Definition and differential
- Radiolucent bone destruction - haematological cause = myeloma until proven otherwise
- Distinguish from metastatic solid tumour, and from benign lesions (fibrous dysplasia, bone cysts)
Epidemiology
- Multiple myeloma - lytic lesions present in a majority at diagnosis
- Median age at myeloma diagnosis ~65-70yrs; consider in older adults with back pain + anaemia + renal impairment
Mechanisms and causes
- Myeloma - plasma cells upregulate RANKL, downregulate OPG -> unopposed osteoclast activation, coupled with suppressed osteoblast activity -> pure lytic lesions with no reactive sclerosis (unlike most solid-tumour bone mets, which can be mixed/sclerotic)
- Other hameatological causes: Langerhans cell histiocytosis (esp. skull lesions in children), lymphoma with bone involvement
- Non-haematological differential: metastatic carcinoma (breast, lung, renal, thyroid, prostate - though prostate classically sclerotic), primary bone tumours
Myeloma-directed work-up
- Whole-body low-dose CT (or MRI/PET-CT) - now preferred over skeletal survey (plain films) - more sensitive for lytic lesions
- Serum/urine electrophoresis + immunofixation, serum free light chains
- FBE (anaemia), UEC (renal impairment), corrected calcium (CRAB criteria: Calcium, Renal, Anaemia, Bone)
- Bone marrow biopsy - clonal plasma cell percentage confirms diagnosis
- Bone lesions themselves are not routinely biopsied if myeloma work-up is positive - risk of pathological fracture
Systemic (myeloma) management
Systemic (myeloma)
- Bisphosphonate (zoledronic acid) or denosumab - all patients with lytic bone disease, regardless of whether systemic anti-myeloma therapy is also given - reduces skeletal-related events
- Denosumab preferred if renal impairment
- Dental check + avoid invasive dental work before starting - osteonecrosis of the jaw risk
- Anti-myeloma therapy (proteasome inhibitor/IMiD/anti-CD38-based regimens +/- autologous transplant) - treats the underlying clone
Local/orthopaedic management
Local/orthopaedic
- Radiotherapy - localised painful lesions, cord compression, impending fracture
- Prophylactic fixation - long bone lesions at high fracture risk (per Mirels criteria)
- Vertebroplasty/kyphoplasty - selected painful vertebral collapse
- Analgesia (avoid NSAIDs if renal impairment)
Associations
- Hypercalcaemia, renal impairment, anaemia (CRAB - myeloma end-organ damage criteria)
- Pathological fracture, spinal cord compression (vertebral involvement)
- Amyloidosis - can coexist with myeloma (AL amyloid from clonal light chains)
Course
- Skeletal-related events (fracture, cord compression, need for radiotherapy/surgery) are a major cause of morbidity in myeloma
- Lytic lesions generally do not heal/recalcify even with successful treatment - structural risk persists, ongoing bone-protective therapy continued
- Spinal cord compression from vertebral collapse/plasmacytoma - oncological emergency, urgent MRI + dexamethasone + radiotherapy/surgery
8 of 8 sections written · drafted 2026-09-13