Dietary Supplements for Postmenopausal Osteoporosis
Published on Nutritional Outlook (http://www.nutritionaloutlook.com)
Dietary Supplements for Postmenopausal Osteoporosis
November 22, 2014 | Women's Health [1], Magazine [2], Joint/Bone Health [3]
By Irfan Qureshi [4]
A rundown on the latest research
Maintaining healthy bone density with increasing age is a significant health challenge. Centers for
Disease Control and Prevention (CDC) estimates suggest that 9% of U.S. adults over the age of 50
have osteoporosis (per World Health Organization criteria), while nearly half of all adults 50 and
older have decreased bone mass.1 Osteoporosis affects both men and women alike; however, the
prevalence is substantially higher in women. The same CDC report estimates that 16% of women
have osteoporosis, while 4% of men qualify for this diagnosis. In addition, up to 61% of women aged
50 and older in the United States have decreased bone mass.
Hormonal changes occurring with age as a result of menopause contribute significantly to low bone
mass in women. Specifically, decreased levels of estrogen after menopause cause declines in levels
of osteoprotegerin (a protein secreted by osteoblasts, the cells responsible for bone building).
Osteoprotegerin antagonizes the process of bone resorption (breakdown) that is mediated by
osteoclasts (cells responsible for bone breakdown).
Normally, estrogen, when present at premenopausal levels, stimulates the production of
bone-building osteoprotegerin, enhancing bone structural density. With menopausal changes and
associated reductions in estrogen, however, osteoclast activity is increased, leading to decreased
bone mass and, in many cases, postmenopausal osteoporosis in women. Ultimately, this leads to
lowered bone mineral density and changes in bone structure, resulting in reduced bone strength and
increased risk of fractures.2
Lifestyle Strategies for Optimal Bone Density
Menopause-related changes in estrogen levels begin occurring 2–3 years prior to the last menstrual
cycle in women, initiating bone loss. The accelerated rate of bone loss continues through menopause
for up to 5–10 years. Evidence also suggests that even the lower levels of estrogen in
postmenopausal women confer some protection against further acceleration of bone loss by
preserving levels of osteoblast activity.2 Given the prolonged period of bone loss occurring around
menopause, however, it becomes more prudent to take measures earlier in life to compensate for
this inevitable decrease in bone mineral density.
Peak bone mass is achieved during the third decade of life. While genetic factors have a large
influence, modifiable lifestyle and nutritional factors play significant roles in this process.
Physical exercise programs, including strength training, resistance exercise, and balance and
coordination activities, can help maintain or increase bone mineral density in the spine and the hip
and have been shown to decrease the risk of falls in individuals with osteoporosis. Furthermore, it
seems that a combination of high-intensity training such as jogging or running, along with other
weight-bearing activity, may be most effective for supporting bone mineral density both at the
lumbar spine and hip.3 Elisa Marques and colleagues from the University of Porto in Portugal
conducted a study to compare the effects of resistance exercise and aerobic exercise on bone
mineral density and physical function in older women.4 They found that, over an eight-month period,
the resistance-exercise protocol induced significant benefits in bone mineral density at the hip and
overall muscle composition as well as improved overall functional balance. Aerobic exercise over the
same time frame improved functional balance but had no favorable effects on bone mineral density.
Beyond physical activity, nutritional choices are crucial for preserving bone mineral density in
postmenopausal women. An inadequate intake of food, specifically in the form of decreased protein
intake, contributes to decreased bone mass and a reduction in skeletal muscle mass. Researchers
from the University of São Paulo in Brazil studied the differences in protein intake in elderly women
over the age of 65 with or without sarcopenia (age-related loss of muscle mass) to evaluate the
intake level of protein related to improved bone mineral density and muscle mass.5 The investigators
found that women consuming more than 1.2 g of protein/kg body weight daily had significantly
higher muscle, bone, and fat mass than those consuming less protein on a daily basis, indicating that
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Dietary Supplements for Postmenopausal Osteoporosis
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increased protein intake had positive impacts on bone density and muscle composition.
In another study, researchers at the University of Connecticut’s (Farmington, CT) Anne Kenny, MD,
Center on Aging found that increased protein intake in postmenopausal women aged 60–90 years
was associated with enhanced physical performance in both the upper and lower extremity
compared to those women consuming lower-protein diets (less than 0.8 g/kg body weight daily).6
The average protein intake of this group was 1.1 g /kg body weight per day.
