Relationships between iodine nutrition status, and bone mineral density and bone metabolism: a cross-sectional study of 1207 thyroid disease-free adults in China

There is a history of those with thyroid issues being encouraged to take iodine supplementation. Indeed, at the level of iodised salt, this is often national policy. (Though not in the UK.)

However, some sources encourage consumption of iodine in quantities far greater than the highest levels found in diet. Japan is often quoted as having the highest population intake of iodine of any of the larger countries of the world - typically around 3 milligrams a day is quoted.

This paper claims to identify an association between higher iodine intake levels and bone mass density, osteopenia and osteoporosis.

Relationships between iodine nutrition status, and bone mineral density and bone metabolism: a cross-sectional study of 1207 thyroid disease-free adults in China

Published online by Cambridge University Press:  10 April 2025

Zheng Zhou, Jinjin Liu, Baoxiang Li, Yun Chen, Yanhong He, Bingxuan Ren, Qiuyang Wei, Meihui Jin, Yao Chen, Haiyan Gao, Siyuan Wan, Lixiang Liu and Hongmei Shen

Abstract

Little is known about the association between iodine nutrition status and bone health. The present study aimed to explore the connection between iodine nutrition status, bone metabolism parameters, and bone disease (osteopenia and osteoporosis). A cross-sectional survey was conducted involving 391, 395, and 421 adults from iodine fortification areas (IFA), iodine adequate areas (IAA), and iodine excess areas (IEA) of China. Iodine nutrition status, bone metabolism parameters and BMD were measured. Our results showed that, in IEA, the urine iodine concentrations (UIC) and serum iodine concentrations (SIC) were significantly higher than in IAA. BMD and Ca2+ levels were significantly different under different iodine nutrition levels and the BMD were negatively correlated with UIC and SIC. Univariate linear regression showed that gender, age, BMI, menopausal status, smoking status, alcohol consumption, UIC, SIC, free thyroxine, TSH, and alkaline phosphatase were associated with BMD. The prevalence of osteopenia was significantly increased in IEA, UIC ≥ 300µg/L and SIC > 90µg/L groups. UIC ≥ 300µg/L and SIC > 90µg/L were risk factors for BMD T value < -1.0 SD. In conclusion, excess iodine can not only lead to changes in bone metabolism parameters and BMD, but is also a risk factor for osteopenia and osteoporosis. 

Keywords
Water iodine concentrations, BMD, Iodine nutrition, Bone metabolism

Abstract and full paper (as PDF) open access:

DOI:  10.1017/S0007114525000790

https://www.cambridge.org/core/journals/british-journal-of-nutrition/article/relationships-between-iodine-nutrition-status-and-bone-mineral-density-and-bone-metabolism-a-crosssectional-study-of-1207-thyroid-diseasefree-adults-in-china/B98904C377A39F1D7EBA2BE9485971DC

TSH inhibits osteoclast differentiation through AMPK signaling pathway

There are many reasons to question this paper. Not least that the research is in specific strain of mice which have had genetic modification. Doesn't necessarily invalidate the paper but does require careful assessment - more than we can achieve with the limited access.

If TSH levels such as those without thyroid issues exhibit are sufficient to make such an impact as appears to be claimed, then we need to consider many issues beyond the usual insistence that we lower our doses of thyroid hormone to achieve a TSH in - let us suggest - a range like 0.5 to 2.0.

Of course, even if that range were agreed, we have to ask whether it is likely that having four times as much TSH (at 2.0) as the lower level (0.5) is entirely acceptable. And we need to investigate with urgency whether TSH levels of 5, 10 or more have their own negative effects. Remember, we are told that many who are hypothyroid should not be treated until TSH reaches 10. Or to look at that the other way round, twenty times as much TSH as is needed 

We also need to suggest that those who cannot secrete sufficient TSH should receive continuing dosing with TSH. For example, those who have pituitary issues. And question what to do in subclinical hyperthyroidism? The obvious inference being that if they are sufficiently hyperthyroid to have a low/suppressed TSH, then they would need to be treated without waiting for overt hyperthyroidism. (Though the question of which treatment is another matter.) With a similar issue arising in those who have had suppressed TSH due to overt hyperthyroidism, or relatively high doses of thyroid hormone as has long been prescribed post-cancer treatment.

Mention of the AMPK signaling pathway is also of interest because AMPK is influenced by thyroid hormone. Therefore we see that while AMPK is activated by TSH it is also increased by thyroid hormone treatment. You cannot look at the effect of TSH without also looking at the effects of thyroid hormone. Perhaps they balance out? Or it might be necessary to look at all twelve variants of AMPK?

I suggest that the worst of all worlds might occur when someone has low TSH in conjunction with low thyroid hormone levels. A state which occurs when patients are dosed by TSH alone when their TSH level, for whatever reason, fails to rise.

Also important to consider that there are numerous slightly different forms of TSH. Treating them as all having an identical effect is questionable.

TSH inhibits osteoclast differentiation through AMPK signaling pathway

Wenwen Zhang a b c d e 1, Yu Chen a b c d e 1, Yan Wang a b c d e, Yanman Zhou f, Honglin Guo a b c d e g, Jin Xu a b c d e

Received 8 January 2025, Revised 13 March 2025, Accepted 24 March 2025, Available online 27 March 2025, Version of Record 1 April 2025.

Abstract

Purpose

It is believed that osteoporosis (OP) is associated with hyperthyroidism as a result of the elevation in thyroxine levels. However, patients with subclinical hyperthyroidism, which is characterized by decreased levels of thyroid-stimulating hormone (TSH) alone, are at equal risk of osteoporosis. Research has shown that TSH receptor (TSHR) is expressed on osteoclasts, but whether TSH directly regulates osteoclasts and the underlying mechanisms remain unclear.

Methods

In this study, we used osteoclast precursor cell conditional TSHR-knockout (TSHR CKO) mouse to study the effects of TSHR knockout on bone metabolism in mice and the changes in osteoclast differentiation in vitro. Transcriptomics was used to identify differentially expressed genes and signaling pathways.

Results

In vitro, experiments confirmed that TSH inhibited osteoclast differentiation in mouse RAW264.7 monocyte/macrophage cell line and targeted the key signaling pathway AMPK by RNA-seq sequencing. We found TSHR CKO mice exhibited decreased femoral biomechanics and damaged bone microstructure. The serum levels of bone resorption marker were increased, accompanied by an increase in the number of osteoclasts.

Conclusion

TSH inhibits osteoclast differentiation by activating the AMPK signaling pathway, and exerts an osteoprotective effect. This study will provide guidance for the diagnosis and treatment of osteoporosis. TSH structural analogs or AMPK activators are expected to provide new ideas for the development of drugs to prevent and treat osteoporosis.

Limited access to abstract and a few key points:

https://www.sciencedirect.com/science/article/abs/pii/S0378111925002306