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March 27, 2008

15 Min Read
Nutrition for Bone Health

References

Bones are the body’s structure and support system. Made mostly of collagen and minerals, bone is living, growing tissue, according to the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS).

Collagen, a protein that provides framework, and calcium phosphate, a mineral that adds strength and hardens, make bone strong and flexible. Throughout life, bones are constantly renewed through a two-part process, resorption and formation. In resorption, old bone tissue is broken down and removed by cells known as osteoclasts. During bone formation, new bone tissue is laid down to replace the old by osteoblasts. These two opposite functions are regulated by hormones, including calcitonin, estrogen (in women) and testosterone (in men). Osteoporosis develops when bone removal occurs too quickly or replacement occurs too slowly or both. People are more likely to develop osteoporosis, a condition in which the bone weakens and deteriorates, creating an increased risk of fractures, if they do not reach their maximum peak bone mass during the crucial bone building years. NIAMS added that women are more likely than men to develop osteoporosis, since women have smaller, thinner bones, and can lose bone tissue rapidly in the first four to eight years after menopause, due to the sharp decline in production of estrogen.

Public awareness on the importance of bone health is rising, as television ads tout drugs for preventing osteoporosis and magazines encourage readers to drink more milk for strong bones. There is also a wide range of bone supplements that have appeared on the market, allowing consumers to select one that best fits their age, condition and ailments.

Classic Calcium

Calcium is the healthy bone standby. An essential mineral for the growth and maintenance of bones and teeth, consistent calcium intake is required throughout life; calcium deficiency can lead to osteoporosis, a condition in which the bone weakens and deteriorates, creating an increased risk of fractures.

Interventions with calcium have supported its bone-building claims. In an 18-month study, researchers found a daily calcium supplement (555 mg/d) boosted bone mineral content (BMC) in teenage girls with low habitual calcium intake (n=96).1 Compared with the control group, the supplemented group showed significantly greater gains in BMC over the 18-month intervention; in addition, bone mineral density (BMD) was significantly greater for all skeletal sites, and concentrations of bone resorption markers and parathyroid hormone were significantly lower in the supplemented group than in the control group. However, after 42 months, gains in BMC and BMD and differences in bone resorption were no longer evident, suggesting calcium acts by suppressing bone turnover, which is reversed upon supplement withdrawal. A similar study evaluated the effects of calcium supplement and milk intake on BMD and growth in children.2 Researchers concluded both milk and calcium intakes could significantly improve children’s BMD; however, compared with the control group, increasing milk intake also significantly promoted growth and development compared to the calcium supplement group.

Another study on BMD and the effects of low habitual calcium intake was conducted by researchers at Changhai General Hospital, Singapore, using a group of elderly subjects (n=77) with hip fractures.3 Mean daily calcium intake was 650 mg, and only six patients had a daily calcium intake above 1,000 mg/d. Further, patients with BMD in the osteoporotic and osteopenic ranges had no significant difference in dietary calcium intake.

Calcium supplementation is obviously important, but it’s also crucial to balance calcium intake with magnesium supplementation. Magnesium deficiency has been shown to be a key factor in bone loss and osteoporosis.4 One study from the University of Tennessee concluded that greater magnesium intake was significantly related to higher BMD.5 In the trial, 2,038 older and white men and women aged 70 to 79 had their dietary intake of magnesium assessed using a semi-quantitative food frequency questionnaire, and supplement data was collected based on a medication inventory. Researchers found magnesium intake was positively associated with BMD. A similar study from the University Graduate School of Medical and Dental Sciences, Japan, investigated a possible association between magnesium intake and bone mass in young adult women.6 Subjects consisted of 106 female university students aged 19 to 25 years. Calcium and magnesium intakes were evaluated using the duplicate sampling method; spinal and femoral BMD were measured. Researchers did not find an association between magnesium intake and bone mass in young women, concluding calcium intake needs to be included as an important, potential confounding factor when exploring such an association.


Special K

Vitamin K is an essential vitamin for growing bones. It comes in two forms, vitamin K1 (phylloquinone), which is found in green leafy vegetables, and vitamin K2 (menaquinone), primarily seen in fermented cheese or other foods.

In adult bone, vitamin K contributes as a co-factor in the carboxylation of osteocalcin, but in children, the significance of vitamin K in bone-mass acquisition is less known, according to a two-year study from the University Medical Centre Utrecht, Netherlands.7 The study followed 307 children with a mean age of 11.2 years and assessed their skeletal BMC. The researchers found those children with improved vitamin K status over the two-year period resulted in better BMC and improved bone mass of the whole body.

