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Other micronutrients and bone health

Vitamin K

Vitamin K is needed for the production and functioning of a compound called osteocalcin.  Osteocalcin is the second most abundant protein in bone after collagen, and it is required for bone mineralization. Some lines of evidence suggest that low dietary intake of vitamin K or low vitamin K status could contribute to low BMD and increased risk of fragility fractures in the elderly, via a reduced functioning of osteocalcin (6,7). However, the possible mechanisms whereby suboptimal vitamin K intake and status affect bone metabolism are not well understood at present, and there is not yet adequate clinical trial evidence that adding vitamin K would be effective in either preventing or treating osteoporosis.

B vitamins and homocysteine

Recent observational studies suggest that high homocysteine levels in the blood may be associated with lower BMD and increased hip fracture risk in older persons (8,9). Homocysteine is an amino acid that has been linked with increased risk of cardiovascular disease. It is thought that it might also have adverse effects on bone, by interfering with the formation of the main protein in bone, collagen. Homocysteine levels in the blood may rise if there is inadequate intake of vitamin B6, vitamin B12 and folic acid, which play a role in the chemical reactions that change homocysteine into other amino acids for use by the body, and therefore help to keep it out of harm’s way. It is not yet known whether deficiencies in these vitamins are potentially modifiable risk factors for osteoporosis.

Vitamin A

The role of vitamin A in osteoporosis risk is controversial.  Vitamin A is present ‘pre-formed’ in foods of animal origin, as a compound called retinol. Some plant foods contain a precursor of vitamin A, in the form of a group of compounds called carotenoids. It is known that consumption of very high amounts of vitamin A have adverse effects on bone (plus the liver and skin), but the findings of studies looking at vitamin A intakes in normal diets are conflicting. One population-based observational study in postmenopausal American women found an association between high levels of vitamin A intake and hip fracture risk (10), and a similar population-based study in Swedish men found an association between blood retinol levels (but not blood carotenoid level) and fracture risk (11).

However, another study – in which blood levels of vitamin A compounds were measured in a large cohort of elderly British women – found no indication of increased risk of hip or other fractures with higher vitamin A intakes, either from the diet or fish oil supplements (12). Further research is clearly needed in this area, although many countries currently caution against taking fish liver oil supplements and a multivitamin supplement concurrently, as this could lead to an excessive intake of vitamin A.

Magnesium

The mineral magnesium is involved in calcium homeostasis, and in the formation of hydroxyapatite. Severe experimental magnesium deficiency results in abnormal bone structure and function (13), but this level of depletion is rarely observed in generally well nourished human populations. Magnesium is fairly widespread in the food chain; however, the elderly could potentially be at risk of mild magnesium deficiency, as magnesium absorption decreases and renal excretion of magnesium increases with age. Older persons are also more likely to be taking certain medications that can increase magnesium loss in the urine, such as loop and thiazide diuretics, cancer medications or antibiotics. However, there are no studies to date which demonstrate that magnesium supplementation is useful either in preventing bone loss or reducing fracture risk.

Zinc

The mineral zinc is a constituent of the hydroxyapatite mineral crystals of bone, and plays a role in the regulation of bone turnover. Zinc is also needed for the correct functioning of an enzyme called alkaline phosphatase, which is required for bone mineralization. Severe zinc deficiency is usually seen in conjunction with calorie and protein malnutrition, which is associated with impaired bone growth in children. However, milder degrees of zinc deficiency have been reported in the elderly and could potentially contribute to poor bone status.  An observational study in middle-aged and elderly men showed that men with the lowest blood zinc levels had lower BMD than men with the highest blood zinc levels, and also that dietary zinc intake and blood levels were lower in men with osteoporosis than in men without osteoporosis (14). Another study in postmenopausal women indicated that the bone-trophic effects of zinc could be mediated, at least in part, via a decrease in the blood levels of insulin-like growth factor-I (IGF-I), a compound that stimulates bone formation (15).

