Good Evening!
Clinical Nutrients for Osteoporosis
by Tori Hudson, ND
Numerous modifiable and non-modifiable factors influence the risk of developing
osteoporosis. This article provides the practitioner with an understanding of
supplementary clinical nutrients and their effect on bone loss and fractures.
Lifestyle modifications and nutrient supplementation may be able to reduce the
risk of osteoporosis and the associated debilitating fractures. For women who
have already been diagnosed with osteoporosis, these nutritional factors can
serve as an adjunct to conventional therapies to slow bone loss and, more
importantly, decrease the risk of fractures.
NUTRITIONAL SUPPLEMENTATION
Calcium
Adequate calcium intake has an established role in maintaining bone health,
primarily in very young women and the elderly. However, calcium is only modestly
effective for slowing the loss of bone mineral density in peri- and early
postmenopausal women. Calcium supplementation also appears to have an important
role in improving the efficacy of pharmaceutical agents used to treat bone loss
and osteoporosis.
Prior to the Women's Health Initiative study, there was no clear evidence that
higher calcium intake decreased fracture risk.1 A meta-analysis of prospective
cohort studies and clinical trials found that higher calcium intake and calcium
supplementation were not associated with a lower incidence of hip fractures.2 In
a 2004 meta-analysis of randomized controlled trials, supplementation with
500-2,000 mg per day of calcium had only a modest benefit on bone density in
postmenopausal women: the difference in the amount of bone loss between calcium
and placebo was 2.05% for the total body, 1.66% for the lumbar spine, and 1.64%
for the hip.3 Two trials within this meta-analysis suggested a modest and
nonsignificant benefit with calcium supplementation and the risk of nonvertebral
fractures. In the Women's Health Initiative, which enrolled more than 36,000
postmenopausal women, supplementation with 1,000 mg per day of calcium and 400
IU per day of vitamin D decreased the risk of hip fractures nonsignificantly by
12%, when compared with placebo. However, when the analysis was restricted to
women who took the tablets at least 80% of the time, calcium plus vitamin D
significantly decreased hip fractures by 29% compared with placebo.4
Other calcium studies also showed a beneficial effect on bone loss. In
postmenopausal women, calcium supplementation has been shown to decrease bone
loss by as much as 50% at nonvertebral sites. The effects were greatest in women
whose baseline calcium intake was low, in older women, and in women with
established osteoporosis.5 In a study by Elders et al,6 a significant decrease
in vertebral bone loss was observed with supplementation of 1,000 to 2,000 mg
per day of calcium for 1 year. Bone loss was also less in the calcium group than
in the control group after 2 years, but the difference was no longer
statistically significant.
Dietary calcium is essential throughout a woman's life, and requirements
increase with advancing age, in part due to reduced calcium absorption and
decreased renal calcium conservation. However, calcium supplementation by itself
is not effective in preventing the accelerated bone loss that occurs in the
first few years after menopause. Ten years postmenopausally, calcium
supplementation again becomes effective in reducing age-related bone loss.7
While consuming an adequate amount of calcium is important, it is too often
overemphasized, supplemented at excessive doses, and is only one of many
nutritional and lifestyle factors that play a role in promoting bone health.
Vitamin D
Vitamin D enhances intestinal calcium absorption, thereby contributing to a
favorable calcium balance in the body. Increased calcium absorption also reduces
parathyroid-hormone-mediated bone resorption. In the United States, most infants
and young children have adequate vitamin D consumption from fortified milk.
During adolescence, however, the consumption of dairy products drops off, and
inadequate vitamin D intake is more likely to adversely affect calcium
absorption.
Several large randomized controlled trials have found that the combination of
calcium and vitamin D had no significant effect on fracture risk.1,8,5
However, a meta-analysis of randomized controlled trials in elderly
postmenopausal women found that a dose of 700 – 800 IU per day of vitamin D was
associated with significant reductions in the risk of hip and nonvertebral
fractures.9 Especially in older women, vitamin D in combination with calcium
supplementation reduced the rate of postmenopausal bone loss.10 Vitamin D has
also been shown to improve muscle strength11 and balance12, thereby reducing the
risk of falling.13
Magnesium
Magnesium is a cofactor for alkaline phosphatase, which plays a role in bone
mineralization. Low magnesium status is common in women with osteoporosis, and
magnesium deficiency is associated with abnormal bone mineral crystals.14 Some
women with reduced bone mineral density do not have an increased fracture rate,
possibly because their bone mineral crystals are of high quality, due in part to
high levels of magnesium. In a group of postmenopausal women, supplementation
with 250-750 mg per day of magnesium for 6 months, followed by 250 mg per day
for 6-18 months, resulted in an increase in bone density in 71% of women. This
increase was noteworthy, because it occurred without calcium supplementation.15
Strontium
Strontium is a non-radioactive earth element physically and chemically similar
to calcium. Strontium ranelate is the specific strontium salt used in clinical
trials for osteoporosis, but this form of strontium is not available in the U.S.
