Bone turnover markers (CTX and P1NP): do you have a baseline?

Posted by mayblin @mayblin, Mar 27, 2024

Currently i am on forteo therapy with a couple bone markers tests done. However, I didnt have ctx or p1np tested before the start of forteo as a baseline, regrettably.

It is known that the CTX value varies greatly among different individuals, with a very wide range. For post menopausal women, the range could be 34 - 1037 pg/ml; while for perimenopausal women 34-635 pg/ml. Different labs also have a slight different range values.

CTX, a bone resorption (breakdown) marker, is heavily influenced by a number of factors, such as food intake, circadian variation and exercise/life style, etc.

Bone remodeling is a dynamic and complex process. CTX itself may not fully reveal the whole picture. The bone building marker P1NP, is a lot less influenced by external factors. Taking both into consideration at the same time may shed more lights than looking at CTX or P1NP alone.

For those who had their CTX and P1NP tested before treatment with a bone drug, could you share the results if you don't mind? Thanks a lot!

Interested in more discussions like this? Go to the Osteoporosis & Bone Health Support Group.

@mayblin

Hi @casstk thank you very much for sharing!

There were studies done on the circadian variations in serum CTX. According to one publication, CTX peaked in early morning hours (~5am) and reached a trough around 14:00 in the afternoon. It was not affected by 5 days of bed-rest, by absence of a normal diurnal variation in cortisol production, or by absence of a normal light cycle (blindness). Peak and trough differed in the magnitude of 80% on average.

Your 2024 baseline ctx and p1np were nice, especially with p1np at 72. However if the above observation applies, then your baseline ctx reading probably would turn out to be higher if your blood draw was earlier, say at 8am regardless of your sleeping pattern/schedule. I don't know what other members think, but I felt blood draw at 9:30am is considered late. This being said, it is important to get blood draw at consistent time for proper comparison,

How Long have you been on HRT? What dose and form of estradiol you are using? Are you on testosterone?

The relationship between serum estradiol level and bone effects (specifically on ctx) puzzles me. With a low dose 0.025mg/day transdermal E2 patch, my blood estradiol level moved only a few points to 21 from baseline 18. However, my ctx went down to 163 from 793 at end of forteo treatment. Of course discontinuing forteo had effects on ctx but still, that's a whopping change.

When your tymlos/forteo gets approval, are you planning to use it alone or with HRT as a combination? I'm very interested in hearing this aspect of planning from you. And, please share when your corrected CTX lab result is available if you could. Thank you!

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@mayblin, I take my Forteo at night before bed, then have been having my blood work done at 8AM the next day. I stop all supplements 2 days beforehand. My CTX has been high at 1238 and P1NP was 190. Do you think that I should skip my Forteo shot before my next blood draw so there is no Forteo influence on the results?

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@drsuefowler

@mayblin, I take my Forteo at night before bed, then have been having my blood work done at 8AM the next day. I stop all supplements 2 days beforehand. My CTX has been high at 1238 and P1NP was 190. Do you think that I should skip my Forteo shot before my next blood draw so there is no Forteo influence on the results?

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I took my Tymlos shot before getting bloodwork, and my CTX seemed mysteriously high compared to a prior test. Just to be on the safe side, I'd skip the shot the night before. Missing one day won't matter.

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@drsuefowler

@mayblin, I take my Forteo at night before bed, then have been having my blood work done at 8AM the next day. I stop all supplements 2 days beforehand. My CTX has been high at 1238 and P1NP was 190. Do you think that I should skip my Forteo shot before my next blood draw so there is no Forteo influence on the results?

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@drsuefowler you could try and see if it will make a difference by skipping a dose in the night. The trick is you dont know if changes in new lab results are due to the maneuver in injection timing or passage of time in treatment, unless you do two labs closer together (within a week or two)- one with old dosing time and one with skipping a dose then compare the results. Like @njx58 pointed out, missing a dose won't hurt in the overall treatment. From what i read, dosing adherence were never 100% as some clinical studies tabulated, I can't recall the #% though. I definitely missed a dose here and there but I don't think my end results were affected.

Here is a link for the study of a single dose teriparatide on serum p1np and urine ntx (a similar measure of resorption), scroll down to Fig b and c:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3923119/
Ir seems urine ntx reached a peak between 4-8 hours post one single injection. My thinking is both ctx and p1np are elevated after many months' daily injections of pth analog especially teriparatide, neither bone markers will fluctuate dramatically due to timing of the injection - don't know for sure unless we can get the info from publications. Hope other members chime in with what they know.

High ctx during Forteo (I recall you had high ctx during tymlos as well ?) might be of concern. I have some notes from an endo. Will send them to you when I locate them. They might be useful.