Of course, no discussion on preventive strategies for osteoporosis can be complete without
highlighting the importance of calcium and vitamin D intake, both of which are often low in
postmenopausal women. Vitamin D regulates calcium balance. Low intake levels of calcium and
vitamin D can induce increased levels of parathyroid hormone, leading to increased bone resorption
and an increased risk of fractures.2 Research suggests that up to 50% of women with osteoporosis
may have vitamin D insufficiency.
In a recent review, researchers comprising members of the European Society for Clinical and
Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended that the minimum
threshold for vitamin D sufficiency for bone health is a serum 25-hydroxy vitamin D concentration of
20 ng/mL. Below this serum level, ESCEO advises supplementation with vitamin D. Research has
shown that levels of parathyroid hormone and markers of bone turnover are significantly lower in
individuals with vitamin D levels above the 20 ng/mL threshold as opposed to individuals with levels
below this mark.7 Dietary intake of calcium-rich foods should be increased, and supplemental forms
of calcium can be considered to maintain adequate intake. Sun exposure results in the majority of
vitamin D production in the body. Failing adequate sun exposure, supplements are a prudent choice
to ensure sufficient vitamin D intake.
Nutritional Alternatives for Osteoporosis
Standard pharmaceutical approaches to the treatment of osteoporosis include hormone-replacement
therapy (HRT) (to replace reduced levels of estrogen), selective estrogen receptor modulators (drugs
that bind to the estrogen receptor with high affinity), and bisphosphonates, a class of drugs that
includes Fosamax (alendronate). While effective at increasing bone mineral density and inhibiting
bone breakdown, these therapies often have unacceptable side-effect profiles and
contraindications.2 For these reasons, nutritional and more natural alternatives for osteoporosis
prevention are appealing.
Genistein
Genistein is an isoflavone most often derived from soy that has phytoestrogenic effects. Asian
women with a high soy intake have been found to have a decreased risk of osteoporosis.
Phytoestrogens are plant-derived compounds that have weak estrogen-like effects, as they are able
to bind to estrogen receptors. Because of the affinity for estrogen receptors, and the concern
regarding side effects associated with estrogen-replacement therapy, genistein is a viable option for
counteracting the menopausal loss of estrogen and alleviating menopausal symptoms.
The safety of genistein was assessed in a three-year study consisting of daily supplementation with
54 mg daily. Genistein showed no significant changes in mammographic breast density
measurements or in endometrial thickness, indicating a promising safety profile.8
Marco Atteritano and colleagues from the University of Messina in Italy evaluated the bone health
benefits associated with the intake of a genistein-containing supplement (54 mg/day) or placebo
after a 1- and 2-year treatment in 138 postmenopausal women with decreased bone mineral
density.9 Researchers found that the genistein supplement significantly increased bone mineral
density in the femur and lumbar spine. In addition, quantitative ultrasound parameters (used to
evaluate fracture risk and bone architecture and elasticity) showed significant improvements with
genistein supplementation.
A more recent randomized placebo-controlled pilot study was conducted by Joan Lappe and
colleagues from Creighton University to evaluate a combination supplement containing genistein,
the polyunsaturated omega-3 fatty acids EPA and DHA, and vitamins D3 and K1 on bone mineral
density in postmenopausal women.10 The study duration was six months, with a daily dose of the
supplement providing 30 mg of synthetically derived genistein (geniVida; DSM Nutritional Products;
Parsippany, NJ). The women in the group supplementing with the genistein blend maintained bone
mineral density assessed at the femoral neck, while the placebo group showed significant decreases
in bone mineral density. Assessed at Ward’s triangle (a specific fracture-prone area of the femur),
the genistein group showed an average increase in bone mineral density of 2.3%, whereas the
placebo group declined by 1.1% on average. These studies indicate the ability of genistein to support
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Dietary Supplements for Postmenopausal Osteoporosis
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and enhance bone mineral density as well as several parameters of healthy bone architecture.