Strontium in large doses stimulates bone formation and reduces bone resorption.
In a phase 2 clinical trial, 2 g per day of oral strontium ranelate (containing
680 mg per day of elemental strontium) for three years was shown to reduce the
risk of vertebral fractures and to increase bone mineral density in 1,649
postmenopausal women with osteoporosis.16
In the first year, there was a 49% reduction in the incidence of vertebral
fractures in the strontium ranelate group and 41% reduction at the end of three
years. After adjusting for artifact effect on imaging, a 6.8% increase in bone
mineral density was seen at the lumbar spine after 3 years of strontium
supplementation.. There was also an 8.3% increase at the femoral neck, but there
was insufficient data to adjust it for an artifact effect, and therefore it is
not clear as to how accurate this is.
In a two year trial 353 postmenopausal women with osteoporosis and a history of
at least one vertebral fracture received a placebo or one of three different
doses of strontium: 170 mg per day, 340 mg per day or 680 mg per day.17 A small
increase in lumbar bone mineral density was seen with each dose of strontium,
but the difference compared with placebo was statistically significant only for
the highest dose. The incidence of new vertebral fractures was lowest (38.8%)
with the lowest dose of strontium, vs. 54.7%, 56.7% and 42.0% in the placebo,
340 mg per day and 680 mg per day groups, respectively.
Strontium chloride is the most common form of strontium used in U.S.
supplements. This form of strontium has not been the subject of published
research. Due to potential adverse effects of higher doses of strontium,
including rickets, bone mineralization defects, and interference with vitamin D
metabolism, it may be prudent to use low doses until more research is conducted.
Zinc
Zinc is essential for the formation of osteoblasts and osteoclasts, and it
enhances the biochemical action of vitamin D. Zinc is also is necessary for the
synthesis of various proteins found in bone. Low zinc levels have been found in
the serum and bone of elderly people with osteoporosis.18
Copper
A deficiency of copper is known to produce abnormal bone development in growing
children, and may be a contributing cause of osteoporosis. In vitro studies have
shown that copper supplementation inhibits bone resorption.19,20 In a
double-blind trial, supplementation with 3 mg per day of copper for 2 years
significantly decreased bone loss in postmenopausal women.21
Manganese
A deficiency of manganese may be one of the lesser known but more important
nutritional factors related to osteoporosis. Manganese deficiency causes a
reduction in calcium deposition in bone. Manganese also stimulates
mucopolysaccharide production, which provides a framework for the calcification
process.22
Zinc, Copper, and Manganese
In a double-blind study of postmenopausal women, the combination of zinc,
copper, manganese, and calcium appeared to be more effective than calcium alone
for preventing bone loss in postmenopausal women.23
Boron
Boron supplementation reduces urinary excretion of calcium and magnesium and
increases serum levels of 17beta-estradiol and testosterone in postmenopausal
women.24 These observations suggest that boron supplementation could help
prevent bone loss.
Silicon
During bone growth and the early phases of bone calcification, silicon has an
essential role in the formation of cross-links between collagen and
proteoglycans. In animals, silicon-deficient diets have produced abnormal skull
development and growth retardation,25 and supplemental silicon partially
prevented trabecular bone loss in ovariectomized rats.26
Other Nutritional Factors
Folic Acid and Vitamin B12
Accelerated bone loss in menopausal women may in part be due to increased levels
of homocysteine, a breakdown product of methionine. Homocysteine has the
potential to promote osteoporosis if it is not eliminated adequately. In a
prospective study, women with high homocysteine levels had almost twice the risk
of nonvertebral osteoporotic fractures as did women with low homocysteine
levels. There was no association in that study between homocysteine levels and
bone mineral density at either the femoral neck or the lumbar spine, which
suggests that the reduction in fracture risk was due to an improvement in bone
quality.27 Folic acid promotes the remethylation of homocysteine to methionine,
and supplementing postmenopausal women with this nutrient results in significant
reductions in homocysteine levels. Vitamin B12 has also been shown to reduce
homocysteine levels.28 In a double-blind study of stroke victims with elevated
homocysteine levels, daily supplementation with 5 mg of folic acid plus 1,500
mcg of vitamin B12 for two years reduced hip fracture incidence by 78%, compared
with placebo.29
Vitamin B6
Vitamin B6 also plays a role in homocysteine metabolism. In people with the
genetic disorder homocystinuria, vitamin B6 supplementation reverses the
elevated levels of homocysteine.30 Animal studies have shown that vitamin B6
deficiency can prolong fracture healing time,31 impair cartilage growth, cause
defective bone formation,32 and promote osteoporosis.33 Vitamin B6 may also
influence progesterone production and exert a synergistic effect on
estrogen-sensitive tissue. Laboratory evidence of low vitamin B6 status appears
to be common, even among healthy individuals.34
Vitamin C
Vitamin C promotes the formation and cross-linking of some of the structural
proteins in bone. Animal studies have shown that vitamin C deficiency can cause
osteoporosis35 and it has been known for decades that scurvy, a disease caused
by vitamin C deficiency, is also associated with abnormalities of bone.