In a double blind, controlled trial, 452 men and women (60 to 80 years) were randomized to receive a multivitamin that contained either 500 mcg/d or no K1, plus a daily calcium (600 mg elemental calcium) and vitamin D (400 IU) supplement.8 Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial. The researchers found no differences in changes in BMD measurements at any of the anatomical sites. The group that received the phylloquinone had significantly higher K1 levels and a significantly lower percent of undercarboxylated osteocalcin concentrations.

Another study supporting the theory that vitamin K helps maintain bone density was conducted at the University of Maastricht, Netherlands.9 In the three-year, placebo-controlled trial, researchers tested whether BMC and femoral neck width (FNW) in 325 postmenopausal women were affected by taking 45 mg/d of vitamin K2 (MK-4, menatetrenone). K2 did not affect BMD, but did increase BMC and FNW. In addition, the K2-treated women’s hip bone strength remained unchanged during the intervention period, whereas in the placebo group, bone strength decreased significantly.

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Impressive Ipriflavone

Ipriflavone, a synthetic isoflavone, is commonly used to maintain BMD and prevent osteoporosis, especially in postmenopausal women. Ipriflavone works by inhibiting bone resorption by osteoclasts and enhancing osteoblast bone formation activity. A study from Italy determined the safety and efficacy of ipriflavone (IP) in established osteoporosis.10 Researchers enrolled 149 elderly, osteoporotic women (65 to 79 years) with prevalent vertebral fractures in two multi-center, double blind, two-year studies. They received either oral IP (200 mg/tid at meals) or matching placebo, plus 1 g/d oral calcium. A significant increase in forearm BMD was obtained after IP treatment. Urinary hydroxyproline was significantly decreased in IP-treated patients, suggesting a reduction in bone turnover rate. Further, a reduction of incident vertebral fractures was observed in IP-treated women compared with control subjects. The study also suggests that IP may also improve bone pain and mobility, and the data shows long-term treatment with IP may be considered safe, and may increase bone density and possibly prevent fractures in elderly patients with established osteoporosis.

Another study using in vitro and in vivo legs looked at the effects of IP on caged layers’ (hens) bone metabolism.11 IP was found to regulate the functional balance between osteoblasts and osteoclasts, enhancing bone formation. Based on these in vitro findings, researchers conducted a 70-day in vivo trial using 500 hens that were fed diets containing 0, 15, 25, 50 and 100 ppm of IP. Egg production increased in hens fed 25 ppm and decreased in hens fed 50 and 100 ppm, when compared with the controls and hens fed 15 ppm (P < 0.05). Egg weight, shell quality, BW, and serum P, Ca, estrogen and bone mineral content were not affected by inclusion of ipriflavone in the diet. Hens consuming 25 ppm of ipriflavone had greater serum alkaline phosphatase and bone gla protein levels than controls. Researchers stated that adding 25 ppm of ipriflavone to the feed "appears to be close to an ideal level for clinical treatment of osteoporosis because of improved egg production while maintaining bone mineral content."

Not all of the findings on IP have been universally positive. One randomized, placebo-controlled study evaluated the effect of IP (600 mg/d) against bone loss in premenopausal, ovariectomized women (n=37) and postmenopausal women (n=52).12 In the early-stage group, the IP group showed a 6.7-percent decrease in BMD from baseline levels, whereas the placebo group showed a 10.7-percent decrease at 12 months of treatment, and 7.1-percent (IP) and 12.6-percent (placebo) decreases at 24 months of treatment. In the late-stage group, there was a 0.3-percent increase in BMD in the IP group and a 2.3-percent decrease in the placebo group at 6 months of treatment (P < 0.01), and similar changes were seen at 18 months (1.4 percent-increase and 3.9-percent decrease; P < 0.01). IP suppressed bone loss compared with placebo; however, it did not prevent acute bone loss in the early stage following ovariectomy.



Soy Strength

Soy isoflavones are phytonutrients known as flavonoids. The main isoflavones are genistein and daidzein, found almost exclusively in soy. Isoflavones are phytoestrogens, which mimic some of the effects estrogen has in the body. Because estrogen is key to bone strength, and menopause causes estrogen levels to substantially drop, soy isoflavones have been studied for their possible ability to reduce bone loss. A recent article in Menopause stated that in vitro and animal studies have shown that soy isoflavones act in multiple ways to exert their bone-supporting effects; they act on both osteoblasts and osteoclasts via genomic and nongenomic pathways.13 While epidemiological studies and clinical trials suggest soy isoflavones have beneficial effects on BMD, bone turnover markers, and bone mechanical strength in postmenopausal women, there are conflicting results related to differences in study design, estrogen status of the body, metabolism of isoflavones among individuals, and other dietary factors. Thus, many scientists conclude the long-term safety of soy isoflavone supplements remains to be demonstrated.

