CR and osteoporosis

[Saul]

Dear ALL,

 

I've just sent an email to Prof. James Whitfield, distinguished retired Prof. of the Canadian CRC in Ottawa -- Prof. Whitfield is one of the world's leading experts on osteoporosis:

 

As you recommended in 2013, I switched from Forteo to Prolia; this showed an improvement in my last Dexa (a little under two years ago); however, according to the former head of Orthopedics here at UR, this improvement is illusory.

After switching to Prolia, I noticed that my nails became much weaker:  Posts in the Calorie Restriction Society Website suggest that this is normal for those practicing Calorie Restriction.

However, I recall that nail strength correlates with bone density -- so to me this suggests the likelihood of
worsened osteoporosis.

Happily, my endocrinologist (Professor Steven Wittlin, Head of Endocrinology at UR Medicine) has put me back on Forteo (at my request).

I've been on daily injections of Forteo for a little under two weeks -- almost immediately, my nails grew hard -- I haven't seen them like this for more years than I can remember.

Also:  My nails are growing faster.  Previously, I didn't need to cut them more than once a month -- now, probably about every 2.5 weeks.

This (almost immediate) change in nails -- harder nails, faster growing nails -- if it translates to bones -- suggests improved changes in bone density, and in growth of new bones -- in other words,  Forteo having
it's usual osteogenic effects.

As usual, I'd very much appreciate your thoughts on that.

Concerning my daughters:  The oldest, Ashira, is halfway through the MD/PhD program at NYU; she is married, with a 5 month old son -- my first grandson!

The youngest, Meira, finished her Bachelor's Degree at UNC Chapel Hill, major Economics, and is currently working for KPMG (a large international tax firm); she has a boyfriend who I fully approve of.

Both daughters, my son-in-law and grandson came to stay with us for the first two days of Passover last weekend.  (Both daughters live in Lower Manhattan.)



  -- Saul

On 02/16/2013 02:27 PM, James Whitfield wrote:

Hi Saul: It seems that for a period Forteo works  but then the response

slows down. This is known to happen. It might be wise to put pauses into the

Forteo treatment. During a pause the bone would regain its osteogenic

responsiveness  to Forteo as you have in fact seen. During the pause you

could try the RANKL blocker. In other words try a pulsed treatment.

How are the girls?

<Jim>

-----Original Message-----

From: Saul Lubkin [

mailto:saul.lubkin@rochester.edu

]

Sent: February-16-13 12:44 PM

To: James F. Whitfield

Cc: Steven Wittlin

Subject: Possibility and wisdom of taking Forteo and with Prolia

Dear Prof. Whitfield,

It's a pleasure to contact you again!  I hope that life has been good to

you, and that your new research interest in Alzheimer's disease has been

progressing well.

My personal reason for writing you concerns, as usual, osteoporosis, about

which you of course continue to be one of the world's leading experts.

Let me describe my current situation:

I've been on Forteo for quite a while, and it's been improving my bone

density at multiple sites.

As I noted, in 2008, my Endocrinologist, Dr. Wittlin, noted little if any

improvement on my dexa.  So I was switched to a biphosphonate.

After 6 months on the biphosphonate, my bone density plummeted.  So, I went

back to Forteo, and bone density began building up again, at a good pace.

And I've been on Forteo up to and including the present.

However, I've had a Dexa last Monday -- and it showed little change in the

spine, a small loss of bonethe femoral necks (-6.4%) and a small gain in the

trochanters (+1.9%).

Dr. Wittlin thought it might be best to switch me to Prolia.

My understanding is that Prolia binds to RANKL, which is expressed by

osteoblasts, preventing RANKL from binding to RANK, expressed by

pre-osteoclasts, and thus preventing the pre-osteoclasts from developing

into osteoclasts, thus reducing the normal bone resorption accomplished by

osteoclasts, and therefore helping -- not really to build new bone, but

reduce the rate at which bone is resorbed.

In this effect, it resembles the effect of biphosphonates; both also reduce

the remodelling rate.

Because of my bad experience with biphosphonates, I am very reluctant to try

a drug that resembles the effect of biphosphonates -- although admittedly by

a very different pathway.

Continuing with Forteo, I think, is likely to at least maintain what gains I

currently have achieved, and prevent rapid loss of bone density.

The possibility has occurred to me of taking BOTH Forteo and Prolia.

I recall that previous studies have shown that, taking both Forteo and

biphosphonates is essentially equivalent to taking biphosphonates alone

-- the effects of Forteo overwhelm those of the biphosphonates.