Vitamin K
Vitamin K is required for the production of the bone protein, osteocalcin.
Osteocalcin draws calcium to bone tissue, enabling calcium crystal formation.
Osteocalcin provides the protein matrix for mineralization and is thought to act
as a regulator of bone mineralization.36 Vitamin K plays a key role in the
formation, remodeling, and repair of bone by attracting calcium to the site of
this protein matrix.37 A low dietary intake of vitamin K seems to increase the
risk of osteoporotic hip fractures in women, according to data from the Nurses'
Health Study.38
There are various forms of vitamin K, but the human trials have been done on
vitamin K1 (phylloquinone) and menaquinone-4, (MK4, a form of vitamin K2).
In a double-blind study, 452 men and women (ages 60-80 years) received a
multiple vitamin/mineral supplement that provided 600 mg per day of calcium and
400 IU per day of vitamin D, plus either 500 mcg per day of vitamin K1 or no
vitamin K1.39 Bone mineral density (determined by dual-energy x-ray
absorptiometry) and bone turnover were measured at 6, 12, 24 and 36 months.
There were no differences in bone mineral density at the femoral neck, lumbar
spine, or total body, between the two treatment groups, indicating that vitamin
K1 did not enhance the effects of calcium, vitamin D, and other nutrients in
this patient population. In the double-blind ECKO trial,40 a daily 5-mg
supplement of vitamin K1 for 2 to 4 years did not protect against age-related
decline in bone mineral density in postmenopausal women with osteopenia, but
significantly fewer women in the vitamin K group than in the placebo group had
fractures.
Epidemiological evidence has shown associations between low dietary intake of
vitamin K and increased bone loss in elderly men and women. A 2006 meta-analysis
of 13 randomized controlled trials41 that gave vitamin K1 or menaquinone-4 (a
form of vitamin K2) supplements for longer than 6 months reported data on bone
loss and fracture rates. All but one study showed a reduction in bone loss with
supplemental vitamin K. All 7 of the 13 studies that reported fracture data were
in Japanese individuals and used menaquinone-4. Most of these trials used a high
dose, 45 mg/day.
While the recommended dietary intake of vitamin K is 90-120 mcg per day, the
optimal dose and form of vitamin K supplementation to achieve a protective
effect on bone loss and fracture reduction is not known. The majority of studies
used menaquinone-4 at doses approximately 400-fold higher than dietary
recommendations for vitamin K1. An additional issue is that these studies have
been conducted almost exclusively in Japanese postmenopausal women. This
population group may have unique dietary, environmental, and/or genetic factors,
so it is not clear whether the findings from these studies can be generalized to
other populations. In contrast to the 7 positive Japanese studies, a
double-blind trial in 381 postmenoapusal women received either phylloquinone 1
mg/day, MK4 45 mg/day or placebo for 12 months.42 No effect of phylloquinone or
MK4 on the bone density of the lumbar spine or proximal femur was observed.
Two long-term trials have previously been done evaluating the effect of vitamin
K1 supplementation on bone loss. In one study using 1 mg per day of vitamin K1
plus calcium and vitamin D for 3 years in postmenopausal women ages 50-60
years,43 bone loss was reduced at the femoral neck but there was no beneficial
effect on spine bone density. In a second study,44 200 mcg per day of vitamin K1
plus calcium and vitamin D given for two years to non-osteoporotic women aged 60
years or older resulted in a modest increase in bone mineral density of the
radius, but not the femoral neck.