Intervention studies have sought to clarify the situation. For example, an animal study tried to determine whether ingestion of isoflavones before ovariectomy could prevent bone loss following the removal of ovaries.14 Wistar rats received a normal or isoflavone-rich (25 mg/d) diet for one month, prior to bilateral ovariectomy; one group of rats continued on the isoflavone-rich diet after the operation. Two months after intervention, researchers examined markers of bone metabolism and found no significant changes. When compared with the sham-operated rats fed a normal diet, BMD of ovariectomized rats decreased significantly; pre-ovariectomy ingestion of an isoflavone-rich diet did not prevent bone loss. Dietary isoflavones did not prevent the development of post-ovariectomy bone loss; however, researchers found long-term ingestion of an isoflavone-rich diet increased BMC after ovariectomy in young rats.

Another rat study tried to determine whether soy isoflavones would provide bone protection through lifelong exposure.15 Sixty female Wistar rats were fed either a standard diet (n=30) or the same food enriched with isoflavones (0.87 mg/g of diet) (n=30) for one month, then kept on the diet during pregnancy and lactation. At weaning, female pups were each assigned to one of four nutritional groups; within each experimental group, animals were split into two groups, fed either the standard or the IF-rich diet. Rats perinatally or life-long exposed to the isoflavone-rich diet exhibited higher body weight and fat mass at 24 months of age. Peak bone mass was achieved between six and 12 months and did not differ between groups. In animals perinatally exposed to IF, BMD continued to increase.

In humans, it appears soy isoflavone consumption can exert beneficial effects on bone. A meta-analysis out of Peking University, China, included 10 randomized controlled trials related to the effects of soy isoflavone intake on spine BMD or BMC.16 Spine BMD in subjects who consumed isoflavones increased significantly in comparison to subjects who did not consume isoflavones; isoflavone intake versus placebo intake also increased spine BMC, with borderline significance. The favorable effects were found to be more significant when more than 90 mg/d of isoflavones were consumed. One study examined the effect soy isoflavones have in preventing estrogen-related bone loss.17 The double blind, placebo-controlled, randomized trial used 203 Chinese women, aged 48 to 62 years, assigned to three treatment groups with daily doses of placebo (1 g starch; n=67), mid-dose (0.5 g starch, 0.5 g soy extracts, and approximately 40 mg isoflavones; n=68), and high dose (1.0 g soy extracts and approximately 80 mg isoflavones; n=68). Researchers found soy isoflavones have a mild, but significant, independent effect on the maintenance of hip BMC, esepcially in postmenopausal women with low initial bone mass. A similar, nationwide study on women’s health found that ethnicities with higher, lifelong dietary soy intake (Japanese and Chinese, specifically), had higher spine and femoral neck BMD.18

There are many natural options to support bone health. With the wealth of research and evidence supporting the efficacy of bone supplements, it’s possible to have a lifetime of strong, healthy bones. 

Additional Support

Beyond the usual suspects, there are several other nutritional compounds with adjunctive benefits to bone health.

Vitamin B12:A study from Wageningen University, Netherlands, found in a study of 194 elderly men and women, osteoporosis occurred more often among women whose vitamin B12 status was considered marginal or deficient than in women who had normal amounts of B12.19

Vitamin C: Vitamin C is essential in the formation of collagen and proteoglycan, and has been shown to minimize arthritis in guinea pigs.20 Other studies have shown vitamin C levels are related to BMD, which may lend itself as a preventive aid for osteoporosis.21

Phosphorus:Combined with calcium, phosphorus seems to have a large impact on bone health. In one study, nine groups of male rats were fed a diet with nine varying levels of calcium and phosphorus levels (using calcium carbonate, dicalcium phosphate or tricalcium phosphate) for 28 days.22 At equal levels of calcium supplementation, the two phosphorsous-containing salts promotes greater improvement in all bone variables measured.

Lycopene:In one study, researchers found lycopene stimulated parameters in cells that are crucial to bone formation, while simultaneously preventing bone resorption.23 Another study indicated lycopene may be able to prevent osteoporosis by regulating osteoblast activity.24

Editor's Note: Looking for more on bone & joint health? Visit the online bone & joint health category online.

