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It is clear the pain is not just a somatic manifestation but a complex neurohormonal pathology

This activates downstream signaling, including c-Fos, which subsequently activates nuclear factor of activated T cells 1 (NFATc1), ultimately promoting the expression of various osteoclast differentiation genes (e.g., tartrate-resistant acid phosphatase (TRAP), acid phosphatase 5 (ACP5), matrix metallopeptidase 9 (MMP9), and ATPase H + transporting V0 subunit d2 (ATP6)), thereby enhancing the osteoclast differentiation capacity of monocytes (43)

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Following endocytosis, Fe is reduced to Fe by the six-transmembrane epithelial antigen of the prostate 3 (STEAP3), and subsequently stored in mitochondria, the endoplasmic reticulum, ferritin, and the iron pool