KoACT Calcium–Collagen Complex
Bone is composed of a combination of proteins and minerals, with approximately 70% of the weight
deriving from calcium, phosphate, and other minerals. The remainder of the composition includes
water and matrix proteins. Nearly 90% of this matrix is composed of collagen, which contributes
significantly to bone strength.11
While calcium and other minerals are critical for bone structure, a more complete strategy for
optimal bone strength may be to provide minerals in combination with collagen to support the bone
tissue matrix. Designed to provide a combination of nutrients essential to bone tissue, KoACT (AIDP;
City of Industry, CA) is a patented chelated (bonded) compound of calcium and collagen that was
developed with this strategy in mind.
Behram Arjmandi from Florida State University and colleagues conducted a 12-month pilot clinical
trial to evaluate the benefits of KoACT calcium–collagen chelate in postmenopausal women with
decreased bone density.12 Thirty-nine women were assigned to receive either 5 g of the
calcium–collagen chelate daily containing 500 mg of elemental calcium and 200 IU vitamin D in a
collagen matrix (treatment group), or simply 500 mg of calcium along with 200 IU vitamin D
(control). Evaluations included total body bone mineral density and bone mineral density
assessments at the hip and spine. Serum markers of bone turnover were also measured at baseline,
6, and 12 months.
Serum markers of bone turnover were significantly more favorable at six months in the treatment
group compared to the control, while the calcium–collagen chelate also significantly prevented the
loss of whole-body bone mineral density versus the control treatment after 12 months. These
promising results indicated the superiority of the calcium–collagen complex compared to calcium
alone in supporting bone mineral density in postmenopausal women.
Vitamin K2
Vitamin K2 is an umbrella term for a number of related compounds known as menaquinones.
Menaquinones have various numbers of isoprenoid units attached to their core, which reflects the
length of their side chain and contributes to their name designation. Two of the more commonly
available forms of vitamin K2 for supplementation purposes include MK-4 (four isoprenoid units in
the side chain) and MK-7 (seven isoprenoid units).
Vitamin K2 plays a crucial role in maintaining bone health via its ability to activate osteocalcin, a
calcium-binding protein found in the bloodstream that takes calcium out of circulation and delivers it
to bone matrix. Research has found that circulating osteocalcin is a measure of bone formation.13
However, menaquinones may have additional unique benefits for bone health. Emory University’s
Masayoshi Yamaguchi, PhD, and M. Neale Weitzmann, PhD, demonstrated that menaquinones
facilitate both pro-anabolic and anti-catabolic effects on bone cells.14 Menaquinones were shown to
suppress the activation of NF-kB, a signaling molecule that mediates the inflammatory process. By
suppressing this molecule, menaquinones stimulated the production of osteoblasts while suppressing
the production of osteoclasts.
Human studies on vitamin K2 both in the form of MK-4 and MK-7 support the bone health benefits of
this vitamin. In a recently published three-year study, Martinus Knapen and colleagues from the
Netherlands assessed the benefits of 180 mcg daily of MK-7 versus a placebo on maintenance of
bone mineral density and bone strength in healthy postmenopausal women.15 MK-7 supplementation
was found to significantly slow the age-related decline in bone mineral content and bone mineral
density assessed at the lumbar spine and neck of the femur, while also increasing bone strength.
Furthermore, MK-7 supplementation was significantly associated with less loss of vertebral height in
the mid-back region. These findings suggest that MK-7 significantly impacts bone density and
strength in postmenopausal women.
The menaquinone MK-4 (a shorter-chain form of vitamin K2) has also been well studied for its ability
to support bone health, generally in doses up to 45 mg/day. A recent study by Noriko Koitaya and
colleagues from the National Institute of Health and Nutrition in Tokyo investigated whether a much
lower dose of MK-4 (1.5 mg/day) would have similar benefits for bone health in postmenopausal
women aged 50–65.16 Participants were divided into a placebo and treatment arm and treated for 12
months. Serum uncarboxylated osteocalcin concentrations were assessed at baseline and found to
be elevated in both groups. At both 6 and 12 months, serum concentrations of uncarboxylated
osteocalcin were significantly lower in the MK-4 group compared to placebo, indicating significant
improvement in the activity of this calcium-transport protein. After 12 months, the group
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Dietary Supplements for Postmenopausal Osteoporosis
Published on Nutritional Outlook (http://www.nutritionaloutlook.com)
supplementing with MK-4 showed no decrease, while the placebo group showed a significant decline
in bone mineral density assessed at the forearm, suggesting that even a low dose of MK-4 taken
long-term is beneficial.
