Bone health superheroes: Magnesium, collagen, and vitamin K2

November 20, 2019

Osteoporosis impacts 200 million women worldwide and affects an estimated 75 million people—men and women—just in Europe, the United States, and Japan, according to recent International Osteoporosis Foundation estimates.1 Worldwide, osteoporosis is responsible for nearly nine million fractures every year. Nearly 25% of annual hip fractures occur in men. Hip fractures are a significant cause of mortality; in men, the overall mortality rate in the first 12 months following a hip fracture is approximately 20%. These sobering statistics highlight the need for men and women to consider interventions to support bone health throughout life.

While eating a healthy diet, getting enough weight-bearing exercise, and ensuring calcium and vitamin D adequacy are good first steps in a nutritional and lifestyle plan to stop or slow down bone loss, research suggests this may not be enough. Several other nutritional compounds are known to play a major role in supporting bone health, and combining these with traditional strategies may be necessary to optimize the building blocks the body needs for healthy bones. These emerging contenders include magnesium, collagen, and vitamin K2. Current research show all three hold significant promise as adjunct therapies to the mainstays of bone health nutrition. Because of the fundamental roles they play in maintaining and growing healthy bone, leaving them out may not be a wise option.


Magnesium: Vitamin D’s Best Friend

Magnesium is an essential mineral that acts as a critical cofactor for hundreds of biochemical reactions in the body. With respect to bone health specifically, its importance can’t be overstated. As the fourth most abundant mineral in the human body, nearly half of total body magnesium stores lie in bone tissue. Animal studies reliably show that a low-magnesium diet adversely affects bone strength, while human population-based studies repeatedly have found that dietary levels of magnesium are positively associated with bone mineral density.2

Magnesium may work in several ways to promote healthy bones. Laboratory studies have found that low extracellular levels of magnesium promote the production of osteoclasts in bone tissue, cells responsible for bone breakdown. At the same time, low magnesium levels interfere with the proliferation of osteoblasts, cells that build bone. Overall, this favors a decrease in bone strength. Laboratory and human studies further demonstrate that magnesium has a suppressive effect on parathyroid hormone (PTH) secretion in situations where serum calcium levels are marginally low, leading to a protective effect on bone by allowing calcium to remain in bone tissue where it’s necessary for enhanced bone strength.2

Evidence indicates that magnesium plays a crucial role in the activation and function of vitamin D. A recent review suggests that nearly all of the enzymes that metabolize vitamin D require magnesium as a cofactor.3 The relationship between magnesium and vitamin D is codependent. Vitamin D improves intestinal magnesium absorption, while magnesium is necessary as a cofactor for the vitamin D–binding protein. In addition, metabolism of vitamin D in the liver and kidneys into its active form requires magnesium. Thus, vitamin D is unable to effectively play its role in influencing the growth of bone tissue by regulating calcium and phosphate balance without the presence of magnesium.

In a recent two-year follow-up cohort study including 113,683 individuals in Japan undergoing hemodialysis, Yusuke Sakaguchi from Osaka University Graduate School of Medicine (Suita, Japan) and colleagues found that those with lower serum magnesium levels had a significantly higher risk of hip fractures than those with higher serum magnesium levels.2 Each 1 mg/dl increase in magnesium level was associated with a 14.3% decrease in the risk of fracture. The researchers also found that magnesium levels mildly above the normal range (mild hypermagnesemia) were more beneficial in reducing fracture risk in this cohort, indicating additive benefits of higher magnesium levels. Previous research by the same group linked mild hypermagnesemia to improved survival in hemodialysis patients; it is possible that the reduction in hip fractures associated with elevated magnesium is a contributing factor to the enhanced survival rates.

Further evidence in support of the beneficial effects of magnesium comes from a cohort study including 156,575 men and women aged 39 to 72. Led by Alisa Welch from the University of East Anglia (Norwich, UK), investigators assessed measurements of muscle and bone health indicators from individuals that were a part of the UK Biobank cohort.4 These measurements were compared to dietary intake levels of magnesium. Clinically significant differences were found in grip strength, fat free mass, and bone mineral density in both men and women when assessed across quintiles of dietary magnesium intake. Specific to bone mineral density, higher magnesium intake led to greater bone mineral density measurements in men and women. While these benefits were more pronounced in men, the bone mineral density differences were also significantly higher in women with greater dietary magnesium intake, reinforcing the importance of magnesium for bone health.


