Dynamics of Bone Disease Biomarkers Dickkopf-1 and Sclerostin in Patients with Multiple Myeloma
Open accessAbstract
Dickkopf-1 (DKK-1) and sclerostin are essential Wnt/β-catenin pathway inhibitors, playing an important role in multiple myeloma bone disease (MBD). We aimed to examine the serum DKK-1 and sclerostin variations in newly diagnosed multiple myeloma (NDMM) patients at diagnosis and in the course of therapy, including autologous stem cell transplantation (ASCT). This study included 41 NDMM-patients and 33 controls. MBD was assessed by whole-body low-dose computed tomography. DKK-1 and sclerostin were assayed by commercial ELISA kits. At diagnosis, NDMM-patients revealed significantly higher DKK-1 and sclerostin values (p < 0.0001), showing dependence on disease stage (lowest in ISS-I and highest in ISS-III: p < 0.0012 and p < 0.025, respectively, for both proteins). Bone lesions revealed significant positive correlation with both DKK-1 (p < 0.05) and sclerostin (p < 0.0001). In the course of therapy, significant reduction, more prominent after ASCT, was observed for both parameters in each treatment point compared to the baseline (p < 0.0001). Markedly lower sclerostin (p < 0.01) and DKK-1 (p < 0.05) values were observed in patients with complete and very good partial response compared to those with partial response, stable, or progressive disease. Sclerostin and DKK-1 in NDMM patients reflect the MBD severity and the effect of therapy. Both proteins could represent a novel tool for better disease monitoring and effectiveness of therapy.
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Inhibitors targeting DKK1 have shown efficacy in treating MM by restoring Wnt/β-catenin pathway activity.
“Inhibitors targeting DKK1 have shown efficacy in treating MM by restoring Wnt/β-catenin pathway activity [127].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [127]
The Introduction (page not provided) reports that an anti-DKK-1 antibody improved bone formation in a murine MM model. It does not establish efficacy in treating MM patients or directly show restoration of Wnt/β-catenin activity by DKK-1 inhibitors; the reported Wnt stimulation involved a separate Wnt-receptor antibody. (LLM, conf=0.87)
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- Authors
- Gerov, V., Gerova, D., Micheva, I., Nikolova, M., Mihaylova, G., & Galunska, B.
- Affiliations
- University Hospital St. Marina (BG)
- Medical University of Varna (BG)
- Corresponding author
- Gerov, Vladimir
- Venue
- Journal of Clinical Medicine
- Publisher
- MDPI AG
- Published
- 2023-07-01
- Volume
- 12
- Issue
- 13
- Pages
- 4440
- ISSN
- 2077-0383 (ISSN-L)
- PMC
- PMC10342782
- OpenAlex
- W4382940746
- Cited by
- 13
- References
- 40
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 1
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Clinical Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Fund “Science”, Medical University of Varna (ΦH-98/19)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Bone health and treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- DKK1, sclerostin, multiple myeloma, Wnt/β-catenin signaling, autologous stem cell transplantation, serum biomarkers, disease surveillance, treatment response, bone lesions, International Staging System, low-dose CT
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