This suggests to me (correctly or not?) that Forteo combined with Prolia

would not slow the remodelling rate -- my guess is, that the enhanced

remodelling induced by Forteo would persist.  It's possible that the Prolia

might be effective in reducing the rate of maturation of pre-osteoclasts, as

it usually does; and that the combination might thus be effective in growing

bone, in my type of osteoporotic:  A slow remodeller.

Your thoughts on this would be much appreciated -- and if you think that the

combination might be worth a try, I'd like to try it, if possible.

At any rate, it's a pleasure to contact you again; and let me again

congratulate you on your being awarded the much justified title of "Emeritus

Researcher for Life".

    -- Saul

 

[AlPater]

You might be interested in the below paper, Saul.

 

Relationship between bone turnover and density with teriparatide, denosumab or both in women in the DATA study.

Tsai JN, Burnett-Bowie SM, Lee H, Leder BZ.

Bone. 2016 Nov 11;95:20-25. doi: 10.1016/j.bone.2016.11.009. [Epub ahead of print]

PMID: 27840301

http://sci-hub.cc/10.1016/j.bone.2016.11.009

Abstract

BACKGROUND:

While changes in biochemical markers of bone turnover (BTM) have been reported to predict changes in bone mineral density (BMD), the relationship between changes in BMD and BTMs with combined antiresorptive/anabolic therapy is unknown.

METHODS:

In the DATA study, 94 postmenopausal osteoporotic women (ages 51-91) received either teriparatide 20-mcg SC daily, denosumab 60-mg SC every 6months, or both for 2years. Pearson's correlation coefficients ® were calculated to determine the relationship between baseline and early changes in BTMs (as well as serum sclerostin) and 2-year changes in BMD.

RESULTS:

In women receiving teriparatide, baseline BTMs did not correlate with 2-year BMD changes though 12-month increases in osteocalcin and P1NP were associated with 2-year increases in spine BMD. In women receiving denosumab, spine and hip BMD gains correlated with both baseline and changes in P1NP and C-telopeptide. In women receiving combined teriparatide/denosumab, while both baseline and decreases in P1NP were associated with spine BMD gains, distal radius increases were associated with less CTX suppression. Neither baseline nor changes in serum sclerostin correlated with BMD in any treatment group.

SUMMARY AND CONCLUSIONS:

In women treated with teriparatide or denosumab, early BTM changes (increases and decreases, respectively) predict 2-year BMD gains, especially at the spine. In women treated with combined teriparatide/denosumab therapy, BMD increases at the distal radius were associated with less suppression of bone turnover. These results suggest that efficacy of combination therapy at cortical sites such as the radius may depend on residual bone remodeling despite RANKL inhibition.

KEYWORDS:

Bone formation; Bone resorption; Bone turnover markers; Denosumab; Osteoporosis; Teriparatide

[mikeccolella]

Also might be interested in the book "Vitamin k2 -and the calcium paradox."

[James Cain]

i know hormone therapy is contentious, but testosterone replacement therapy could prove useful in your situation. Aging and CR both reduce testosterone, and all of these contribute to reduced BMD, and research shows that TRT increases BMD. There are other considerations such as the potential contribution of TRT to prostate and cardiovascular issues, though I'd say that CR would largely protect you from these concerns, and that if low BMD is the limiting factor in your life quality and potentially long-term health, TRT may be the "least bad" option. It's something to consider, anyway.

[Saul]

Hi James!

Quite honestly, your solution is the least intelligent -- testosterone is globally.anabolic, and will reduce both healthspan and lifespan.

 

Prolia is a.lot better than Fosimax -- I began taking it, after Teriparitide stopped improving bone density. (Prolia and Fosimax both slow remodelling -- hardly a desirable trait -- bones that aren't remodelled sufficiently will tend to develop flaws -- but it'S (at best) a placeholder between Forteo periods.

 

However, happily, Forteo is working for me again, and I'm back to daily injectons!

Dexa showed I lost BMD during the Prolia period, as expected, but not too much.

My BMD is now MUCH BETTER than it was prior to starting Forteo.

(And, my CR'd bones are probably of higher bone quality than an ad libbur with the same BMD.)

-- Saul

[drewab]

Quite honestly, your solution is the least intelligent -- testosterone is globally.anabolic, and will reduce both healthspan and lifespan.

 

 

 

Will it? Where's some of the evidence?

[Saul]

It will.  Search the Forums and archives of the old List.

 

Al?  Can you give him (a couple dozen) Links?

 

Thanks,

 

  --  Saul