan MT, et al. The effect of smoking at different life stages on bone mineral density in elderly men and women. Osteoporos Int 1996;6:2408.
79. Law MR, Hackshaw AK. A meta-analysis of cigarette smoking, bone mineral density and risk of hip fracture: recognition of a major effect. BMJ 1997;315:8416 [review].
80. Anderson JJB, Ambrose WW, Garner SC. Biphasic effects of genistein on bone tissue in the ovariectomized, lactating rat model (44243). Proc Soc Exp Biol Med 1998;217:34550.
81. Potter SM, Baum JA, Teng H, et al. Soy protein and isoflavones: Their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 1998;68(suppl):1375S9S.
82. Head KA. Ipriflavone: an important bone-building isoflavone. Altern Med Rev 1999;4:1022 [review].
83. Melhus H, Michaelsson K, Kindmark A, et al. Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Int Med 1998;129:7708.
84. LeBoff MS, Kohlmeier L, Hurwitz S, et al. Occult vitamin D deficiency in postmenopausal US women with acute hip fracture. JAMA 1999;281:150511.
85. Diamond T, Smerdely P, Kormas N, et al. Hip fracture in elderly men: the importance of subclinical vitamin D deficiency and hypogonadism. Med J Aust 1998;169:13841.
86. Nordin BEC, Baker MR, Horsman A, Peacock M. A prospective trial of the effect of vitamin D supplementation on metacarpal bone loss in elderly women. Am J Clin Nutr 1985;42(3):4704.
87. Graafmans WC, Lips P, Ooms ME, et al. The effect of vitamin D supplementation on the bone mineral density of the femoral neck is associated with vitamin D receptor genotype. J Bone Miner Res 1997;12:12415.
88. Heikinheimo RJ, Inkovaara JA, Harju EJ, et al. Annual injection of vitamin D and fractures of aged bones. Calcif Tissue Int 1992;51:10510.
89. Lips P, Graafmans WC, Ooms ME, et al. Vitamin D supplementation and fracture incidence in elderly persons. Ann Intern Med 1996;124:4006.
90. Komulainen M, Tupperainen MT, Krger H, et al. Vitamin D and HRT: No benefit additional to that of HRT alone in prevention of bone loss in early postmenopausal women. A 2.5-year randomized placebo-controlled study. Osteoporos Int 1997; 7:12632.
91. Heikinheimo R, Sievanen H, Jantti P, et al. Vitamin D treatment and bone mineral density in the aged. Maturitas 1996;23:S7780.
92. Chapuy MC, Arlot ME, Duboeuf F, et al. Vitamin D3 and calcium to prevent hip fractures in elderly women. N Engl J Med 1992;327:163742.
93. Dawson-Hughes B, Dallal GE, Krall EA, et al. Effect of vitamin D supplementation on wintertime and overall bone loss in healthy postmenopausal women. Ann Intern Med 1991;115:50512.
94. Dawson-Hughes B, Harris SS, Krall EA, et al. Rates of bone loss in postmenopausal women randomly assigned to one of two dosages of vitamin D. Am J Clin Nutr 1995;61:11405.