Life Extension Magazine®
Man holding hip due to vitamin D deficient fracture

Fracture Prevention

A startling 50% of women and 20% of men will experience an osteo-porotic fracture after age 49. The enormity of suffering and mortality has generated studies seeking ways to reduce bone fracture risk.

By William Faloon.

William Faloon
William Faloon

A report published in the Journal of the American Medical Association analyzed the degree of osteoporotic fracture reduction that occurred in response to vitamin D and calcium supplementation.1

This meta-analysis found that combining low doses ofvitamin D (400 IU to800 IU) with high calcium intake (1,000 mg to 1,200 mg) reduced risk of any fracture by 6% and hip fracture by 16%.

The problem is that more than two million fractures occur each year in the United States related to osteoporosis.2

If people rely only on calcium and vitamin D, this means 1.9 million fractures will continue to occur each year.

To put today’s vitamin D deficit in perspective,baseline vitamin D blood levels in the vitamin D only segment of this meta-analysis ranged from 10.6 ng/mL to 26.3 ng/mL.

This is far less than the 50 ng/mL to 80 ng/mL of 25-hydroxyvitamin D blood levels that many groups consider optimal.

Observational studies included in this meta-analysis found that for each10 ng/mL increase in25-hydroxyvitamin D there was an associated 7%reduced relative risk for any fracture and20% reduced relative risk for hip fracture.

The analysis published in the Journal of American Medical Association (JAMA) further validates how low-cost nutrients can decrease today’s osteoporosis/ fracture epidemic.

This editorial describes other methods to lower fracture risk.

Insufficient Potencies

The expectation that calcium and/or vitamin D can meaningfully protect against osteoporosis and fracture risk has caused a lot of studies to be designed in ways that often fail to show comprehensive bone benefits.

A meta-analysis published in JAMA showed a reduced fracture risk in response to vitamin D and calcium supplements. There was no benefit when taking vitamin D alone.1

A look at studies on vitamin D supplementation alone (included in this analysis) reveals baseline vitamin D blood levels ranging from deficiency at 10.6ng/mL to an insufficient level of 26.3 ng/mL of 25-hydroxyvitamin D.

The average vitamin D3 dose used in these studies was 833 IU a day.

Among the clinical trials in the vitamin D-only part of the meta-analysis, this low vitamin D dose (833 IU/day) was associated with a median blood level change of 8.4 ng/mL of 25-hydroxyvitamin D.

This means virtually none of the people evaluated in the JAMA study achieved optimal blood levels of 25-hydroxyvitamin D.

Studies using low potencies have been the subject of misguided media reports claiming there is no value to taking bone-building supplements.

The reality is no single nutrient can be counted on to maintainbone integrity when confrontedwith the degenerative changes that occur with normal skeletal aging.

Vitamin Deficits Increase Fractures

Doctor examining x-ray of hand

A 2019 study linked vitamin K deficits and other deficiencies to increased fracture rates.3

In this study, a Japanese group looked at associations of multiple vitamin deficiencies and incident fractures in women.3

They used homocysteine blood levels as an indicator of B-vitamin status. Homocysteine is higher in people deficient in certain B-vitamins.

Blood levels of 25-hydroxy-vitamin D were used to assess vitamin D status.

Vitamin K status was evaluated by measuring a protein (undercarboxylated osteocalcin) that vitamin K favorably influences to maintain bone density.

The human study subjects were divided into four groups:

  • No vitamin deficiency
  • Single deficiency (of either vitamin D, vitamin K or B-vitamins)
  • Double deficiencies (of either vitamin D, vitamin K or B-vitamins)
  • Triple deficiencies (of vitamin D, vitamin K and B-vitamins)

A total of 889 women were included in this analysis, with an average age of about 68 and average follow-up of about 6.3 years.

Incident fractures were observed in 29.7% of subjects This finding alone shows how frequent fractures are in women averaging only 68 years.

The study found that the number ofvitamin deficiencies was associated with a25% increased risk of incident fracture. This association persisted even after adjustment for sources of potential confounding.

The authors of this study concluded:

“Accumulation of vitamin deficiencies was related to incident fractures.”

This study supports data Life Extension® reported in the 1990s showing the role of vitamin/mineral deficiencies in osteoporosis and fracture risk.4

Warfarin Users Beware

Woman taking warfarin pill

Those with atrial fibrillation, aortic valve replacement, deep vein thrombosis, and other conditions require powerful anti-coagulant drugs to reduce the risk of a clot forming inside a blood vessel (thrombosis).

For decades, the drug of choice in these situations was a vitamin K antagonist drug called warfarin (Coumadin®). Warfarin works by inhibiting the synthesis and activation of vitamin K.5,6

Not only does warfarin disable beneficial vitamin K activity (such as keeping calcium in bones and out of arteries), but warfarin users are put on strict diets that are extremely low in vitamin K.

