Multiple Myeloma — Orthopaedic View

Multiple myeloma (MM) is the most common primary malignancy of bone in adults over 40 years. It is a neoplasm of plasma cells (terminally differentiated B-lymphocytes) arising in the bone marrow. While myeloma is primarily managed by haematology, it frequently presents to orthopaedic surgeons with bone pain, pathological fractures, spinal cord compression, and hypercalcaemia — all requiring surgical or procedural intervention. Understanding the disease biology, the unique radiological pattern, the haematological workup, and the orthopaedic management principles is essential.

• Epidemiology: incidence approximately 6 per 100,000 per year; peak age 65–70 years; median age at diagnosis 69 years; slightly more common in males and in Black populations; 5-year survival has improved dramatically from ~25% (1990s) to ~55–60% with modern treatment (bortezomib, lenalidomide, autologous stem cell transplantation); skeletal involvement at diagnosis occurs in approximately 80% of patients
• Pathophysiology of bone destruction in myeloma: myeloma plasma cells produce RANKL and inhibit OPG (osteoprotegerin) → massive osteoclast activation → widespread lytic bone destruction; DKK-1 (Dickkopf-1) produced by myeloma cells inhibits the Wnt signalling pathway in osteoblasts → suppressed bone formation; the net result is `pure osteolysis` without any reparative new bone formation — this is why myeloma lesions are `cold` on isotope bone scan (no osteoblast activity → no new bone → no technetium uptake); DKK-1 also explains why serum alkaline phosphatase is often NORMAL or LOW in myeloma (despite extensive bone destruction) — in contrast to metastatic carcinoma where ALP is elevated

• Additional SLiM-CRAB criteria (2014 International Myeloma Working Group update): S — Sixty percent or more plasma cells on bone marrow biopsy; Li — Light chain ratio ≥100 (involved:uninvolved); M — More than one focal lesion on MRI ≥5 mm; these `biomarkers of malignancy` indicate ultra-high risk smouldering myeloma requiring treatment even without CRAB symptoms

• Pathological fracture of the proximal femur: the most common orthopaedic surgical emergency in myeloma; indication for prophylactic or therapeutic intramedullary nailing or endoprosthetic replacement; intramedullary nail (cephalomedullary nail) is preferred for impending or established subtrochanteric or femoral shaft fractures — provides immediate stability and allows early weight-bearing; arthroplasty (hemiarthroplasty or total hip replacement) is preferred when the femoral head/neck is destroyed or when fracture pattern is not amenable to nailing; pre-operative radiotherapy (RT) to the lesion followed by surgical stabilisation reduces local recurrence; a critical principle: in myeloma, the ENTIRE femur should be protected if femoral fixation is performed — a nail spanning the full length protects against developing lesions elsewhere in the femur (use of a short nail leaving the distal femur unprotected risks a second pathological fracture through an unrecognised distal lesion)
• Spinal cord compression in myeloma: an oncological emergency; presents with back pain, progressive weakness, sensory loss, and urinary/bowel dysfunction; MRI of the whole spine urgently; treatment — high-dose dexamethasone immediately (reduces cord oedema and has direct anti-myeloma effect); radiotherapy to the compressing lesion (myeloma is radiosensitive — 30 Gy over 10 fractions); surgical decompression (posterior laminectomy ± anterior corpectomy ± instrumented fusion) for failure of RT, mechanical instability, or severe cord compression with rapid neurological deterioration; surgical decompression in myeloma is a palliative procedure — oncological control is the primary aim
• Vertebral augmentation — vertebroplasty and kyphoplasty: for painful vertebral compression fractures in myeloma without neurological compromise; both involve percutaneous injection of polymethylmethacrylate (PMMA) bone cement into the collapsed vertebral body under fluoroscopic guidance; kyphoplasty first inflates a balloon tamp to create a cavity and restore vertebral height before cement injection (reducing cement leakage risk compared to vertebroplasty); both procedures provide rapid and reliable pain relief; cement leakage into the spinal canal or venous system is the main risk; contraindicated when there is posterior cortex destruction with canal compromise (cement could leak into the cord)
• Bisphosphonate therapy: zoledronic acid (4 mg IV every 3–4 weeks) or denosumab (anti-RANKL monoclonal antibody) are standard for all myeloma patients with bone involvement; reduces skeletal-related events (pathological fractures, need for radiation or surgery, hypercalcaemia); osteonecrosis of the jaw (ONJ) is a recognised complication of long-term bisphosphonate therapy — dental assessment and any necessary dental work must be completed before starting bisphosphonates; invasive dental procedures should be avoided during treatment; drug holidays may be considered after 2 years of therapy

• Myeloma = most common PRIMARY bone malignancy in adults >40; plasma cell neoplasm; CRAB criteria (Hypercalcaemia, Renal failure, Anaemia, Bone lesions); IgG most common M-protein
• Bone scan is COLD (falsely negative) in myeloma — DKK-1 inhibits osteoblasts → no new bone formation → no Tc-99m uptake; use WBLDCT or PET-CT instead
• ALP normal or LOW in myeloma despite extensive osteolysis — DKK-1 mechanism; contrast with metastatic carcinoma (ALP elevated); ALP elevation in myeloma = suspect healing fracture, concurrent Paget`s, or secondary malignancy
• Rouleaux formation on blood film (red cells stack like coins — elevated immunoglobulins); markedly elevated ESR; normochromic normocytic anaemia; hypercalcaemia; elevated total protein and globulins
• WBLDCT has replaced skeletal survey — detects lytic lesions 2–3× more sensitively; NICE recommends WBLDCT for all myeloma staging; bone scan unreliable
• Proximal femoral myeloma: nail the entire femur (full-length nail) — protects against second fracture through distal unrecognised lesion; arthroplasty if head/neck destroyed; pre-op RT + surgery
• Spinal cord compression: emergency; IV dexamethasone immediately; RT (myeloma is radiosensitive); surgery for RT failure, mechanical instability, or rapid neurology deterioration
• Vertebroplasty / kyphoplasty: rapid pain relief for vertebral compression fractures; PMMA cement; kyphoplasty restores height + lower cement leak risk; contraindicated if posterior cortex destroyed with canal compromise
• Bisphosphonates: zoledronic acid standard; reduces skeletal events; ONJ complication — dental review before starting; avoid invasive dental procedures during treatment
• Pepper-pot skull on plain X-ray: multiple punched-out lytic lesions without sclerotic rim; pathognomonic of myeloma; also seen in hyperparathyroidism (brown tumours) — distinguish by clinical context and biochemistry