Multiple Myeloma: Impact on the Skeletal System - a Review of the Literature
DOI:
https://doi.org/10.12775/QS.2025.48.66878Keywords
multiple myeloma, myeloma bone disease, osteoclastogenesis, osteoblasts, OPG, RANKLAbstract
Background. Multiple myeloma is a cancerous disease of the hematopoietic system marked by the uncontrolled proliferation of monoclonal plasma cells within the bone marrow. Bone disease is a characteristic feature and a diagnostic criterion of multiple myeloma.
Aim. This paper aims to discuss the pathophysiological mechanisms underlying bone damage in multiple myeloma and to present current diagnostic and therapeutic approaches designed to improve clinical outcomes in patients affected by myeloma bone disease.
Material and methods. A review of the scientific literature from the past eight years was conducted using topic-specific keywords, primarily through databases such as PubMed and Google Scholar.
Results. Bone mass loss is a complex process that involves elevated osteoclast activity, impaired osteoblast function, and the release of pro-inflammatory cytokines, resulting in a disruption of the balance between bone resorption and formation. As a consequence, patients may develop chronic bone pain, pathological fractures, and postural changes. Therapeutic strategies that aim to slow the course of the disease and inhibit osteoclast activity are essential for minimizing the risk of skeletal-related complications and markedly enhancing patients' quality of life.
Conclusion. Multiple myeloma is a malignancy that frequently leads to bone damage. This review discusses the underlying mechanisms, diagnostic methods, and current treatments aimed at preventing skeletal complications and improving patient outcomes
References
1. Cowan AJ, Green DJ, Kwok M, et al. Diagnosis and Management of Multiple Myeloma: A Review. JAMA. 2022; 327(5): 464–477, doi: 10.1001/jama.2022.0003
2. Firth J. Haematology: multiple myeloma. Clin Med (Lond). 2019; 19(1): 57–60,
doi: 10.7861/clinmedicine.19-1-58
3. Padala SA, Barsouk A, Barsouk A, et al. Epidemiology, Staging, and Management of Multiple Myeloma. Med Sci (Basel). 2021; 9(1): 3, doi: 10.3390/medsci9010003
4. Silberstein J, Tuchman S, Grant SJ. What is multiple myeloma? JAMA. 2022; 327(5): 497, doi: 10.1001/jama.2021.25306
5. Zamagni E, Cavo M, Fakhri B, et al. Bones in Multiple Myeloma: Imaging and Therapy. Am Soc Clin Oncol Educ Book. 2018; 38: 638–646, doi: 10.1200/EDBK_205583
6. Marino S, Roodman GD. Multiple Myeloma and Bone: The Fatal Interaction. Cold Spring Harb Perspect Med. 2018; 8(8): a031286, doi: 10.1101/cshperspect.a031286
7. Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 Patients With Newly Diagnosed Multiple Myeloma. Mayo Clin Proc. 2003; 78(1): 21–33, doi: 10.4065/78.1.21
8. Bernstein ZS, Kim EB, Raje N. Bone Disease in Multiple Myeloma: Biologic and Clinical Implications. Cells. 2022; 11(15): 2308, doi: 10.3390/cells11152308
9. Dmoszyńska A, Walter-Croneck A, Usnarska-Zubkiewicz L, et al. Zalecenia Polskiej Grupy Szpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowego oraz innych dyskrazji plazmocytowych na rok 2015. Acta Haematol Pol. 2015; 46:159–211, doi: 10.2478/ahp-2018-0024
10. Charliński G, Jurczyszyn A. Non-secretory multiple myeloma: Diagnosis and management. Adv Clin Exp Med. 2022; 31(1): 95–100, doi: 10.17219/acem/141455
11. Gundesen MT, Lund T, Moeller HEH, et al. Plasma Cell Leukemia: Definition, Presentation, and Treatment. Curr Oncol Rep. 2019; 21(1): 8,
doi: 10.1007/s11912-019-0754-x
12. Iqbal QUA, Majid HJ. Plasmacytoma. StatPearls [Internet], StatPearls Publishing, Treasure Island (FL) (2023) (dostęp 2025.11.25)
13. Kaseb H, Annamaraju P, Babiker HM. Monoclonal Gammopathy of Undetermined Significance.StatPearls [Internet], StatPearls Publishing, Treasure Island (FL) (2025) (dostęp 2025.11.25)
14. Pasiarski M, Kowalik A, Stelmach A, et al. Monoclonal gammopathy of undetermined significance – the role of genetic and infectious agents in the pathogenesis of the disease. Acta Haematol Pol. 2014; 45(2): 166–170, doi: 10.1016/j.achaem.2014.04.006
15. Goldschmidt H. Multiples Myelom – bald heilbar? [Multiple myeloma-soon curable?]. Internist (Berl). 2021; 62(5): 562–570, doi: 10.1007/s00108-021-01010-3
16. Salhotra A, Shah HN, Levi B, et al. Mechanisms of bone development and repair. Nat Rev Mol Cell Biol. 2020; 21(11): 696–711, doi: 10.1038/s41580-020-00279-w
17. Zdzisińska B, Kandefer-Szerszeń M. Rola RANK/RANKL i OPG w szpiczaku plazmocytowym. Postepy Hig Med Dosw (Online). 2006; 60: 471–482.