Collagen Peptides: Structural Support for a Strong Foundation

Collagen is a vital structural protein for bone that forms the backbone of bone’s mechanical strength. It is made up of three polypeptide strands forming a unique triple helix where the amino acid glycine is in every third position. The other two amino acids most commonly represented in collagen are proline and hydroxyproline. As the most abundant protein in mammals, collagen represents 30% of total protein in the body, while in bone and other connective tissue it represents 80%. In bone, collagen is intertwined with minerals, including calcium apatite crystals. The minerals are responsible for the stiffness and rigidity of bone, and collagen provides skeletal toughness and defines its shape. Nearly 95% of collagen in bone is type I, while type II collagen is also present.5 Research suggests that type I collagen synthesis promotes osteoblast growth and enhances bone mineral density.6

The ability of bone to resist mechanical forces and fractures is dependent on both the quantity of bone tissue (i.e. the amount of mineralization) as well as the quality (i.e. the structural organization of the collagen backbone). Age-related changes can have a significant impact on the collagen framework, leading to reduced bone strength and elasticity, making bone more prone to fractures (such as in osteoporosis). One factor affecting collagen is estrogen deficiency, which decreases collagen maturation rate. Aging also increases the overall metabolism of collagen, leading to a fragile bone matrix. Research further suggests that the formation of advanced glycation end products (AGEs) in bone tissue occurs with aging, weakening the integrity of the collagen backbone.5 Interestingly, laboratory studies in pre-osteoblasts from mice show that collagen peptides from a bovine source were able to enhance the growth and proliferation of osteoblasts and encourage the formation of mineralized bone matrix, highlighting its bone-protective effects.7 These factors attest to the importance of replenishing collagen in addition to the key bone-supportive vitamins and minerals in order to maintain healthy bones.

  1. Facts and Statistics. International Osteoporosis Foundation. Accessed July 28, 2019.
  2. Sakaguchi Y et al. “Magnesium and risk of hip fracture among patients undergoing hemodialysis.” Journal of the American Society of Nephrology, vol. 29, no. 3 (March 2018): 991-999
  3. Uwitonze AM et al. “Role of magnesium in vitamin D activation and function.” The Journal of the American Osteopathic Association, vol. 118, no. 3 (March 1, 2018): 181-189
  4. Welch AA et al. “Dietary magnesium may be protective for aging of bone and skeletal muscle in middle and younger older age men and women: cross-sectional findings from the UK Biobank Cohort.” Nutrients. Published online October 30, 2017.
  5. Daneault A et al. “Biological effect of hydrolyzed collagen on bone metabolism.” Critical Reviews in Food Science and Nutrition, vol. 57, no. 9 (June 13, 2017): 1922-1937
  6. Porfírio E et al. “Collagen supplementation as a complementary therapy for the prevention and treatment of osteoporosis and osteoarthritis: a systematic review.” Revista Brasileira de Geriatria e Gerontologia, vol. 19, no. 1 (January/February 2016)
  7. Liu J et al. “Bovine collagen peptides compounds promote the proliferation and differentiation of MC3T3-E1 pre-osteoblasts.” PLoS One. Published online June 13, 2014.
  8. König D et al. “Specific collagen peptides improve bone mineral density and bone markers in postmenopausal women—a randomized controlled study.” Nutrients. Published online January 16, 2018.
  9. Akbari S et al. “Vitamin K and bone metabolism: a review of the latest evidence in preclinical studies.” BioMed Research International. Published online June 27, 2018.
  10. 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
  11. Rønn SH et al. “Vitamin K2 (menaquinone-7) prevents age-related deterioration of trabecular bone microarchitecture at the tibia in postmenopausal women.” European Journal of Endocrinology, vol. 175, no. 6 (December 2016): 541-549