Menaquinone-7 (a form of vitamin K2), which is derived from natto (fermented
soybeans) has been found in animal studies to be more potent and more
bioavailable, and to have a longer half-life, than menaquinone-4. In a study of
Japanese postmenopausal women, a significant inverse association was found
between natto consumption and the incidence of hip fractures.45
Conclusion
The most effective approach to osteoporosis is prevention. The risk of
developing osteoporosis may be reduced by optimizing peak bone mass in the
younger years and by minimizing subsequent bone loss in elderly women. In order
to maximize peak bone mass (even in the context of hereditary and other
non-modifiable risk factors), lifestyle habits, proper nutrition with a whole
foods diet, moderate exercise, and avoiding tobacco and excessive alcohol
consumption should begin during childhood and adolescence and continue
throughout life. The physician is encouraged to maintain a key interest in
dietary habits that promote optimal bone health, and include nutritional
supplementation that may favorably alter patients' risk and provide optimal bone
strength, bone architecture, and bone density with reduced risk for fractures
later in life.
References
1Porthouse J, Cockayne S, King C, et al. Randomised controlled trial of calcium
and supplementation with cholecalciferol for prevention of fractures in primary
care. BMJ 2005;330:1003-1009.
2Bischoff-Ferrari H, Dawson-Hughes B, Baron J, et al. Calcium intake and hip
fracture risk in men and women: a meta-analysis of prospective cohort studies
and randomized controlled trials. Am J Clin Nutr 2007;86:1780-1790.
3Shea B, Wells G, Cranney A, et al. Meta-analyses of therapies for
postmenopausal osteoporosis. VII. Meta-analysis of calcium supplementation for
the prevention of postmenopausal osteoporosis. Endocr Rev 2002; 23:552-559.
4Jackson R, LaCroix A, Gass M, et al. for the Women's Health Initiative
Investigators. Calcium plus vitamin D supplementation and the risk of fractures.
N Engl J Med 2006;354:669-683.
5Cumming RG. Calcium intake and bone mass: a quantitative review of the
evidence. Calcif Tissue Int 1990;47:194-201.
6Elders PJ, Netelenbos JC, Lips P, et al. Calcium supplementation reduces
vertebral bone loss in perimenopausal women: a controlled trial in 248 women
between 46 and 55 years of age. J Clin Endocrinol Metab 1991;73:533-540.
7Licata AA. Prevention and osteoporosis management. Cleve Clin J Med
1994;61:451-460.
8Grant A, Avenell A, Campbell M, et al for the RECORD Trial Group. Oral vitamin
D3 and calcium for secondary prevention of low-trauma fractures in elederly
people (Randomised Evaluation of Calcium OR vitamin D, RECORD): a randomised
placebo-controlled trial. Lancet 2005;365:1621-1628.
9Bischoff-Ferrari H, Willett W, Wong J, et al. Fracture prevention with vitamin
D supplementation: a meta-analysis of randomized controlled trials. JAMA
2005;293:2257-2264.
10Dawson-Hughes B, Dallal G, Krall E, et al. A controlled trial of the effect of
calcium supplementation on bone density in postmenopausal women. N Engl J Med
1990;23:878-883.
11Bischoff H, Stahelin H, Dick W, et al. Effects of vitamin D and calcium
supplementation on falls: a randomized controlled trial. J Bone Miner Res
2003;18:343-351.
12Pfeifer M, Begerow B, Minne H, et al. Effects of a short-term vitamin D and
calcium supplementation on body sway and secondary hyperparathyroidism in
elderly women. J Bone Miner Res 2000;15:1113-1118.
13Bischoff-Ferrari H, Dawson-Hughes B, Willett W, et al. Effect of vitamin D on
falls: a meta-analysis. JAMA 2004;291:1999-2006.
14Cohen L, Kitzes R. Infrared spectroscopy and magnesium content of bone mineral
in osteoporotic women. Isr J Med Sci 1981;17:1123-1125.
15Stendig-Lindberg G, Tepper R, Leichter I. Trabecular bone density in a two
year controlled trial of peroral magnesium in osteoporosis. Magnes Res
1993;6:155-163.
16Mounier P, Roux R, Seaman E, et al. The effects of strontium ranelate on the
risk of vertebral fracture in women with postmenopausal osteoporosis. N Engl J
Med. 2004 Jan 29;350:459-468.
17Meunier, P, Slosman, D, Delmas, P, 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.((Note: Only the first word of the title should be
capitalized.))
18Atik OS. Zinc and senile osteoporosis. J Am Geriatr Soc 1983;31:790-791.
19Follis 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 1955;97:405-409.
20Smith R, Smith J, Fields M, Reiser S.. Mechanical properties of bone from
copper deficient rats fed starch or fructose. Fed Proc 1985;44:541.
21Eaton-Evans J, McIlrath EM, Jackson WE, et al. Copper supplementation and the
maintenance of bone mineral density in middle-aged women. J Trace Elem Exp Med
1996;9:87-94.
