Multiple Myeloma
Multiple Myeloma is a malignant plasma cell disorder that causes bone marrow infiltration, excessive monoclonal protein production, and skeletal destruction through osteoclast activation and osteoblast suppression. It primarily affects older adults and commonly presents with bone pain, anaemia, renal dysfunction, and recurrent infections.
Radiographs reveal multiple “punched-out” lytic lesions, while MRI and PET/CT detect marrow and systemic involvement. Diagnosis is based on CRAB criteria and serum or urine monoclonal protein detection. Treatment involves proteasome inhibitors, immunomodulatory agents, corticosteroids, and autologous stem cell transplantation, complemented by bisphosphonates for bone protection and surgery for pathological fractures.
Prognosis has improved with modern therapies, yet relapse remains common, requiring multidisciplinary and long-term management.
Definition
Multiple Myeloma (MM) is a malignant plasma cell neoplasm characterized by clonal proliferation within the bone marrow, excessive production of monoclonal immunoglobulins (M-protein), and widespread skeletal destruction. It accounts for approximately 10% of all haematologic malignancies and is the most common primary malignant bone tumor in adults.
Pathophysiology
Neoplastic plasma cells stimulate osteoclast activity through cytokines such as RANKL and IL-6, causing osteolytic lesions, hypercalcemia, and bone pain. Osteoblast inhibition results in poor bone repair, while bone marrow infiltration leads to anaemia, thrombocytopenia, and immunodeficiency.
Epidemiology
Most cases occur between the ages of 60 and 70, with a slight male predominance. Higher incidence is reported in individuals of African descent and in patients with pre-existing monoclonal gammopathy of undetermined significance (MGUS).
Clinical Features
Patients typically present with bone pain (spine, ribs, pelvis), fatigue, recurrent infections, or anaemia. Advanced cases may show renal dysfunction, hypercalcaemia, and pathological fractures. Spinal involvement can cause cord compression and neurological deficits.
Diagnostic Criteria (CRAB Features)
C – Hypercalcaemia (>11 mg/dL)
R – Renal failure (creatinine >2 mg/dL)
A – Anaemia (Hb <10 g/dL)
B – Bone lesions (osteolytic defects or pathological fractures)
Laboratory Findings
Serum protein electrophoresis showing an M-spike, Bence–Jones proteinuria, elevated ESR, β2-microglobulin (prognostic marker), and normocytic anaemia. Bone marrow biopsy confirms clonal plasma cell infiltration (>10%).
Imaging
X-ray: Multiple “punched-out” lytic lesions, diffuse osteopenia, and vertebral collapse.
MRI: Detects early marrow involvement and spinal cord compression.
PET/CT: Evaluates disease activity, metastasis, and response to therapy.
Differential Diagnosis
Metastatic carcinoma (breast, lung, prostate), lymphoma, fibrous dysplasia, and hyperparathyroidism (Brown tumor).
Treatment
Systemic Therapy: Proteasome inhibitors (bortezomib), immunomodulators (lenalidomide, thalidomide), corticosteroids, and autologous stem cell transplantation in eligible patients.
Bone Protection: Bisphosphonates or denosumab to reduce skeletal complications.
Radiotherapy: Used for local pain control or impending fractures.
Surgery: Indicated for pathological fractures or spinal instability; fixation should consider poor bone quality and systemic disease status.
Prognosis
Median survival ranges from 5–7 years, improved by novel agents and transplantation. Prognosis depends on cytogenetic abnormalities and treatment response. Relapse is common, emphasizing lifelong follow-up.
Orthopaedic Relevance
Orthopaedic surgeons often first detect myeloma through evaluation of unexplained fractures or lytic bone lesions. Surgical management should be planned after biopsy confirmation and multidisciplinary discussion, prioritizing pain relief and stabilization.
Key Points
Most common primary malignant bone tumor in adults.
Radiographs show characteristic “punched-out” lytic lesions without periosteal reaction.
Multimodal therapy combining systemic and supportive care is essential.
Orthopaedic intervention focuses on maintaining function and stability.
References
Rajkumar SV. Multiple Myeloma: 2024 Update on Diagnosis, Risk-Stratification, and Management. Am J Hematol. 2024;99(5):846–865.
Terpos E, et al. Advances in the Diagnosis and Management of Myeloma Bone Disease. Nat Rev Rheumatol. 2023;19(1):36–52.
Kyle RA, Rajkumar SV. Multiple Myeloma. N Engl J Med. 2004;351(18):1860–1873.