Protein

Adequate dietary protein intake is essential for bone health. Insufficient protein intake is detrimental both for the acquisition of bone mass during childhood and adolescence, and for the preservation of bone mass with ageing.  Poor nutritional status, particularly with respect to protein, is common in the elderly, and appears to be more severe in patients with hip fracture than in the general ageing population (16). As well as adverse effects on skeletal integrity, protein under nutrition also leads to reduced muscle mass and strength which is itself a risk factor for falls.


In the Framingham prospective cohort study, elderly men and women with lower total and animal protein intakes had greater rates of hip and spine bone loss than subjects consuming higher amounts of protein (17). There is also evidence that increasing protein intake has a favourable effect on BMD in elderly men and women receiving calcium and vitamin D supplements, suggesting synergistic effects of these nutrients in improving skeletal health (18). Randomized clinical trials in elderly patients with hip fracture have demonstrated the beneficial effects of giving protein supplements on the clinical outcome following surgery to repair the fracture. Protein supplementation resulted in fewer deaths, shorter hospital stays, and a greater likelihood of return to independent living (19-21).

One of the mechanisms by which increasing protein intake may have favourable effects on bone is via an increase in the blood levels of IGF-I, which is a key compound involved in promoting bone formation (16). Serum levels of IGF-I are exquisitely sensitive to fluctuations in dietary protein intake. In studies in which healthy children or adults were given extra servings of milk in their diets, and hence extra protein, significant increases in serum IGF-I were observed compared with control subjects (22, 23). Serum IGF-I also increased in elderly hip fracture patients given pure protein supplements (20). In addition, recent studies suggest that certain amino acids may promote calcium absorption from food in the intestine (24).

Despite the above research evidence that dietary protein is beneficial for bone health, and for recovering hip fracture patients, there has nevertheless been speculation that a higher dietary protein intake could have negative effects on calcium metabolism and possibly induce bone loss. However, the majority of scientific evidence – including that from clinical trials – supports beneficial effects of protein intake on bone health, and highlights the risks associated with protein insufficiency and malnutrition.

Fruits and vegetables

In population-based observational studies, higher fruit and vegetable consumption has been demonstrated to have beneficial effects on bone mineral density in elderly men and women (25).

Evidence for a beneficial effect of fruits and vegetables on bone health was provided by the Dietary Approaches to Stopping Hypertension (DASH) intervention trials, carried out in men and women of ages 23-76 years (26). Although the DASH studies were designed to investigate how diet could prevent heart disease, one of them investigated whether the total dietary pattern could also influence bone health. In the bone study, half of the subjects were asked to modify their whole dietary pattern, and consume a diet rich in fruits, vegetables and low-fat dairy products and low in sodium (the DASH diet), and the other half continued with their regular diets. Over a period of a few months, the DASH diet improved markers of bone and calcium metabolism (chemicals in the blood), which could potentially result in improved bone density if continued over the long term.

Phytoestrogens

Phytoestrogens are compounds in plant foods that act like weak estrogens in the human body, and it is thought that they could therefore have similar bone-protective effects as the estrogen that is naturally produced in the body. One class of phytoestrogens – soy isoflavones – has received much attention.  In some epidemiological studies in Asian populations, where soy foods are traditionally consumed, higher isoflavone intake was associated with higher bone mineral density. Among Caucasian populations, a few intervention studies in pre- and postmenopausal women examining the effect of soy isoflavones on bone density have been carried out but the findings are unclear, possibly because they were of short duration, involved relatively few subjects, and used varying sources and amounts of the isoflavones (27). More research is needed in this area, but these early findings are not promising.