22Leach R, Muenster A, Weign E. Studies on the role of manganese in bone
formation. II. Effect upon chondroitin sulfate synthesis in chick epiphyseal
cartilage. Arch Biochem Biophys 1969;133:22-28.
23Strause L, Saltman P, Smith KT, et al. Spinal bone loss in postmenopausal
women supplemented with calcium and trace minerals. J Nutr 1994;124:1060-1064.
24Nielsen FH. Boron—an overlooked element of potential nutritional importance.
Nutr Today 1988;Jan/Feb:4-7.
25Anonymous. Silicon and bone formatin. Nutr Rev 1980; 38:194-195.
26Hott M, de Pollak C, Modrowski D, Marie P. Short-term effects of organic
silicon on trabecular bone in
mature ovariectomized rats. Calcif Tissue Int 1993, 53:174-179.
27Van Neurs J, Dhonukshe-Rutten R, Pluijm S, et al. Homocysteine levels and the
risk of osteoporotic fractures. N Engl J Med 2004;350:2042-2090.
28Brattstrom L, Hultbnerg B, Mardebo J. Folic acid responsive postmenopausal
homocysteinemia. Metabolism 1985;34:1073-1077
29Sato Y, Honda Y, Iwamoto J, et al. Effect of folate and mecobalamin on hip
fractures in patients with stroke: a randomized controlled trial. JAMA
2005;293:1082-1088.
30Barber G, Spaeth G. Pyridoxine therapy in homocystinuria. Lancet 1967;1:337.
31Dodds RA, Catterall A, Bitensky L, Chayen J. Abnormalities in fracture healing
induced by vitamin B6 deficiency in rats. Bone. 1986;7:489-495.
32Silberberg R, Levy BM. Skeletal growth in pyridoxine deficient mice. Proc Soc
Exp Biol Med.1948;67:259-263.
33Benke PJ, Fleshood HL, Pitot HC. Osteoporotic bone disease in the
pyridoxine-deficient rat. Biochem Med. 1972;6:526-535.
34Azuma J, Kishi T, Williams RH, Folkers K. Apparent deficiency of vitamin B6 in
typical individuals who commonly serve as normal controls. Res Commun Chem
Pathol Pharmacol 1976;14:343-348.
35Hyams DE, Ross EJ. Scurvy, megaloblastic anemia and osteoporosis. Br J Clin
Pract 1963;17:332-340.
36Ducy, P, Desbois C, Boyce B, et al. Increased bone formation in
osteocalcin-deficient mice. Nature. 1996;382(6590):448-452.
37Booth SL, Tucker KL, Chen H, et al. Dietary vitamin K intakes are associated
with hip fracture but not with bone mineral density in elderly men and women. Am
J Clin Nutr 2000;71:1201-1208.
38Feskanich D, Weber P, Willett WC, et al. Vitamin K intake and hip fractures in
women: a prospective study. Am J Clin Nutr 1999;69:74-79.
39Booth S, Dallal G, Shea K, et al. Effect of vitamin K supplementation on bone
loss in elderly men and women. J Clin Endocrinol Metab 2008;93:1217-1223.
40Cheung A, Tile L, Lee Y, et al. Vitamin K supplementation in postmenopausal
women with osteopenia (ECKO Trial): A randomized controlled trial. PLoS Med.
2008 Oct 14;5(10):e196.
41Cockayne S, Adamson, J, Lanham-New S, et al. Vitamin K and prevention of
fractures. Systematic review and meta-analysis of randomized controlled trials.
Arch Intern Med 2006;166:1256-1261.
42Binkley N, Harke J, Krueger D, et al. Vitamin K treatment reduces
undercarboxylated osteocalcin but does not alter bone turnover, density or
geometry in healthy postmenopausal, North American women. J Bone and Mineral
Research 2009;24(6):983-991.
43Braam L, Knapen M, Geusens P, et al. Vitamin K1 supplementation retards bone
loss in postmenopa-usal women between 50 and 60 years of age. Calcif Tissue Int
2003;73:21-26.
44Bolton-Smith C, McMurdo M, Paterson C, et al. 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;22:509-519.
45Kaneki M, Hedges S, 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.
Clinical Nutrients for Osteoporosis
by Tori Hudson, ND
Numerous modifiable and non-modifiable factors influence the risk of developing
osteoporosis. This article provides the practitioner with an understanding of
supplementary clinical nutrients and their effect on bone loss and fractures.
Lifestyle modifications and nutrient supplementation may be able to reduce the
risk of osteoporosis and the associated debilitating fractures. For women who
have already been diagnosed with osteoporosis, these nutritional factors can
serve as an adjunct to conventional therapies to slow bone loss and, more
importantly, decrease the risk of fractures.