Age-related changes in bone density are a significant challenge for postmenopausal women, and the
consequences can often be dire. The key to lifelong healthy bones is ensuring optimal nutritional
practices are stressed at an early age and continued through menopause and beyond. Enhancing
pre- and postmenopausal nutrient intake by adding targeted supplemental nutrients—calcium,
vitamin D, vitamin K2, genistein, and collagen chief considerations among them—can help create a
solid foundation for bone building and maintenance.
References
1. Looker AC et al., “Osteoporosis or low bone mass at the femur neck or lumbar spine in older
adults: United States, 2005–2008,” NCHS data brief no 93. Hyattsville, MD: National Center
for Health Statistics. 2012.
2. Maeda SS et al., “An overview on the treatment of postmenopausal osteoporosis,” Arquivos
Brasileiros de Endocrinologia e Metabologia, vol. 58, no. 2 (March 2014): 162–171
3. Lirani-Galvão AP et al., “Physical approach for prevention and treatment of osteoporosis,”
Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 54, no. 2 (March 2010): 171–178
4. Marques EA et al., “Effects of resistance and aerobic exercise on physical function, bone
mineral density, OPG and RANKL in older women,” Experimental Gerontology, vol. 46, no. 7
(July 2011): 524–532
5. Genaro PD et al., “Dietary protein intake in elderly women: Association with muscle and bone
mass,” Nutrition in Clinical Practice. Published online ahead of print August 8, 2014
6. Gregorio L et al., “Adequate dietary protein is associated with better physical performance
among post-menopausal women 60-90 years,” The Journal of Nutrition, Health & Aging, vol.
18, no. 2 (2014): 155–160
7. Rizzoli R et al., “Vitamin D supplementation in elderly or postmenopausal women: a 2013
update of the 2008 recommendations from the European Society for Clinical and Economic
Aspects of Osteoporosis and Osteoarthritis (ESCEO),” Current Medical Research and Opinion,
vol. 29, no. 4 (April 2013): 305–313
8. Marini H et al., “Breast safety and efficacy of genistein aglycone for postmenopausal bone
loss: a follow-up study,” The Journal of Clinical Endocrinology and Metabolism, vol. 93, no. 12
(December 2008): 4787–4796
9. Atteritano M et al., “Genistein effects on quantitative ultrasound parameters and bone
mineral density in osteopenic postmenopausal women,” Osteoporosis International, vol. 20,
no. 11 (November 2009): 1947–1954
10. Lappe J et al., “Effect of a combination of genistein, polyunsaturated fatty acids and vitamins
D3 and K1 on bone mineral density in postmenopausal women: a randomized,
placebo-controlled, double-blind pilot study,” European Journal of Nutrition, vol. 52, no. 1
(February 2013): 203–215
11. Young MF, “Bone matrix proteins: their function, regulation, and relationship to
osteoporosis,” Osteoporosis International, vol. 14, suppl. 3 (2013): S35–542
12. Arjmandi J et al., “A calcium–collagen chelate dietary supplement prevents bone loss in
postmenopausal women with osteopenia,” The Journal of the Federation of American
Societies for Experimental Biology, vol. 28, no. 1 (April 2014) suppl. LB421
13. Booth SL et al., “The role of osteocalcin in human glucose metabolism: marker or mediator?”
Nature Reviews. Endocrinology, vol. 9, no. 1 (January 2013): 43–55
14. Yamaguchi M et al., “Vitamin K2 stimulates osteoblastogenesis and suppresses
osteoclastogenesis by suppressing NF-kB activation,” International Journal of Molecular
Medicine, vol. 27, no. 1 (January 2011): 3-14
15. Knapen MH et al., “Three-year low-dose menaquinone-7 supplementation helps decrease
bone loss in healthy postmenopausal women,” Osteoporosis International, vol. 24, no. 9
(September 2013): 2499–2507
16. Koitaya N et al., “Low-dose vitamin K2 (MK-4) supplementation for 12 months improves bone
metabolism and prevents forearm bone loss in postmenopausal Japanese women,” Journal of
Bone and Mineral Metabolism, vol. 32, no. 2 (March 2014): 142-150
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Dietary Supplements for Postmenopausal Osteoporosis
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