Reduced Bone Mass and Increased Osteocyte Tartrate-Resistant Acid Phosphatase (TRAP) Activity, But Not Low Mineralized Matrix Around Osteocyte Lacunae, Are Restored After Recovery From Exogenous Hyperthyroidism in Male Mice

Research output: Contribution to journalResearch articleContributedpeer-review


  • Eva Maria Wölfel - , University Hospital Hamburg Eppendorf (Author)
  • Franziska Lademann - , Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Haniyeh Hemmatian - , University Hospital Hamburg Eppendorf (Author)
  • Stéphane Blouin - , Ludwig Boltzmann Institute of Osteology, AUVA Trauma Centre Wien (Author)
  • Phaedra Messmer - , Ludwig Boltzmann Institute of Osteology, AUVA Trauma Centre Wien (Author)
  • Lorenz C Hofbauer - , Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Björn Busse - , University Hospital Hamburg Eppendorf (Author)
  • Martina Rauner - , Department of internal Medicine 3, University Hospital Carl Gustav Carus Dresden (Author)
  • Katharina Jähn-Rickert - , University Hospital Hamburg Eppendorf (Author)
  • Elena Tsourdi - , University Hospital Carl Gustav Carus Dresden, Department of Internal Medicine 3 (Author)


Hyperthyroidism causes secondary osteoporosis through favoring bone resorption over bone formation, leading to bone loss with elevated bone fragility. Osteocytes that reside within lacunae inside the mineralized bone matrix orchestrate the process of bone remodeling and can themselves actively resorb bone upon certain stimuli. Nevertheless, the interaction between thyroid hormones and osteocytes and the impact of hyperthyroidism on osteocyte cell function are still unknown. In a preliminary study, we analyzed bones from male C57BL/6 mice with drug-induced hyperthyroidism, which led to mild osteocytic osteolysis with 1.14-fold larger osteocyte lacunae and by 108.33% higher tartrate-resistant acid phosphatase (TRAP) activity in osteocytes of hyperthyroid mice compared to euthyroid mice. To test whether hyperthyroidism-induced bone changes are reversible, we rendered male mice hyperthyroid by adding levothyroxine into their drinking water for 4 weeks, followed by a weaning period of 4 weeks with access to normal drinking water. Hyperthyroid mice displayed cortical and trabecular bone loss due to high bone turnover, which recovered with weaning. Although canalicular number and osteocyte lacunar area were similar in euthyroid, hyperthyroid and weaned mice, the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL)-positive osteocytes was 100% lower in the weaning group compared to euthyroid mice and the osteocytic TRAP activity was eightfold higher in hyperthyroid animals. The latter, along with a 3.75% lower average mineralization around the osteocyte lacunae in trabecular bone, suggests osteocytic osteolysis activity that, however, did not result in significantly enlarged osteocyte lacunae. In conclusion, we show a recovery of bone microarchitecture and turnover after reversal of hyperthyroidism to a euthyroid state. In contrast, osteocytic osteolysis was initiated in hyperthyroidism, but its effects were not reversed after 4 weeks of weaning. Due to the vast number of osteocytes in bone, we speculate that even minor individual cell functions might contribute to altered bone quality and mineral homeostasis in the setting of hyperthyroidism-induced bone disease. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).


Original languageEnglish
Pages (from-to)131-143
Number of pages13
JournalJournal of Bone and Mineral Research
Issue number1
Publication statusPublished - Jan 2023

External IDs

Scopus 85142382807
WOS 000888219800001
ORCID /0000-0002-8691-8423/work/142236061


Research priority areas of TU Dresden

DFG Classification of Subject Areas according to Review Boards

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  • Mice, Male, Animals, Osteocytes, Osteolysis, Tartrate-Resistant Acid Phosphatase, Drinking Water, Mice, Inbred C57BL, Minerals, Hyperthyroidism/complications, Osteocytic osteolysis, Hyperthyroidism, Bone mineralization, Secondary osteoporosis, OSTEOCYTES, BONE MINERALIZATION, OSTEOCYTIC OSTEOLYSIS, HYPERTHYROIDISM, SECONDARY OSTEOPOROSIS