As a result, long-term warfarin users may suffer vascular calcification and bone loss, as has been shown in some studies.7,8

Fractures in Warfarin Users

A study published in October 2019, conducted in Denmark, looked at osteoporotic fracture incidence in people prescribed various types of anti-coagulant drugs. Warfarin was the only vitamin K antagonist drug while the other drugs did not have vitamin K antagonistic effects.9

This study found overall fracture risk was low in this population, but that those prescribed non-warfarin anticoagulant drugs (like Xarelto® and Eliquis®) had significantly lower risk of osteoporotic fractures.

A similar study published in January 2020 conducted in Taiwan looked at atrial fibrillation patients treated with warfarin or non-vitamin K antagonist drugs.10

Compared to warfarin treatment, drugs that did not block vitamin K were associated with an 18% lower risk of osteoporosis.

The box at the top of this column shows the data obtained in the sub-group analysis of this study relating to different anti-coagulant drugs.

The study authors noted the lower osteoporosis risk became significantly better in those with longer treatment duration and concluded:

“Compared with warfarin, rivaroxaban and apixaban were associated with a significantly lower risk of osteoporosis in patients with atrial fibrillation.”

Life Extension® has suggested for decades that warfarin users consult their doctor about supplementing with a low dose of vitamin K2 (45 mcg a day) and adjusting warfarin dose slightly upward to maintain desired INR/pro-thrombin time levels. This can enable one to achieve anti-coagulant benefits without completely depriving the body of vitamin K. More about vitamin K and warfarin can be reviewed at: www.LifeExtension.com/warfarin

Effect of Vitamin K on Bone Density and Fractures

As scientific debates continue, studies published in 2019-2020 point to a role that vitamin K has in maintaining healthy bones.

One meta-analysis of randomized, controlled trials found that the odds for a clinical fracture were lower in those supplementing with vitamin K compared to controls.11

Protecting Bone Marrow

Formation of cells within bone marrow

The spongy tissue inside our bones is known as thebone marrow. It contains stem cells that can develop into immune cells, red blood cells, mesenchymal stem cells, and platelets.

Given the involvement of bone-marrow-derived cells in the maintenance and formation of the different blood cellular components, a group of researchers investigated how the vitamin K antagonist drug warfarin can adversely impact the bone marrow microenvironment including mesenchymal stem cells, macrophage immune cells and vital hematopoietic stem cells.13

Using various in vitro assays, this group showed how vitamin K antagonists adversely alter bone physiology and cause a staggering eight-fold reduction in functional hematopoietic stem cells.

These scientists pointed out that vitamin K antagonist drugs (like warfarin) are not directly toxic to hematopoietic stem cells but impair them via other mechanisms.

Without providing a causal link, this paper associates the use of vitamin K antagonists with a potential increased risk of myelodysplastic syndrome.

About three out of every 10 patients with myelodysplastic syndrome (about 30%) develop leukemia,14 which is notoriously difficult to treat.

More human research is needed to assess the ability of vitamin K in maintaining healthy bone marrow.

The authors of this same study, however, said there was “insufficient” evidence to confirm these findings in post-menopausal or osteoporotic patients and that:

“There are too few trials to draw conclusions for other patient groups.”

My rebuttal to these pessimistic conclusions is that many vitamin K trials use lower-than-optimal doses of vitamin K and some use only vitamin K1, which does not convert into vitamin K2 in all persons.12

And of course, I would never say vitamin K2 by itself is enough to provide comprehensive skeletal support, as evidenced by the Japanese study cited earlier whereby multiple nutrient deficiencies markedly increase fracture incidence.

Review of Accumulated Evidence

A review of the accumulated evidence that vitamin K plays a protective role in age-related disorders such as cardiovascular disease, osteoarthritis and osteoporosis was published in August 2019.15

This assessment identified novel roles that have emerged for vitamin K that extend beyond its ability to keep calcium in bones and out of one’s arteries and soft tissues.

Of interest was evidence that vitamin K reduces “inflammaging” by suppressing NF-kB (nuclear factor-kappa B).15

This 2019 review highlights the valuable whole-body benefits that can be attained with proper vitamin K status.

Bones Need Hormones

The major regulator of bone remodeling in men and women is the sex hormone estrogen.16

Other hormones that influence bone density include testosterone, DHEA, and growth hormone.17,18

With aging, many of these hormone levels plummet and accelerate loss of bone density.

Many men and women use bioidentical hormone replacement therapy to maintain youthful hormone levels and support healthy bones.

Comprehensive blood tests enable maturing men and women to achieve optimal hormone balance.

Pregnenolone is a “mother” hormone that can cascade in the body into bone-supporting hormones estrogen, progesterone, testosterone, and DHEA.

A review article published in 2020 describes many of the anti-aging properties of DHEA including its potential to help maintain strong bones.17

Restore Bone Integrity

Doctor talking with patient on bone loss

No single therapy adequately protects against skeletal deterioration that occurs with normal aging.

