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Iron overload diseases are commonly associated with low bone mass. Increased bone resorption by osteoclasts as well as decreased bone formation by osteoblasts have been implicated in bone loss under iron overload conditions. However, the exact contribution of individual cell types has not yet been formally tested. In this study, we aimed to investigate the role of osteoclast precursors in iron overload\u2010induced bone loss. To that end, we used clodronate liposomes to deplete phagocytic cells (including macrophages and osteoclast precursors) in male C57BL\/6J mice that were exposed to ferric derisomaltose. Bone microarchitecture and bone turnover were assessed after 4\u2009weeks. The application of clodronate resulted in the efficient depletion of circulating myeloid\u2010lineage cells by about 70%. Depletion of osteoclast precursors mitigated iron overload\u2010induced trabecular bone loss at the lumbar vertebrae and distal femur. While clodronate treatment led to a profound inhibition of bone turnover in control mice, it significantly reduced osteoclast numbers in iron\u2010treated mice without further impacting the bone formation rate or serum PINP levels. Our observations suggest that even though bone formation is markedly suppressed by iron overload, osteoclasts also play a key role in iron overload\u2010induced bone loss and highlight them as potential therapeutic targets.<\/jats:p>","DOI":"10.1002\/iub.2928","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T12:21:16Z","timestamp":1731932476000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Depletion of macrophages and osteoclast precursors mitigates iron overload\u2010mediated bone loss"],"prefix":"10.1002","volume":"77","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-1575-7827","authenticated-orcid":false,"given":"Vanessa","family":"Passin","sequence":"first","affiliation":[{"name":"Department of Medicine III &amp; Center for Healthy Aging Medical Faculty and University Hospital Carl Gustav Carus, Dresden University of Technology  Dresden 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