A Different View on Bone Protection

[MateoBeach]

Replied to a question about bone protective medications on another forum today, and thought it might be of interest to some here at FPC. So pasting it here. Full disclosure: I have been taking denosumab (Prolia or Xgeva) for over 5 years and currently have normal bone density. I also take Calcium supplement daily and Vitamin D3 with K2 when in wintery months when not getting much Sun.

I have a different take on bone protective therapies for us with APC. We know our disease is ultimately progressive and probably will die either with it or from it. By end stage, over 90% will have multiple bone metastasis with often severe pain and pathological fractures.Bone protective medications, chiefly denosumab and zolendronic acid. Are used as treatments for osteopenia/osteoporosis as shown on a DEXA scan. But they also have been shown to reduce those adverse “skeletal related events” in APC.

Furthermore, there is some clinical evidence from trials that these medications may reduce formation of new bone metastasis by altering the bone micro environment. And everyone on long term ADT is at risk for progressive ongoing bone demineralization, despite Ca and Vit D use.

On the other hand there is in erased risk of osteonecrosis of the jaw, ONJ, from these medications. But the risk is on the order of 3%, and is lower if you have good dental status and hygiene. So get to the dentist and have all needed work done before starting. In that case, the benefits appear to far outweigh the risks for those with APC, even if you don’t yet have osteopenia. That is my view and approach: to get out ahead of it and protect my bones preemptively. The lower dose of denosumab, Prolia every six months seems a reasonable conservative approach. Along with regular dental hygiene and care.

Also, after some years on denosumab, when it is stopped ther can be some rebound drop in bone density. So it is a good idea to transition by using an oral bisphosphonate such as weekly alendronate for a period of time, perhaps 6 months.

Be Safe &Well (as Cujoe reminds me) Paul / MB

[cujoe]

Doc Pablo,

I was directed to the full component of nutritional components needed to get calcium into bones (and not in kidneys, joints, and/or arteries) by the prolific-but-now-completely-erased member who spends 1/2 year in FL and 1/2 in NC mtns. In June of 2021 I posted on the topic in response to an erroneous and, IMO, very misleading article in MedPage Today. The thread content of the post is a bit disjointed due to the erased member's missing replies, but the post still contains information pointing to the need of K2, Mg, and B to assure that Ca and D3 are completing their task.

While your post raises issues not addressed in this earlier post, the one from last year does provide a foundation for getting the best results from Ca + D3 supplementation. It is unfortunate that many (most?) PCa and BCa patients are directed to take Ca & D3 without the supporting nutritional elements to "complete their job". I also suggest that PCa patients should be cautious about Ca supplementation due to it being a possible agonist for PCa; i.e., make sure that supplementation + dietary contributions stay under the 1000-1200 mg RDA limit. Here is a link to that post from June of 2021:

With Supplements, ADT in Prostate Cancer of Little Threat to Bone Density - "Ca & Vit D supplementation alone may suffice" . . . Really????

healthunlocked.com/fight-pr...

Here is NIH factsheet for Ca:

ods.od.nih.gov/factsheets/c...

And here is just one of many research papers that implicate Ca and PCa. (This one seems to implicate dairy sources and maybe a U-shaped risk curve for total Ca intake.)

Dairy foods, calcium intakes, and risk of incident prostate cancer in Adventist Health Study-2, American Journal of Clinical Nutrition, 2022 Aug 4.

pubmed.ncbi.nlm.nih.gov/356...

It seems that cold weather has finally arrived here in the mid-Atlantic, so think fondly of us "northeasterners" as you bask in your Cabo sun.

Keep it S&W, Ciao - K9 Terror

[cujoe]

Hey, Casa Pablo-on-the-Beach,

Tonight, someone reminded me of this from 3 years back that is also relevant to your post topic:

New strategies against bone metastases from prostate cancer - Science Daily

healthunlocked.com/fight-pr...

[NPfisherman in reply to cujoe]

K9 Enemy of the State,

A solid article 3 years ago, and still answers needed today. What CPI drugs to choose, and then there is the sequencing issues. Good problems that need answers. We continue to see the markers moved forward towards the elusive chronic disease state. Time will get us there ..

DD

[cujoe in reply to NPfisherman]

NPakaDD,

Your perspective on the article from 3 years ago provides a skin-in-the-game, 1st person perspective. Most valuable to those who follow you, read here, and come to trust your inputs.

Keep it coming. Ciao - K9

[NPfisherman]

Pablito el medico,

While I do not currently take bone protective meds, I do have a dexascan to monitor how the bone health is doing. When I get to osteopenia level, then my MO will put me on Prolia most likely. I am far more interested in being put on Osteodex, which may be the answer for those that have bone mets. This is a drug pointed out to me by TheTopBanana.

Osteodex has passed Phase 2B with flying colors, and just needs to go through Phase 3, but it's all about the Benjamins, and finding a partner for 50+ million dollar investment for the trial. Some info below:

news.cision.com/dextech/r/d...

This could be a real game changer in bony metastasis. Keep an eye on this one... The Science is Coming !!!...when Big Pharma says it will !!!

#$%^&* BIG PHARMA, ETC...

DonP

[MateoBeach in reply to NPfisherman]

yes, looks like they need a deep pocket partner for a Phase 3. Been sitting there since the Phase IIb. Guanine as the cytotoxic component is curious.

dextechmedical.com/en/candi...

[NPfisherman]

Pablito,

I will need to do a deep dive on why guanine, a dna building block...does it disrupt the cancer matrix in bone when added to alendronate?? Thus, toxic to cancer... Hmm ... another cancer mystery...

DD

[MateoBeach in reply to NPfisherman]

perhaps they are actually referring to guanine-quadruplex which is a coordinated structure like a chelator than can carry and deliver an active molecule or isotope? Or variations of G-4 as potential therapeutics?

ncbi.nlm.nih.gov/pmc/articl...

[NPfisherman in reply to MateoBeach]

El Medico,

The G4 complex or quadriplex offers several ways for potential utilization in cancer treatment. As more targets develop and new drugs arrive, it gives me hope that some combination will get us there to chronic disease and eventually...cure.. Thanks for the information. ..

DonP

[MateoBeach]

That is a tough question as there is no clear answer as to when to drop Zometa or Prolia/Xgeva. Up to 5 years might be okay but risks accumulate with time. It is perhaps best to transition to an oral bisphosfonate such as weekly Alendronate or similar for a transition when they are stopped to prevent rebound bone mineral loss. That is my plan, anyway.

[MateoBeach in reply to MateoBeach]

”Life is what happens while we are busy making other plans.”