Full list of references available on the next page.

1. Lambert HL et al. "Calcium supplementation and bone mineral accretion in adolescent girls: an 18-mo randomized controlled trial with 2-y follow-up." Am J Clin Nutr. 2008; 87.2: 455-62.

2. Li N et al. "Evaluation of milk intake and calcium supplement on bone mineral density and growth in children through Meta-analysis" Zhonghua Yu Fang Yi Xue Za Zhi. 2007; 41.3: 172-5.

3. Lee YH et al. "Inadequate dietary calcium intake in elderly patients with hip fractures." Singapore Med J. 2007; 48.12: 1117-21.

4. 5. Rude RK, Gruber HE. “Magnesium deficiency and osteoporosis: animal and human observations.” J Nutr Biochem. 2004;15(12):710-6. www.elsevier.com/locate/jnutbio 

5. Ryder KM et al. “Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects.” J Am Geriatr Soc. 2005; 53.11: 1875-80.

6. Nakamura K et al. "Magnesium intake and bone mineral density in young adult women." Magnes Res. 2007; 20.4: 250-3.

7. van Summeren MJ et al. "Vitamin K status is associated with childhood bone mineral content." Br J Nutr. 2008; epub ahead of print.

8. Booth SL et al. "Effect of Vitamin K Supplementation on Bone Loss in Elderly Men and Women." J Clin Endocrinol Metab. 2008; epub ahead of print.

9. Knapen MH et al. "Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women." Osteoporos Int. 2007; 18.7: 963-72.

10. Agnusdei D et al. "Efficacy of ipriflavone in established osteoporosis and long-term safety." Calcif Tissue Int. 1997; 61.1: S23-7.

11. Yao J et al. "Effects of ipriflavone on caged layer bone metabolism in vitro and in vivo." Poult Sci. 2007; 86.3: 503-7.

12. Katase K et al. "Effects of ipriflavone on bone loss following a bilateral ovariectomy and menopause: a randomized placebo-controlled study." Calcif Tissue Int. 2001; 69.2: 73-7.

13. Atmaca A et al. “Soy isoflavones in the management of postmenopausal osteoporosis.” Menopause. 2008; epub ahead of print.

14. Tsuang YH et al. “Isoflavones prevent bone loss following ovariectomy in young adult rats.” J Orthop Surg. 2008; 3.1: eEpub ahead of print.

15. Mardon J et al. “Influence of lifelong soy isoflavones consumption on bone mass in the rat.” Exp Biol Med (Maywood). 2008; 233.2: 229-37.

16. Ma DF et al. “Soy isoflavone intake increases bone mineral density in the spine of menopausal women: meta-analysis of randomized controlled trials.” Clin Nutr. 2008; 27.1: 57-64.

17. Chen YM et al. "Soy isoflavones have a favorable effect on bone loss in Chinese postmenopausal women with lower bone mass: a double-blind, randomized, controlled trial." J Clin Endocrinol Metab. 2003; 88.10: 4740-7.

18. Greendale GA et al. "Dietary soy isoflavones and bone mineral density: results from the study of women's health across the nation." Am J Epidemiol. 2002; 155.8: 746-54.

19. Dhonukshe-Rutten RA et al. "Vitamin B12 status is associated with bone mineral content and bone mineral density in frail elderly women but not in men." J Nutr. 2003; 133.3: 801-7.

20. Lamers RJ et al. "Identification of disease- and nutrient-related metabolic fingerprints in osteoarthritic Guinea pigs." J Nutr. 2003; 133.6: 1776-80.

21. Ilich JZ et al. "Bone and nutrition in elderly women: protein, energy, and calcium as main determinants of bone mineral density." Eur J Clin Nutr. 2003; 57.4: 554-65.

22. Shapiro R, Heaney RP. "Co-dependence of calcium and phosphorus for growth and bone development under conditions of varying deficiency." Bone. 2003; 32: 532-40.

23. Rao LG et al. "Lycopene I-effect on osteoclasts: lycopene inhibits basal and parathyroid hormone-stimulated osteoclast formation and mineral resorption mediated by reactive oxygen species in rat bone marrow cultures." J Med Food. 2003; 6.2: 69-78.

24. Kim L et al. "The effects of lycopene, a carotenoid antioxidant from tomato, on the growth and differentiation of SaOS-2 cells in vitro." The 23rd Annual Meeting of the American Society of Bone and Mineral Research, Phoenix: Oct. 12-16, 2001.

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