ArticleExperimental hematology & oncology2025
Healing of lytic lesions and restoration of bone health in multiple myeloma through sclerostin inhibition.
Article in Experimental hematology & oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Protocol for the enrichment of endosteal and periosteal mesenchymal cells from murine bone for single-cell transcriptome analysis.STAR protocols · 2026Article
- Osteocytes in the Metastatic Bone Niche: Mechanistic Pathways and Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeting NOTCH3 to eradicate dormant and therapy-resistant multiple myeloma cells.Journal of experimental & clinical cancer research : CR · 2026Article
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Authors and funding
23 authors.
Funding
Abstract
backgroundMultiple 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.
methodsTo 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.
resultsScl-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.
conclusionsOur 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.
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