Circulating sRANKL, Periostin, and Osteopontin as Biomarkers for the Assessment of Activated Osteoclastogenesis in Myeloma Related Bone Disease.
Vladimir GerovDaniela GerovaIlina MichevaMiglena NikolovaMilena PashevaNeshe NazifovaBistra GalunskaPublished in: Cancers (2023)
The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls ( p < 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation ( p < 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others ( p < 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment.
Keyphrases
- newly diagnosed
- end stage renal disease
- multiple myeloma
- bone marrow
- ejection fraction
- computed tomography
- low dose
- chronic kidney disease
- stem cell transplantation
- prognostic factors
- magnetic resonance imaging
- mesenchymal stem cells
- body composition
- risk factors
- cell therapy
- high dose
- artificial intelligence
- signaling pathway
- cell proliferation
- electronic health record
- deep learning
- inflammatory response
- endoplasmic reticulum stress
- contrast enhanced
- human health