{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:19:40Z","timestamp":1783070380011,"version":"3.54.6"},"reference-count":20,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Global Blood Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Sickle cell disease (SCD), the most common inherited blood disorder in the United States, affects approximately 100,000 individuals annually. A major complication of SCD is sickle cell bone disease, which results in substantial bone loss comparable to osteoporosis. Previous work showed that treatment with GBT1118, a sickle hemoglobin polymerization inhibitor, improved bone formation and reduced bone resorption in humanized SCD mice. However, its effects on bone material and mechanical properties were unknown. To address this, four-month-old control and SCD mice were fed vehicle or GBT1118 chow for two months. Hematocrit levels, significantly reduced in SCD mice of both sexes, were restored by GBT1118 treatment, confirming its efficacy in improving anemia. Raman spectroscopy revealed increased mineral-to-organic matrix ratios in SCD femurs of both sexes and elevated carbonate-to-phosphate ratios in males, none of which were altered by GBT1118. Mechanical testing showed decreases in ultimate stress and Young\u2019s modulus in female SCD femurs, with no significant differences in males nor rescue by GBT1118. Thus, while GBT1118 improved hematological parameters, it failed to restore the impaired bone material properties observed in SCD mice, highlighting the need for additional therapeutic strategies to address bone fragility in sickle cell disease.<\/jats:p>","DOI":"10.3390\/cells15131209","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:59:47Z","timestamp":1783065587000},"page":"1209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["GBT-1118 Rescued Impaired Bone Formation but Failed to Rescue Material Properties in Humanized Sickle-Cell-Disease Murine Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-6855-3664","authenticated-orcid":false,"given":"Kai","family":"Clarke","sequence":"first","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikhil","family":"Menon","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Dental Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7140-254X","authenticated-orcid":false,"given":"Tannin","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Dental Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5187-4427","authenticated-orcid":false,"given":"Alix","family":"Deymier","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Dental Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marja","family":"Hurley","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Department of Medicine, School of Medicine, UConn Health, Farmington, CT 06032, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","first-page":"240","article-title":"GBT1118, a voxelotor analog, protects red blood cells from damage during severe hypoxia","volume":"14","author":"Tarasev","year":"2022","journal-title":"Am. 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