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@loriesco

my thoughts is do more research and you will find out why these markers have to be taken with a grain of salt in the short haul. My specialist only did it because I complained and wanted baselines. Then I read the research, and it is indeed unreliable by themselves. It is just a tool from year to year. Looked at over a few years. You didn't say the break between your testing.
Do a DEXA WITH A TBS SCORE a year apart and see how that looks. I can tell you my regular DEXAS were okay over 20 years with the last one saying I had come out of ostopenia even! Then I had cervical surgery and my C5 fell apart in their hands! I asked the surgeon how it could be and he explained they are standardized tests, and as well, your body bones have different density requirements. Nobody ever did a DEXA on my neck! So don't worry!

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Loriesco, I have a different take on bone markers. And you may be correct.
Bone markers might have helped identify the bone fragility in the cervical neck and you could have been given protective medication in advance of the surgery.
As it was your bone markers in 24 indicate bone loss.
Bone markers in 25 indicate even greater bone loss.
If you took a bisphosphonate your CTX would drop at least 20% P1NP might drop slightly
Most importantly, if you take the coveted Tymlos or Forteo your P1NP WON'T DROP . If the drug is working you'll probably increase P1NP the usual 100% or more.
Since the 1990s bone markers have become reliable with new agents and some standardization.
It seems in your case bone markers would have been more reliable than dxa.
I await your response in good faith.

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@mayblin

@drsuefowler you could try and see if it will make a difference by skipping a dose in the night. The trick is you dont know if changes in new lab results are due to the maneuver in injection timing or passage of time in treatment, unless you do two labs closer together (within a week or two)- one with old dosing time and one with skipping a dose then compare the results. Like @njx58 pointed out, missing a dose won't hurt in the overall treatment. From what i read, dosing adherence were never 100% as some clinical studies tabulated, I can't recall the #% though. I definitely missed a dose here and there but I don't think my end results were affected.

Here is a link for the study of a single dose teriparatide on serum p1np and urine ntx (a similar measure of resorption), scroll down to Fig b and c:
https://pmc.ncbi.nlm.nih.gov/articles/PMC3923119/
Ir seems urine ntx reached a peak between 4-8 hours post one single injection. My thinking is both ctx and p1np are elevated after many months' daily injections of pth analog especially teriparatide, neither bone markers will fluctuate dramatically due to timing of the injection - don't know for sure unless we can get the info from publications. Hope other members chime in with what they know.

High ctx during Forteo (I recall you had high ctx during tymlos as well ?) might be of concern. I have some notes from an endo. Will send them to you when I locate them. They might be useful.

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Thanks @mayblin. I will think about maybe having two blood draws. You are
right though, if I just skipped a dose, I couldn't compare the results with
the previous ones. Yes, my CTX was high with Tymlos as well. The article is
very interesting.

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@njx58

I took my Tymlos shot before getting bloodwork, and my CTX seemed mysteriously high compared to a prior test. Just to be on the safe side, I'd skip the shot the night before. Missing one day won't matter.

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Interesting @njx58 that it looked like the shot increased your CTX right
away. I have already missed a dose a time or two, so I'm not worried about
that. I think the medication stays in my system longer than just 4 hours. I
have been getting the blood work 10 hours after my shot. Thanks for posting.

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I started Tymlos mid October 2024, having had a rebound from discontinuation of 2 1/2 years of Prolia, with oral Boniva following for almost a year, then having 3 vertebral compression fractures within four months. The endocrinologist (I am desperately seeking a new one that knows about osteoporosis!)
did not get a baseline P1NP when I began the Tymlos. Now I know how important it is to have these numbers, so I requested them at the 3 month check. At that time the CTX was 713, the P1NP was 112. Just had them repeated, at 5 mos into Tymlos, and the P1NP is still 112, the CTX is now 635. I do have a baseline CTX at treatment start (Oct) which was 613. So I believe that I am possibly having a good response to the drug bc according to Great Bones there should be an initial rise in CTX and in the P1NP. I pray this is a good result so far. Does anyone have thoughts about my assessment, negative or positive?

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@gently

Loriesco, I have a different take on bone markers. And you may be correct.
Bone markers might have helped identify the bone fragility in the cervical neck and you could have been given protective medication in advance of the surgery.
As it was your bone markers in 24 indicate bone loss.
Bone markers in 25 indicate even greater bone loss.
If you took a bisphosphonate your CTX would drop at least 20% P1NP might drop slightly
Most importantly, if you take the coveted Tymlos or Forteo your P1NP WON'T DROP . If the drug is working you'll probably increase P1NP the usual 100% or more.
Since the 1990s bone markers have become reliable with new agents and some standardization.
It seems in your case bone markers would have been more reliable than dxa.
I await your response in good faith.

