Localized bone pain with an osteolytic profile

Specialty: Hematology.

• Neoplastic focal skeletal pain
• bone pain due to lytic lesions
• punch pain

Why it occurs

• Multiple myeloma (neoplasm of clonal plasma cells that secrete osteoclast-activating cytokines such as RANKL and inhibit osteoblasts through the Wnt pathway, causing destruction of the bone matrix with focal lytic lesions that are extremely painful and prone to pathological fractures)
• Primary or secondary bone lymphoma (neoplastic infiltration of the bone stroma with local lysis due to compression and tumor enzymes)
• Acute lymphoblastic or myeloblastic leukemia (massive clonal expansion within the spinal cavity increases intraosseous pressure, manifesting especially in the long bones of children and young adults)
• Aggressive systemic mastocytosis (mast cell infiltration of the bone marrow with local release of histamine and osteolytic cytokines)
• Secondary bone metastases from solid tumors (breast, prostate, lung or kidney cancer, as the main differential diagnosis).

Initial workup

Serial conventional radiographs of the complete skeleton (bone series: skull, total spine, pelvis and long bones; will reveal classic lytic "punched out" lesions without peripheral osteoblastic reaction); magnetic resonance imaging (MRI) of the entire spine and pelvis or low-dose whole-body CT (techniques with greater sensitivity than plain radiography to detect incipient lytic lesions and evaluate spinal canal involvement); bone marrow aspirate and biopsy with immunohistochemical study (to confirm percentage of clonal plasma cells >10%); serum and urinary protein electrophoresis combined with immunofixation (detection of the M component) and quantification of free light chains in serum (altered kappa/lambda ratio); blood analysis with levels of total calcium corrected for albumin, phosphorus, serum creatinine, albumin, beta-2-microglobulin and LDH.

Standard management

• Zoledronic acid — potent intravenously administered bisphosphonate; selectively inhibits the activity of osteoclasts, reducing bone pain, the risk of pathological fractures and hypercalcemia crises; requires fine adjustment according to creatinine clearance and calcium and vitamin C supplementation if active hypercalcemia is not present
• Denosumab — monoclonal antibody directed against RANKL; It potently inhibits the maturation of osteoclasts, indicated in multiple myeloma with severe renal dysfunction as it is not cleared through the kidneys.
• Bortezomib — proteasome inhibitor for subcutaneous or intravenous use, a mainstay in the treatment of multiple myeloma that induces apoptosis of plasma cells and indirectly promotes osteoblastic regeneration
• Dexamethasone (high-potency corticosteroid essential to reduce perilesional bone edema, calm the associated neuropathic pain and reduce serum calcium by blocking its intestinal absorption).