biostudies-literatureSabol HMNIA NIH HHSUAMS Winthrop P. Rockefeller Cancer Institute Voucher ProgramNCI NIH HHSNIGMS NIH HHSNIH HHSNeye Fonden and Aase og Ejnar Danielsens Fond108https://www.ebi.ac.uk/biostudies/studies/S-EPMC12372396biostudies-literatureUnknown14(1)<h4>Background</h4>Multiple myeloma (MM) is associated with a debilitating bone disease that poses significant therapeutic challenges. MM bone disease is characterized by increased bone resorption and suppression of osteoblasts, which hinders the repair of damaged bone. Sclerostin, an antagonist of Wnt signaling, is elevated in MM patients, and its inhibition with a neutralizing antibody (Scl-ab) has been shown to restore osteoblast function in mouse models of MM. However, it remains unclear whether Scl-ab can promote skeletal repair, enable effective tumor control when combined with anti-cancer agents, or improve bone health in MM patients.<h4>Methods</h4>To investigate these knowledge gaps, we used preclinical MM mouse models and patient-derived samples. We also characterize the impact of Scl-ab on cancer and osteoblastic cells isolated from mouse models through bulk and single-cell RNA sequencing. Lastly, we performed a retrospective analysis of the efficacy of Scl-ab to improve bone health in patients with MM in remission.<h4>Results</h4>Scl-ab promoted skeletal repair and enabled tumor suppression by an anti-cancer agent in various animal models of established MM bone disease. MM tumors suppressed Wnt signaling and decreased the number of osteoblasts and osteo-CAR cells, and treatment with Scl-ab reversed these effects. Treatment with Scl-ab increased bone mass and repaired bone in patients with MM in remission, even when combined with maintenance chemotherapy.<h4>Conclusions</h4>Our findings highlight the potent bone-healing effects of Scl-ab and its potential as an adjuvant to anti-cancer therapy, offering a promising approach to improve clinical outcomes and the quality of life for MM patients.Experimental hematology & oncologyHealing of lytic lesions and restoration of bone health in multiple myeloma through sclerostin inhibition.PMC12372396U01 AG075227F31 CA284655NAP20 GM103625P20GM125503P20 GM125503R01 CA209882R01 CA241677R37 CA251763F31CA284655Schinke CHackney JStambough JBBustamante-Gomez CFrontier AAnloague AEbetino FHWardell CPSabol HMNester MRNookaew IKaur JPaxton BCAmbrogini EDrake MTBarnes CLMann DZangari MDelgado-Calle JDiaz-delCastillo Mvan Rhee FKhan SNaqvi SfalseHealing of lytic lesions and restoration of bone health in multiple myeloma through sclerostin inhibition.<h4>Background</h4>Multiple myeloma (MM) is associated with a debilitating bone disease that poses significant therapeutic challenges. MM bone disease is characterized by increased bone resorption and suppression of osteoblasts, which hinders the repair of damaged bone. Sclerostin, an antagonist of Wnt signaling, is elevated in MM patients, and its inhibition with a neutralizing antibody (Scl-ab) has been shown to restore osteoblast function in mouse models of MM. However, it remains unclear whether Scl-ab can promote skeletal repair, enable effective tumor control when combined with anti-cancer agents, or improve bone health in MM patients.<h4>Methods</h4>To investigate these knowledge gaps, we used preclinical MM mouse models and patient-derived samples. We also characterize the impact of Scl-ab on cancer and osteoblastic cells isolated from mouse models through bulk and single-cell RNA sequencing. Lastly, we performed a retrospective analysis of the efficacy of Scl-ab to improve bone health in patients with MM in remission.<h4>Results</h4>Scl-ab promoted skeletal repair and enabled tumor suppression by an anti-cancer agent in various animal models of established MM bone disease. MM tumors suppressed Wnt signaling and decreased the number of osteoblasts and osteo-CAR cells, and treatment with Scl-ab reversed these effects. Treatment with Scl-ab increased bone mass and repaired bone in patients with MM in remission, even when combined with maintenance chemotherapy.<h4>Conclusions</h4>Our findings highlight the potent bone-healing effects of Scl-ab and its potential as an adjuvant to anti-cancer therapy, offering a promising approach to improve clinical outcomes and the quality of life for MM patients.2025-01-01T00:00:00Z2025 Aug2026-06-30T03:25:08.688Z2026-06-30T03:19:55.092ZS-EPMC123723964084732310.1186/s40164-025-00699-4