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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\u2009weeks, followed by a weaning period of 4\u2009weeks 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\u2013mediated 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\u2009weeks 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. \u00a9 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).<\/jats:p>","DOI":"10.1002\/jbmr.4736","type":"journal-article","created":{"date-parts":[[2022,11,4]],"date-time":"2022-11-04T08:06:37Z","timestamp":1667549197000},"page":"131-143","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["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"],"prefix":"10.1093","volume":"38","author":[{"given":"Eva Maria","family":"W\u00f6lfel","sequence":"first","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg 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Department Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phaedra","family":"Messmer","sequence":"additional","affiliation":[{"name":"Vienna Bone and Growth Center Vienna Austria"},{"name":"Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of OEGK and AUVA Trauma Centre Meidling 1st Medical Department Hanusch Hospital Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8691-8423","authenticated-orcid":false,"given":"Lorenz C.","family":"Hofbauer","sequence":"additional","affiliation":[{"name":"Center for Healthy Aging, Technische Universit\u00e4t Dresden Medical Center Dresden Germany"},{"name":"Department of Medicine III Technische Universit\u00e4t Dresden Medical Center Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-8073","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Busse","sequence":"additional","affiliation":[{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rauner","sequence":"additional","affiliation":[{"name":"Center for Healthy Aging, Technische Universit\u00e4t Dresden Medical Center Dresden Germany"},{"name":"Department of Medicine III Technische Universit\u00e4t Dresden Medical Center Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9338-831X","authenticated-orcid":false,"given":"Katharina","family":"J\u00e4hn-Rickert","sequence":"additional","affiliation":[{"name":"Mildred Scheel Cancer Career Center Hamburg, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf Hamburg Germany"},{"name":"Department of Osteology and Biomechanics University Medical Center Hamburg-Eppendorf Hamburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9582-1906","authenticated-orcid":false,"given":"Elena","family":"Tsourdi","sequence":"additional","affiliation":[{"name":"Center for Healthy Aging, Technische Universit\u00e4t Dresden Medical Center Dresden Germany"},{"name":"Department of Medicine III Technische Universit\u00e4t Dresden Medical Center Dresden Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,4]]},"reference":[{"issue":"2","key":"2024012714083933800_jbmr4736-bib-0001","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1210\/endrev\/bnab028","article-title":"Secondary osteoporosis","volume":"43","author":"Ebeling","year":"2022","journal-title":"Endocr 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