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Hi @gently, I am a little confused. And, maybe my post wasn't clear enough. It had to be read in contect to the previous message. I was responding to the concern about having baselines for the P1NP and CTX. My doctor didn't offer the baseline but gave it to me when I asked. After i had done more reading I remember reading how it wasn't critical or definitive. So it made sense why my very serious doctor wasn't concerned about doing them. My surgery was in 2023 and my DEXAs never indicated anything more than osteopenia. In fact - I had come out of it. So the paper-thin cervical vertebrates were a shock to everyone. My bone marker tests were done in 2024 - all of them - the new DEXA with the TBS, the two CTX and P1NPs which looked good after starting the bone meds and things did what they should have over the 6 month interval.
I haven't done anything yet in 2025. So I was confused by "Bone markers in 25 indicate even greater bone loss" . I did one round of Reclast and I'm on the TYMLOS and the CTX and P1NP did what they statistically were supposed to do. (I don't remember off hand what that was).
But my visits to the Orthopedic Surgeon continue to get me summaries of "demineralized" bones along with the MRI reads. So I'll just stay with it all!

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@loriesco

Hi @gently, I am a little confused. And, maybe my post wasn't clear enough. It had to be read in contect to the previous message. I was responding to the concern about having baselines for the P1NP and CTX. My doctor didn't offer the baseline but gave it to me when I asked. After i had done more reading I remember reading how it wasn't critical or definitive. So it made sense why my very serious doctor wasn't concerned about doing them. My surgery was in 2023 and my DEXAs never indicated anything more than osteopenia. In fact - I had come out of it. So the paper-thin cervical vertebrates were a shock to everyone. My bone marker tests were done in 2024 - all of them - the new DEXA with the TBS, the two CTX and P1NPs which looked good after starting the bone meds and things did what they should have over the 6 month interval.
I haven't done anything yet in 2025. So I was confused by "Bone markers in 25 indicate even greater bone loss" . I did one round of Reclast and I'm on the TYMLOS and the CTX and P1NP did what they statistically were supposed to do. (I don't remember off hand what that was).
But my visits to the Orthopedic Surgeon continue to get me summaries of "demineralized" bones along with the MRI reads. So I'll just stay with it all!

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loriesco the summaries of demineralized bones sounds very interesting. Can you tell me more. Do these summaries include, well, which bones. Could they have done this for your neck before the bone-crumbling surgery. It seems like this is a new technique with MRI involving different sequences. I'd be curious about what type of reading you get. Numbers?
Information about bone matrix before surgery is so crucial.
I was responding to the information that on the anabolics P1NP numbers lessen. Which they do after you've been on it for while, plateau at 6 to 12 months and then lessen.
I love the way you "paint the street," with your responses.
How often do you get the summaries.

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@jennirdh

I started Tymlos mid October 2024, having had a rebound from discontinuation of 2 1/2 years of Prolia, with oral Boniva following for almost a year, then having 3 vertebral compression fractures within four months. The endocrinologist (I am desperately seeking a new one that knows about osteoporosis!)
did not get a baseline P1NP when I began the Tymlos. Now I know how important it is to have these numbers, so I requested them at the 3 month check. At that time the CTX was 713, the P1NP was 112. Just had them repeated, at 5 mos into Tymlos, and the P1NP is still 112, the CTX is now 635. I do have a baseline CTX at treatment start (Oct) which was 613. So I believe that I am possibly having a good response to the drug bc according to Great Bones there should be an initial rise in CTX and in the P1NP. I pray this is a good result so far. Does anyone have thoughts about my assessment, negative or positive?

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Hi @jennirdh , I am very sorry to hear that you suffered vertebrae compression fractures related to prolia rebound. Hope you have a speedy and great recovery that lead to minimal aftereffects.

Your bone makers are very interesting and thank you very much for sharing them. Since you had 5 shots of prolia then followed with boniva for 11 months (please correct me if I got this wrong), your bone markers may still reflect some tailend effects of prolia cessation, in other words, they might reflect the combined effects of prolia cessation (end stage) and early stage of tymlos' therapy.

To me, the good news is CTX is stabilizing. I have a neutral view towards your latest two p1np readings as you don't have a baseline. Some people get p1np increase only in early months of tymlos treatment as shown in clinical studies. So your p1np 112 might be the "spike" but there is no baseline to compare with - let's hope this is it! I agree with you on the importance of a baseline. I don't have any either prior to my forteo treatment. Later when I needed it, it was too late. I could've easily used a double dose of estradiol after Forteo which clearly was proven not necessary by bone markers as well as dxa results.

Curious, was your CTX monitored during Boniva?

Wish you the best, and a great success with Tymlos!

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