NUTRITIONAL SUPPLEMENTATION
Calcium
Adequate calcium intake has an established role in maintaining bone health,
primarily in very young women and the elderly. However, calcium is only modestly
effective for slowing the loss of bone mineral density in peri- and early
postmenopausal women. Calcium supplementation also appears to have an important
role in improving the efficacy of pharmaceutical agents used to treat bone loss
and osteoporosis.
Prior to the Women's Health Initiative study, there was no clear evidence that
higher calcium intake decreased fracture risk.1 A meta-analysis of prospective
cohort studies and clinical trials found that higher calcium intake and calcium
supplementation were not associated with a lower incidence of hip fractures.2 In
a 2004 meta-analysis of randomized controlled trials, supplementation with
500-2,000 mg per day of calcium had only a modest benefit on bone density in
postmenopausal women: the difference in the amount of bone loss between calcium
and placebo was 2.05% for the total body, 1.66% for the lumbar spine, and 1.64%
for the hip.3 Two trials within this meta-analysis suggested a modest and
nonsignificant benefit with calcium supplementation and the risk of nonvertebral
fractures. In the Women's Health Initiative, which enrolled more than 36,000
postmenopausal women, supplementation with 1,000 mg per day of calcium and 400
IU per day of vitamin D decreased the risk of hip fractures nonsignificantly by
12%, when compared with placebo. However, when the analysis was restricted to
women who took the tablets at least 80% of the time, calcium plus vitamin D
significantly decreased hip fractures by 29% compared with placebo.4
Other calcium studies also showed a beneficial effect on bone loss. In
postmenopausal women, calcium supplementation has been shown to decrease bone
loss by as much as 50% at nonvertebral sites. The effects were greatest in women
whose baseline calcium intake was low, in older women, and in women with
established osteoporosis.5 In a study by Elders et al,6 a significant decrease
in vertebral bone loss was observed with supplementation of 1,000 to 2,000 mg
per day of calcium for 1 year. Bone loss was also less in the calcium group than
in the control group after 2 years, but the difference was no longer
statistically significant.
Dietary calcium is essential throughout a woman's life, and requirements
increase with advancing age, in part due to reduced calcium absorption and
decreased renal calcium conservation. However, calcium supplementation by itself
is not effective in preventing the accelerated bone loss that occurs in the
first few years after menopause. Ten years postmenopausally, calcium
supplementation again becomes effective in reducing age-related bone loss.7
While consuming an adequate amount of calcium is important, it is too often
overemphasized, supplemented at excessive doses, and is only one of many
nutritional and lifestyle factors that play a role in promoting bone health.
Vitamin D
Vitamin D enhances intestinal calcium absorption, thereby contributing to a
favorable calcium balance in the body. Increased calcium absorption also reduces
parathyroid-hormone-mediated bone resorption. In the United States, most infants
and young children have adequate vitamin D consumption from fortified milk.
During adolescence, however, the consumption of dairy products drops off, and
inadequate vitamin D intake is more likely to adversely affect calcium
absorption.
Several large randomized controlled trials have found that the combination of
calcium and vitamin D had no significant effect on fracture risk.1,8,5
However, a meta-analysis of randomized controlled trials in elderly
postmenopausal women found that a dose of 700 – 800 IU per day of vitamin D was
associated with significant reductions in the risk of hip and nonvertebral
fractures.9 Especially in older women, vitamin D in combination with calcium
supplementation reduced the rate of postmenopausal bone loss.10 Vitamin D has
also been shown to improve muscle strength11 and balance12, thereby reducing the
risk of falling.13
Magnesium
Magnesium is a cofactor for alkaline phosphatase, which plays a role in bone
mineralization. Low magnesium status is common in women with osteoporosis, and
magnesium deficiency is associated with abnormal bone mineral crystals.14 Some
women with reduced bone mineral density do not have an increased fracture rate,
possibly because their bone mineral crystals are of high quality, due in part to
high levels of magnesium. In a group of postmenopausal women, supplementation
with 250-750 mg per day of magnesium for 6 months, followed by 250 mg per day
for 6-18 months, resulted in an increase in bone density in 71% of women. This
increase was noteworthy, because it occurred without calcium supplementation.15
Strontium
Strontium is a non-radioactive earth element physically and chemically similar
to calcium. Strontium ranelate is the specific strontium salt used in clinical
trials for osteoporosis, but this form of strontium is not available in the U.S.
Strontium in large doses stimulates bone formation and reduces bone resorption.
