Addition of an ARSI to standard ADT significantly increases the risk of fractures and falls in men with prostate cancer

[Graham49]

Jones C, Gray S, Brown M, et al. Risk of fractures and falls in men with advanced or metastatic prostate cancer receiving androgen deprivation therapy and treated with novel androgen receptor signalling inhibitors: a systematic review and meta-analysis of randomised controlled trials. Eur Urol Oncol. Published online February 19, 2024. doi:10.1016/j.euo.2024.01.016

[Cape1]

I don’t see a link

[Graham49 in reply to Cape1]

Risk of Fractures and Falls in Men with Advanced or Metastatic Prostate Cancer Receiving Androgen Deprivation Therapy and Treated with Novel Androgen Receptor Signalling Inhibitors: A Systematic Review and Meta-analysis of Randomised Controlled Trials

Craig Jones a b, Struan Gray a b, Michael Brown b, Janet Brown c, Eugene McCloskey c, Bhavan P. Rai d, Noel Clarke a b, Ashwin Sachdeva a b

doi.org/10.1016/j.euo.2024....

[vintage42]

I think we knew that ADT + ARSI weakened bones. My Uro wanted to me to start the bone agent Prolia as soon as I got on Orgovyx + Abiraterone a few months ago, to get ahead of bone density loss.

I declined after reading Prolia's side effects, wanting to wait until a 1-year DEXA scan. So, should Prolia be taken before or after density loss?

[Jewelrylady in reply to vintage42]

My husband is on Prolia and has had two injections so far with no side effects. I have a friend who is a rehab doctor and she has been on Prolia for 4 years with no side effects. I know everyone responds differently, but it’s good to hear the good, too. Reading about the side effects was so scary, but hearing about my friends experience changed my husbands mind about taking it. He already had osteoporosis before his cancer diagnosis.

[Derf4223]

If one waits, there is another question or 2-3 with taking any med: what are the odds you will no longer be a candidate? My MO told me that blood etc numbers have to be within certain ranges in order to get Prolia. And you can take it to the bank that other illnesses may also exclude someone. IMO the odds of being excluded for these types of reasons are greater than the odds of SE's. In addition, if you are concerned about ONJ risk, that is mitigated by having good regular dental care. My MO required a letter from my dentist in order to start Prolia, and my dentist suggested some work that would have otherwise been delayable then. I've been having dental checkups every 6 months for many years anyway. I know having healthy teeth and gums is a prime disease-preventer on its own rights.

[janebob99]

This is a very important paper. Thanks for bringing it to our attention.

It makes sense that 2nd generation anti-androgens (ARSI's) block the action of testosterone (and likely DHT) at sites in the body other than just the prostate gland (e.g., bone cells). An interesting question is: Does an ARSI also block the action of estrogen at bone cells, since estrogen has a very similar structure to the testosterone molecule? If so, then that would explain the increased rate of fractures in men taking ARSI's.

Bob

[Cooolone]

Thanks for the link... But another Retrospective Study which can as easily identify "Association" as it does here in the thread Title with "Causation" or the implied effect.

When reading the discussion (sect 3.7) it identified such as well. My question is answered when it identified >75yrs of age being in the higher group for bone breaks, identifies the difference with certain therapy, but not vs the general population for this age. Etc.

It is good to see the data, and there's well known association for prolonged ADT and it's effects to the body. Also identified in the discussion is weighing the risk benefit bias of the effectiveness adding the ARSI to treating the PCa.

Hmmmmm... Always a conundrum! Keeps the mind spinning for sure, lol.

Thanks for posting!

[London441]

We know that this combination is hard on the bones, but we also know that for the foreseeable future it is the frontline treatment for metastatic Pca. Bone strengthening drugs work, also at a cost that varies.

Don’t forget the only thing to fight it that you have total control over: weight bearing exercise. Studies about the bone degrading effects of these drugs never look at what and how much patients exercise, but statistically 65%+ do not exercise regularly at all.

Muscle wasting with age eventually degrades bone activity all by itself without the intervention of regular exercise. Inactivity accelerates the process, this is proven . ADT and ARSI drugs is gas on that fire.

Regular resistance training provides patients the opportunity to make a substantial difference, but relatively few do it.

[MomOfMaisy]

My husband’s oncologist keeps wanting to put him on Zometa to strengthen his bones. He also has small mets to scapula and 2 ribs. Before he can go on that, though, he will need to have any dental work taken care of. He needs a dental implant and I know that process can take awhile. His DEXA bone density scan is normal as his Vitamin D level. I’m hoping it will stay normal. He’s a bit afraid of taking it because of the side effect osteonecrosis of the jaw. They say it’s rare, but I’ve read about it from wives of men who have had it.

[j-o-h-n]

With Pca, anyway you turn, you're fucked...............

Good Luck, Good Health and Good Humor.

j-o-h-n

[maley2711 in reply to j-o-h-n]

That about says it all!!!