Thyroid stimulating hormone and bone mineral density: Evidence from a two-sample Mendelian randomization study and a candidate gene association study
March 2018 Journal of Bone and Mineral Research
DOI10.1002/jbmr.3426
Nicolien A van Vliet et al
Abstract
With population aging, prevalence of low bone mineral density (BMD) and associated fracture risk are increased. To determine whether low circulating thyroid stimulating hormone (TSH) levels within the normal range are causally related to BMD, we conducted a two-sample Mendelian randomization (MR) study. Furthermore, we tested whether common genetic variants in the TSH receptor (TSHR) gene and genetic variants influencing expression of TSHR (eQTLs) are associated with BMD. For both analyses, we used summary-level data of genome-wide association studies (GWAS) investigating BMD of the femoral neck (N = 32,735) and the lumbar spine (N = 28,498) in cohorts of European ancestry from the Genetic Factors of Osteoporosis (GEFOS) Consortium. For the MR study, we selected 20 genetic variants that were previously identified for circulating TSH levels in a GWAS meta-analysis (N = 26,420). All independent genetic instruments for TSH were combined in analyses for both femoral neck and lumbar spine BMD. In these studies, we found no evidence that a genetically determined 1 standard deviation (SD) decrease in circulating TSH concentration was associated with femoral neck BMD (0.003 SD decrease in BMD per SD decrease of TSH, 95% C.I. -0.053; 0.048, P = 0.92) or lumbar spine BMD (0.010 SD decrease in BMD per SD decrease of TSH, 95% C.I. -0.069; 0.049, P = 0.73). A total of 706 common genetic variants have been mapped to the TSHR locus and expression loci for TSHR. However, none of these genetic variants were associated with BMD at the femoral neck or lumbar spine. In conclusion, we found no evidence for a causal effect of circulating TSH on BMD, nor did we find any association between genetic variation at the TSHR locus or expression thereof and BMD. This article is protected by copyright. All rights reserved
Written by
diogenes
Remembering
To view profiles and participate in discussions please or .
PHEW! Thank you, Diogenes! The doctor who prescribed NDT whilst I was in US told me that my extremely low TSH was 'exactly where I want you to be', and I came to UK to be told I had given myself osteoporosis because of it and to stop taking the medication. A Dexa revealed I was 'average for my age' so I continue to take NDT by self-medicating. Life is too short to suffer the misery of hypothyroid symptoms.
Thank you Diogenes this is music to my ears as I'm off to see endo on Wednesday and I know my TSH is definitely suppressed so if anything is said I will have this to show them, great!
Will only be slight if at all. Risks don't suddenly jump into reality just because a lower TSH range limit is passed. It's a very gradual change, if indeed there is one at all. Some people may react, others not.
I already have osteopenia because of past hypercalcemia but I need my T4 over the top to convert enough T3, so my TSH is always below range, just have to hope I can dodge further damage if indeed there is any risk. Thanks as always for your expert info.
My wife has been "over the top" for FT4 with undetectable TSH for 50 years. Tests show no bone thinning whatever. So the combination of high FT4 and no bone harm is possible. An anecdote only, I know, but there will be many similar.
THANK YOU ! It's so comforting to read your post . It puts to rest that Dr's that treat us by TSH and scare us with having low TSH can cause osteoporosis is a big humbug . It confirms that the Free-T's are what really counts .
Thank you for this further confirmation: suppressed TSH does not inevitably lead to osteoporosis.
This is welcome evidence for those of us who need supraphysiological doses of T3 to overcome peripheral resistance that we need not worry unduly. Our little sub-group of hypos may have other problems to concern us down the line, but we can cross crumbling bones off the list.
Its well known that hyperthyroidism, where TSH is very low or undetectable, gives rise to increased risk of bone thinning. This is due partly to direct action of TSH on osteocytes, cells concerned with bone density. The converse isn't true, that bones thicken on high TSH - one is ill in a way that obviously needs urgent treatment before any such thing could happen
I suspect (but don't know) that high T4 and T3 are related to bone breakdown and when you are hyper they don't get rebuilt correctly. Low TSH from meds when the frees are in range wouldn't have the same effect.
Probably because effects on bone density aren't just related to TSH. We know that in hyperthyroidism, TSH is suppressed and FT3 high. In this case bone density will be affected both by TSH suppression and the extra metabolic activity activated by high FT3. On medication with suppressed TSH, FT3 is "normal" so the joint effects don't apply.
In this case, what are we to do if we suffer from partial peripheral insensitivity to thyroid hormone? Very large doses of T3 are required, which inevitably raise FT3 far above range. The heart tends to respond to T3 long before other tissues do, but beta blockers can help with cardiac overstimulation.
John Lowe didn't find much evidence of overstimulation in his patients with TH resistance (whether peripheral or general resistance). What are your thoughts on this subject?
Sorry, I should have said 'my' heart. Under supervision, I very gradually increased my T3 to 150 mcg once daily (seems to work better) by mid-2016, but then heart rhythm changed to the patternless irregularity that suggests AF. I dropped the dose, of course, but hypo symptoms crept back quite quickly. I suspect I will have to rely on beta blockers if I raise the T3 again to a level that is effective for my general health.
Thanks for you very clear response. I wonder if bouts of large amounts of dumping of thyroid hormones when ones thyroid is dying causing hyper symptoms is identical to hyperthyroidism and has the same negative impact on heart and bones. I presume it must do as I was initially diagnosed as hyperthyroid I told doc they had mixed up my results with someone else! I became extremely agitated a few days later.
Thanks! That makes sense to me given my history. When my TSH was very low on NDT my dexa scan put me in the top 1% of the population for bone density. My bones (ribs) broke when I was undiagnosed for years with hypothyroidism and was undermedicated on Levothyroxine. I seem to be ok on NDT.
Found the original article. Thanks for highlighting it. I'll be keen to share this with my Endocrinologist who is a rather well known name in Thyroid Health. What bothers me more though isn't the Osteoperosis risk that some seem to believe - it's the assumption that suppressed TSH carries Cardiovascular Risk. Neither my GP or my Endo will allow me to keep my TSH as minimal as possible without warning me that my "heart won't like that" ... this is despite the fact I feel ALOT better when TSH is next to zero.
Me too - my heart pains are much reduced with a low TSH and taking NDT. They were almost as bad as prior to diagnosis, on levothyroxine. I have DIO2 gene for poor conversion of T4 to T3 so can only surmise it is the T3 helping my heart work better.
A few years ago Clutter replied to a post of mine about this thus:
Ithink a lot of information on over medication in hypothyroid patients has been extrapolated from high FT3 and suppressed TSH in hyperthyroid patients causing AF and osteporosisas well as research on elderly people (whom I remember were also bedridden, pretty much ) as you mentioned. The Rotterdam Study into atrial fibrillation finds no association between TSH and AF and a meta-analysis of patients with TSH suppressed <0.1 found one extra hip fracture per 1,000 patient-years.
This is going straight to my GP who can’t seem to understand that suppressed TSH is not the end of the world. Mind you he thought T4 was active and T3 inactive and had never even heard of RT3.!
Thank you.
That is so interesting. Are there any links with B12 and folate absorption with bone mineral density? Think I saw a recent post where you could recommend private testing for B12 and
folate deficiency. Hope this isn't a silly question.
Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.
Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.
Bone density Thuroid meds /HRT
New here, undiagnosed, Normal TSH Low T4