In a phase 2 clinical trial, 2 g per day of oral strontium ranelate (containing
680 mg per day of elemental strontium) for three years was shown to reduce the
risk of vertebral fractures and to increase bone mineral density in 1,649
postmenopausal women with osteoporosis.16
In the first year, there was a 49% reduction in the incidence of vertebral
fractures in the strontium ranelate group and 41% reduction at the end of three
years. After adjusting for artifact effect on imaging, a 6.8% increase in bone
mineral density was seen at the lumbar spine after 3 years of strontium
supplementation.. There was also an 8.3% increase at the femoral neck, but there
was insufficient data to adjust it for an artifact effect, and therefore it is
not clear as to how accurate this is.
In a two year trial 353 postmenopausal women with osteoporosis and a history of
at least one vertebral fracture received a placebo or one of three different
doses of strontium: 170 mg per day, 340 mg per day or 680 mg per day.17 A small
increase in lumbar bone mineral density was seen with each dose of strontium,
but the difference compared with placebo was statistically significant only for
the highest dose. The incidence of new vertebral fractures was lowest (38.8%)
with the lowest dose of strontium, vs. 54.7%, 56.7% and 42.0% in the placebo,
340 mg per day and 680 mg per day groups, respectively.
Strontium chloride is the most common form of strontium used in U.S.
supplements. This form of strontium has not been the subject of published
research. Due to potential adverse effects of higher doses of strontium,
including rickets, bone mineralization defects, and interference with vitamin D
metabolism, it may be prudent to use low doses until more research is conducted.
Zinc
Zinc is essential for the formation of osteoblasts and osteoclasts, and it
enhances the biochemical action of vitamin D. Zinc is also is necessary for the
synthesis of various proteins found in bone. Low zinc levels have been found in
the serum and bone of elderly people with osteoporosis.18
Copper
A deficiency of copper is known to produce abnormal bone development in growing
children, and may be a contributing cause of osteoporosis. In vitro studies have
shown that copper supplementation inhibits bone resorption.19,20 In a
double-blind trial, supplementation with 3 mg per day of copper for 2 years
significantly decreased bone loss in postmenopausal women.21
Manganese
A deficiency of manganese may be one of the lesser known but more important
nutritional factors related to osteoporosis. Manganese deficiency causes a
reduction in calcium deposition in bone. Manganese also stimulates
mucopolysaccharide production, which provides a framework for the calcification
process.22
Zinc, Copper, and Manganese
In a double-blind study of postmenopausal women, the combination of zinc,
copper, manganese, and calcium appeared to be more effective than calcium alone
for preventing bone loss in postmenopausal women.23
Boron
Boron supplementation reduces urinary excretion of calcium and magnesium and
increases serum levels of 17beta-estradiol and testosterone in postmenopausal
women.24 These observations suggest that boron supplementation could help
prevent bone loss.
Silicon
During bone growth and the early phases of bone calcification, silicon has an
essential role in the formation of cross-links between collagen and
proteoglycans. In animals, silicon-deficient diets have produced abnormal skull
development and growth retardation,25 and supplemental silicon partially
prevented trabecular bone loss in ovariectomized rats.26
Other Nutritional Factors
Folic Acid and Vitamin B12
Accelerated bone loss in menopausal women may in part be due to increased levels
of homocysteine, a breakdown product of methionine. Homocysteine has the
potential to promote osteoporosis if it is not eliminated adequately. In a
prospective study, women with high homocysteine levels had almost twice the risk
of nonvertebral osteoporotic fractures as did women with low homocysteine
levels. There was no association in that study between homocysteine levels and
bone mineral density at either the femoral neck or the lumbar spine, which
suggests that the reduction in fracture risk was due to an improvement in bone
quality.27 Folic acid promotes the remethylation of homocysteine to methionine,
and supplementing postmenopausal women with this nutrient results in significant
reductions in homocysteine levels. Vitamin B12 has also been shown to reduce
homocysteine levels.28 In a double-blind study of stroke victims with elevated
homocysteine levels, daily supplementation with 5 mg of folic acid plus 1,500
mcg of vitamin B12 for two years reduced hip fracture incidence by 78%, compared
with placebo.29
Vitamin B6
Vitamin B6 also plays a role in homocysteine metabolism. In people with the
genetic disorder homocystinuria, vitamin B6 supplementation reverses the
elevated levels of homocysteine.30 Animal studies have shown that vitamin B6
deficiency can prolong fracture healing time,31 impair cartilage growth, cause
defective bone formation,32 and promote osteoporosis.33 Vitamin B6 may also
influence progesterone production and exert a synergistic effect on
estrogen-sensitive tissue. Laboratory evidence of low vitamin B6 status appears
to be common, even among healthy individuals.34
Vitamin C
Vitamin C promotes the formation and cross-linking of some of the structural
proteins in bone. Animal studies have shown that vitamin C deficiency can cause
osteoporosis35 and it has been known for decades that scurvy, a disease caused
by vitamin C deficiency, is also associated with abnormalities of bone.