18. Raje NS, Bhatta S, Terpos E. Role of the RANK/RANKL pathway in multiple myeloma. Clin Cancer Res. 2019; 25(1): 12–20, doi: 10.1158/1078-0432.CCR-18-1537
19. Yi L, Gai Y, Chen Z, et al. Macrophage colony-stimulating factor and its role in the tumor microenvironment: novel therapeutic avenues and mechanistic insights. Front Oncol. 2024; 14: 1358750, doi: 10.3389/fonc.2024.1358750
20. Jurczyszyn A, Gdula-Argasińska J, Kosmaczewska A, et al. Rola mikrośrodowiska szpiku kostnego w patogenezie szpiczaka plazmocytowego. Postepy Hig Med Dosw (Online). 2015; 69: 521–533.
21. Roodman GD. Osteoblast function in myeloma. Bone. 2011; 48(1): 135–140,
doi: 10.1016/j.bone.2010.06.016
22. Liu C, Chu D, Kalantar-Zadeh K, et al. Cytokines: From Clinical Significance to Quantification. Adv Sci (Weinh). 2021; 8(15): e2004433, doi: 10.1002/advs.202004433
23. Luo G, Li F, Li X, et al. TNF-α and RANKL promote osteoclastogenesis by upregulating RANK via the NF-κB pathway. Mol Med Rep. 2018; 17(5): 6605–6611,
doi: 10.3892/mmr.2018.8698
24. Zamagni E, Cavo M, Fakhri B, et al. Bones in Multiple Myeloma: Imaging and Therapy. Am Soc Clin Oncol Educ Book. 2018; 38: 638–646, doi: 10.1200/EDBK_205583
25. Giannopoulos K, Jamroziak K, Usnarska-Zubkiewicz L, et al. Zalecenia Polskiej Grupy Szpiczakowej dotyczące rozpoznawania i leczenia szpiczaka plazmocytowego oraz innych dyskrazji plazmocytowych na rok 2022/23. Polska Grupa Szpiczakowa. (dostęp 2025.11.25)
26. Torkian P, Azadbakht J, Bonaffini A, et al. Advanced Imaging in Multiple Myeloma: New Frontiers for MRI. Diagnostics (Basel). 2022; 12(9): 2182,
doi: 10.3390/diagnostics12092182
27. Dmoszyńska A. Leki immunomodulujące – przełom w leczeniu nowotworów hematologicznych. Acta Haematol Pol. 2013; 44(4): 370–377.
28. Cremers S, Drake M, Ebetino F, et al. Pharmacology of bisphosphonates. Br J Clin Pharmacol. 2019; 85(6): 1052–1062, doi: 10.1111/bcp.13867
29. Drake M, Clarke B, Khosla S. Bisphosphonates: Mechanism of Action and Role in Clinical Practice. Mayo Clin Proc. 2008; 83(9): 1032–1045, doi: 10.4065/83.9.1032
30. He B, Zhao J, Zhang M, et al. Zoledronic acid and fracture risk: a meta-analysis of 12 randomized controlled trials. Eur Rev Med Pharmacol Sci. 2021; 25(3): 1564–1573
doi: 10.26355/eurrev_202102_24865
31. Chatziravdeli V, Katsaras G, Katsaras D, et al. A systematic review and meta-analysis of interventional studies of bisphosphonates and denosumab in multiple myeloma and future perspectives. J Musculoskelet Neuronal Interact. 2022; 22(4): 596–621.
32. Johansen M, Levring M, Stokbro K, et al. Novel Developments in the Treatment of Multiple Myeloma-Associated Bone Disease. Cancers (Basel). 2023; 15(23): 5585,
doi: 10.3390/cancers15235585
33. Terpos E, Zamagni E, Lentzsch S, et al. Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group. Lancet Oncol. 2021; 22(3): e119–e130,
doi: 10.1016/S1470-2045(20)30559-3
34. Coluzzi F, Rolke R, Mercadante S. Pain Management in Patients with Multiple Myeloma: An Update. Cancers (Basel). 2019; 11(12): 2037, doi: 10.3390/cancers11122037
35. Innao V, Allegra A, Ginaldi L, et al. Reviewing the Significance of Vitamin D Substitution in Monoclonal Gammopathies. Int J Mol Sci. 2021; 22(9): 4922, doi: 10.3390/ijms22094922
36. Wu D, Li L, Wen Z, et al. Romosozumab in osteoporosis: yesterday, today and tomorrow. J Transl Med. 2023; 21(1): 668, doi: 10.1186/s12967-023-04563-z
37. Toscani D, Bolzoni M, Ferretti M, et al. Role of Osteocytes in Myeloma Bone Disease: Anti-sclerostin Antibody as New Therapeutic Strategy. Front Immunol. 2018;9:2467, doi: 10.3389/fimmu.2018.02467
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Copyright (c) 2025 Aleksandra Stupecka, Kamil Ciechomski, Wiktoria Cecuła, Joanna Rypel-Bośka, Natalia Siuta , Marcin Migiel, Izabela Brynczka, Klaudia Goleniewska, Jakub Miaśnikiewicz
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