A comprehensive set of interventions should be considered, including cutting back on unhealthy lifestyle choices and ensuring that adequate potencies of every bone-building nutrient and hormone are consumed.

Some individuals may wish to consider bioidentical hormone replacement to ensure optimal hormone balance.

I know that many of you are engaging in intermittent fasting or other forms of reduced calorie intake.

While there are enormous benefits to these practices, a potential downside is that one may not ingest enough calcium, magnesium, boron, vitamins D and K, and other nutrients required to maintain bone density.

The good news for consumers is that bone-building, multi-nutrient formulas are affordable because the ingredients they contain (calcium + magnesium + boron + vitamins D + K) are not expensive.

You can further enhance bone health by avoiding lifestyle factors that increase fracture risk and discuss with your doctor whether any of your medications (such as warfarin or proton pump inhibitors) might be undermining your bone strength.

What Causes Bone Loss?

Bone is living tissue that undergoes a continual self-regeneration process called remodeling. Remodeling removes old bone and replaces it with new bone.19,20

With aging this balance shifts to favor greater boneremoval (resorption) and less new bone formation.

The result is osteoporosis and increased fracture risk.21

A variety of factors markedly accelerate loss of bone density and strength. Of course menopause is one, but also the use of drugs likecorticosteroids and proton-pump inhibitors (PPIs), smoking tobacco, drinking excess alcohol, and anti-testosterone treatment for prostate cancer (known as hormone ablation) are a few of the most notable culprits.22-25

Weight-bearing exercise, good nutrition, and maintaining hormone balance help protect aging bones.26,27

Health-conscious individuals are often surprised when a bone density test reveals osteopenia (loss of bone density, but not to a degree that increases fracture risk) or osteoporosis (deterioration in bone density with increased fracture risk).28

Maturing people should recognize that bone density peaks early in life (between 18-30 years) and progressively declines thereafter.29

In This Month’s Issue…

Doctor overlooking brain scans

Calorie restriction can extend healthy longevity, but few people consistently adhere to reduced food intake. Certain nutrients are discussed on page 36 that mimic biological effects that occur in response to reduced food intake.

A hallmark of cellular aging is damaged DNA. An article on page 58 describes the ability of tocotrienols to protect against DNA damage that accelerates systemic aging.

If you wonder where all this is leading, page 48 has an exclusive interview with Harvard geneticist Dr. George Church who is developing gene therapies aimed at eliminating all human viruses and reversing biological aging.

The steps taken to protect against degenerative aging today will enable more of you to benefit from extended healthy lifespans that may be less than 10 years away.

For longer life,

For Longer Life

William Faloon

References

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2. Myneni VD, Mezey E. Regulation of bone remodeling by vitamin K2. Oral Dis. 2017 Nov;23(8):1021-8.

3. Kuroda T, Uenishi K, Ohta H, et al. Multiple vitamin deficiencies additively increase the risk of incident fractures in Japanese postmenopausal women. Osteoporos Int. 2019 Mar;30(3):593-9.

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10. Huang HK, Liu PP, Hsu JY, et al. Risk of Osteoporosis in Patients With Atrial Fibrillation Using Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin. J Am Heart Assoc. 2020 Jan 21;9(2):e013845.

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14. Available at: https://www.cancer.org/cancer/myelodysplastic-syndrome/about/what-is-mds.html. Accessed June 30, 2020.

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19. Kylmaoja E, Nakamura M, Tuukkanen J. Osteoclasts and Remodeling Based Bone Formation. Curr Stem Cell Res Ther. 2016;11(8):626-33.

20. Prior JC. Progesterone for the prevention and treatment of osteoporosis in women. Climacteric. 2018 Aug;21(4):366-74.

21. Almeida M. Aging mechanisms in bone. Bonekey Rep. 2012 Jul 1;1:102.

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24. Andersen BN, Johansen PB, Abrahamsen B. Proton pump inhibitors and osteoporosis. Curr Opin Rheumatol. 2016 Jul;28(4):420-5.

25. Lipton A, Smith MR, Ellis GK, et al. Treatment-induced bone loss and fractures in cancer patients undergoing hormone ablation therapy: efficacy and safety of denosumab. Clin Med Insights Oncol. 2012;6:287-303.

26. Daly RM. Exercise and nutritional approaches to prevent frail bones, falls and fractures: an update. Climacteric. 2017 Apr;20(2):119-24.

27. Kalkan R, Tulay P. The Interactions between Bone Remodelling, Estrogen Hormone and EPH Family Genes. Crit Rev Eukaryot Gene Expr. 2018;28(2):135-8.

28. Available at: https://www.ncbi.nlm.nih.gov/books/NBK499878/. Accessed July 6, 2020.

29. Weaver CM, Gordon CM, Janz KF, et al. The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016 Apr;27(4):1281-386.