Vitamin K
Vitamin K is required for the production of the bone protein, osteocalcin.
Osteocalcin draws calcium to bone tissue, enabling calcium crystal formation.
Osteocalcin provides the protein matrix for mineralization and is thought to act
as a regulator of bone mineralization.36 Vitamin K plays a key role in the
formation, remodeling, and repair of bone by attracting calcium to the site of
this protein matrix.37 A low dietary intake of vitamin K seems to increase the
risk of osteoporotic hip fractures in women, according to data from the Nurses'
Health Study.38
There are various forms of vitamin K, but the human trials have been done on
vitamin K1 (phylloquinone) and menaquinone-4, (MK4, a form of vitamin K2).
In a double-blind study, 452 men and women (ages 60-80 years) received a
multiple vitamin/mineral supplement that provided 600 mg per day of calcium and
400 IU per day of vitamin D, plus either 500 mcg per day of vitamin K1 or no
vitamin K1.39 Bone mineral density (determined by dual-energy x-ray
absorptiometry) and bone turnover were measured at 6, 12, 24 and 36 months.
There were no differences in bone mineral density at the femoral neck, lumbar
spine, or total body, between the two treatment groups, indicating that vitamin
K1 did not enhance the effects of calcium, vitamin D, and other nutrients in
this patient population. In the double-blind ECKO trial,40 a daily 5-mg
supplement of vitamin K1 for 2 to 4 years did not protect against age-related
decline in bone mineral density in postmenopausal women with osteopenia, but
significantly fewer women in the vitamin K group than in the placebo group had
fractures.
Epidemiological evidence has shown associations between low dietary intake of
vitamin K and increased bone loss in elderly men and women. A 2006 meta-analysis
of 13 randomized controlled trials41 that gave vitamin K1 or menaquinone-4 (a
form of vitamin K2) supplements for longer than 6 months reported data on bone
loss and fracture rates. All but one study showed a reduction in bone loss with
supplemental vitamin K. All 7 of the 13 studies that reported fracture data were
in Japanese individuals and used menaquinone-4. Most of these trials used a high
dose, 45 mg/day.
While the recommended dietary intake of vitamin K is 90-120 mcg per day, the
optimal dose and form of vitamin K supplementation to achieve a protective
effect on bone loss and fracture reduction is not known. The majority of studies
used menaquinone-4 at doses approximately 400-fold higher than dietary
recommendations for vitamin K1. An additional issue is that these studies have
been conducted almost exclusively in Japanese postmenopausal women. This
population group may have unique dietary, environmental, and/or genetic factors,
so it is not clear whether the findings from these studies can be generalized to
other populations. In contrast to the 7 positive Japanese studies, a
double-blind trial in 381 postmenoapusal women received either phylloquinone 1
mg/day, MK4 45 mg/day or placebo for 12 months.42 No effect of phylloquinone or
MK4 on the bone density of the lumbar spine or proximal femur was observed.
Two long-term trials have previously been done evaluating the effect of vitamin
K1 supplementation on bone loss. In one study using 1 mg per day of vitamin K1
plus calcium and vitamin D for 3 years in postmenopausal women ages 50-60
years,43 bone loss was reduced at the femoral neck but there was no beneficial
effect on spine bone density. In a second study,44 200 mcg per day of vitamin K1
plus calcium and vitamin D given for two years to non-osteoporotic women aged 60
years or older resulted in a modest increase in bone mineral density of the
radius, but not the femoral neck.
Menaquinone-7 (a form of vitamin K2), which is derived from natto (fermented
soybeans) has been found in animal studies to be more potent and more
bioavailable, and to have a longer half-life, than menaquinone-4. In a study of
Japanese postmenopausal women, a significant inverse association was found
between natto consumption and the incidence of hip fractures.45
Conclusion
The most effective approach to osteoporosis is prevention. The risk of
developing osteoporosis may be reduced by optimizing peak bone mass in the
younger years and by minimizing subsequent bone loss in elderly women. In order
to maximize peak bone mass (even in the context of hereditary and other
non-modifiable risk factors), lifestyle habits, proper nutrition with a whole
foods diet, moderate exercise, and avoiding tobacco and excessive alcohol
consumption should begin during childhood and adolescence and continue
throughout life. The physician is encouraged to maintain a key interest in
dietary habits that promote optimal bone health, and include nutritional
supplementation that may favorably alter patients' risk and provide optimal bone
strength, bone architecture, and bone density with reduced risk for fractures
later in life.
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