Research Paper Volume 13, Issue 17 pp 21029—21039

Familial longevity is associated with lower baseline bone turnover but not differences in bone turnover in response to rhTSH

Ana Zutinic1, , Ferdinand Roelfsema2, , Hanno Pijl2, , Bart E. Ballieux3, , Rudi G.J. Westendorp4, , Gerard J. Blauw1, , Diana van Heemst1, ,

  • 1 Department of Internal Medicine, Division of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands
  • 2 Department of Internal Medicine, Division of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Leiden, The Netherlands
  • 3 Department of Clinical Chemistry and Laboratory Medicine, Leiden University Medical Center, Leiden, The Netherlands
  • 4 Public Health and Centre for Healthy Aging, University of Copenhagen, Copenhagen, Denmark

Received: January 29, 2021       Accepted: August 28, 2021       Published: September 7, 2021
How to Cite

Copyright: © 2021 Zutinic et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Context: Offspring from long-lived families have a different thyroid status than controls, characterised by higher circulating levels of thyroid stimulating hormone (TSH) and similar levels of thyroid hormone. Expression of the TSH receptor has previously been observed on various extrathyroidal tissues, including bone. However, potential physiological consequences of differences in circulating TSH as observed in familial longevity on bone tissue remain unclear.

Objective: Based on the hypothesis that TSH may inhibit bone resorption, we explored whether offspring of long-lived families have lower bone turnover than controls at baseline as well as following a challenge with recombinant human TSH (rhTSH).

Methods: Bone turnover markers CTX and P1NP were measured in fasted morning samples from 14 offspring and 12 controls at baseline and at 24 hour intervals following 0.1 mg rhTSH i.m. administration for four consecutive days.

Results: At baseline, mean (SEM) CTX was 0.32 (0.03) ng/ml in offspring and 0.50 (0.04) ng/ml in controls, p < 0.01, whereas mean (SEM) P1NP was 39.6 (3.2) ng/ml in offspring and 61.8 (6.6) ng/ml in controls, p < 0.01. Following rhTSH administration, both CTX and P1NP levels transiently increased over time and normalized towards baseline after 72 h (general linear modelling: CTX time p = 0.01, P1NP time p < 0.01); the response was similar between offspring and controls.

Conclusions: Bone turnover markers were lower at baseline in offspring from long-lived families than in controls but increased similarly following an rhTSH challenge.


ANOVA: Analysis of variance; ALT: Alanine transaminase; AST: Aspartate transaminase; BMI: Body mass index; CTX: Collagen type 1 C-terminal cross-linked telopeptide; fT4: Free thyroxine; fT3: Free triiodothyronine; GFR: Glomerular filtration rate; GH: Growth hormone; GLM: General linear modelling; LLS: Leiden Longevity Study; P1NP: N-terminal propeptide of type 1 collagen; rhTSH: Recombinant human thyroid stimulating hormone; RRID: Research reference identifier; T3: Triiodothyronine; T4: Thyroxine; Tg: Thyroglobulin; TPO: Thyroid peroxidase; TSH: Thyroid stimulating hormone.