Vitamin K: High Doses of MK-4 and MK-7 Show Promising Results

@daisy17 - I agree w/you re: the lack of FDA approval NOT negating possible benefits. My integrative dr is considering LDN low-dose naltrexone to address my rising TPO thyroid antibodies numbers.

I've read numerous articles on MK-4, the Japanese studies, etc. What I can't seem to find is whether or not the therapeutic dose is sufficient to maintain gains following a bone drug. I suspect there would be a blunting effect for a few months while the drug is dissipating, but will the MK-4 eventually 'catch up' with the gains?

@dmr4ever
Thank you for sharing.

Regarding supplementation - Doctors are clear about taking calcium and vitamin D which are not FDA approved medications but supplements. When I asked about vitamin K for bone health I was told "no proven benefit". I take that to mean no proper studies, clinical trials etc. like they have to do with prescription drugs for results? It is a bit confusing that calcium and D (sometimes by prescription) are highly recommended but not K? Osteoporosis treatment is vague; I take K anyway.

@jozer
I take: 180mcg Menaquinone-7 (MK7) - TrueVantage brand and
45,000 mcg (45 mg) of vitamin K2 (menaquinone-4) - Life Extension K2 High Potency brand

I don't think doctors have much interest in vitamins and supplements, other than calcium and Vitamin D. Japan has done studies that found Vit K is beneficial.

Here's a study published by the National Library of Medicine in 2022 that says:
"6. Conclusions
VK supplements showed a small impact on the BMD in postmenopausal or osteoporotic females. A clinically significant effect was seen on clinical and vertebral fractures. The additive effect of VK was found more efficacious. It is positively effective when used in combination or with concomitant therapy. However, the VK2 form displayed a major role in bone formation and was found more effective than its other forms. The meta-analysis of the studies concluded that VK helps to decrease the overall fracture risk, but little evidence showed an insignificant effect on BMD. Long-term use of VK with high dose intake proved to have a beneficial role in increasing BMD and helping to reduce fracture risk in adults. Therefore, more studies are required to strengthen the support of VK as an anti-osteoporotic treatment.
https://pmc.ncbi.nlm.nih.gov/articles/PMC9138595/

@daisy17 What is interesting to me is that bisphosphonates are found to increase BMD but studies shows they offer minimal fracture prevention benefits.

On the other hand, this study says that Vit K may not increase BMD but offers benefits in preventing fractures.

BMD is important, but more important is fracture prevention.

@daisy17 BMD is important; it is what we measure and medicate according to results but the only reason (I think?) we treat osteoporosis is to prevent fractures...or am I missing something?!? I believe the goal first and foremost is to prevent fractures (why else would we medicate) and the resulting disability that can come with them.

@jozer @daisy17 You can see the related 2025 FDA change in what they accept for drug development, swapping fracture risk for BMD change. I applaud the goal of getting new, hopefully better, drugs faster. Not sure about what the unintended consequences of this will be.

FDA Qualifies Total Hip Bone Mineral Density (BMD) as Surrogate Endpoint for Osteoporosis Drug Development
https://www.fda.gov/drugs/drug-safety-and-availability/fda-qualifies-total-hip-bone-mineral-density-bmd-surrogate-endpoint-osteoporosis-drug-development
EXCERPT: " ... percentage change from baseline at 24 months in total hip BMD ... . This biomarker can be used as a validated surrogate endpoint for assessment of investigational therapies for post-menopausal women with osteoporosis at risk for fracture in phase 3 clinical trials, providing an alternative to fracture endpoints."

@kfhoz Wow, that is interesting. The reasoning was to make it easier for drug companies to get their drugs to market because it won't take as long for them to conduct studies on a drug's effectiveness or possible harm. But isn't the real goal of any bone drug to reduce fractures? I mean, if your BMD improves on the DEXA test, but your bone isn't stronger so fractures will be prevented, what is the benefit to the patient?

Personally, I don't see this as good news for patients. Many of us already distrust the drug companies that now have bone drugs on the market because they or doctors don't adequately inform patients of the side effects and what fracture benefit the patient will receive. If BMD improves, but we are left with bones that are not only not stronger, but possibly weaker, the only ones benefitting are the drug companies.

This article explains (please note the comment about fluoride): "Moving from doing trials with fractures as the endpoint to a surrogate marker, which could be BMD after 24 months, is going to change the opportunities for pharma to produce new drugs for osteoporosis. We’ve had no new drugs since 2019 because the companies won’t make that investment,” said Bente Langdahl, MD, PhD... a clinical professor endocrinology and internal medicine in Denmark.

Historically, the need for fracture risk reduction as an endpoint grew out of clinical trials of fluoride treatments, according to Langdahl. The fluoride was incorporated into bone, but unexpectedly it led to poor bone quality that actually increased the risk of fracture. “That was a scare. Before that, you could have a drug approved by BMD changes, but because of that specific drug, FDA and EMA [European Medicines Agency] and all the other regulatory agencies said, ‘that’s not good enough.’ But now, so much more is done before the studies with respect to bone quality analysis in animals, so we know it’s not fragile bone they [build]. So maybe now is the correct time” to reestablish surrogate markers, she said."
https://www.medscape.com/viewarticle/what-bmds-impact-surrogate-osteoporosis-endpoint-2025a1000p2b

@kfhoz I've already replied to your comment, but have been thinking about this ever since. New FDA guidelines allow drug companies to market new bone drugs without providing proof that taking them will result in fewer fractures. The drug companies only have to prove that the drugs raise BMD (bone mineral density). It's then assumed that higher BMD will most likely result in fewer fractures.

We already know that the newer bone drugs are so expensive that most health insurance policies won't cover them, as they can cost thousands of dollars a month. Meaning these drugs are very profitable for the drug companies.

Also, studies have shown that at least 50% of individuals over the age of 50 who experience a fracture do not have osteoporosis. This indicates that fractures can occur even in those with normal bone density. https://academic.oup.com/jcem/article/104/8/3514/5427152

We also know that the FDA has been known to approve medications without requiring the drug manufacturers to actually prove that they work -- or that they won't cause undue harm. https://www.msn.com/en-us/health/other/the-fda-is-approving-drugs-without-evidence-they-work/ar-AA1G9znW

This doesn't make me feel very hopeful or have trust in any current or new bone meds.

@daisy17 I also have some misgivings about the FDA changes, but the goal is to make the medications less expensive to trial and thus maybe more option and less expensive for us. I have been a tiny bit involved in medical research and doubt that the individual drugs as profitable as they seem on the surface. It is amazingly expensive to develop and trial a drug. Most drugs fail to get approved, and the successful ones have to cover the costs of all of the failures.

EXAMPLE: The history of strontium ranelate for osteoporosis is a sad chapter on many fronts. The drug company could not do the expensive trials on better-known strontium citrate SrC because there is no way for them to get their money back. Not-for-profit entities do not have enough funds to do full RCT out to fracture risk. I doubt that the change in the FDA policy will be sufficient for SrC research to be publicly funded, but it is a step in that direction. Note: I do not take strontium because of insufficient research. But it might work and I wish someone could do more research.