References

  1. Booth SL, Tucker KL, Chen H, et al. (2000) Dietary vitamin K intakes are associated with hip fracture but not with bone mineral density in elderly men and women. Am J Clin Nutr 71:1201-08.
  2. Iwamoto J, Takeda T, Sato Y (2004) Effects of vitamin K2 on osteoporosis. Curr Pharm Des 10:2557-76.
  3. McLean RR, Jacques PF, Selhub J, et al. (2004) Homocysteine as a predictive factor for hip fracture in older persons. N Engl J Med 350:2042-49.
  4. Morris MS, Jacques PF, Selhub J (2005) Relation between homocysteine and B-vitamin status indicators and bone mineral density in older Americans. Bone 37:234-42.
  5. Feskanich D, Singh V, Willett WC, et al. (2002). Vitamin A intake and hip fractures among postmenopausal women. JAMA 287:47-54.
  6. Michaelsson K, Lithell H, Vessby B, et al. (2003) Serum retinol levels and the risk of fracture. N Engl J Med 348:287-94.
  7. Barker ME, McClosky E, Saha S, et al. (2005) Serum retinoids and beta-carotene as predictors of hip and other fractures in elderly women. J Bone Miner Res 20:913-20.
  8. Schwarz R (1990). Magnesium metabolism. In: Nutrition and Bone Development, ed. DJ Simmons, Oxford University Press, New York, pp. 148-63.
  9. Hyun TH, Barrett-Connor E and Milne DB (2004) Zinc intakes and plasma concentrations in men with osteoporosis: the Rancho Bernardo Study. Am J Clin Nutr 80:715-21.
  10. Devine A, Rosen C, Mohan S, et al. (1998) Effects of zinc and other nutritional factors on insulin-like growth factor I and insulin-like growth factor binding proteins in postmenopausal women. Am J Clin Nutr 68:200-6.
  11. Rizzoli R and Bonjour J-P (2004) Dietary protein and bone health. J Bone Miner Res 19:527-31.
  12. Hannan MT, Tucker KL, Dawson-Hughes B, et al. (2000) Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study. J Bone Miner Res 15:2504-12.
  13. Dawson-Hughes B and Harris SS (2002) Calcium intake influences the association of protein intake with rates of bone loss in elderly men and women. Am J Clin Nutr 75:773-79.
  14. Delmi M, Rapin CH, Bengoa JM, et al. (1990) Dietary supplementation in elderly patients with fractured neck of the femur. Lancet 335:1013-16.
  15. Schurch MA, Rizzoli R, Slosman D, et al. (1998) Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, doubleblind, placebo-controlled trial. Ann Intern Med 128:801-09.
  16. Tkatch L, Rapin CH, Rizzoli R, et al. (1992) Benefits of oral protein supplementation in elderly patients with fracture of the proximal femur. J Am Coll Nutr 11:519-25.
  17. Cadogan J, Eastell R, Jones N, et al. (1997) Milk intake and bone mineral acquisition in adolescent girls: randomised, controlled intervention trial. BMJ 315:1255-60.
  18. Heaney RP, McCarron DA, Dawson-Hughes B, et al. (1999) Dietary changes favorably affect bone remodeling in older adults. J Am Diet Assoc 99:1228-33.
  19. Kerstetter JE, O’Brien KO, Caseria DM, et al. (2005) The impact of dietary protein on calcium absorption and kinetic measures of bone turnover in women. J Clin Endocrinol Metab 90:26-31.
  20. Tucker KL, Hannan MT, Chen H, et al. (1999) Potassium, magnesium, and fruit and vegetable intakes are associated with greater bone mineral density in elderly men and women. Am J Clin Nutr 69:727-736.
  21. Lin PH, Ginty F, Appel LJ, et al. (2003) The DASH diet and sodium reduction improve markers of bone turnover and calcium metabolism in adults. J Nutr 133:3130-66.
  22. Spence LA, Lipscombe ER, Cadogan J, et al. (2005) The effect of soy protein and soy isoflavones on calcium metabolism in postmenopausal women; a randomized crossover study. Am J Clin Nutr 81:916-22.
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